ISSN:0306-0012    

DOI:10.1039/CS97201FX009

出版商:RSC    

年代:1972

数据来源: RSC

ISSN:0306-0012    

DOI:10.1039/CS97201BX011

出版商:RSC    

年代:1972

数据来源: RSC

摘要:

Conformational Studies on Small Molecules* By E. B. Wilson MALLINCKRODT CHEMICAL LABORATORY, HARVARD UNIVERSITY, CAMBRIDGE, MASSACHUSETTS 02138, U.S.A. 1 Introduction In recent years, conformational analysis has attracted a great deal of attention and much effort. Various experimental methods have been applied to a large number of chemical species to determine the orientations about single bonds which are the most stable, and the many implications regarding reactivity, etc. have been widely discussed.1-6 For small molecules such as 1,Zdisubstituted ethanes it was Mizushimae in the 1930s who showed that these tended to occur as trans and gauche forms (see Figure 1). Since these differ merely by a rotation of about 120” around the carbon-carbon single bond, which, for small substituents at least, does not require the molecule to surmount a very large potential energy barrier, it is not normally possible to separate these rotational isomers, rotamers, or conformers in the liquid or gaseous phases.Besides the intrinsic interest which chemists have in structure, there are a number of good reasons for studying the conformations of molecules. One is the biological importance of this phenomenon.’ As is well known, the exact way a protein chain folds into a compact, biologically active molecule, such as an enzyme, involves very specific conformational choices. If the chain is unfolded into an extended form, the biological activity is normally lost. In a number of cases it has been shown that such an uncoiled protein, when given the proper environment, i.e.solvent, temperature, pH, will spontaneously refold to its active form. Naturally, it would be desirable to be able to predict the conformations, angular distortions, relative energies, barrier heights, etc. from sound and convincing theoretical or empirical bases. This is clearly a complicated problem, * Based upon Centenary Lecture delivered at Glasgow, Sheffield, and Bristol during March 1971. See, for example, the review of the work of Barton and Hassel (Nobel awards, 1969) by E. L. Eliel, Science, 1969, 166, 718.* 0. Hassel and B. Ottar, Acfu Chern. Scund., 1947,1,929. a D. H. R. Barton, ‘The Principles of Conformational Analysis’, in ‘Les Prix Nobel en 1969’, Norstedt and Soner, Stockholm, 1970, pp.119-129. E. L. Eliel, N. L. Allinger, S. J. Angyal, and G. A. Morrison, ‘Conformational Analysis’, Interscience, New York, 1965. M. Hanack, ‘Conformational Theory’, Academic Press, New York, 1965. S. Mizushima, ‘Structure of Molecules and Internal Rotation’, Academic Press, New York, 1954, p. 24. ‘I J. T. Edsall, in ‘Structural Chemistry and Molecular Biology’, ed. A. Rich and N. Davidson, W. H. Freeman and Co., San Francisco, 1968, p. 89. 293 1 Conformotional Studies on Small Molecules Figure 1 (a) trans and (b) gauche rorumers of 1,Z-dichforoethane but many systems have been set up for the purpose of doing this.* One reason for collecting more experimental data on small rotamer species is to provide See, J.E. Williams, P. J. Stang, and P. von R. Schleyer, Ann. Rev.Phys. Chem., 1968, 19, 531. Wilson checks on these published computational methods, and, where they meet these tests, to enable the predictive methods to be extended to wider classes of molecules. A more basic aim is to acquire fundamental information about non-bonded forces within molecules. Even though our knowledge of bonded forces is far from adequate, it is considerably more advanced than our understanding of non-bonded forces ;this situation needs improvement. 2 Experimental Techniques A great many experimental techniques have been used to gain information about rotamers. Mizushima6 and others found that i.r. and Raman spectroscopy were particularly useful.Often the crystalline form has a simpler spectrum than the liquid or gas, leading to the assumption that the crystal contains only one form while the extra lines in the other phases are assignable to the other form (or forms). This view was strengthened by the observation that the two sets of lines in the liquid or gas have different temperature coefficients of intensity. Incidentally, measurements of such intensity coefficients (which are hard to make accurately) give values for the energy difference between the rotameric forms. Electron diffraction ~tudies~~~J~ and the change with temperature of the average dipole moment6 have also been employed, and have been particularly important in the early history of the subject. Still another method uses acoustic dispersion or absorption measurements.11J2 In more recent years the most used tool has surely been n.m.r., particularly over a range of (low) temperatures.For many compounds, by lowering the temperature the rate of interconversion of the rotamer forms can be reduced sufficiently so that two sets of n.m.r. lines can be observed, one set for each rotamer. At higher temperatures, these first broaden, then merge, and finally sharpen to one set of lines representing the rapidly interconverting molecule. From such measurements, and others related to them, values for the free energy of activation at the barrier between rotamer forms can be found and some inferences (not always conclusive) drawn about the conformations present.13 This technique is responsible for much of our present knowledge about con- formations, but has been confined to liquids and solutions.However, microwave spectroscopy can give much more detailed and more certain information about rotamers than any of the other methods.14 It has serious limitations: it can be applied so far only to rather simple molecules and has, in the past, required considerable effort for each molecule. For this reason 0. Bastiansen, ref. 7, p. 640. lo Y.Morino and K. Kuchitsu, J. Chem. Phys., 1958, 28, 175. l1 M. Eigen and L. de Maeyer, in ‘Techniques of Organic Chemistry’, ed. A. Weissberger, Interscience, New York, 1963, 2nd edn., vol. VIII/2, p. 895. l8 E. Wyn-Jones and W. J. Orville-Thomas, ‘Molecular Relaxation Processes’, Chem.SOC. Special Publ., 1966, No.20, p. 209. l3 H. Booth, ‘Applications of ‘H N.M.R. to the Conformational Analysis of Cyclic Com- pounds’, Progr. N.M.R. Spectroscopy, ed. J. W. Emsley, J. Feeney, and L. H. Sutcliffe, Pergamon Press, Oxford, 1969, ch. 3. l4 V. W. Laurie, Accounts, Chem. Res., 1970, 3, 331. Conformational Studies on Small Molecules it has been mainly of value in providing detailed information on some basic molecules, useful as a check on theories or as a source of fitted parameters for empirical theories. There are several approaches to a problem like this which can be defended. The most obvious is to assemble all the pertinent information from all sources, all techniques, and then attempt a grand synthesis which will account for every- thing.Attractive as this approach sounds, it has serious drawbacks. First, few have the energy, or the breadth of understanding, to undertake such a project in view of the massive amount of literature. Secondly, it is a rare person who can critically examine many different fields and reject the unreliable or patently false data that unfortunately are all too abundant. It takes only a few wrong numbers to destroy any attempt at explanation. Finally, it is often easy to introduce enough parameters so that a large but finite amount of data is fitted with a meaningless theory. An alternative is to adopt a very parochial viewpoint and attempt to construct a theory which is based entirely, or almost entirely, on information from one technique alone, information which is carefully assessed and judged to be reliable.If this can be done, then the conclusions can be compared with those drawn independently by others from other sources of information. If various techniques in a truly independent way lead to the same conclusions, we can properly have vastly more confidence in them than otherwise. 3 The Microwave Method In microwave spectroscopy a given molecule is under observation only during the time between two collisions, since almost all collisions cause transitions to other rotational states. Rotamer species rapidly interconvert, but mostly this reaction requires collisions. The result is that the microwave spectrum of a compound which occurs in two or more conformations normally contains the transitions of all the rotameric forms present in sufficient abundance, just as in the case of a mixture of stable, non-reactive species.Further, the high resolving power available lessens the chances that lines of one rotamer will cover up lines of another, although this does sometimes happen. An exceptional situation occurs when quantum mechanical tunnelling is important. This will be discussed later. Consequently, it is possible in suitable cases to analyse the spectra of the separate rotamers and in principle to obtain for each form all the information usually extractable from the microwave spectrum of a single, pure species. This includes structure, particularly the value of the dihedral angle, dipole moments, low vibration frequencies, especially the torsional frequency, barriers to internal rotation of methyl groups, etc.15 Particularly interesting is the collection of information which can lead to the determination of a potential function for rotation about the single bond from one rotamer to the others.Some of the limitations of the microwave method are being a little eased by J. E. Wollrab, ‘Rotational Spectra and Molecular Structure’, Academic Press, New York, 1967. Wilson various current developments. The availability of commercial microwave spectro- meters greatly speeds the collection of data and may make possible improved accuracy of intensity measurements. This greater speed and ease should lead to quicker analyses and also encourage more studies of vibrational satellites and isotopic forms. The extended use of microwave-microwave double resonance and, more recently, of radio frequency-microwave double resonance has also aided the assignment of difficult spectra.Computer averaging techniques provide greater sensitivity, which can often be critical. In addition to these experimental developments, there have been several extensions of the theory of the rotational spectra, of molecules with an internal degree of freedom.16-la Table 1 lists some of the molecules for which two or more rotamers have been identified and studied by microwave spectroscopy. It is based upon the list compiled by Morino and Hirota20 but contains more recent entries, kindly supplied by Dr. F.Wodarczyk. Also shown is the nature of the rotamers, such as cis, gauche, etc., with the more stable form underlined, where known. Besides these molecules, a great many have been studied in which only one form was observed, although there are reasons to believe that a second form exists, perhaps with insufficient dipole moment or too high an energy [see Table 1 (ii)]. A con-siderable number of additional species are known to be under investigation currently in many laboratories. Table 1 Molecules studied by microwave spectroscopy (i) Molecules with at least two stable forms identified The following molecules are arranged according to the bond about which hindered rotation leading to the different rotameric forms takes place. The designation of the stable forms refers to the relative orientations of the under- lined functional groups.More stable form is underlined. Molecule Dihedral Stable forms Ref. angle (") c-c (sp3-sp3) n-Propyl fluoride CH3CH2CH2F_ 117 trans gauche-n-Propyl chloride CH3CH2CH2g 110 trans gauche n-Propyl bromide CH3CH2CH2E trans gauche-n-Propyl iodide CH3CH2CHzI trans gauche n-Pr opano 1 C&13CH2CH20H 116 trans gauche n-Propyl cyanide CH3CH2CH2CN. trans gauche-n-Prop ylace tylene CH3CH2CH2CiCH 115 trans gauche l6 R. Meyer and E. B. Wilson, J. Chem. Phys., 1970, 53, 3969. l7 J. V. Knopp and C. R. Quade, J. Chem. Phys., 1970, 53, 1. 18H. M. Pickett, J. Chem. Phys., 1972, 56, 1715. A. Bauder, E. Mathier, R. Meyer, M. Ribeaud, and H.H. Gunthard, Mol. Phys., 1968,15, 597. ao Y. Morino and E. Hirota, Ann. Rev. Phys. Chem., 1969, 20, 139. Conformational Studies on Small Molecules Table 1 (cont.) Molecule Dihedral Stable forms Ref. angle (") n-Propyl isocyanide trans gauche h n-Butyraldehyde 101 trans gauche i Cyclohexyl fluoride axial equatorial j C-N Piperidine axial equatorial k Ethylamine trans gauche 1 c-0 Edhanol 126 trans gauche rn Isopropanol trans gauche n Ethyl formate 95 tram gauche o-Ethyl nitrate 95 * gauche p c-s Ethanet hiol trans gauche q Ethyl methyl sulphide CH3CH2SCH3 trans gauche r transIsopropanethiol (CH3)ZCESg -gauche s c-c (sp2-sp3) 3-Fluoropropene CHZ=CHCH2I_F 125 LS gauche t 3-Chloropropene CH2=CHCH2CJ 122 cis gauche II Ally1 cyanide CH 2=CHCH 2C-N c& gauche v But-1-ene CH2=CHCH2CJ3 cis gauche w Propionaldehyde CH,CH,CHO_ 131 cis gauche x Propionyl fluoride CH3CH2CQF 120 Cis gauche y Fluoroacetyl fluoride F_CH,COE 180 cis trans 2-Chloroacetaldehyde &'JCHzCHQ cis tram aa Cyclopropane-carbaldeh yde Cis ZS 66 Cyclopropanecarbony1 fluoride C@ trans cc 298 Wilson Molecule Dihedral Stable forms Ref.angle (") c-c (sp2-sp2) Acryloyl fluoride CH,=CHCOF 180 sym-cis sym-trans dd Acrylic acid CHz=CHCOOH 180 cis trans 2-Furfuraldehyde c$CHe 180 cis tms $c0 Miscellaneous Nitrous acid EON9 180 cis trans gg Methyl nitrite CH30NQ cis trans hh inner outer iiMe thylhy drazine CH3NEJNEJ --Acet aldoxime CHSCH-N9.H 180 cis trans jj (ii) Molecules with one rotameric form identified Molecule Form found Ref.1-Chloro-2--fluoroet hane -FCH2CH2Cl gauche kk 1,2-Difluoroethane _FCH,CH,E gauche 11 1,l,ZTrifluoroethane EJF2CCH2E gauche mm 2-HaIogenoethanols ZCH2CHQH gauche nn (X = F, C1, or Br) Ethylene glycol HeCH2CH2gH gauche 00 Cyclopropylme than01 PP CXLCycloprop ylamine trans 44pi;Cycl opr opylp hosphine trans rr 0 l-Fluoro-2,3-epoxypropane gauche ss p:"zE Halogenocyclobutanes equatorial tt (X = F or Cl) Morpholine equatorial uu Conformational Stirdies on Small Molecules Table 1 (cont.) Molecule Form found Ref. Go1,2-EpoxycycIopen tene boat vv Prop-2-yn-l -ol HC-CCH,O_H gauche ww Prop-Zyne-1-thiol HCrCCH,SB gauche xx AIIyI alcohol CH ,=CHCH@H gauche YY Prop-2-ene-1-thiol CH,=CHCH,SH gauche ZZ Allylamine CH,=CHCHzPJHz N cis, lone pair trans aaa Methyl ethyl ketone CH ,COCH ,CH3 frans bbb Fluoroacetone CH,CQCH,F trans ccc Glycolaldehyde HQCHZCHQ planar cis ddd Acraldehyde H,C=CHCHG sym-trans eee 1-Methylacraldehyde CH ,=C(CH,)CHO sym-trans fff Methyl vinyl ketone CH3CGCH=CHz sym-trans ggg Formic acid BcoolJ trans hhh trans-Crotonaldehyde CH&H=CHCHQ sym-trans iii Methyl formate CH,OCHO_ cis iJY-Methyl vinyl ether CH,OCH=CH, cis kkk OH non-planar, 111 structure as shown H/\H as shown mmm Glyoxal HCQCHQ trans (no spectrum) Biacetyl CH3CQCQCHS trans (no spectrum) nnn trans (no spectrum) Fluoroprene H&=CHFC=C_Hz sym-trans 000 Isoprene H&=CH(CH3)C=CH2 sym-trans PPP 1,1 -Difluorobutadiene F,C_=CHCH=GHa sym-trans 944 Wilson Molecule Form found Ref.1,l -Difluoro-3-methyi- butadiene sym-trans rrr a E. Hirota, J. Chem. Phys., 1962,37,283; b T. N. Sarachman, J. Chem. Phys., 1963, 39,469; C T. N. Sarachman, 23rd Symposium on Molecular Structure and Spectroscopy, The Ohio State University, Columbus, Ohio, 1968, paper N7; S. Armstrong, Appl. Spectroscopy, 1969, 23, 575; d T. N. Sarachman, 24th Symposium on Molecular Structure and Spectroscopy, The Ohio State University, Columbus, Ohio, 1969, paper U9; e L. M. Imanov, A. A. Abdura-khmanov, and R. A. Ragimova, Optics and Spectroscopy, 1967, 22, 456; ibid., 1969, 26, 75; Phys. Letters (A), 1970, 32, 123;fE.Hirota, J. Chem. Phys., 1962, 37, 2918; B F. Wodarczykand E. B. Wilson, J. Chem. Phys., 1972,56, 166; D. Damiani and A. M. Mirri, Chem. Phys. Letters, 1971, 10, 351; h M. J. Fuller, personal communication; f P. L. Lee and R. H. Schwendeman, 25th Symposium on Molecular Structure and Spectroscopy, The Ohio State University, Columbus, Ohio, 1970, paper C10; L. Pierce and R. Nelson, J. Amer. Chem. SOC.,1966, 88,216; L. Pierce and J. F. Beecher, J. Amer. Chem. SOC., 1966,88,5406; C. C. Costain, P. J. Buckley, and J. E. Parkin, Chem. Comm., 1968,668; 1 Y. S. Li, 24th Symposium on Molecular Structure and Spectroscopy, The Ohio State University, Columbus, Ohio, 1969, paper 01 ;na L. M. Imanov and Ch. 0. Kadzhar, Optics and Spectroscopy, 1963, 14, 157; J.Michielsen-Effinger, Ann. SOC. sci. Bruxelles, Ser. ZZZ, 1964, 78, 223; J. Phys. (Paris), 1969, 30, 336; M. Takano, Y. Sasada, and T. Satoh, J. Mol. Spectroscopy, 1968, 26, 157; Y. Sasada, M. Takano, and T. Satoh, J. Mol. Spectroscopy, 1971, 38, 33; S. Kondo and E. Hirota, J. Mol. Spectroscopy, 1970,34,97; A. A. Abdurakhmanov, M. N. Elchiev, and L. L. Imanov, Zzvest. Akad. Nauk Azerb. S.S.R., Ser. jiz.-mat. i tekh. Nauk, 1970, 58; O J. M. Riveros and E. B. Wilson,J. Chem. Phys., 1967,46,4605; p D. G. Scroggin and J. M. Riveros, personal communication; Q Ch. 0. Kadzhar, A. A. Abbasov, and L. M. Imanov, Optics and Spectroscopy, 1968, 24, 334; Zzvest. Akad. Nauk Azerb. S.S.R.,Ser. jz.-mat. i tekh. Nauk, 1968, 71; M. Hayashi, W.Ohno, and H. Murata, Symposium on Molecular Structure, Chem. SOC. Japan, 1968, Tokyo, paper 1A8; S. Yamada, M. Hayashi, and H. Murata, Symposium on Molecular Structure, Chem. SOC. Japan, Tokyo, 1968, paper 1A7; J. H. Griffiths, Symposium on Molecular Structure and Spectroscopy, The Ohio State University, Columbus, Ohio, 1970, paper C3; t E. Hirota, J. Chem. Phys., 1965, 42, 2071; P. Meakin, D. 0. Harris, and E. Hirota, J. Chem. Phys., 1969,51,3775;U E. Hirota, J. Mol. Spectroscopy, 1970,35,9; K. V. L. N. Sastry, V. M. Rao, and S. C. Dass, Canad.J. Phys., 1968,46,959; S. Kondo, E. Hirota, and Y. Morino, J. Mol. Spectroscopy, 1968, 28, 471 ; S. S. Butcher and E. B. Wilson. J. Chem. Phys., 1964, 40, 1671; Y 0. L. Stiefvater and E. B. Wilson, J. Chem. Phys., 1969, 50, 5385; ZE.Saegebarth and E. B. Wilson, J. Chem. Phys., 1967, 46, 3088; R. G. Ford, personal communication; bb H. N. Volltrauer and R. H. Schwendeman, J. Chem. Phys., 1971, 54, 260; CC H. N. Volltrauer and R. H. Schwendeman, J. Chem. Phys., 1971,54,268; dd J. J. Keirns and R. F. Curl, jun., J. Chem. Phys., 1968,48,3773;ee K. Bolton, N. L. Owen, and J. Sheridan, Nature, 1968, 218, 266;ffF. Moennig, H. Dreizler, and H. D. Rudolph, Z. Naturforsch., 1965,20, 1323; gg A. P. Cox and R. L. Kuczowski, J. Amer. Chem. SOC.,1966,88,5071; A. P. Cox, A. H. Brittain, and D. J. Finnigan, Trans. Faraduy SOC.,1971, 67,21 79;hh W. D. Gwinn, R. J. Anderson, and D. Stelman, Symposium on Gas Phase Molecular Structure, Austin, Texas, 1968, paper M2; D.Stelman, Diss. Abs., 1965, 25, No. 64-9094; R. P. Lattimer and M. D. Harmony, J. Chem. Phys., 1970,53,4575; jj R. S. Rogowski and R. H. Schwendeman, J. Chem. Phys., 1969, 50, 397; kkI. A. Mukhtarov, Doklady Akad. Nauk S.S.S.R.,1957, 115, 486; Zzvest. Akad. Nauk S.S.S.R.Ser.fiz., 1958, 22, 1154; Optika i Spektroskopiya, 1959, 6, 260; Zzvest. Akad. Nauk Azerb. S.S.R.,Ser. fiz.-mat. i tekh. Nauk, 1964,6,37; I1S. S. Butcher, R. A. Cohen, andT. C. Rounds, J. Chem. Phys., 1971,54,4123; mm I. A. Mukhtarov, Doklady Akad. Nauk S.S.S.R.,1963, 148, 566; ibid., 1963, 151, 1076; Optika i Spektroskopiya, 1963, 14, 728; ibid., 1964, 16, 360; ibid., 1964, 16, 910; nn R. G. Azrak and E. B. Wilson, J. Chem. Phys., 1970, 52, 5299; K. S. Buckton and R. G. Azrak, J.Chem. Phys., 1970, 52, 5652; 00 H. Mollendal, personal communication; pp W. V. F. Brooks, K. V. L. N. Sastry, Symposium on Molecular Structure and Spectroscopy, The Conformational Studies on Small Molecules Table 1(cont.) Ohio State University, Columbus, Ohio, 1968, paper E5; 44 D. K. Hendricksen and M.D. Harmony, J. Chem. Phys., 1969, 51, 700; rr L. A. Dinsmore, C. 0. Britt, and J. E. Boggs, J. Chem. Phys., 1971,54,915; 88 S. C. Dass, A. Bhannik, W. V. F. Brooks, and R. M. Lees, J. Mol. Spectroscopy, 1971, 38, 281 ;tt H. Kim and W. D. Gwinn, J. Chem. Phys., 1966, 44, 865; w J. J. Sloan and R. Kewley, Canad. J. Chem., 1969,47,3453; w W. J. Lafferty, J. Mol. Spectroscopy, 1970,36, 84; ww E. Hirota, J. Mol. Spectroscopy, 1968, 26, 335; C.0.Kadzhar, G. A. Abdullaev, and L. M. Imanov, Zzvest. Akad. Nauk Azerb. S.S.R.,Ser. $z.-mat. i tekh. Nauk, 1969, 3, 26; K. Bolton, N. L. Owen, and J. Sheridan, Nature, 1968, 217, 164; zsK. Bolton and J. Sheridan, Spectrochim. Acta, 1970, A26, 1001;w A. N. Murty and R. F. Curl, jun., J. Chem. Phys., 1967,46,4167; K. V. L. N. Sastry, S. C. Dass, W. V. F. Brooks, and A. Bhaumik, J. Mol. Spectroscopy, 1969, 31,54; aaa G. Roussy, J. Demaison, I. Botskor, and H. D. Rudolf, J. Mol. Spectroscopy, 1971, 38, 535; bbb L. Pierce, C. K. Chang, M. Hayashi, and R. Nelson, J. Mol. Spectroscopy, 1969, 32, 449; CCC E. Saegebarth and L. C. Krisher, J. Chem. Phys., 1970, 52, 3555; ddd K. M. Marstokk and M. Mollendal, J. Mol. Structure, 1970,5,205; E. A. Cherniak and C.C. Costain, J. Chem. Phys., 1966,45, 104; P. Wagner, J. Fine, J. W. Simmons, and J. H. Goldstein, J. Chem. Phys., 1957, 26, 634; K. Kuchitsu, T. Fukuyama, and Y. Morino, J. Mol. Structure, 1969, 4,41; fff M. Suzuki and K. Kozima, J. Mot. Spectroscopy, 1971, 38, 314; BBBP. D. Foster, V. M. Rao, and R. F. Curl, jun., J. Chem. Phys., 1965, 43, 1064; hhh M. Suzuki and K. Kozima, Bull. Chem. SOC. Japan, 1969, 42, 2183; If* D. R. Lide, jun., Trans. Amer. Cryst. ASSOC., 1966, 2, 106; M. Suzuki and K. Kozima, Bull. Chem. SOC. Japan, 1969,42,2183; S. L. Hsu and W. H. Flygare, Chem. Phys. Letters, 1969, 4, 317; M R. F. Curl, jun., J. Chem. Phys., 1959,30, 1529; Xkk P. Cahill, L. P. Gold, and N. L. Owen, J. Chem. Phys., 1968, 48, 1620; w C. Hirose and R.F. Curl, jun., J. Mol. Spectroscopy, 1971,38, 358; mmm V. M. Rao and R. F. Curl, jun., J. Chem. Phys., 1964, 40, 3688; nnn D. R. Lide, jun., Trans. Amer. Cryst. ASSOC., 1966,2,106; Ooo D. R. Lide,jun., J. Chem. Phys., l962,37,2074;PPpD. R. Lide,jun. and M. Jen, J. Chem. Phys., 1964,40,252; S. L. Hsu, M. Kemp, J. Pochan, R. Benson, and W. H. Flygare, J. Chem. Phys., 1969, 50, 1482; qQQ R. A. Beaudet, J. Chem. Phys., 1965,42,3758; rrr Y. S. Huange and R. A. Beaudet, J. Mol. Spectroscopy, 1970, 34, 1 ;ma S. L. Hsu and W. H. Flygare, J. Chem. Phys., 1970,52, 1053; ttt 0. L. Stiefvater, 21st Symposium on Molecular Structure and Spectroscopy, The Ohio State University, Columbus, Ohio, 1966. 4 The Molecular Model The observed spectra can often, but not always, be interpreted as two (or some- times three) different rigid rotor spectra, each with its own set of moments of inertia and each with its own satellite lines arising from low-lying vibrationally excited states.The two sets of ground-state moments of inertia may be related to one another by a simple rigid rotation of one part of the molecular model relative to the other part, about the single bond between them. More often some additional changes of structure, not usually very large, have to be introduced as well on going from one rotamer to the other. In other words, the rigid-rigid one-degree-of-freedom model is often not completely adequate, except as a first approximation. To the extent that values for the bond distances and other angles can be assumed known, and that the rigid-rigid model is adequate, the values of the dihedral angle for the various rotamers can be calculated to fit the observed moments of inertia (Figure 2).When the rigid-rigid model is not quite adequate, distortions of other angles can be somewhat arbitrarily introduced and the dihedral angles still estimated to fit the six moments of inertia. Table 1 shows some diheral angles determined in this manner; (where one form is planar or has some special symmetry, this can sometimes be verified by independent arguments). If enough isotopic species were studied, the structures of the various Wilson A/MHZ 4100 --8800 -8500 II I ' 818400 tooo tloo 120' 130° T40° # Figure 2 Plot of predicted rotational constants versus dihedral angle ($or propionyl fluoride), compared with experimental values rotamers could presumably be determined without any assumption concerning distances or angles, but little work of this degree of completeness has been attempted.21 Rough supporting information on the dihedral angles can be obtained from the dipole moment components along the three principal axes, obtainable from the microwave spectra via the Stark effect.Conventional bond moment values can be combined vectorially and plotted as a function of the dihedral angle. Comparison with the observed values then gives estimates for the dihedral angles. Among the various vibrational satellites observed, usually one set (often the strongest set) can be assigned to molecules in the first excited state of torsional motion, and perhaps several other sets to the second, third, etc.excited levels of this same (approximate) normal co-ordinate (Figure 3). These are particularly interesting and useful. Intensity measurements on these, relative to the same rotational transition for molecules in their ground vibrational state, give the relative populations of the excited states, and hence, from the Boltzmann factor e-AE'RT, the energy of excitation dE (corrections having been made for any differences in statistical weight). These same torsional energy values can sometimes be observed directly in the 21 But see E. Hirota, J. Chem. Phys., 1965, 42, 2071. Conformational Studies on Small Molecules bv202 truns guuche b c u/GHz Figure 3 Vibrational satellite transitions for torsional mode ($or ethyl formate) far4.r.spectrum and it is very desirable to have information from both tech- niques to avoid errors of interpretation in both types of spectra, errors which have occured in the past. The torsional energies essentially yield the curvature of the torsional potential energy function at the minimum position corresponding to a particular rotamer. If sufficiently accurate information on the higher excited states can be obtained, anharmonicity can be estimated and the deviation of the lower part of the potential wells from parabolic shape approximated (usually only rather roughly). The energy difference between different rotamers can be obtained in principle -and approximately in practice-by measuring the relative intensities of two rotational transitions, one from each rotamer, and taking into account the line- widths, linestrengths, and statistical weights of the two transitions, and the dipole moment components of the two rotamers.Neither the rotational or vibrational partition function is involved in this calculation since one is con- cerned here with the relative populations of two specific rotational levels. 5 Fitting the Potential Energy Function In the one-vibration approximation, the potential energy is treated as a function of one variable. In the further approximation of two connected rigid parts, the one variable is taken to be the dihedral angle of internal rotation, $.The potential energy V($) can then be expanded in a Fourier series V(+) = +CVn(1 -cosn#) (1) (for the common case where there is a plane of symmetry at $ = 0). This series must be limited in practice to a small number of terms. This limitation amounts 304 Wilson to a physical assumption concerning the nature of V($); namely, that the function is a relatively smooth and simple one, without sharply peaked barriers, for example. This assumption is important because most of the experimental information is drawn from molecules which are in rather low energy states, so that much accuracy cannot be expected for parts of the potential of much higher energy. Since steric repulsions are normally thought to change rapidly with distance, it might be imagined that very sharp peaks could occur as non-bonded atoms essentially came in ‘contact’.However, the deformation of bond angles does not require much energy and will take place in such a manner as to reduce and often round offsharp peaks. Figure 4 shows the parts of the potential func- 4 Figure 4 Typical potential energy curve as function of dihedral angle; heavy portions are more reliably determined tion on which one can most easily get information.? When quantum mechanical tunnelling is observable, additional restrictions on the relevant peak can be formulated. The dihedral angle, the torsional frequencies of the two rotamers (when there are just two non-equivalent forms), and the energy difference permit the fitting of four Fourier coefficients and it is still an open question as to how sufficient this is.In some cases the anharmonicity of one or two forms has also been estimated, permitting approximate values for five or six Fourier coefficients to be obtained. Figure 5 shows the V($) thereby calculated for propionyl fluoride.22 The great problem is that of accuracy and a knowledge of accuracy. In some cases a valuable additional piece of information is obtainable. When the potential function has two (or more) equivalent minima, as for example two symmetrically related gauche forms, quantum mechanical tunnelling may be noticeable. This will split the otherwise doubly (or triply) degenerate energy levels into two levels.With a suitable dipole moment, transitions from one to P Note added in proof: recent studies by I. Warren have shown that high-energy portions of the potential energy are indeed very poorly determined. ** 0. L. Stiefvater and E. B. Wilson, J. Chem. Phys., 1969, 50, 5385. Conformational Studies on Small Molecules V(+)/cai mol-1 "211 0 150C 7\A/ ,\ IOOC soa I I I I I I, r -60' 0' 60. 120. 18O0 240. 300. dihedral angle 4-Figure 5 Potential energy function fitted to propionyl fluoride data, showing observsd and calculated torsional energy levels (observed values carry error estimates) the other of these components, combined with a change in rotational energy, may appear in the microwave region. The contribution of the tunnelling may range from negligible to very large.When it is small, the effect may show as a doubling of certain types of rotational lines. This was observed in the case of ally1 fl~oride,'~ and yields the extent of the tunnelling splitting. The great value of this information is that it is substantially influenced by the barriers between the equivalent forms, even though the molecules being observed are in low-lying states. An approximate for the tunnelling splitting An for the nth pair of split levels is An = hv/n An2 An = exp [(2~/h) [2m(V -En)]"' dxs:' where hv is the difference (En+l-En)(treated as approximately independent P. Meakin, D. 0.Harris, and E. Hirota, J. Chew. Phys., 1969, 51, 3775. a4 D. M. Dennison and G. E. Uhlenbeck, Phys.Rev., 1932,41,313. Wilson of n), En is the mean energy of the slightly split nth pair, Vis the potential energy as function of co-ordinate x, m is the effective mass, and x1 is the first point for x > 0 where V = En. This shows that the tunnelling is dependent upon the square root area in the non-classical region, i.e. In other examples the transition from one tunnelling state to the other is not allowed, but the tunnelling nevertheless influences the spectrum because of a more complicated effect, the coriolis coupling of the internal motion and the overall rotation. This effect is influenced by the tunnelling and has been of great value for three-fold symmetric barriers, notably in the case of methyl group internal rotation.It can also, however, have an observable effect in the two-fold case,17~1s~25-2sfrom which the tunnelling splitting can be extracted and then used to obtain barrier information. If the tunnelling splitting is small compared with the rotational transition frequencies, the rotational spectra, ignoring the splitting, may still approximate that of a rigid rotor. In other cases, the contribution of the tunnelling may dominate. These latter can be very difficult to analyse. Most of the above consideiations are still of value if the model is somewhat generalized so that $ is no longer simply the dihedral angle between two rigid parts, but is a more generalized co-ordinate which mixes in some deformations of the two halves as they rotate relative to one another.A beginning has been made towards a theoretical treatment of such a model, from which one might ultimately hope to extract information about the deformations which take place during the internal motion.la Conversely if theoretical predictions of these 'bending back' effects are available, their influence on the microwave spectrum can be predicted and then tested. A. Contributions to the Potential Energy.-One of the ultimate objects of these studies is to acquire information about the forces which lead to the potential V(4).It is presumably sufficient to start with the Born-Oppenheimer approxi- mation for separating the electronic from the nuclear motion. The potential V(4) then represents the electronic energy of the system with the nuclei fixed in a sequence of positions measured by the co-ordinate 4.This electronic energy includes all the coulombic attractions and repulsions of the electrons and nuclei and also the electronic kinetic energy, these being related by the virial theorem:29 S.S. Butcher and C. C. Costain, J. Mol. Spectroscopy, 1965, 15, 40. 2e D. 0. Harris, H. W. Harrington, A. C. Luntz, and W. D. Gwinn, J. Chem. Phys., 1966, 44, 3467. L. H. Sharpen and V. W. Laurie, J. Chem. Phys., 1968,49, 3041. sa L. H. Sharpen, J. Chem. Phys., 1968, 48, 3552. *9 J. C. Slater, J. Chem. Phys., 1933, 1, 687. Conformational Studies on Small Molecules where (T) and (Ve) are expectation values of the kinetic and potential energies of the electrons (including internuclear repulsion), Ee is the Born-Oppenheimer electronic energy, and the xi are the nuclear co-ordinates.At this point it becomes of possible advantage to break down the forces on the nuclei into parts to be evaluated empirically, parts such as steric repulsion, dipole-dipole interaction, etc. This procedure has been widely used for de~ades,~O-~~but often with unnecessary apologies for using ‘classical mechanics’ instead of quantum mechanics. In this review the following types of forces will be considered: 1 Double bond character due to resonance 2 Hydrogen bonding 3 ‘Barrier forces’ 4 Steric repulsion 5 Electrostatic forces such as dipole-dipole 6 Valence bond stretching and bending forces 7 Inductive forces 8 Dispersion or van der Waals forces It seems quite reasonable to seek parameterized forms for these forces with parameters adjusted to fit the experimental data. Such a project requires means to calculate structures, energies, etc., from the postulated force laws and trial parameters, so that they may be compared with experiment.There is no difficulty in principle in doing this, but in practice rather large and elaborate computer programs are required. These seek, for example, for configurations of minimum energy-the equilibrium configurations-by various minimization schemes. Since this area has recently been well reviewed,8 no detailed analysis of these schemes will be given here. Instead, a discussion of some of their basic assump- tions and ways of validating them will be offered.The forces listed earlier all have physical reality (although perhaps some areas of indefinite overlap). Thus, when two atoms are forced too close together, there is no doubt that they will repel each other. Qualitatively, therefore, all of the current attempts at calculating structures, conformations, isomerization energies, etc. by compounding empirical force laws must have some measure of validity, especially in extreme cases. The difficulty comes when there is a close balance of forces so that the correctness of the overall calculation depends critically on the quantitative accuracy of the force laws. At the quantitative level, a basic and often unstated assumption is involved: that the force laws and parameters used are truly transferable from one molecule to another.This is a reasonable assumption to try, but it has not yet been directly verified. A second and obvious assumption is that the various force laws used are sufficiently correct in form. At this point it is well to agree on the criteria by which one should judge the T. L. Hill, J. Chem. Phys., 1946,14, 465. 31 F. H. Westheimer and J. E. Mayer, J. Chem. Phys., 1946,14,733. 32 F. H. Westheimer, in ‘Steric Effects in Organic Chemistry’, ed. M. S. Newman, J. Wileyand Sons, New York, 1956,ch. 12. Wilson success of a computational procedure such as those under discussion. They all involve, either very directly or in a hidden way, a very large number of adjustable parameters. Therefore, it is perhaps not too surprising if a fairly large number of known experimental values can be reasonably well fitted with a suitable choice of values for the parameters. It is not easy to see how the number of parameters can be much reduced; there remains the possibility of increasing the amount of experimental data to be fitted and this is exactly one reason for more microwave studies of rotameters.It may be worthwhile to look at some of the experimental information to see if it is susceptible to any qualitative interpretations. Without a large mass of data, any attempt at rationalization, whether qualitative or quantitative, is hazardous because we are very sure that many different types of forces can be important, and this makes it too easy to invent ad hoc explanations for each molecular example.Nevertheless, one might hope to select examples in which it is reasonable to expect that most of the forces in our list are small, thus permit- ting an interpretation in terms of a few major contributors. (i) Barrier forces. In the absence of double-bond character, hydrogen bonding, large electrostatic effects, and strong steric repulsions due to a close approach, the three-fold term +&(l-cos 3$) is often the largest. Further, there is a slight suggestion in the available data that this term depends mainly on the nature of the axial bond.33 In many of the computer systems, there is included a fixed three-fold barrier potentialdepending upon the nature of the axial bond only.Naturally, it should be possible to analyse these barrier potentials into more basic components and many efforts have been made to do so. For the simplest case, that of ethane, a considerable variety of approximate SCF-MO treatments have given numerical results reasonably close to the experimental barrier, despite the fact that the barrier is the difference between two energies, each vastly larger than the differen~e.~*-~' Furthermore, the breakdown into components such as electron-nuclear repulsion, electron-electron repulsion, etc. seems to differ considerably from one approx- imation to another despite the fact that their resultant, the total barrier, does This makes it difficult at the present to discuss the origins of barriers in physical terms.Therefore, we shall assume that barriers exist and hope that they do constitute a transferable portion of the potential, until the further accumula- tion of data shows this to be untenable. The barrier force alone, viewed in this simplified way, would lead to 120" angles between the rotamers and little energy difference. We shall provisionally assume that deviations from this condition indicates the presence of other s3 E. Saegebarth and E. B. Wilson, J. Chem. Phys., 1967,46, 3088. 34 R. M. Pitzer and W. N. Lipscomb, J. Chem. Phys., 1963, 39, 1995. s6 R. M. Pitzer, J. Chem. Phys., 1964, 41, 2216. s6 W. H. Fink and L. C. Allen, J. Chem. Phys., 1967, 46,2261. L. Pedersen and K. Morokuma, J. Chem. Phys., 1967,46, 3941. se I. R. Epstein and W.N. Lipscomb, J. Amer. Chem. SOC.,1970, 92, 6094. 309 Conformational Studies on Small Molecules forces, e.g. steric or electrostatic. Table 2 gives some barrier values which very tentatively might be transferred to more complicated molecules. Table 2 Some prototype three-fold barriers /cal mol-l a \/ -c-c-C2HB 2928b /\ \/-C-C CH3CH=CH2 1978 /\ \/-c-o CH,OH 1070 / \/-C-N CH3NH2 1980 /\ \/-C-Si-CH,SiH, 1670 /\ \/O -c-c CH3CHO 1167 /\H a From J. E. Wollrab, 'Rotational Spectra and Molecular Structure', Academic Press, New York, 1967, appendix 9; b S. Weiss and G. E. Leroi, J. Chem. Phys., 1968,48,862. (ii) Double bond character. The energy barrier between cis-and trans-isomers for typical ethylenic compounds is much higher than the barriers between normal rotational isomers.There are many species in which the bond about which the rotation can occur is not a pure single bond but has some double bond character, because of conjugation or resonance. An example where this effect would be expected is butadiene, in which the central bond is shorter than a normal single H H H I I I H IH-c\C_C'. C-ti n-c\ C-IIHH AC"F-H H cis trans 310 Wilson bond and two forms, differing by 180" rotation, would be expected. Some substituted butadienes have been studied by microwave spectroscopy and only the trans-forms found.39 Likewise in methyl formate40 the central 0-C bond .o would be expected to acquire some double bond character.Again, despite several searches, no microwave evidence for a second form has been reported. It is interesting to note that Pauling's qualitative picture, which uses 'banana bonds' to represent a double bond, predicts the preference for sym-trans over sym-ci~.~~~~~ In nitric H 0\/O--N '0 /the planar form is found, as expected for an 0-N bond with some double \ bond character, and two forms differing by 180" presumably occur but are equivalent. In CHBONOand HONO two forms are fo~nd~~r~~ differing by a 180" rotation around the central 0-N bond. Many other examples of this effect have been studied, by other techniques such ae S. L. Hsu, M. K. Kemp, J. M. Pochan, R. C. Benson, and W. H. Flygare, J. Chem. Phys., 1969, 50, 1482.40 R. F. Curl, jun., J. Chem. Phys., 1959, 30, 1529. L. Pauling, Proc. Nut. Acad. Sci. U.S.A., 1958, 44, 21 1. 4s J. D. Dunitz and P. Strickler, ref. 7, p. 595. 43 A. P. Cox and J. M. Riveros, J. Chem. Phys., 1965,42, 3106; D. J. Milfen and J. R. Morton, J. Chem. SOC.,1960, 1523. 44 D. Stelman, Diss. Abs., 1965, 25, No. 64-9094. 45 A. P. Cox, A. H. Brittain, and D. J. Finnigan, Trans. Furaday SOC.,1971, 67, 2179. 31 1 Conformational Studies on Small Molecules as n.m.r., as well.46 It is important to note that the two-fold contribution to the barrier can be dominant even when there is only a small amount of double bond character. (iii) Hydrogen bonding. Internal hydrogen bonding is another force which has been postulated to be important in determining the conformations of appro- priate molecules. It is generally considered that hydrogen bonding can play a role when the hydrogen is bonded to oxygen or nitrogen and when the geometry is such that it can approach at the proper distance to another oxygen, nitrogen, a halogen, or perhaps to electrons from a double bond or a conjugated ring.Many studies have been made of such systems using the i.r. (especially the shift of the OH stretching frequency) and n.m.r. spectra as riter ria.^' These can give a semi-quantitative ordering of the strength of the hydrogen bond. Microwave spectroscopy has begun to be applied to some of these molecules. Thus Murty and studied ally1 alcohol and found that the conformation they could identify (presumably therefore the dominant one) was the one which brought the 0-H hydrogen close to the C=C double bond.Similarly, a rather detailed study of 2-chloroethan0l~~ (ClCH,CH,OH) shows that, of the nine conformations which might be expected in terms of the normal C-C and C-0 three-fold barrier potentials, one equivalent pair in which the hydrogen is close guoche -CLCH&HzOH Figure 6 Structure foundfor main species of chloroethano 46 T. H. Siddall and W. E. Stewart, Progr. N.M.R. Spectroscopy, 1969, 5, 33. “G. C. Pimentel and A. L. McClellan, ‘The Hydrogen Bond’, W. H. Freeman and Co., San Francisco, 1960. 48 A. N. Murty and R. Curl, J. Chem. Phys., 1967, 46,4176. 4B R. G. Azrak and E. B. Wilson, J. Chem. Phys., 1970,52, 5299. Wilson to the chlorine is definitely observed.No lines were assigned to any other conformations, which may, however, be present in small amounts, as indicated by i.r. st~dies.~~-~~ The geometry is not favourable for a very strong hydrogen bond, because the CI-H-0 group is very non-linear (Figure 6) and in fact the OH shift in the i.r. is quite small. It may not be surprising, therefore, that the chlorine quadrupole hyperhe structure leads to a practically cylindrically symmetric field gradient tensor, oriented along the C-Cl bond, just as if the ‘H-bonding’ had no influence on the electron cloud around the chlorine. If there were much covalent character to C1 ---H or much charge transfer, one would expect these to influence the field gradient.Moreover, the C-CI and 0-H bonds are very nearly parallel, just the orientation one would expect from the electrostatic interaction of the normal C-Cl and 0-H dipoles. This result naturally cannot be generalized to all internal hydrogen bonds. For example, a different situation seems to hold for 2-formyl 6-hydroxyfulvene7 now under investigation by Pi~kett.~~ The observation of alternating intensities suggested an effectively symmetric 0 * -H * -0 bond which would then permit the molecule to have two equivalent resonating structures as shown in Figure 7, I H-C H-C-\ /!!-t-c\ H-C-H-C \yH \C//”-”b 1 1 H H Figure 7 Two resonant formsfor hydrogen bonded 2-formyl-6-hydroxyfulvene an arrangement which should be considerably favoured by the resonance energy.However, a small barrier could still exist at the central hydrogen position, through which the hydrogen could rapidly tunnel. The preliminary results with the deuteriated species suggest the latter situation. Other molecules showing conformations compatible with weak internal O0 M. Kuhn, W. Luettke, and R. Mecke, 2. analyt. Chem., 1959, 170, 106. 61 P. J. Krueger and H. D. Mettee, Canad. J. Chem., 1964, 42, 326. Oa P. Buckley, P. Giguere, and M. Schneider, Canad. J. Chem., 1969, 47,901. *3 H. M. Pickett, personal communication. Con formational Studies on Small Molecules hydrogen bonding include, CH2FCH20H,64 CH2BrCH20H,4v CF3CH2NH2,66 NH2CH2CH20H,66and CH=CCH20H.S7 (iv) Steric repulsion.It is of course obvious that steric repulsion must exist but it is more difficult to agree on its quantitative laws. Qualitatively, and to some extent quantitatively, steric repulsion should produce several effects in the microwave spectra of rotamers. The potential energy as a function of internal rotation should be influenced, especially where two atoms approach each other within the sum of their van der Waals radii. This effect appears quite definite in the case of ethyl formate68 (Figure 8) and also ethyl nitrate,sv for example, for -180" -m0 -ao 0" 6cP 1x)" ,180"+ Figure 8 Approximate potential function for ethyl .formate showing small dihedral angle and high cis energy, presumably due to steric repulsion which the dihedral angle for the gauche form was found at 95" instead of 120" and the derived potential energy curve goes to high but not well defined values in the cis (180') configuration.Another effect expected is an opening up of certain bond angles in the rotamer with the stronger steric repulsions. Not many really complete structural studies have been made, but the moment of inertia data for ethyl formate,s8 fluoro- K. S. Buckton and R. G. Azrak, J. Chem. Ph-ys., 1970, 52, 5652. 5B I. Warren and E. B. Wilson, J. Chem. Phys., 1972, 56, 2137. 56 R. E. Penn, presented at the Symposium on Molecular Structure and Spectroscopy, Ohio State University, Columbus, Ohio, 1968, paper N11. 57 E. Hirota, J. Mol. Spectroscopy, 1968, 26, 335. 58 J. M. Riveros and E. B. Wilson, J.Chem. Phys., 1967,46,4605. 69 D. Scroggin, Ph.D. Thesis, Harvard University, 1971. 3 14 Wilson acetyl fluoride,33 and ethyl nitrate,6g require some distortion from the rigid- rigid model in the direction qualitatively called for by steric forces. Thus the I\ CCO angle in fluoroacetyl fluoride appears to be about 6"larger in the form with F eclipsing 0 than in the other form, presuniably because of F ---0 repulsion. Quantitatively the situation is unsatisfactory, because of the number of different atom pairs which occur, each requiring two or more parameters. It is difficult to make meaningful comparisons between the many different non- bonded force laws currently being used in empirical calculations; they cannot properly be isolated from the other terms in the total potential energy expression.Thus some authors do and some do not employ valence-type interaction force terms, some use coulombic interactions between charges centred on atoms (even for hydrocarbons), one author measures the non-bonded interaction from an origin displaced along the bond from the hydrogen nucleus, etc. All of these alternatives will have an effect on the non-bonded repulsion terms. It is, there- fore, necessary to base a judgment on the overall success of the various total treat men t s . (v) Electrostatic forces. Another force which is surely important is that due to charges transferred from one part of the molecule to another. Dipole moments are reasonably well accounted for in terms of transferable bond dipole moments so it has long been supposed that dipole-dipole interactions can be important.Again there is qualitative information which can be comfortably explained in these terms. For fluoroacetone,so only a form with F trans to 0 has been found, despite the 0 II H\ H C \V\\C CH3 I F fact that a methyl group (and some examples of substituted methyls) attached to a doubly bonded carbon usually prefers to have an H (or X) atom eclipsing the 0 or C at the other end of the double bond (see allyl fluoride,21 allyl chloride,61 propionaldehyde,s2 p~opylene,~~ and the more stable form of a~etaldehyde,~~ fluoroacetyl flu~ride~~). In none of these examples, however, is there such an obvious dipole-dipole repulsion favouring the trans conformation as one would expect between the C=O and C-F dipoles in fluoroacetone.A series in which it is tempting to invoke dipole-dipole interaction,6s even 6o E. Saegebarth and L. C. Krisher, J. Chem. Phys., 1970, 52, 3555. "lE. Hirota, J. Mol. Spectroscopy, 1970, 35, 9. 6z S. S. Butcher and E. B. Wilson, J. Chem. Phys., 1964, 40, 1671. 63 D. R. Herschbach and L. C. Krisher, J. Chem. Phys., 1958, 28, 728. R. W. Kilb, C. C. Lin, and E. B. Wilson, J. Chem. Phys., 1957, 26, 1695. G. J. Szasz, J. Chem. Phys., 1955, 23, 2449. Conformational Studies on Small Molecules though it is perhaps less certain, consists of the simpler n-propyl derivatives. It was pointed out some time ago,ss from i.r. evidence, that some of these slightly prefer the gauche rather than the trans form, i.e. H3C\,,c--czi ,H x H3C Ic-C’hH ,H H‘4 \ H-Y \ H H H x gauche trans CN9 71 C=H,72Microwave studies have been made with X = F,67C1,68Br,69970 -OH,73 and NC,74 and all appear to favour gauche or to be nearly neutral (X = CH, is supposed to favour trans, from other eviden~e~~~~~).The dipole moments, especially the change from one form to the other in n-propylacetylene, suggest that CH3-C has a small group moment with the CH, end positive.72 The interaction of this with the negative dipole of the C-X group could be the forces5 counterbalancing the expected steric repulsion (for which there is some evidence from the dihedral and other angles). The dipole-dipole would be a longer-range force than the steric repulsion, so that it is possible to think of distinguishing their effects.For point dipoles in a vacuum, the interaction potential is well known and many quantitative calculations were made in the past with this basis. Unfor- tunately there are three difficulties which cast considerable doubt on the reli- ability of such numerical results. First, it is not clear where the point dipoles should be located. Second, it is very dubious to assume that quadrupole and higher terms can be neglected (if indeed the multipole expansion converges, even in a practical sense). Finally, some workers assign a dielectric constant, somewhat arbitrarily chosen, to account for the effect of the intervening electron distribution. These difficulties suggest caution and reliance on empiricism; nevertheless, electrostatic forces are surely important.(vi) Other farces. One expects dipole-induced-dipole forces, also van der Waals or dispersion attraction. In large molecules with flat ring substituents, such as 66 N. Sheppard, Adv. Spectroscopy, 1959, 1, 228. 67 E. Hirota, J. Chem. Phys., 1962, 37, 283. 6*T.N. Sarachman, J. Chem. Phys., 1963, 39,469. T. N. Sarachman, presented at the Symposium on Molecular Structure and Spectroscopy, Columbus, Ohio, 1968, paper N7. 70 S. Armstrong, Appl. Spectroscopy, 1969, 23, 575. 71 E. Hirota, J. Chem. Phys., 1962, 37, 2918. F. Wodarczyk and E. B. Wilson, J. Chem. Phys., 1972, 56, 166. A. A. Abdurakhmanov, R. A. Ragimova, and L. M.Imanov, Phys. Letters (A), 1970, 32, 123. M. Fuller, personal communication. 76 K. Kuchitsu, Bull. Chem. SOC., Japan, 1959, 32, 748. 7e R. A. Bonham and L. S. Bartell, J. Amer. Chem. SOC.,1959, 81, 3491. DNA, these have been postulated to be of major importance. In small molecules this force should be small, and so far microwave data does not seem to have led to any definite information on the subject. B. Fluoroacetyl Fluoride.-The conformations found for fluoroacetyl namely with the halogen in the methyl group cis or trans to the other fluorine, instead of the expected trans and skew conformations, pose a real puzzle (Figure 9). Clearly a rather large (1 -cos 24) term is needed, with a positive coefficient, Figure 9 Less stable form of fluoroacetyl fluoride i.e.minima at the cis and trans angles. Otherwise stated, some attractive force making the cis position more stable, or some repulsive force raising the ener-gy of the 90" angle, is required. Strong van der Waals attractions would do it, but the distances involved are such as to suggest repulsion rather than attraction. The normal three-fold barrier favours trans and is a maximum at cis. A dipole-dipole interaction could stabilize trans but only, it would appear, with a con- comitant conversion of the cis minimum into a maximum. One possibility is some double-bond character in the FCH,-CH, bond, such as could arise from resonance forms involving F with a formal charge. Another idea which has been suggested is incipient hydrogen bonding C-H * -0 made favourable by the effect of the three electronegative atoms. This situation may be a warning that nature is more complicated than we had hoped and that even transferability cannot always be expected.At any rate, none of the major quantitative empirical computer programs would seem cap- able of handling this example.* * It should be noted that a CND0/2 calculation gave the correct conformations for this molecule (L. Saunders, personal communication). It would be interesting to test this approx- imation on many rotamer pairs. Conformational Studies on Small Molecules 6 Conclusion The microwave method is being applied to more and more molecules and its power and accuracy is gradually increasing.It provides data which must be fitted by any calculational procedure which claims physical validity. There is a strong need to increase the accuracy further and to make more cross-comparisons with the results of other methods, such as i.r. Raman, n.m.r., etc. The selected molecules discussed above suggest that there exist cases in which one or two of the commonly postulated intramolecular forces can qualitatively explain the microwave results. For these it should not be difficult to get semi- quantitative fits by parameter adjustment with conventional force laws. On the other hand, the real test of such quantitative formulae is for molecules with several forces opposing one another. Much more experimental data will have to be acquired before really satisfactory tests can be made, because of the neces- sarily large number of parameters.Furthermore, some of the examples suggest that, for some kinds of molecules at least, additional effects may have to be included in the treatment and that transferability is not yet guaranteed. It would therefore appear wise to reserve judgment on the validity of pre- dictions made with the aid of current empirical force laws, particularly outside of narrow molecular classes, except possibly in those cases where qualitative considerations alone seem convincing. In the meantime various types of a priori quantum mechanical calculations are advancing in power and in time may provide the predictive method of choice for simpler molecules. Besides the very great debt I owe to the students and post-doctoral fellows who have worked on individual rotational isomer pairs, with whom I have had much beneficial discussion, I should especially like to thank Dr. 0. Stiefvater and Dr. F. Wodarczyk. I am also grateful to the National Science Foundation for research support and to the John Simon Guggenheim Memorial Foundation for a fellowship.

ISSN:0306-0012    

DOI:10.1039/CS9720100293

出版商:RSC    

年代:1972

数据来源: RSC

摘要:

CENTENARYLECTURE Three-dimensional Structures and Chemical Mechanisms of Enzymes By W. N. Lipscomb DEPARTMENT OF CHEMISTRY, HARVARD UNIVERSITY, CAMBRIDGE, MASSACHUSETTS 02138, U.S.A. 1 Introduction Three-dimensional structures, established by X-ray diffraction methods, are now known for over 30 proteins.* including many enzymes. Although the enzymes of known structure are mainly limited to single-chain, hydrolytic, extracellular molecules, some general qualitative conclusions can be drawn, as outlined below, from this restricted class of enzymes. Later, when more studies of three-dimensional structures of multisubunit proteins are available, additional and different general principles may be expected to emerge. Conformation is discussed here primarily as it relates to activity of enzymes in the crystal, in solution, and in biological systems.Probable mechanisms for activity are outlined in the light of the stable, static complexes of enzymes in the crystal as deduced by X-ray diffraction studies. Of the several enzymes for which fairly extensive studies of such complexes have been made, those dis- cussed below include carboxypeptidase A, chymotrypsin, ribonuclease S, and lysozyme. Partial answers will be sought for the following questions, frequently asked when lectures on protein structures are presented. (i) Is the conformation of the enzyme in the crystal like that in solution? (ii) Are these crystalline complexes, now required to be stable for hours or days for X-ray work, closely Ielated to functional enzyme-substrate complexes? (iii) How close is the functional binding complex, inferred from these studies, to the transition state of the enzyme-substrate reaction? (iv) What potentially catalytic groups from the enzyme, solution or substrate can approach readily the substrate’s reactive region? (v) Is the primary bonding region for product similar to that for the * Myoglobin, Lysozyme, Carboxypeptidase A, &bonuclease A, Ribonuclease S, a-Chymo-trypsin, Papaine, Subtilisin BPN’, Elastase, Oxyhemoglobin, Deoxyhemoglobin, Insulin, Chymotrypsinogen, Oxidized and Reduced Cytochrome c, Rubredoxin, Staphylococcal Nuclease, Insect Hemoglobin, Lamprey Hemoglobin, Subtilisin Carlsberg, Carbonic Anhydrase, y-Chymotrypsin, Lactate Dehydrogenase, Cytochrome b5, High Potential Iron Protein, Trypsin, Trypsin Inhibitor (pancreatic), Carp Muscle Ca-Binding Protein, Flavo- doxin, Subtilisin NOVO, Thermolysin, Concanavalin A, Malate Dehydrogenase, and Ferro- doxin. Recent studies of many of these proteins have appeared in ref.1. Volume XXXVI of Cold Spring Harbor Symposium in Quantitative Biology, 1971, Cold Spring Harbor Laboratory, Long Island, 1972. Three-dimensional Structures and Chemical Mechanisms of Enzymes corresponding part of the substrate? (vi) Why are enzymes so large? (vii) Can we obtain structures of enzyme complexes of rapidly cleaved substrates? These, of course, are detailed questions related ultimately to why enzymes act so speci-fically and why they cause a reaction to proceed more rapidly than the un- catalysed reaction by factors sometimes approaching lo7.2 Conformation The existence of nearly complete order to atomic dimensions in a protein crystal was indicated from the time of the first X-ray diffraction photographs of a protein, pepsin.2 Moreover, the essential role of the mother liquor in maintaining crystalline order was also recognized,2 and has remained a consistent feature of protein crystals studied since that time. A recent surveyS suggests that the solvent occupies about 43% of the volume of protein crystals, but specific examples range from 27 to 65%. Some important consequences are that intermolecular contacts occur only over roughly 30% of the surface of a globular protein in a crystal, that these contacts do not usually block the diffusion of small substrates, products, or inhibitors into the active site cavity or cleft, and that most side- chains of the protein have environments in the crystal rather like those in solu- tion.While it is probable that most peptide polymers do not have a strongly preferred configuration, the X-ray evidence suggests that most enzymes which show X-ray data to high resolution do have definite molecular structures. The evidence that these structures are not greatly changed in other environments is sometimes less direct. We turn to some examples. The renaturation of ribonu~lease,~ with full activity and its synthe~is,~.~ provide strong evidence of the uniqueness of those conformational aspects related to activity.A comparison of the two molecules of a-chymotrypsin in totally different environments within the same crystal structure shows very few differences, mostly in flexible side-chains of the enzyme,' but one important, possibly functional, change occurs in the positions of the extended polypeptide chain Ser-214-Trp-215-Gly-216.*Other differences occur in residues 9-1 3 and 73-77, and appear to be due to intermolecular contacts. On slightly less secure grounds, one may compare ribonuclease ABand ribonuclease S,l0 or the J. D. Bernal and D. Crowfoot, Nature, 1934, 133, 794. a B. W. Matthews, J. Mol. Biol., 1968, 33, 491.* C. J. Epstein, R. F. Goldberger, and C. B. Anfinsen, Cold Spring Harbor Symposium on Quantitative Biology, 1963, 28, 439. B.Gutte and R. B. Merrifield, J. Amer. Chem. SOC., 1969, 91, 501. R. Hirshmann, R. F. Nutt, D. F. Veber, R. A. Vitali, S.L. Varga, T. A. Jacob, F. W. Holly, and R. C. Denkewalter, J. Amer. Chem. SOC.,1969, 91, 507. J. J. Birktoft, B. W. Matthews, and D. M. Blow, Biochem. Biophys. Res. Comm., 1969, 37, 131.* A. Tulinsky, Alpbach Conference on Protein Structures. 1972. G. Kartha, J. Bello, and D. Harker, Nature, 1967, 213, 862. lo H. W. Wyckoff, D. Tsernoglou, A. W. Hanson, J. R. Knox, B. Lee, and F. M. Richards, J. Biol. Chem., 1970, 245, 305; F. M. Richards and H. W. Wyckoff, in 'The Enzymes', ed. P. D. Boyer, Academic Press, New York, 3rd Edn., 1971, p. 647. 320 Lipscomb pair subtilisin BPN’ll and subtilisin NOV0,12 or the a and 16 chains of hemo-globin13-15 along with myogl~bin,~~~~~ or the or a-and y-chymotryp~ins,~~J~ three serine enzymes a-chymotrypsin,l* trypsiq20 and elastase.21B22 While there are well documented differences within these comparisons, and a few instances of partial disorder in parts of some pr~teins,~J~~~~ the general conclusion is that the structures are definitive and largely independent of these environmental differences.It is more difficult to make comparisons between conformations of a molecule in solution and the crystal. The difficult experiment of locating relative heavy- atom positions within a molecule by X-ray scattering from has never been attempted. However, high-resolution lH n.m.r., first applied2* to lysozyme, ribonuclease, cytochrome c, myoglobin, and hemoglobin, provides information about local environments and conformational changes.It would seem clear, now that the structures of both oxidized26 and redu~ed~~.~~ cytochrome c are known, that the very large conformational differences for this substance are in contrast to that noted so far for singlechain enzymes. More recent lH n.m.r. studies have provided striking correlation of histidine and tyrosine environments in ribonuclease A2*and in staphylococcal nuclea~e,~~,~~ both sets of studies supporting the correlation with these aspects of structures found in the crystalline phases.10~31~32These comparisons extend to complexes of inhibitors at the active l1 (a) J.Kraut, in ‘The Enzymes’, ed. P. D. Boyer, Academic Press, New York, Vol. 3, 3rd Edn., p. 547;(b) R. A. Alden, C. S. Wright, and J. Kraut, Phil. Trans. Roy. Soc., 1970, B257, 119. I* J. Drenth, W. G. J. Hol, J. N. Jansonius, and R. Koekock, ref. I, p. 107. M. F. Perutz, H. Muirhead, J. M.Cox, and L. C. G. Goaman, Nature, 1968, 219, 5150. l4 M. F. Perutz, Proc. Roy. SOC.,1969, B173, 113. l6 M.F.Perutz, Nature, 1970, 228, 5273. l6 J. C.Kendrew, R. E. Dickerson, B. E. Strandberg, R. G. Hart, D. R. Davies, D. C. Phillips, and V. C. Shore, Nature, 1960, 185,471 1. l7 H. C. Watson in ‘Progress in Stereochemistry’, ed. B. J. Aylett and M. M. Harris, Butter- worth, London, 1969,Vol. 4,p. 299. J. J. Birktoft, D. M. Blow, R. Henderson, and T.A. Steitz, Phil. Trans. Roy. SOC.,1970, B257, 67. l9 D. M.Segal, G. H. Cohen, D. R. Davies, J. C. Powers, and P. E. Wilcox, ref. 1,p. 85. *O R. M. Stroud, L. M. Kay, and R. E. Dickerson, ref. 1, p. 125. 21 D. M. Shotton and H. C. Watson, Phil. Trans. Roy. SOC.,1970, B257, 111. 2* D. M. Shotton, N. J. White, and H. C. Watson, ref. 1, p. 91. l3 P. A.Vaughan, J. H. Sturdivant, and L. Pauling, J. Amer. Chem. SOC.,1950,72,5477. *4 C. C. McDonald and W. D. Phillips, J. Amer. Chem. SOC.,1967, 89, 6332. R. E. Dickerson, T. Takano, D. Eisenberg, 0. B. Kallai, L. Samson, A. Cooper, and E. Margoliash, J. Biol. Chem., 1971, 246, 1511. *( T.Takano, R. Swanson, 0. B. Kallai, and R E. Dickerson, ref. 1, p. 397. A. G. RedfieId and R. D. Gupta, ref. 1, p.405. D. H. Meadows, G. C. K. Roberts, and 0.Jardetzky, J. Mol. Biol., 1969,45,491. as 0. Jardetzky, ‘Molecular Properties of Drug Receptors’ (Proceedings of the Ciba Sym- posium, 1970),ed. R. Porter and M. O’Connor, London, 1970,p. 113. 30 J. L. Markley and 0.Jardetzky, J. Mol. Biol., 1970,50, 223. 31 A. Arnone, C. J. Bier, F. A. Cotton, V. W. Day, E. E. Hazen, jun., D. C. Richardson, J. S. Richardson, and A. Yonath, J. Biol. Chem., 1971,246, 2302. 3* F. A. Cotton and E. E. Hazen, jun., in ‘The Enzymes’, ed. P. D. Boyer, Academic Press, New York, 1971,Vol. 4,3rd Edn., p. 153. Three-dimensional Structures and Chemical Mechanisms of Enzymes site of both of these enzymes, including the accompanying conformational changes. Conformations in the active sites in the molecule in solution or crystal can be compared by testing for enzymatic activity.Crystalline a-chymotrypsin shows about the same activity as in Also, reactions with inhibitors, such as N-tosyl phenylalanyl chloromethyl ketone, occur1* in a way which is thought to be productive for longer substrates in the region of Ser-214-Trp-215-Gly-21 6.1° Also, activity towards smaller substrates is known for ribon~clease,~~~~~ lyso-z~me,~~ There are, however, some situations where the activity, and ~apaine.~~ or reactivity of groups, is reduced in the crystal. The reactivity of ferrihemo- globin with azide ion is some 21 times lower in the crystal than in and the carboxylation of one histidine of myoglobin proceeds more readily in the crystal than in Alcohol dehydrogenase shows a thousand-fold decrease in activity as one goes from solution to and carboxypeptidase A,, shows, similarly, about a 300-fold The spectroscopic behaviour of arsenoazo-Tyr-248-carboxypeptidaseis also interpreted41 to indicate sub- stantial differences between the crystal and solution states, but a re-investiga- tionq2 of this effect shows that the behaviour is confirmed for carboxypeptidase A, (for which the crystal structure is unknown), but that carboxypeptidase A, (the known structure) shows similar behaviour in the crystalline and solution states. There exists therefore the possibility that if activity is modified in one crystalline phase, it may be possible in many cases to find a different crystalline phase in which the activity is not substantially different from that in solution, One of the strongest cautions about X-ray studies to date of protein structures is that atoms are located at best to only 0.48, or so in the enzyme, and usually somewhat less accurately in the static complexes, and yet activity can depend critically upon a finer level of atomic positions.An interesting illustration is that the active-site functional groups in u-chymotryp~in~~~~* and chymotryp- ~inogen~~do not differ greatly. However, the conformations of the nearby portion 214-216 are different and the ‘active site’ histidine is misaligned by some 15 to 20°, but even so it is not yet clear why chymotrypsinogen is inactive. One further possibility is that chymotrypsin, but not chymotrypsinogen, can carry out a sequence of conformational changes throughout the course of the enzyme- 33 L.A. A. Sluyterman and M. J. M. de Graaf, Biochem. Biophys. Actu, 1969, 171,277. a4 M. Doscher and F. M. Richards, J. Biol. Chem., 1963,238, 2399. 36 J. Bello and E. F. Nowoswiat, Biochim. Biophys. Acta, 1965, 105, 325. 36 L. G. Butler and J. A. Rupley, J. Biol. Chem., 1967, 242, 1077. 37 B. Chance and A. Ravilly, J. Mol. Biol., 1966, 21, 195. 3B T. E. Hugli and F. R. N. Gurd, J. Biol. Chem., 1970,245, 1930, 1939. 3s H. Theorell, B. Chance and Y. Yonetani, J. Mol. Biol., 1966, 17, 513. 40 F. A. Quiocho and F. M. Richards, Biochemistry, 1966, 5, 4062. 41 J. T. Johansen and B. L. Vallee, Proc. Nut.Acad. Sci. U.S.A., 1971, 68, 2532. 4a F. A. Quiocho and W. N. Lipscomb, to be published. 43 D. M. Blow, in ‘The Enzymes’, ed. P. D. Boyer, Academic Press, New York, Vol. 3, 3rd Edn., p. 185. 44 T. A. Steitz, R. Henderson, and D. M. Blow, J. Mol. Biol., 1969, 46,337. 45 J. Kraut, in ‘The Enzymes’, ed. P. D. Boyer, Academic Press. New York. Vol. 3.3rd Edn., p. 165. Lipscomb substrate reaction. In spite of these qualifications, it seems probable that for most single subunit enzymes the important conformational aspects are very similar in the crystal and in solution, and hence, by inference, in the physio- logical medium. We now turn to our examples. 3 Carboxypeptidase A 48-48 This enzyme cleaves, preferentially, aromatic or large aliphatic amino-acids with neutral side-chains from the C-terminal end of a polypeptide substrate.The complete polypeptide backbone of the enzyme is shown in Figures 1 and 2. The Zn2+ binding region is in Figure 3. A section of electron density of the enzyme-substrate complex (dotted) superimposed on the electron density of the enzyme (solid contours) is shown in Figure 4, the resulting models of the Figure 1 Polypeptide chain in carboxypeptidase A. The Zn2+ ion at the active site is near the centre of this drawing, and the three ligands to the Zn2+from the protein are shown as arrows from or-carbons of His-69, Clu-72, and His-196. The a-carbons are shown as dots, and the peptide units as line segments 46 W. N. Lipscomb, Accounts Chem. Res., 1970, 3, 81.47 J. A. Hartsuck and W. N. Lipscomb, in ‘The Enzymes’, ed. P. D. Boyer, Academic Press, New York,Vol. 3, 3rd Edn., p. 1. 48 F. A. Quiocho and W. N. Lipscomb, Adv. Protein Chem., 1971, 25, 1. Three-dimensionalStructures and Chemical Mechanisms of Enzymes Figure 3 Binding of Zn2+to N-1 of His-69 (right), to N-1 of His-196 (above), and to 0 of Glu-72. The fourth ligand, a water molecule to be displaced by the substrate’s carbonyl oxygen, is directly towards the reader from Zn, but is not shown in the Figure enzyme and enzyme-substrate complex are in Figure 5 (facing p. 326), and mechanistic implications are suggested in Figure 6. The major conclusions of this study are (first) that there are very large con- formational changes, especially of the side-chain of Tyr-248, when the substrate binds, and (second) that the only two side-chains of the protein which can approach within Van der Waals contact with atoms of the substrate’s scissile bmd are Glu-270 and Tyr-248.The positive charges of Arg-145 and of the (ZnL,)+ complex, where L is a protein ligand, serve to bind, respectively, the C-terminal carboxylate group of the substrate, and this substrate’s carbonyl group, which is expected to be polarized by the (ZnL,)+ group. These binding groups, together with hydrophobic binding of the Gterminal side-chain in the enzyme’s pocket, strain the peptide bond which is to be cleaved. Thus, the tlireedimensional structure indicates that a mechanism of cleavage may involve, in the immediate neighbourhood, Glu-270, Tyr-248, and HzO. In the optimum pH range just over 7, one may reasonably expect Glu-270 to be anionic, and Tyr-248 to be neutral.Hence we suggest that the proton donor is Tyr-248 or HzO, and that the nucleophile is Glu-270 or H,O (Figure 6). Binding in this region of carboxypeptidase A has been studied to 2.0 A resolution for Gly-Tyr, to 2.8 A resolution for Phe-Gly-Phe-Gly, and at 6 A rssolution for about a dozen substrates, inhibitors, products or other analogues, but for no esters. The possibility of binding shifted to one of the five important s~bsites~~of carboxypeptidase A requires that an extended series of studies be made, in order that the active site not be confused with a subsite. This is an important general qualification for X-ray studies of enzyme complexes.48 N. Abramowitz, I. Schechter, and A. Berger, Biochem. Biophys. Res. Comm., 1967, 29, 862. Figure 2 Stereoview from a different angle, along the -y direction from the top to the bottom of Figure I, showing especially the large twisted pleated sheet structure in the centre of the carboxypeptidase A molecule. (a) Side-chains are shown for Arg-145, Tyr-248, and Glu-270 before substrate is added. (b) The same three side-chains are shown after addition of the sub-strate, benzoxycarbon~~lalan.vlalanyltyrosine.(Stereoviewers may be obtained, for example, from Ward’s Natural Science Establishment, Inc., Rochester, New York, Model 25, W295 1.) x, 0 1 2A Figure 4 A section of experimental electron density in the xy plane through part of the substrate glycyl-L-tyrosine.The phenyl and carboxylate groups of Gly-Tyr are partly in this plane. The OH, Ca, and probable position of the amino-group are also indicated. Movement of Arg-145 to the position G is indicated by negative contours added at the initial position, and dotted contours at the new position. Negative contours in the region of Glu-270 also indicate another conformntional change in the enzyme when GI-v-Tyr is bound Lipscomb HC-C02 ..........Arg' 145 His -2n-His69 I H His -Zn-His 69 AH........ HO-Tyr 196 I ........... ....... H-0-Tyr 248 196 1 .....'''.o I 240 Glu XC72 Glu -CG 270 His-Zn-His69 I His -2n-His69 1 196 I NZ ......NH..... loHzl 0--Tyr248 H -NH GIu-CO 270 270 Figure 6 (a) Binding of glycyl-L-tyrosine to carboxypeptidase A. (b) Probable change of bindingfrom the non-productive complex to the productive complex [(a) to (b)], inferred from model building of longer substrates. (c) Indirect attack of GIu-270 promoting the attack of a water molecule on the carbon of the substrate's carbonyl group polarized by interaction with Zn. (c') Alternative, direct attack of Glu-270 on the substrate's carbonyl carbon, to be followed by hydrolysis of the resulting anhydride intermediate, which has not so far been detected In the absence of evidence for an intermediate, how can one test the mechan- istic proposals further ? If the pathway involves the acylenzyme intermediate (anhydride), and if cleavage of the anhydride occurred with some reasonable probabilities on either side of the bridging oxygen, then one could incorporate lS0into the enzyme by carrying out substrate-cleavage in Hz180.Substitution of the medium by H2160,and subsequent cleavage of a substrate in a few turn- overs may then incorporate lSOinto the substrate.However, if no lSOis in the final substrate one cannot be sure whether Glu-270 promotes the attack of H20 or whether the anhydride is unsymmetrically cleaved. Hence, a negative result is ambiguous, but a positive result would indicate that some fraction of the pathway would involve the anhydride intermediate. This experiment has not yet been carried out. 00 I' 0s Figure 7(b) Enlarged view of Figure 7(a)showing N-formyl-L-tryptophan as heavy lines, His-57, and Ser-195.The Trp ring is parallel to the polypeptide chain along the lower centre of the Figure. Figure 5 (c) Stereoview along -y of about a quarter of the carboxypeptidase A molecule, showing the cavity, the Zn atom, and the functional groups Arg-145 (right), Tyr-248 (above), and Glu-270 (left). (d) Stereoview of the same region, after the addition of glycyl-L-tyrosine (heavy open circles), showing the new positions of Arg-145, Tyr-248, and Glu-270. The guani- dinium movement is 2 A, the OH of Tyr-248 moves 12 A, and the carboxylate of Glu-270 moves 2 A when Gly-Tyr binds to the enzyme Figure 5 (e)Enlarged view of Figure 5(c), showing Arg-145 (right), Glu-270 (left), and Tyr-248(top).The Zn is shown as the largest circle near the centre of the drawing. Figure 5 (f) Enlarged view of Figure 5(d), showing the substrate Gly-Tyr as hemy open circles. Final positions after conformational changes are indicated for Arg-145 (right), Glu-270 (left), and Tyr-248 (top). Figure 7(a) Position of N-formyl-I.-tryptophan (heavy lines) in the active site i-gr a-chymotrypsin. The aromatic ring is in the pocket of the enzyme, and the carboxylate group of this virtual substrate is near Ser-195 and His-57. Q Figure lO(a) Position of a dinucleoside phosphate analogue (heavy lines) in the active site of ribonuclease S. The bond to be cleaved, adjacent to the phosphorus atom in this analogue, is P-CH, instead of P-0.Hid-112 is in an ordered position parallel to the purine ring, and the pyrimidine ring is in the position established earlier from a simpler inhibitor. Figure 10(b) Enlarged view of hay of Figure lO(a), showing the substrate in heavy circles and lines. His-12 is the right. His-119 at the left is parallel to the purine ring. The largest atom is the phosphorus, and the bond to be cleaved is the P-0 bond extending toward the left. This 0 atom was replaced by a CH, group in the X-ray work in order to obtain binding of a non-cleavable substrate analogue d ACTIVE SITE + HEXASACCHARIDE Figure 12 Stereoview of the N-acetylglucosamine hexamer in the active site and cleft of a portion of the lysozyme molecule.Ring D, fourth from the top of the substrate, is shown in the distorted half-chair conformation. Rings A, B, and c (top)are positioned from difference electron density, while rings D, E, and F (bottom) are extrapolared by model building Lipscomb 4 Ch~o~yps~l8s4~,44950 Before the X-ray study was carried out, the chemical evidence for a serinebl (later shown from sequence studies to be Ser-195) and for a hi~tidine~~~~~(later shown to be His-57) both at the active site was excellent. Also, for some sub-strates, an acylenzyme intermediate was kn~~n.~~-~~ ACYLATION OF CHYMOTRYPSIN A H DEACYLATION OF CHYMOTRYPSIN A 0 CAI H' 0 Figure 8 (a) Acylation steps in hydrolysis of a substrate by or-chymotrypsin.(b) Deacylation steps are supposed to be the reverse of the acylation step, but with HaO replacing the original leaving group H,NR. The enzyme is returned to its original form when His+-57 donates a proton to Ser--195. G. P. Hess, in 'The Enzymes', ed. P. D. Boyer, Academic Press, New York,Vol. 3, 3rd Edn., p. 213. K1 E. F. Jansen, M. D. F. Nutting, and A. K. Balls, J. Biol. Chem., 1949, 179, 201. bs B. R. Hammond and H. Gutfreund, Biochem. J., 1955, 61,187. 6s G. Schoellman and E. Shaw, Biochem Biophys. Res. Comm., 1962,7,36. 64 A. K. Balls and H. N. Wood,J. Biol. Chem., 1956, 219,245. 65 M. Caplow and W. P. Jencks, Biochemistry, 1962,1,883; B. Hartley and B. Kilby, Biochem. J., 1954, 56, 288. 6s I. B. Wilson in 'The Mechanism of Enzyme Action', ed.W. D. McEIroy and B. Glass, Johns Hopkins Press, Baltimore, Maryland, 1954. 327 Three-dimensional Structures and Chemical Mechanisms of Enzymes The structure of a-chymotrypsin and of its complex with N-formyl-L-trypto- phan4* (Figure 7) indicate that this inhibitor, or virtual substrate, binds with its aromatic group in the pocket of the enzyme. The carbon of the carboxylate group of the N-formyl-L-tryptophan is close to the oxygen of Ser-195. The two oxygens of this carboxylate group appear to be hydrogen-bonded to the OH of Ser-195 and to N, of His-57. By contrast to carboxypeptidase A, a-chymo-trypsin shows little if any change in the geometry of the active site when this inhibitor is bound. Assuming a close relationship of this complex to an active enzyme-substrate interaction, we see that the probable nucleophile Ser-195 and the probable proton donor His-57, in the acylation step (Figure 8a), are in Van der Waals contact with the atoms of the peptide bond to be cleaved.The de- acylation step is just the reverse, but with a water molecule replacing the leaving group (Figure 8b). These conclusions are based upon extrapolation of this complex to long peptide substrates. The amide of the N-formyl-L-tryptophan can easily be moved (0.7-0.8 .$) so that it couId form a hydrogen bond to the backbone carbonyl of Ser-214, and it is proposed that binding of a longer peptide substrate be continued along this direction to form a short antiparallel pleated sheet with Ser-214, Trp-215, and Gly-216.Some evidence that this may be reasonable is the position of binding of the inhibitor shown in Figure 9. This complex was obtained by reacting the corresponding chloroketone at His-57, and then deriving the atomic positions from an X-ray diffraction study.19 Although a longer peptide binds to the enzyme also in the other direction, toward the carboxylate end, neither model-building nor an X-ray diffraction study have yielded a satis- factory structure for this part of the enzyme-substrate complex. H 0 H N etc. I y2 OH Ser 214 Figure 9 (a) Antiparallel pleated sheet found in the reaction product of acetyl alanyl glycyl phenylaranyl chloromethyl ketone with His-57 of a-chymotrypsin. The prorein sequence Gly-2 16-Trp-215-Ser-214 can also be seen in Figure 7 L&scomb Figure 9 (b) Chymotrypsin AY inhibited by acetyl-Ala-Ala-Phe-chloromethyl ketone after loss of C1 when reacted with His-57.(c) Proposed enzyme-ester intermediate showing acetyl-Ala- Ala-Phe acylating Ser-I95 of chymotrypsin A,, Three-dimensional Structures and Chemical Mechanisms of Enzymes A buried charge of Asp-102, which is hydrogen-bonded to His-57 in turn hydrogen-bonded to Ser-195, may help to activate the catalytic region.67 While it is improbable that protons can be transferred in hydrogen bonds across a large ‘pH gradient’, it does seem possible that this system provides the easiest route for the lines of force of this charge to escape to a region of higher local dielectric constant.This same hydrogen-bonded system has subsequently been found in other serine enzymes. Charges are also buried by the substrate in carboxypeptidase A and in lysozyme. 5 Ribonuclease AIO Chemical evidence for the participation of two his ti dine^^*,^^ and one lysine in the active site of ribonuclease led to an early reasonable proposal of a mech-anism.s0-s2 However, the detailed stereochemistry has become clear only recently, and the role of Lys-41 is still not understood. A portion of the structure of ribonuclease S, along with a dinucleoside phosphate substrate analoguelo is shown in Figure 10. The pyrimidine ring of this analogue is in the same position as that found earlier for several smaller inhibitors which showed occupancy curves similar to those for these inhibitors in The position of His-119 is now ordered, as compared with some disorder in earlier studies, and is parallel to the purine ring of this dinucleoside phosphate analogue.The only two side-chains of the protein which are in contact with the oxygen atoms of the phosphate group (if one replaces the CH2-P of this analogue by 0-P) are the rings of His-119 (N,) and His-12 (N3).If Lys-41 is salt-linked to this phosphate it must be hydrogen-bonded through a water molecule. There are two steps in the hydrolysis of a dinucleoside phosphate.64 The first step is a transesterification in which the 2’-oxygen of the ribose ring adjacent to the pyrimidine is the nucleophile. For example, if cytidylyl adenosine (CpA) is hydrolysed, this step produces cytidine-2’,3’-cyclic phosphate and adenosine.The stereochemistry of this step can clearly be carried out without pseudorota- tion,66 as shown in Figure ll(a), if one starts from the binding stage shown in Figure 10 (see plates section between pp. 326 and 327). The second step, again using CpA as an example, is the attack of water finally yielding cytidine-3’-phosphate as the product. However, the stereochemistry of this stage of the reaction depends upon the direction of attack of the water molecule on phosphorus, and cannot be derived from the X-ray results. The 57 D. M. Blow, J. J. Birktoft, and B. S. Hartley, Nature, 1969, 221, 337. 58 E. A. Barnard and W. D. Stein,J.Mol. Biol., 1959, 1, 339. 5sA.M. Crestfield, W. H. Stein, and S. Moore, J. Biol. Chem., 1963, 238, 2421. 6o D. Findlay, D. G. Herries, A. P. Mathias, B. R. Rabin, and C. A. Ross, Biochem. J., 1962, 85, 152. 61 A. Deavin, A. P. Mathias, and B. R. Rabin, Nature, 1966,211,252. 6a A. Deavin, A. P. Mathias, and B. R. Rabin, Biochem. J., 1966, 101, 14. 63H. W. Wyckoff, K. D. Hardman, N. M. Allewell, T. Inagami, D. Tsernoglou, L. N. Johnson, and F. M. Richards, J. Biol. Chem., 1967, 242, 3749. 64 J. P. Hummel and G. Kalnitsky, Ann. Rev. Biochem., 1964, 33, 15. 6s F. H. Westheimer, Accounts Chem. Res., 1968, 1, 70. t 0 HOH 0-.-I HO$e+c. + Figure 11 (a) Formation of the cyclic intermediate occurs without pseudorotation in the five- co-ordinate intermediate. (b) Hydrolysis of the jive-co-ordinate intermediate is shown by the upper pathway not involving pseudorotation, or by the lower pathway in which pseudorotation occurs.The choice of pathways id ambiguous in the X-ray results, but an analogous reaction in which one oxygen is replaced by sulphur, another labelled by leO, the third unlabelled and the last two in the sugar suggests that the pathway not involving pseudorotation is the correct one upper pathway of Figure ll(b) is similar to the pathway of formation, except that H,O replaces the leaving group of Figure ll(a); no pseudorotation is involved. The pathway starting at the lower part of Figure ll(b) does involve pseudorotation. A recent experiment,6s in which all five atoms of the five-co- ordinated intermediate are labelled, indicates that the pathway not involving pseudorotation is most probably correct: two of the oxygens at phosphorus are attached to the ribose ring in the cyclic intermediate, one other oxygen is replaced by sulphur, the fourth is lSO,and the fifth is l60in this experiment. 66 D.A. Usher, D. I. Richardson, jun., and F. Ekstein, Nature, 1970, 228, 665. Three-dimensional Structures and Chemical Mechanisms of Enzymes 6 Lysozymes7 The first enzyme, and the second protein, to reach atomic resolution, lysozyme is so far the clearest illustration of strain imposed upon a substrate when it is bound to an enzyme. While the largest rates of enzymatic activity occur near pH 5, ranging from pH 3 to 7, there is also activity at higher ~H’S.~~The discussion here refers to the low pH range.The binding to lysozyme of the trimer of N-acetylglucosamine, (NAG),, has been studied by X-ray diffraction methods in some detaiLs7 This inhibitor fills half of the large groove or cleft in the surface of lysozyme. When these results were extended by model building to a hexamer, the fourth ring could not easily be placed in its chair form, but had to be distorted to a half- chair conformation. In Figure 12 (facing p. 327) the hexamer, (NAGk, is positioned in the cleft of lysozyme. The prominent mode of cleavage of this hexamer, or of the cell-wall type of polymer having alternating NAG and NAM (N-acetylmuramic acid), is cleavage between rings D and E such that the bridging oxygen is retained in the product EF.As shown in Figure 13, the only two side- Figure 13 Enlarged view of one-half of Figure 12 showing the substrate along the centre from top to bottom. The bond to be cleaved extends towards the left from the filled circle in the centre, which is the 0 atom of the scissile C-0 bond. Asp-52 is to the upper left and Glu-35 is in the lower right. The optimal pH range is in a region where Asp-52 is most probably ionized, and Glu-35 is most probably protonated, both in the enzyme and in the enzyme-substrate complex chains of the enzyme in contact with atoms of the substrate’s susceptible bond are Asp-52 and Glu-35, respectively assigned as ionized and un-ionized near pH 5.In extrapolating these results to plausible mechanism^,^^ one must note that the half-chair form of ring D would favour a carbonium ion intermediate. But O7 C. C. F. Blake, G. A. Mair, A. C. T. North, D. C. Phillips, and V. R. Sarma, Proc. Roy. SOC.,1967, B167, 365. See also other papers in this issue pp. 349448. 68 J. A. Rupley. Proc. Roy. SOC.,1967, B167, 416. L. N. Johnson, D. C. Phillips, and J. A. Rupley, ‘Structure, Function and Evolution of Proteins’, Brookhaven Symposia in Biology, 1968, No. 21, p. 120. Lipscomb there are also nucleophiles in the immediate environment, including Asp-52, the acetamido side-chain (Figure 14), and water. The stereochemistry favours either the formation of a carbonium ion, stabilized by the negative charge of Glu 35 i Asp 52 Figure 14 Ring D shown in its distorted half-chair conformation, along with nearby side-chains of lysozyme.The hexamer is alternating N-acetylglucosamine and N-acetylmuramic acid, similar to material from the cell-wall polymer Asp-52, or a partial or complete covalent bond between the ring carbon of the substrate and an oxygen of Asp-52 (Figure 15a, 15b). Attack of the acetamido’s carbonyl oxygen would require gross distortion of the binding, and hence prob- ably does not occur at least when the substrate fragment is still bound. Attack of water produces a retention of configuration, and is favoured as a later reaction on geometrical grounds. Also, the stereochemistry favours Glu-35 as the initial proton donor, in the low pH range, rather than water.7 The Activated Complex The role of strain, seen most clearly in lysozyme, appears also to be of import-ance in the other enzymes discussed here. Concerning the role of enzymes in efficient catalysis of chemical reactions, the most perceptive of the early com- ments is probably that of Pauling,’Oe71 ‘I think that enzymes are molecules that are complementary in structure to the activated complexes of the reactions that they catalyse, that is, to the molecular configuration that is intermediate between the reacting substances and the products of reaction for these catalysed processes. The attraction of the enzyme molecule for the activated complex would thus lead to a decrease in its energy, and hence to a decrease in the energy of activa-tion of the reaction and to an increase in the rate of the reaction.’ Perhaps one ‘O L.Pauling, Nature, 1948, 161, 707. ‘l L. Pauling, American Scientist, 1948, 36, 51. ,) Three-dimensional Structures and Chemical Mechanism of Enzymes ASP-52 ACYL-ENZYME SIDE GROUP R’ OC -+ ROH Figure 15 Three plausible pathways for the hydrolysis of the bond between ring D and the bridging oxygen to ring E. (a) The carbonium ion mechanism is favoured. (b) The acylenzyme pathway requires some distortion in the active site, but cannot be eliminated as yet. (c) The participation of the acetamido side-chain requires large distortions in the enzyme-substrati. complex, but is believed to be favoured in model reactions in solution under certain conditions might change the first part from ‘enzymes are molecules that are complement- ary .. . ’ to ‘. . . enzymes are molecules that become complementary. . . ,’ in order to place some emphasis on the flexibility of binding sites, but Pauling went on to suggest that substrate analogues which resemble the transition state may be more tightly bound to enzymes than are analogues of the substrate itself. Experiments strongly supporting these ideas72 have recently been p~blished.~~*~* It seems very likely that binding and strain towards the transition-state complex is a major source of the catalytic power of enzymes. 7t J. B. S. Haldane, ‘Enzymes’, Longmans Green and Co., New York, 1930, p. 180; R. Lumryin ‘The Enzymes’, ed.P. D. Boyer, H. Lardy, and K. Myrbtick, Academic Press, New York, 1959, Vol. 1, p. 157; W. P. Jencks in ‘Current Aspects of Biochemical Genetics’, ed. N. 0. Kaplan and E. P. Kennedy, Academic Press, New York, 1966, p. 273; W. P. Jencks, ‘Catalysis in Chemistry and Enzymology’, McGraw-Hill Book Co., New York, 1969, p. 282. 73 R. Wolfenden, Nature, 1969, 223, 704; Biochemistry, 1970, 9, 3409; Accounts Chem. Res., 1972, 5, 10; L. N. Johnson and R. Wolfenden, J. Mol. Biol., 1970,47,93; B. Evans and R. Wolfenden, J. Amer. Chem. SOC., 1970, 92,4751. 74 G. E. Lienhard, I. I. Secemski, K. A. Koehler, and R. N. Lindquist, Cold Spring Harbor Symposium on Quantitative Biology, June 1971;I. I. Secemski and G. E. Lienhard, J. Amer. Chem.SOC.,1971,93, 3544; K. A. Koehler and G. E. Lienhard, Biochemistry, 1971,10,2477. Lipscomb 8 Factors other than Strain The effects of local environment in the enzyme or near its surface appear to modify strongly the reactivities of various groups of the enzyme, substrate, or solvent. Examples are given above of charges which are buried by substrates or by conformational changes. One type of example is the change of a pK of a potential catalytic group. Perhaps most spectacular is the change reported by We~theimer’~of the pKnear 6 (about 4.5 units lower than ‘normal’) for the active lysine in acetoacetate decarboxylase. Even when structures are known for an enzyme and its complexes it is difficult to estimate the effects of nearby charges or of local dielectric constants in these effects, which nevertheless can be large.The general effect is the stabilization of states with less absolute charge when a hydrophobic environment is formed. Other factors include the concerted character of the enzyme-substrate reaction, similar in some ways to intramolecular reactions in model compounds. Proximity effects, and the detailed geometry at the reactive atoms, must also be important in moving the reaction co-ordinate along the catalytic pathway. Geometry includes orientation effects, which are perhaps related to minimization of non- bonded repulsions at least as much as to promotion of bonded interactions, but both effects are of interest; this is a gentle comment on orbital steering.9 What Were Those Questions Again? (i) Not all proteins, of course, but probably enzymes which can be crystallized and which show diffraction patterns to atomic resolution will be substantially ordered to the atomic level in the crystalline state. Preliminary enzymatic activity, chemical modification, spectroscopic and especially high-resolution n.m.r. methods can be used to compare conformations in solution with the crystallo- graphic results. The comparisons are favourable so far. (ii) Parts of the protein involved in activity can be compared in chemical modification experiments using real substrates and in three-dimensional proximity in complexes of enzymes with virtual, or slowly cleaved, substrates. The correspondence here is also excellent.(iii) If studies are made on the X-ray structures of a number of sub- strate analogues, inhibitors, and products as bound to the enzyme in the crystals, a pattern of binding can be deduced. It seems likely that one can find substrate analogues in which atoms are only a few to several tenths of an Angstrom from the positions in the transition-state complex of a good substrate with most enzymes which can be studied by X-ray diffraction methods. (iv) The potential catalytic groups, side-chains of the enzyme or even of the substrate itself, are probably to be found in Van der Wads contact with the atoms of the enzymic reaction, or they can be brought into contact largely by rotations about single bonds. (v) Product binding, when studied by X-ray methods, is frequently so specific that bonding shifted to neighbouring subsites is rare.However, results based on one or a few studies can be misleading. Nevertheless, the binding of 7b F. H. Westheimer, ‘Bio-organic Chemistry and Mechanisms’, The Welch Foundation Conferences on Chemical Research, XV,Houston, 1971. Three-dimensional Structures and Chemical Mechanism of Enzymes products often resembles cIosely the binding of that corresponding part of the substrate analogue in the protein molecules in the crystalline phase. Question (vi), 'Why are proteins so large?, requires a separate paragraph, since the answers are not all known. (a) Proteins of definite conformation have hydrophobic regions in the interior regions, and a hydrophilic exterior con- tributing to solubility. (b) These same problems of forming a hydrophobic interior and hydrophilic exterior apply not only to the final form of an enzyme, but also to the proenzyme, and to the portions of the initially formed protein during biosynthesis. (c) The hydrophobic interior may also be important in activating a charged group, either for binding or catalysis, when its environment is changed upon formation of the enzyme-substrate complex.(d)Flexibility is required to allow participation of catalytic groups, and to permit capture of substrate and release of products. (e) The hydrolytic enzymes have relatively extended binding regions, involving some five amino -acids for carboxypeptidase, seven for papaine, and six sugar sites for lysozyme.(f)There are two lines of evidence which suggest that enzymes are large for reasons not well understood. Modification experiments far from an active site can affect activity. The second bit of evidence refers to the very many small shifts of atoms always seen in electron density maps throughout the enzyme when a substrate analogue is bound. These shifts, generally much smaller than those in the active site, may not have a negligible cumulative effect on the activity of an enzyme. Perhaps we shall undei stand them some day; perhaps some protein crystallographer will describe them so that we know what they are! It is likely, then, that enzymes are evolved for binding of substrates, more especially for strain of enzyme-substrate complex towards the transition state, and for the whole sequence of conforma- tional changes involved in the chemical stages of the enzyme-substrate ieaction.The last question also has several answers. Use of storage rings for electron beams may produce a very large increase in X-ray intensity for protein structure investigation. The development of television scanners with electronic image intensifiers will probably reduce the time for X-ray data collection by a factor of about one hundred, and thereby make possible study of complexes of more rapidly cleaved substrates than those now being investigated. Use of low- temperature methods, say about -5O"C, will also slow the enzyme substrate reaction, but one must be careful that the temperature difference does not change the rate-determining step, and that the use of a solvent other than the usual aqueous buffer does not also change the conformation and reaction.The promise of these approaches is very great, and these new methods may then allow us some freedom to give greater attention to the choice of appropriate problems of biochemical importance. For example, the further development of methods for isolation, characterization, and structure determination will yield results for enzymes and other proteins having subunit structures, from which new principles are likely to emerge. I wish to thank D. M. Blow, D. C. Phillips and F. M. Richards for their courtesy in providing stereoviews shown herein.

ISSN:0306-0012    

DOI:10.1039/CS9720100319

出版商:RSC    

年代:1972

数据来源: RSC

摘要:

The 16 and 18 Electron Rule in Organometallic Chemistry and Homogeneous Catalysis By C. A. Tolman cENTRAL RESEARCH DEPARTMENT* EXPERIMENT A L STATION, E. I. DU PONT DE NEMOURS AND COMPANY, WILMINGTON, DELAWARE 19898, U.S.A. 1 Introduction There has been a great increase in interest and activity in recent years in organo- metallic chemistry, especially in the area of homogeneous catalysis by transition- metal complexes. A number of publications have appeared dealing with par- ticular organometallic reactions which occur in catalysis, such as oxidative addition,lJ insertion,, ligand e~change,~ and reactions of complexes with Lewis acids.6A few authors have attempted to outline the principles of catalysis more There appears, however, to be no satisfactory scheme which relates the various reaction types or which permits mechanistic predictions.In this review the various types of organometallic reactions involved in catalysis are organized in a systematic way, and some empirical rules are pre- sented which may be used predictively to restrict the kinds of organometallic compounds which may exist under mild conditions and the types of reactions they may undergo. The tendency of transition metals to form complexes in which the metal has an effective atomic number corresponding to the next higher inert gas has long been recogni~ed.~ There are, however, many exceptions, as illustrated by the following examples : Compound NVE TiClc 8 MeAuPPh, 14 Co(CN),S- 17 Ni(HzO)5z+ 20 The number of valence electrons (NVE) consists of the valence electrons of the * Contribution No.1821. J. P. Collman, Accounts Chem. Res., 1968, 1, 136; J. P. Collman and W. R. Roper, Adv, Organometallic Chem., 1968, 7, 53. J. Halpern, Accounts Chem. Res., 1970, 3, 386. a R. F. Heck, Adv. Chem. Ser., 1965, 49, 181. C. H. Langford and H. B. Gray, ‘Ligand Substitution Processes’, Benjamin, New York. 1965. D. F. Shriver, Accounts Chem. Res., 1970, 3, 231. J. Halpern, Discuss. Faraday SOC.,1968, 46,7. J. Halpern, Adv. Chem. Ser., 1968, 70, 1. * R. Ugo, Chimica e Industria, 1969, 51, 1319. N. V. Sidgwick, ‘The Electronic Theory of Valency’, O.U.P.,London, 1929, p. 163. 16 and 18 Electron Rule in Organometallic Chemistry and Homogeneous Catalysis metal and those electrons donated by or shared with the ligands, and would be 18 for an inert-gas configuration.If, however, one restricts attention to the diamagnetic organometallic complexes of Groups IVB-VIII, essentially all of the well-characterized compounds have 16 or 18 metal valence electrons.lOsll This fact has not generally been adequately appreciated by organometallic chemists. In fact, the literature contains numerous examples of organometallic compounds which, as formulated, appeared to be exceptions to what can be called the 16 and 18 Electron Rule. Careful subsequent study has almostinvari- ably shown that the original formulation was incorrect. The accessibility of 16 and 18 electron configurations also has important consequences for mechanisms of organometallic reactions, as outlined below. Organometallic compounds, for the purposes of this discussion, are transition- metal complexes containing one or more ligands such as CO, N2, CN-, RNC, PR3, P(OR)3, olefin, acetylene, n-allyl, 7r-cyclopentadienyl, 7r-aryl, acyl, -SiR3, -R, or -H.These ‘soft’lB or ‘class b’lSligands are characterized by a high ligand- field strength and covalent bonding character and are the types typically found in homogeneous catalytic reactions such as hydrogenation, hydroformylation, hydrosilylation, and olefin isomerization and oligomerization. The 16and 18 Electron Rule.-Two postulates or rules for organometallic com- plexes and their reactions are proposed.1. Diamagnetic organometallic complexes of transition metals may exist in a significant concentration at moderate temperatures only if the metal’s valence shell contains 16 or 18 electrons. A significant concentration is one that may be detected spectroscopically or kinetically and may be in the gaseous, liquid, or solid state. 2. Organometallic reactions, including catalytic ones, proceed by elementary steps involving only intermediates with 16 or 18 metal valence electrons. It is apparent that application of these rules requires that care be exercised in reaching conclusions on the NVE of a metal complex. Association or dissociation of the compound may occur. For example, Ni[PPh3I4 is substantially dissociated in solution into Ni[PPh3I3 and PPh3.14 r-Ally1 palladium chloride is a 16 electron complex, with chloride ions bridging in a dimeric Polyfunctional ligands may co-ordinate at more than one site, and additional M-C and M-H bonds may form by reaction of a metal with C-H bonds of the ligands.ls When the complex is in solution, there is a potential ambiguity as to whether solvent is co-ordinated.The mere presence of solvent in the analysis of a crystal- line solid is not good evidence for solvent co-ordination. One convenient criterion lo F. Basolo and R. G. Pearson, ‘Mechanisms of Inorganic Reactions’, Wiley, New York, 1967, p. 526. I1 G. E. Coates, M. L. H. Green, and K. Wade, ‘Organometallic Compounds’, 1’01. 2, ‘The Transition Elements’, Methuen and Co., Ltd., London, 1968, p.6. l* R. G. Pearson, Science, 1966, 151, 172. S. Ahrland, J. Chatt, and N. R. Davies, Quart. Rev., 1958, 12, 265. l4 C. A. Tolman, W. C. Seidel, and D. H. Gerlach, J. Amer. Chem. SOC., 1972, 94, 2669. l6 W. E. Oberhansli and L. F. Dahl, J. Organometallic Chem., 1965, 3, 43. G. W. Parshall, Accounts Chem. Res., 1970, 3, 139. Tolman for solution studies is whether the electronic spectrum of the complex is sub- stantially different in different solvents. Frequently a coloured complex will give dramatic colour changes when dissolved in a co-ordinating solvent. For example, Ni[P(O~-tolyl)~]~,~~a red-orange solid, gives red-orange solutions in benzene, tetrahydrofuran, or methylene chloride, in which it remains three-co-ordinate, but gives a colourless solution in acetonitrile, from which the unstable adduct MeCNNi[P(Oo-t olyl) ,I3 has been isolated.’ 2 Typesof Organometallic Reactions Reactions of ligands which do not directly involve the transition metal are ex- cluded from this classification. Some examples of such reactions are methanolysis of Ni(PF& to give Ni(PF,) ,[PF,-n(OMe)n], Friedel-Crafts acylation of ferro- cene, and nucleophilic attack on a co-ordinated carbonyl by methoxide ion.Reactions which involve the transition metal directly can be broken down into five elementary reactions, each with a microscopic reverse. The classification is based upon the changes in number of metal valence electrons, formal oxidation state, and co-ordination number which accompany each reaction.The five elementary reactions are shown with examples in the Table. It will be seen that reactions 1 and 2 involve dissociation and association of ligands whereas 3-5 involve reactions between co-ordinated ligands. The latter can be classified according to the parity of the groups coupled, considering them to be uncharged. Thus coupling of two hydrogen atoms or two m-ally1 groups (odd-odd coupling) is a reductive elimination. Coupling of an odd-electron fragment, such as a n-allyl, with an even one, such as ethylene, is an insertion. Even-even coupling, as between two m-bonded olefin molecules, is oxidative coupling. Some of the terms in the Table are used in a way which may be unfamiliar to the reader and warrant further discussion, The term ‘Lewis base ligand’ is used to include ligands such as CO which are not normally considered as bases, in addition to more usual ones such as phosphines, on the basis that they contribute two electrons to the metal’s valence shell.Lewis acid ligands, such as H+, BF,, and SO,, contribute no valence electrons. In common parlance ‘oxidative addition’ is used to describe an over-all reac- tion in which the formal oxidation state of the metal and the co-ordination number increase by either one or two.2 In this discussion only a concerted one- step reaction which increases both co-ordination number and oxidation state by two is termed an oxidative addition. The narrower definition is used in order to break reactions down into elementary steps and to distinguish between differ- ent types of mechanisms.An increase in co-ordination number by one as in H++CO(CO)[ -HCo(CO), L. W. Gosser and C.A. Tolman, fnorg. Chem., 1970, 10,2350, C. A. Tolman, Inorg. Chem., 1971, 7,1540. Table Elementary organometallic reactions Reverse ri.Reaction dWEa dOSb dNc Example Reaction dNVEdOSdN $ 1. Lewis acid Lewis acid zjligand dissociation 0 0 -1 CpRh(C2H4),S02f SO, + CpRh(C,H,), association 0 0 +l $ or 0 -2 -1 HCo(CO), +H+ + CoC0,-or 0 +2 +1 0 42. Lewis base Lewis base ligand dissociation -2 0 -1 NiL4 +NiL, + L association +2 0 +1 4 3. Reductive Oxidative 33 elimination -2 -2 -2 H,IrCI(CO)L, +H, + IrCl(CO)L, addition +2 +2 +2 0 4. Insertion -2 0 -1 MeMn(CO), +MeCOMn(CO), Deinsertion +2 0 +1 $ 5CFZ-CF, I \ .;I\ Reductive 55.Oxidative coupling -2 +2 0 /Fe(c0)3 decoupling +2 -2 0 a4 3 a Change in the number of metal valence electrons; Change in the formal oxidation state of the metal. The usual convention which regards hydrides, 2alkyls, r-allyls, and 7r-cyclopentadienyls as uninegative ions is used ;C Change in co-ordination number. E is regarded as a Lewis acid ligand association reaction. A two-step reaction, as in is regarded as a Lewis acid ligand association followed by a Lewis base ligand association. Reaction of molecules such as 0, or tetracyanoethylene with a transition metal can be regarded as an oxidative addition in which only part of a multiple bond is broken to form two new metal-ligand bonds, leaving the two Iigands joined.With less electronegative olefins, such as C,H4 or C2F4, it may be more convenient to regard their co-ordination as a Lewis base addition rather than as an oxidative addition. The real extent of electron transfer must be determined by ESCA or some other means. The count of metal valence electrons in either case is the same. The terms 'oxidative coupling' and 'reductive decoupling' are new. The former is used to denote reactions such as that shown in reaction (4), in which the formal oxidation state of the metal increases by two but the co-ordination number does not change. 3 Applications of the Rule to General Organometallic Reactions The 16 and 18 Electron Rule severely restricts the types of reaction which a particular complex may undergo.Dissociation or association of Lewis acid ligands may occur with either 16- or 18-electron complexes. Lewis base ligand dissociation, reductive elimination, insertion, and oxidative coupling are re- stricted to 1%electron complexes. Lewis base ligand association, oxidative addition, deinsertion, and reductive decoupling reactions can occur only with 16-electron complexes. A number of examples from the literature will serve to illustrate these points. A. Lewis Acid Dissociation-Association.-That Lewis acids may react with either 16- or 18-electron complexes is shown by the formation of adducts of BF, with 16-electron IrC1(CO)(PPh,),ls or with 18-electron HR~(T-C~HJ,.~O Other l9 R.N.Scott, D.F. Shriver, and L. Vaska, J. Amer. Chem. SOC.,1968,90, 1079. *O M.P. Johnson and D. F. Shriver, J. Amer. Chem. Soc., 1966, 88, 301. 16 and 18 Electron Rule in Organometallic Chemistry and Homogeneous Catalysis examples of reactions of 18-electron complexes with Lewis acids include forma- tion of [(n-C5H5)Rh(CO)PMePh2Cl]+from (~T-C~H,)R~(CO)PM~P~~ and C1221 and of HNi[P(OEt),14+ from Ni[P(OEt),], and H+.22 B. Lewis Base Dissociation-Association.-Ligand-exchange reactions are the most thoroughly studied type of organometallic reaction, They generally proceed via Lewis base ligand dissociation as a first step for 18-electron complexes and via ligand association for 16-electron complexes. Examples include exchange of CO from Ni(CO)4 by L = CO or PPh3 in reaction (5),23 displacement of H20 fr0m[Co(CN),(H,0)]~- by X-= N3-or SCN- in reaction (6),24and the reaction of pyridine with trans-RPtCI(PEt3)2c~mplexe~in reaction (71a51n these reactions the number beneath each complex indicates the NVE.The initially puzzling observations by Cramer2s that (acac)Rh(C,H,), ex-changes ethylene rapidly on an n.m.r. time scale, whereas (n-C,H,)Rh(C,H,), is very inert to exchange are readily explained. The acetylacetonate complex can exchange via the associative mechanism shown in reaction (8). For the 18-electron (n-C,H,)Rh(C,H,), the associative pathway is blocked. The 16-electron (C,H,)- *lA. J. Oliver arid W. A. G. Graham, Inorg. Chem., 1970, 9, 243. la W. C. Drinkard, D.R. Eaton, J. P. Jesson, and R. V. Lindsey, jun., Znorg. Chem., 1970, 9, 392. *3 J. P. Day, F. Basolo, and R. G. Pearson, J. Arner. Chem. SOC.,1968, 90, 6927. a4 A. Haim and W. K. Wilmarth, Znorg. Chem., 1962, 1, 573. a5 F. Basolo, J. Chatt, H. B. Gray, R. G. Pearson, and B. L. Shaw, J. Chem. Soc., 1961,2207.** R. Cramer, J. Arner. Chem. Soc., 1967, 89,4621. Tolman Ni[P(Oo-tolyl),], exchanges ethylene very rapidly but can be recovered un- changed after prolonged exposure of a solution to vacuum.27 Again, the 16- electron complex can associate a two-electron ligand but does not dissociate. C. Reductive Elimination-Oxidative Addition.-The kinetics of reaction (9), involving reductive elimination of H,, have been studied.28 The rate of the reac- tion is independent of the concentration and nature of L1[L1= CO, P(OMe),, P(OPh),, or PMePhJ as required for rate-determining loss of H, in the mechan- ism shown in reaction (10).The 16-electron intermediate was actually isolated for Ls = P(CaH11)3. Oxidative addition of H, to the 16-electron complex IrCl(CO)(PPh,), is first- order in both H, and Ir complex,2D as required for a concerted reaction. Reac- tion of the 18-electron complex HIr(CO)(PPh,), with HSi(OEt),, as expected, does not occur in a single ~tep.~OThe mechanism found is shown in reaction (11) (L = PPh3, R = OEt). The need to dissociate a ligand from an 18-electron complex before oxidative addition can occur is also shown in the reactions of H, or HCI with EtCOM- (CO),(PPh,),.High concentrations of CO inhibit the formation of aldehyde.s1 Pearson has recently shown that optically active MeCHBrC0,Et reacts with Mn(CO),-with inversion of configurati~n.~~ The 18-electron complex cannot undergo an oxidative addition without first losing a CO ligand. Since CO dis- sociation from Mn(CO),- is extremely slow,,, the reaction is forced to proceed in a way which does not increase the NVE of Mn. The SN~Walden inversion which occurs at the asymmetric carbon can be regarded as a special case of Lewis W. C. Seidel and C. A. Tolman, Inorg. Chem., 1970, 9, 2354. *8 M. J. Mays, R. N. F. Simpson, and F. P. Stefanini, J. Chem. SOC.(A), 1970, 3000. 19 P. B. Chock and J. Halpern, J. Amer. Chem. SOC.,1966, 88, 3511.30 J. F. Harrod and C. A. Smith, Cunad, J. Chem., 1970,48, 870. 31 G. Yagupsky, C. K. Brown, and G. Wilkinson, J. Chem. Soc. (A), 1970, 1392. 32 R. W. Johnson and R. G. Pearson, Chem. Comm., 1970,986. 33 W. Hieber and K. Wollmann, Chem. Ber., 1962, 95, 1552, found no exchange with "CO in 20 h at 40 "C. 343 16 and 18 Electron Rule in Organometallic Chemistry and Homogeneous Catalysis acid ligand association, the bromine leaving with the electron pair it had shared with carbon (reaction 12). H Me \/MeCHBrCOzEt + Mn(CO)~’+[(COlj Mn ----C ---0 Brl’ (12)&+I &-C02 Et On the other hand, reaction of IrCl(CO)(PMePh,), with MeCHBrC0,Et is reported to proceed with retention.34 A concerted oxidative addition with retention of configuration is possible for the Ir complex because it has 16 valence electrons.Lewis acid association with inversion is also possible. D. Insertion-Deinsertion.-The insertion of CO in the reaction of 18-electron MeMn(CO), with L = PPh3 or P(OPh)3 involves CO insertion as a first step, followed by reaction of the 16-electron intermediate with L, as shown in reac- tion (13).35 Insertion followed by ligand association is also consistent with the MeMn(CO), -MeCOMnlCO), 7-MeCoMn(Co)4L (1 3) 18 16 L 18 result that treatment of MeMn(CO), with 14C0 gives an acyl with a non- labelled CO;36 some elegant experiments with 13C0 have demonstrated that the methyl group moves3’ Another type of insertion reaction is illustrated by reaction (14).38The existence of a hydrido-olefin intermediate has been supported by deuterium-labelling experiments3 34 R.G. Pearson and W. R. Muir, J. Amer. Chem. SOC.,1970,92, 5519. 3b R. J. Mawby, F. Basolo, and R. G. Pearson, J. Amer. Chem. SOC.,1964, 86, 3994. ssT.H. CoffieId, J. Kozikowski, and R. D. Closson, J. Org. Chem., 1957, 22, 598; ‘Internat. Conf. on Co-ord. Chem., London, 1959’, The Chemical Society, London (Special Publication No. 13), 1959, p. 126. K. Noack and F. Calderazzo, J. Organometallic Chem., 1967, 10, 101. 38 J. Chatt and B. L. Shaw, J. Chem. SOC.,1962, 5075. J. Chatt, R. S. Coffey, A. Gough, and D. T. Thompson, J. Chem. SOC.(A), 1968,190. Tolman E. Oxidative Coupling-Reductive Decoup1ing.-An example of oxidative coup- ling is given by reaction (15),4O where R = C0,Me and L = PPh3.The reaction R L\ \/" C/R (N,) IrClL, + 2RC"-CR CL -It /\C +N2I L C R/ \R probably proceeds via oxidative coupling of the acetylenes in an (RC,R)IrClL, intermediate. Another example is given in reaction (16).41 The details of the reaction are not known; however, it probably proceeds by oxidative coupling of the olefins in (C2F3H),Ni(PPh3)2. There is a precedent for (olefin),NiL, complexes in (CH ,=CHCN) %Ni(PPh3) 2.42 4 Applicationsof the Rule to Homogeneous Catalytic Reactions Homogeneous catalytic reactions proceed by the same elementary steps (see the Table) as general organornetallic reactions. The unique feature of a catalytic system is that a series of steps is connected in a cyclic way, to form a loop.Mechanisms of some well-studied catalytic processes will now be described in detail. A. Hydroformylation of Olefins by HCO(CO),.~~-T~~ hydroformylation of a terminal olefin is shown in Figure 1. The electron configurations and co-ordina- tion numbers in the dnNn~tation~~ are shown by each complex. The mechanism is basically that of Heck and Bre~low,~~ but modified to show explicitly the 40 J. P. Collman, J. W. Kang, W. F. Little, and M. F. Sullivan, Inorg. Chem., 1968, 7, 1298. 41 J. Ashley-Smith, M. Green, and F. G. A. Stone, J. Chem. Soc. (A), 1969, 3019. 4a G. N. Schrauzer, J. Amer. Chem. SOC.,1960, 82, 1008. 49 For a review see A. J. Chalk and J. F. Harrod, Adv. Organometallic Chem., 1968, 6, 119. 44 dn gives the number of d electrons for a particular oxidation state while N is the co-ordina- tion number.I6R. F. Heck and D. S. Breslow, J. Amer. Chem. SOC.,1961,83,4023. 16and 18 Electron Rule in Organornetallic Chemistry and Homogeneous Catalysis oxidative addition of hydrogen and reductive elimination of aldehyde. The first step of the reaction, starting with HCo(CO),, is Lewis base ligand dissociation from the 18-electron complex to give HCo(CO),. The reactions proceeding clockwise around the loop are then: (2) olefin (Lewis base) association to give an 18-electron hydrido-olefin complex; (3) insertion of olefin to give a 16-electron alkyl; (4) association of CO to give an 18-electron alkyl; (5) insertion of CO to give a 16-electron acyl; (6) oxidative addition by H, to give an 18-electron acyl cobalt dihydride; and (7) reductive elimination of aldehyde product with re- generation of HCo(CO),.Step (8) connects the loop reversibly to a species not on the loop. Inhibition of hydroformylation by high CO pressure is due to reduction in the concentrations of loop species by step (8) and the reverse of (1). d '4. Figure 1 Hydroformylation of a terminal olefin by HCo(CO), Figure 1 has been simplified in that it does not show formation of internal aldehydes, hydrogenation of aldehydes to alcohols and of olefins to alkanes, or olefin isomerization, which also occur in the system. B. Hydrogenation of Olefins with RhCI(PPh,),.-Application of the 16 and 18 Electron Rule to olefin hydrogenation with Wilkinson's catalyst45 is shown in Tolmati Figure 2.Two loops arise from the possibility of co-ordinating hydrogen and olefin in either order. Step (1) represents oxidative addition of hydrogen to the square-planar 16-electron complex to give an 1%electron dihydride. Step (2), Lewis base dissociation, is followed by olefin co-ordination in step (3). Insertion RCHsCH;! d84 I RhClL3 d85 d04 Figure 2 Hydrogenation of a terminal olefin by RhCI(PPhJ3 in step (4) gives an unstable hydrido-alkyl with NVE = 16. Phosphine associa-tion in step (5) gives an 18-electron hydrido-alkyl which produces alkane by reductive elimination, regenerating RhCI(PPh3),. Wilkinson's isolation of (C2H4)RhClL2and observation that the ethylene complex is not readily hydro-genatedq6suggest that step (9) is very slow, so that the bulk of the reaction goes via the loop which contains steps (1)-(6).The inhibition of hydrogenation on addition of triphenylphosphine to the system can be understood in terms of its suppression of ligand dissociation in step (2). The mechanism in Figure 2 is somewhat different from the one originally proposed, which included phosphine ligand dissociation as the first step in the reaction and simultaneous addition of both hydrogens to the double bond. The phosphine-dissociation step was based on a low value for the molecular weight of RhCI(PPh3)3.Molecular weight determinations4' under scrupulously oxygen-free conditions indicated that the 46 J.A. Osborn, F. H. Jardine, J. F. Young, and G. Wilkinson, J. Chem. SOC.(A), 1966,1711. 47 D. D. Lehman, D. F. Shriver, and I. Wharf, Chem. Comm., 1970, 1486. 16 and 18 Electron Rule in Organometallic Chemistry and Homogeneous Catalysis complex does not dissociate to any great extent. This conclusion was also sup- ported by n.m.r. studies.48 Studies49 employing a combination of spectro- photometry and 31P and lH n.m.r., indicate that RhCl(PPh3)3 dissociates only to a very small extent to give a dimer and that its reaction with H, gives H2RhCl(PPh,),,60 rather than HZRhCl(PPh3),S (S = solvent) as originally Dissociation to H2RhC1(PPh3), is slight, but does provide a mecha-nism for ligand exchange. Stepwise rather than simultaneous addition of hydrogens during olefin hydro- genation is indicated by deuteriatiodl and olefin isomerization studies.s2 It should be noted that both formation of RhCl(PPh3)2 and simultaneous addition of hydrogens to the olefin are prohibited by the 16 and 18 Electron Rule.RhCl(PPh,), is already a 16-electron complex and would drop to 14 if a PPh3 were lost. Simultaneous addition of both hydrogens to an olefin would decrease the NVE by 4, and is not allowed since dNVE can only be 0 or f2. C. Olefin Lsomerization by Ni[P(OEt),l4 and H2S04.-An example of a catalytic system involving a Lewis acid is the isomerization of butenes catalysed by Ni[P(OEt),], and HzS04,63 shown in Figure 3. In this case, two steps are required before the metal enters the loop: (1) Lewis acid association with 18-electron NiL, and (2) Lewis base ligand dissociation to give 16-electron HNiL3+.The reader can readily follow through the steps in the loop. Figure 3 is over- simplified in that side-reactions of catalyst decomposition and P(OEt), de- alkylation which occur in the system are not shown. D. Orthodeuteriation of Triary1phosphines.-A catalytic reaction which involves oxidative addition of a transition metal by a C-H bond is the ortho-deuteriation of triaryl phosphine. Triphenylphosphine is converted catalytically under Dz into tri-(2,6-dideuteriophenyl)phosphine by HRUCI(PP~~),,C~H~CH~.~~ The complex HRuC1[P(OPh)J4 also exchanges H for D on the ortho-positions of the ligand phenyl rings, but is a very poor catalyst for the catalytic formation of tri-(2,6-dideuteriophenyl) phosphite; addition of P(OPh), to a solution of HRuCl[P(OPh),], under Dzprevents deuteriation even of the original phosphite ligands.The result can be readily understood in terms of the 16 and 18 Electron Rule. HRuCl(PPh,), is a 16-electron complex and oxidative addition by an ortho-C-H bond can readily proceed. The 18-electron complex HRuCl- [P(OPh),], must dissociate a ligand, in an equilibrium suppressed by added ligand, before oxidative addition can occur. 48 D. R. Eaton and S. R. Suart, J. Amer. Chem. SOC.,1968,90,4170. J. P. Jesson, P. Meakin, and C. A. Tolman, J. Amer. Chem. SOC.,1972, 94, 3240. 50 A. Sacco, R. Ugo, and A. Moles, J. Chem. SOC.(A), 1966; 1670.51 A. S.Hussey and Y. Takeuchi, J. Amer. Chem. SOC.,1969, 91, 672. J. P. Candlin and A. R. Oldham, Discuss. Faraday SOC.,1968, 46, 60. 53 C. A. Tolman, J. Amer. Chem. SOC.,1972, 94, 2994. 54 G. W. Parshall, W. H. Knoth, and R. A. Schunn,J. Amer. Chem. SOC.,1969, 91,4990. Tolman Y Y CbCH2CH-NiH L32' d6s CH3CHzCHzCH2Ni HL32+ I $ 4 CH3 I;, / /I./ '<\xLCH3CH2CH2CH3~/'\@-LNi2++3' A-0 Figure 3 Isomerization of butenes by Ni[P(OEt),], and H,SO,. I-B, c-2-B, and t-2-B represent but-1 -ene, cis-but-2-ene, and trans-but-2-ene. From Ref. 53 5 Apparent Exceptions to the Rule A. Possible Alternative Explanations.-Some compounds appear at first sight to react in an exceptional way. The 1%electron complexes CO(NO)(CO),,~~ and (T-C,H~)R~(CO)~~~ reactions with phosphines to give Co(N0)- undergo SN~ (CO)tL, and (?r-C,H,)Rh(CO)L.Their anomalous behaviour can be explained in terms of an electron rearrangement to make available an empty bonding orbital.,' This rearrangement can be thought of as an intramolecular conversion 55 E. M. Thorsteinson and F. Basolo, J. Amer. Chem. SOC.,1966, 88, 3929. 56 H. G. Schuster-Woldan and F. Basolo, J. Amer. Chem. SOC.,1966, 88, 1657. 57 Ref. 10, p. 571. ,/ 16 and 18 Electron Rule in Organometallic Chemistry and Homogeneous Catalysis of the 18-electron complex into a 16-electron complex. C01lman~~ has recently reported i.r. evidence which suggests that several CoCl,(NO)L, complexes actually exist in solution as an equilibrium mixture of 16-electron [NO- ligand] and 18-electron [NO+ ligand] forms.Angelici and Graham69 have reported a two-term rate law for the reaction of 18-electron Mo(CO), with phosphines such as PBu, : The sN2 path may involve a 20-electron intermediate or, as the authors mention, could involve attack by the phosphine on co-ordinated CO. An X-ray crystal structure determination on PtI,(diars), (diars = o-phenyl-enebisdimethylarsine) shows that the PtII is six-co-ordinate in the crystal, with equal bond distances from Pt to each of the I atoms.60 The bond lengths are, however, exceptionally long, 3.50 A. Though the compound appears to be a 20-electron complex, there is an alternative bonding description, first proposed by Rudes1 for the analogous 13-, which preserves the noble-gas configuration for the central atom.In nitromethane the platinum complex dissociates to give the 18-electron [PtI(diar~),]+.~~ X-Ray crystal structures of tetrabenzylzirconiums2 and tetraben~yltitanium,~~ apparently %electron complexes, have been reported. Both show anomalously small M-C-4 bond angles at the methylene carbons, suggesting participation of ring electrons in the bonding. Definitive evidence for participation of ring electrons in bonding in a benzyl complex has been found in the structure of (h3-4-MeC6H4CH,)(h6-c6H~)Mo(~o)3.6* B. Original Formulation shown to be Incorrect.-There are a number of cases in the organometallic literature where complexes formulated as having other than 16 or 18 metal valence electrons were proposed, but where subsequent work has shown that the original formulation was in error.The absence of dissociation of Wilkinson's hydrogenation catalyst to RhCI(PPh,), has already been men- tioned. The apparent 14-electron complexes Ni(PPh3)266 and Ni[P(Oo-t~lyl)~],~~ were later shown to be the 16-electron complexes (C,H4)Ni(PPh,),67 and (C2H4) Ni[P(Oo-t olyl)&. 27 A 20-electron complex Ni(CN),'- was proposed on the basis of equilibrium studies on Na,Ni(CN), containing various concentrations of added NaCN.68 s* J. P. Collman, P. Farnham, and G. Dolcetti, J. Amer. Chem. SOC.,1971,93, 1788. 59 R. J. Angelici and J. K. Graham, J. Amer. Chem. SOC.,1966, 88, 3568. O0 N. C. Stephenson, J. Inorg. Nuclear Chem., 1962, 24, 791.61 R. E. Rundle, Rec. Chem. Prugr., 1962, 23, 195. 6a G. R. Davies, J. A. J. Jarvis, B. T. Kilbourn, and A. J. P. Pioli, Chem. Comm., 1971, 677. 63 I. W. Bassi, G. Allegra, R. Scordamaglia, and G. Chioccola, J. Amer. Chem. Soc., 1971,93, 3787. 64 F. A. Cotton and M. D. La Prade, J. Amer. Chem. Suc., 1968, 90, 5418. 6s G. Wilke, E. W. Muller, and M. Kroner, Angew. Chem., 1961, 73, 33. M. A. McCall and H. W. Coover, B.P. 1 146 074/1969. c7 G. Wilke and G. Herrmann, Angew. Chem. Internat. Edn., 1962,1, 549. 6* R. A. Penneman, R. Bain, G. Gilbert, L. H. Jones, R. S. Nyholm, and G. K. N. Reddy,J. Chem. SOC.,1963, 2266. Tolmari Later studies showed that the results were consistent with the presence of Ni(CN),,-and Ni(CN),,-, 16- and 18-electron complexes, respectively, and that there was no evidence for the formation of 20-electron Ni(CN),4- even in 4M-NaCN.69 An X-ray crystal-structure determination has shown that the compound originally formulated as MO(CH,S~M~,)~,~~ a 10-electron complex, is actually a cluster compound with a very short Mo-Mo bond di~tance.~‘ The lklectron complex Pt(PPh,), has been proposed as an intermediate in oxidative addition reactions2 of Pt(PPh3), and (C,H4)Pt(PPh,),,72 and in substitution reactions7, of (alkyne)Pt(PPh,),.The compound was first suggested on the basis of low molecular weights for Pt(PPh& and Pt(PPh3)4.74 The prep- aration of a yellow material said to be the ‘probably monomeric species Pt(PPh3),’ has recently been Recent careful physical studies have been made on the platinum(0)-triaryl phosphine-ethylene system which include a combination of molecular weight determinations, spectrophotometry, and lH and slP Thesc studies have shown that Pt(PPh,), and (C,H,)Pt(PPh,), do not dissociate to a detectable extent.Furthermore the behaviour of lineshapes in the n.m.r. spectra on adding C2H4 and/or PPh, to solutions of (C,H,)Pt(PPh,), or Pt(PPh,), requires the associative mechanisms for exchange of ethylene or phosphine expected for these 16-electron complexes. C. Predictions Based on the Rule.-The compound Pd[MeC(CH,PPh,) ,I2 has been prepared in two crystalline forms.77 The a-isomer was said to be a six- co-ordinate 22-electron complex (l), on the basis of a zero dipole moment, whereas the ,&isomer with a dipole moment of 2.25 D was said to be (2). On the basis of the 16 and 18 Electron Rule it would be predicted that the a-isomer is (3).The true co-ordination number of the complexes could readily be estab- lished by 31Pn.m.r. 68 J. S. Coleman, H. Petersen, jun., and R. A. Penneman, Inorg. Chem., 1965,4, 135. 70 G. Yagupsky, W. Mowat, A. Shortland, and G. Wilkinson, Chem. Comm., 1970, 1369. 71 F. Huq, W. Mowat, A. Shortland, A. C. Skapski, and G. Wilkinson, Chem. Comm., 1971, 1079. Dissociation constants for dissociation of Pt(PPh,), and (C2H4)Pt(PPh,), were reported by J. P. Birk, J. Hafpern, and A. L. Pickard, Inorg. Chem., 1968, 7,2672. 7s A. D. Allen and C. D. Cook,Canad.J.Chem., 1964,42, 1063. 74 L. Malatesta and C. Carielld, J. Chem. Soc., 1958, 2323. R. Ugo,G. La Monica, F. Cariati, S.Cenini, and F. Conti, Inorg. Chim. Acta, 1970,4, 390. 78 C. A. Tolman, W. C. Seidel, and D. H. Gerlach, J. Amer. Chem. SOC.,1972, 94, 2669. 77 J. Chatt, F. A. Hart, and H. R. Watson, J. Chem. SOC.,1962, 2537. I6 and 18 Electron Rule in Organometallic Chemistry and Homogeneous Catalysis Bi~(trityl)nickel,~~an apparent 12-electron complex, probably has a bis(r- allyl) structure in which each trityl group donates three Nickelocene is a paramagnetic complex in which the metal appears to have 20 valence electrons. Molecular orbital calculations, assuming a symmetric ferrocene-like structure (h),show that the last two electrons should occupy a strongly anti-bonding doubly degenerate elg orbital.80 This is consistent both with the instability of nickelocene compared with ferrocene and with the observed paramagnetism of the nickel complex.However, it can be predicted that the stable configuration of the compound is (5h-C5H5)(3h-C5H5)Ni, in which one of the rings is displaced off-centre. Easy accessibility of a number of equivalent configurations with a small activation energy between them should give a rapid fluxional behaviour, consistent with the results of recent electron-diffraction measurements on nickelocene vapour.*l Vaskag2 has reported H-D exchange of HIrCl,(PPh& and HRuCl(C0)- (PPh3)3 with D2and suggested that the reactions go via eight-co-ordinate inter- mediates (20-electron complexes) formed in the direct oxidative addition of D, to the above complexes.Vaska has even attributed a special catalytic activity to this type of high co-ordination number (and high NVE) complex.83 A pre-diction that added CO and PPh3 will inhibit the rate of the exchange reaction, indicating that a Lewis base ligand is lost prior to oxidative addition by Dz, is nicely supported by the recent work of Burnett and Morrisons4 which shows that added PPh, inhibits the rate of reaction of H2with HIr(CO)(PPh,), to give H,Ir(CO)(PPh,) 2. In homogeneous catalytic reactions it is to be expected that no reaction steps will be found in which the NVE of the metal in the complex changes by more than two. Thus concerted addition of two hydrogens to an olefinic double bond, coupling of two olefins to form a cyclobutane, and [2 + 21 valence isomerism of polycyclic hydrocarbons to cyclic dienes are excluded on the bases that ANVE = +4 in these reactions.The requirement that ANVE = 0, +2 adds severe re- straints to those proposed by Mango and Schachtschneider based on orbital symmetry considerations.85 There is considerable experimental evidence that catalysis of these reactions by Group VIII metal complexes is stepwise. For example, evidence has been presented to show that valence isomerization of cubane by [Rh(diene)Cl], catalysts proceeds via a non-concerted oxidative addition mechanism.se The products formed by cyclodimerization of penta-l,3-diene are consistent 78 G.Wilke and H. Schott, Angew. Chem. Internat. Edn., 1966, 5, 583. This suggestion has also been made by R. B. King in ‘Annual Surveys of OrganometallicChemistry’, Vol. 3, ed. D. Seyferth and R. B. King, Elsevier, Amsterdam, 1967, p. 403. J. H. Schachtschneider, R. Prins, and P. Ros, Inorg. Chim. Ada, 1967, 1, 462. L. Hedberg and K. Hedberg, J. Chem. Phys., 1970,53, 1228. 8a L. Vaska, Proc. 8th Internat. Con6 Co-ord. Chem. Vienna, 1964, 99. 83 L. Vaska, Znorg. Nuclear Chem. Letters, 1965, 1, 89. M. G. Burnett and R. J. Morrison, J. Chem. SOC.(A), 1971, 2325. F. D. Mango and J. Schachtschneider, J. Amer. Chem. SOC., 1971, 93, 1123. 86 L. Cassar, P. E. Eaton, and J. Halpern, J. Amer. Chem. Soc., 1970, 92, 3515. Tolman with a stepwise rather than a concerted rea~tion.~’ Heimbachaa has also stressed the stepwise nature of reactions of this type, whose concerted reactions are forbidden in the absence of catalysts by the Woodward-Hoffmann rules.8n 6 Conclusion The 16 and 18 Electron Rule in organometallic chemistry is consistent with such a large body of experimental evidence, including studies on reaction mech- anisms, that anyone proposing an exceptional compound or reaction path must bear the burden of proof.The Rule is, however, empirical at this point, and may be subject to exceptions in some cases, especially near the beginning and end of the transition serie~.~~~~~ NyholmgO has discussed the relationship between transition metal, oxidation state, co-ordination number, and ligand type and has nicely correlated a great deal of data with atomic properties such as ionization potentials and electron promotion energies. More quantitative theoretical studies and further experience are now required to define the limits of applicability of the Rule.The basic premise of this review is that 16-and 18-electron configurations are readily accessible to diamagnetic organometallic transition-metal complexes. Species with other configurations or reactions by other paths will generally be so energetically unfavourable by comparison that they are negligible. If this review acts as a goad to the research of others, if only to challenge its generality, it will have served its purpose well, I am indebted to R. Cramer, J.P. Jesson, G. W. Parshall, L. J. Guggenberger, and R. S. Nyholm for helpful discussions, and to G. Wilkinson and P. Heimbach for communication of results prior to publication. Note Added in Proofi The application of the 16 and 18 Electron Rule to catalysis by transition-metal hydride complexes has recently been discussed by C. A. Tolman, ‘Transition Metal Hydrides’, ed. E. L. Muetterties, Marcel Dekker, Inc., New York, 1971, Ch. 6. P. Heimbach and H. Hey, Angew. Chem. Internat. Edn., 1970, 9, 528. P. Heimbach, Aspects of Homogeneous Catalysis, in press. R. B. Woodward and R. Hoffmann, Angew. Chem. Internat. Edn., 1969, 8, 781. R. S. Nyholm, Proc. Chem. Soc., 1961,273; ‘Proc. 3rd Internat. Conf. on Catalysis’, North Holland, Amsterdam, 1965, p. 25.

ISSN:0306-0012    

DOI:10.1039/CS9720100337

出版商:RSC    

年代:1972

数据来源: RSC

摘要:

Electron Spectroscopy By A. D. Baker DEPARTMENT OF CHEMISTRY, QUEENS COLLEGE, CITY UNIVERSITY OF NEW YORK, FLUSHING, NEW YORK 11367, U.S.A. C. R. Brundle SCHOOL OF CHEMISTRY, UNIVERSITY OF BRADFORD, BRADFORD, YORKS. BD7 1DP M. Thompson DEPARTMENT OF CHEMISTRY, UNIVERSITY OF TECHNOLOGY, LOUGHBOROUGH, LEICS. LEll 3TU 1 Introduction Electron spectroscopy (e.s.) may be defined as the study of electrons emitted when matter is irradiated with photons or particles. Figure 1 shows the funda- SOURCE ELECTRON 8 SAMPLE ENERGYElectrons ANALY SER Photons Ions Metastables ELECTRON ELECTRON IENERGY SPECTRA Figure 1 Thefundamental e.s. experiment mental e.s. experiment in which these electrons are both analysed according to their kinetic energies and counted.The resulting plot of count-rate vs energy is known as the ‘electron energy spectrum’. The technique encompasses several closely related but distinct branches; these are ultraviolet photoelectron spectro- scopy (p.e.s.),l X-ray photoelectron spectroscopy, more commonly known as D. W. Turner,A. D. Baker,C. Baker, and C. R. Brundle, ‘Molecular Photoelectron Spectro- scopy’, Wiley, London, 1970. Electron Spectroscopy electron spectroscopy for chemical analysis (ESCA),* Penning ionization spectro- scopy (p.i.s.),” Auger spectroscopy (a.~.),~ ion neutralization spectroscopy (i.n.~.),~and electron impact energy loss spectroscopy (e.i.s.).6 After an intro- duction to their relevance in chemistry, the principles of the techniques and the information that can be derived from them will be discussed in more detail.The bombarding radiations in ESCA and p.e.s. are X-rays and monochro- matic photons in the vacuum-u.v., respectively. The kinetic energies of the ejected electrons differ according to their orbitals of origin, and these energies may be related to the different orbital ionization potentials of the sample atom or molecule. Clearly, measurements such as these are of great importance in the study of electronic configurations of molecules, and for establishing experi- mental data which can be compared with molecular parameters calculated by quantum mechanical methods. X-Rays can eject electrons from both inner-shell and valence-shell orbitals, whereas vacuum-u.v. photons can only eject those in valence-shell orbitals.The experimental result of this is that X-ray work is more useful for the core electrons, while vacuum-u.v. work is useful only for the valence shell. (In general, valence-shell orbitals within a narrow energy range are unresolved in an X-ray excited spectrum.) Therefore, ESCA and p.e.s. are complementary in that the X-ray spectrum can reveal the atomic make-up of the sample (different atoms have distinctive core-electron binding energies), whereas the vacuum-u.v. spectrum can give information about the valence shell, and in particular about molecular bonding and substituent, isomeric, and steric effects. Furthermore, both techniques appear to have considerable potential as tools for the analytical chemist.The use of metastable atoms (e.g. He 2lS and 23S)as ionizing particles for electron spectroscopy (pis.) gives results similar to those obtained with vacuum- U.V. photon sources. In addition, p.i.s. yields information on short-lived com- plexes formed between the bombarding metastable and the target molecule. In the Auger process, electrons are detached from atoms or molecules in a secondary step occurring after initial electron or X-ray bombardment. Such electrons are therefore observed in a standard ESCA spectrometer. The peaks present in an as. spectrum can imply, in a similar manner to those in an ESCA spectrum, that certain atoms are present in the emitting material. At present, the principal application of a.s.is as a sensitive technique for surface analysis. 1.n.s. is a branch of a.s. in which rare-gas ions are used in place of electrons or photons. In e.i.s. monochromatic electrons are allowed to pass through a sample, and the energy spectrum of the emergent electrons is measured. The spectrum reveals (a) K. Siegbahn ei al., ‘ESCA-Atomic, Molecular, and Solid State Structure Studied by Means of Electron Spectroscopy’, Almqvist and Wiksells, Uppsala, 1967; (b) K. Siegbahn et al., ‘ESCA Applied to Free Molecules’, North-Holland, Amsterdam, 1969. a V. CermBk, Coll. Czech. Chem. Comm., 1968, 33,2739. (a) L. A. Harris, Analyt. Chem., 1968, 40, 24A; (b) C. C. Chang, Surface Science, 1971,25, 53. H. D. Hagstrum, Phys. Rev., 1966,150,495. R.S. Berry, Ann. Rev. Phys. Chem., 1969,20, 357. Baker, Brundle, and Thompson discrete peaks where the difference in energy between the incident and emergent beam is equal to an excitation energy of the molecule being studied. The informa- tion obtained is similar to that given by conventional optical absorption spectrc- scopy. Additionally, e.i.s. spectra are useful for complementing and interpreting p.e.s. spectra. 2 Electron Energy Analysers In most of the commercially available electron spectrometers, the electron beam enters the analyser through a narrow slit in the target or ionization chamber. Focusing lenses are sometimes also used. Once inside the analyser, the electrons come under the influence of a deflecting magnetic or electrostatic field, where- upon they describe different paths depending on their energies.For a particular value of the deflecting field, only electrons within a small energy range describe appropriate paths to pass through the exit slit of the analyser. To obtain an electron energy spectrum, the electron flux emerging from this slit is continuously recorded as the deflecting field is changed, thereby bringing electrons of appro- priate energy to a focus in turn. Analysers of this and other types have been reviewed recent1y.l~ 3 Ultraviolet Photoelectron Spectroscopy In a p,e.s. instrument, a sample, normally in the vapour phase, is irradiated with monoenergetic vacuum-u.v. photons (A < 2000 A). These photons are usually generated in a microwave or d.c.discharge lamp; the helium lamp, which pro- duces a copius flux of 584 A photons (hu = 21.22 eV), is most common.* The ionization chamber has two ports, one to admit photons from the lamp, the other to admit sample. A slit a few millimetres wide also permits electrons ejected from the sample molecules to enter the energy analyser (see above). Sample vapour can likewise escape from the ionization chamber through this slit into the chamber housing the analyser, from which it is pumped away. However, a sample flow system, controlled by a needle valve, can be used to maintain a constant pressure in the ionization chamber. The chamber containing the electron energy analysis and detection system is maintained below a pressure of ca. 1 x lo-* Torr by a diffusion pump.A p.e.s. spectrometer is illustrated schematic- ally in Figure 2. Any photoelectron ejected from a sample has kinetic energy, E, which obeys the Einstein equation E = hv -Ii -dEvib -dErot (1) where hv is the energy of the bombarding photon, I1 is one of the ionization ’(a) D. W. Turner, Adv. in Muss Spectrometry, 1968, 4, 755; (b) H. Hafner, J. A. Simpson, and C. E. Kuyatt, Rev. Sci.Instr., 1968, 39, 33; (c) H. Z. Sar-El, ibid., 1970,41, 561. “(a) D. C. Frost, C. A. McDowell, and D. A. Vroom, Phys. Rev. Letters, 1965, 15, 612; (6) J. A. R. Sampson, ‘Techniques of Vacuum Ultraviolet Spectroscopy’, Wiley, New York, 1967; (c) D. W. Turner, Proc. Roy. SOC.,1968, A307, 15; (d)C. R. Brundle and M. B. Robin in ‘Determination of Organic Structures by Physical Methods’, ed. F.Nachod and G. Zucker-man, Academic Press, New York, 1971, Vol. 3, p. 1. Electron Spectroscopy U A ANALVSER P PlRANl OAUOE C CALIBRANT INLET D MFFUSION PUMP Q R LAMP WS INLET RADIATION SOU.RCE E ELECTRON MULTIPLIER S VOLATILE SAMPLE INLE T F FORE PUMP T CHARCOAL TRAP 0 IONIZATION OAUOE X MANIFOLD OAUGE I INVOLATILE SAMPLE INLET Y LAMP OUTLET TO PUMP M MANIFOLD Z COLLISION CHAMBER Figure 2 Schematic view of a typical p.e.s. spectrometer potentials of the molecule, and d&ib and AEmt represent the amount of vibra- tional and rotational excitation energy imparted to the molecular ion formed in the ionizing act. Energy analysis of the electrons leads to a photoelectron spectrum.Different bands in the spectrum relate essentially to the ejection of electrons from the different valence-shell orbitals. Fine structure may be present and is due to the excitation of vibrational and rotational motion in the molecular ions.1.*a,9 The energy scale in published spectra is generally calibrated in terms of ionization potential given in electron volts (eV). This IP scale is more correctly an (hv -E) scale, and is thus a measure of the total energy needed to bring about an ionization process, i.e. the sum of the energy required to overcome an orbital binding energy, plus any vibrational or rotational energy imparted to the ion produced (Zi + d&ib + OErot). The low IP onset of any band corresponds to a molecular ion being formed in its vibrational and rotational ground states A.D. Baker, Accounts Chem. Res., 1970, 3, 17. Baker, Brundle, and Thompson (dEvib + dErot= 0), and gives the minimum energy needed to eject a par- ticular electron from its parent orbital (the adiabatic IP*). Thus, the most straightforward application of p.e.s. is the measurement of IP’s, or binding energies, characterizing electrons in different orbitals. All the IP’s of an atom or molecule which are less than hu can be measured from the different bands in a p.e. spectrum. Since IP’s are the physical realities of orbital eigenvalues, con- siderable importance is attached to their values by those working in theoretical chemistry and on chemical bonding phenomena.Mulliken,lo addressing the Royal Society in 1969, summarized the impact made by p.e.s. in this area by these words :‘Photoelectron spectroscopy has already shown, and will continue to show, unique ability to see down into the depths of molecules. It has given a new reality to the idea of molecular orbitals, by determining quantitative values for their binding energies, and also by giving information about their bonding characteristics.’ It is the shapes of bands within p.e.s. spectra that provide information about the bonding characteristics of the orbitals to which they relate. This is discussed in greater detail el~ewhere~~~d~~ and some examples will be given below, but briefly, broad bands indicate strongly bonding or antibonding character whereas narrow bands imply non-bonding or weakly bonding or antibonding character.Where fine structure is resolved, the spacings of the peaks give the frequencies of vibrational modes in the molecular ion (a spacing of 0.1 eV is equivalent to 806.57 cm -l). Comparison of these frequencies with the corresponding molecular frequencies (measured by Raman or i.r. techniques) affords an additional indication of the bonding character of the electron removed. A lower frequency in an ionic state shows that a reduction in bond force-constant has taken place on ionization, implying that the ejected electron was bonding. Conversely, an increase in frequency suggests that the ejected electron was antibonding. Spectra of complex molecules provide hitherto unobtainable information on electronic effects, e.g.substituent effects, and provide a qualitative method of analysis. Studies of atoms and simple diatomic and triatomic molecules featured prominently in the early years of the development of p.e.s. High-resolution spectrometers frequently enabled vibrational structure to be detected in bands. The bandshapes, ionic vibrational frequencies, and orbital IP’s measured from the spectra allowed the electronic configurations of these molecules to be un- ambiguously assigned, and comparisons to be made with calculated orbital eigenva1ues.l Two spectra of simple molecules illustrating different bandshapes are those of H2and N2(Figure 3). Both these spectra were obtained using 584 A photons.The H2spectrum shows one band corresponding to the only occupied orbital (lsa8) of the hydrogen molecule. A long series of converging peaks stretches across the entire band. The IP value (15.45 eV) of the first peak gives the energy needed to eject an electron from H2 and simultaneously form an * In a few cases it may not be possible for a significant number of ions to be formed in the ground vibrational and rotational states (Franck-Condon principle, see ref. I) in which case the lowest IP, as given by p.e.s., may be higher than the true adiabatic IP. lo R. S. Mulliken, Phil. Trans. Roy. SOC.,1970, A268, 3. 359 4 Electron Spectroscopy I I I I I 15 16 17 18 19 eV ORBITAL IP Figure 3 He 584 A spectra of N,and H2 H,+ ion in its ground vibrational state (v’ = 0).The other peaks correspond to the production of Hz+ions in higher vibrational states. The fifteenth peak is only about 0.2 eV away from the energy needed to dissociate H2+(18.2 eV). The vibrational frequency of the ionic state is 2240 cm-l, compared to 4280 cm-1 of the H, molecule. This large reduction in frequency reflects the much dim- inished bond strength of the ion, indicating that a strongly bonding electron has been removed. The N, spectrum shows three distinct bands. There are actually four orbitals in N, with IP’s less than 21.22 eV*, but two of these (the two n-orbitals) are degenerate, and are represented by just one band in the spectrum. The first and *The electronic configuration of N2is KK(2sa,)x(2so,*)x(2~~)4(2po~)*. Baker, Brundle, and Thompson third bands are similar, in that they both show a strong v’ = 0 peak, and minimal associated structure. This implies that the equilibrium bond lengths in the N2+ ions formed by electron ejections from the first and third orbital levels of N2are both nearly equal to that in the molecule.These results suggest that the orbitals are almost non-bonding, and this is confirmed by the vibrational fre- quencies of the two ionic states being similar to that of the molecular state (Table 1). The second band in the spectrum corresponds to the two degenerate v-orbitals, The most intense peak in this band is associated with the formation of an N2+ ion in its v’ = 1 level.(The energy required to produce the N2+ion in this vibrational level is known as the vertical IP.) There are other peaks of moderate to low intensity for the formation of N2+ ions in much higher vibra- tional levels. This implies that the removal of a n-electron produces an ion with an equilibrium bond length appreciably different from that of the molecule. The considerable decrease in the N-N vibrational stretching frequency on removal of a n-electron (Table 1) confirms the bonding nature of the original orbital. Table 1 Ionization potentials, electronic states, and observed vibrational frequencies of Nz and N2+ Band in Adiabatic Molecule or ion Ztate spectrum IPIeV Vibrational frequencylcm-I N2+ X2Cg+ first 15.58 2150 +N2 J2nu second 16.69 1810 N2+ @CU third 18.76 2390 N2 FCg+ --2345 The conclusions above are in good accord with deductions based on MO theory, and provide the principles upon which the technique can be applied confidently to molecules that are too complex for a rigorous MO treatment.In this regard, it is instructive to compare the measured orbital IP’s for N2with calculations of the orbital eigenvalues (Table 2). According to Koopmws’ Table 2 Calculated and experimental ionization potentials of N2 Orbital Observed vertical IPIeV Koopmans’ theorem IPIeV 2prrU 16.98 17.10a 2PQ 15.58 17.36a 2SOU 18.76 20.92Q aP.E. Cade, K. D. Sales,and A. C. Wahl, J. Chem. Phys., 1966,44, 1973. fheorem,l1 an orbital IP is equal to the negative of the orbital eigenvalue.How- ever, the calculation ignores the influence of other electrons in the molecule which cause an orbital IP to be less than the corresponding orbital eigenvalue. Nevertheless, as IP’s relate to a real situation they are the more relevant to l1 T. Koopmans, Physica, 1934, 1, 104. Electron Spectroscopy studies of bonding and substituent effects. Results for several diatomic and triatomic molecules have been discussed in detail elsewhere.12 Processes observed by p.e.s. are often represented as transitions between molecular and ionic states on a potential energy diagram. For example, Figure 4 ENERGY~ eV HClf *Z+H2+ \I I/ I I I I15 -I I I I I I II II I I I I10 -I I I II II 1 I 1 I I I I I I 1 I t I I I I I I I 5-\iI I 1YC[y2 ~(H~IG~H:) P.E. SPECTRUM I?E.SPECTRUM INTERNUCLEAR OF Hz INTERNUCLEAR OF HCI SEPARAT 10N (Schematic) SEPARATION (Schematic) -Figure 4 Production of ions (H,+ and HClf) in excited vibrational levels causing the presenceof fine structure in spectral bands.Thefirst band of the HCl spectrum is a doublet due to spin-orbit coupling shows the 584 A spectra of H2and HCl schematically together with potential energy curves depicting the transitions that occur. An interesting feature of the HCl spectrum is the doublet character of the first band, corresponding to the ejection of a chlorine 3p lone-pair electron. This doublet arises because spin-orbit coupling can result in HCI+ ions being formed in distinct 2L!',or 2flg states.The energy differential between the two possible ionic states resulting from chlorine 3p lone-pair ionization decreases with increasing molecular size, e.g. there is no evidence of coupling in the first bands of the spectra of MeCI, SiH,CI, and GeH,Cl (Figure 5).13 Furthermore, the three spectra exhibit marked differ-la C. R. Brundle and D. W. Turner, Internat. J. Mass Spectrometry and Ion Phys., 1969,2,195. l3 S. Cradock and E. A, V. Ebsworth, Chem, Comm., 1971, 57. Baker, Brundle, and Thompson 1 1 1 cH,Cl GeH3Cl I I I 11.0 11.5 12.0 cV ORBITAL IP Figure 5 He 584 A spectra of methyl, silyl, and germyl chlorides ences in the shapes of the chlorine 3p bands. Although the chlorine band of MeCl shows more extensive fine structure than that of HCI, the v’ = 0 peak is still the most intense, implying only a very small amount of C-Cl character in this highest occupied orbital.In marked contrast, the most intense peak in the chlorine band of the SiH,Cl spectrum indicates an SiH,Cl+ ion in a state of considerable vibrational excitation. No fine structure is resolved in the GeH,CI spectrum, but the profile of the first IP band again suggests a vibrationally excited ion. These results imply that there is appreciable bonding character asso- ciated with the highest occupied orbitals of SiH,Cl and GeH,CI, consistent with there being (p +d)lrr-bonding through donation of the C1 3p lone-pair into the empty low-lying d-orbitals of the metal atoms. Thus, p.e.s. provides evidence for the significant double-bond character of the metal-to-chlorine linkages in these compounds.Photoelectron spectroscopy has been used extensively to study electronic substituent effects, since the spectra of a series of compounds, AY (Y = sub-stituent), give a direct representation of the manner in which the orbitals of A are modified by different substituents. Both inductive and mesomeric effects Electron Spectroscopy I I I I I 9 10 11 12 18 eV ORBITAL IP Figure 6 He584 A spectra of benzene and chlorobenzene. The latter shows the lifting of n-orbital degeneracy Baker, Brundle, and Thompson can be measured. Thus, the spectra of a series of aliphatic alcohols, ROH, provide a measure of the electron-releasing abilities of different R groups (alkyl) by showing the variations in the IP’s of the oxygen 2p lone-pair e1ectr0ns.l~ The greater the + Z effect associated with an alkyl group, the lower is the oxygen lone-pair IP.Similar effects are found for the iodine 5p lone-pair IP’s in alkyl halides. Furthermore, a plot of the oxygen lone-pair IPS of alcohols against iodine lone-pair IP’s in alkyl iodides is linear,l* demonstrating a consistency of substituent effects from one series of compounds to another. Photoelectron spectroscopy is superior to many other techniques for investigat- ing substituent effects since it shows the changes which occur in the binding energies and bonding characteristics of all valence-shell electrons.This is par- ticularly useful in the study of substituent effects in organic molecules containing .rr-bonds, since here both mesomeric and inductive effects can take place. The spectra of benzene and a series of benzene derivatives have, for example, been reported by Turner et The 584 A spectrum of benzene itself contains several bands corresponding to the valence shell .rr-and a-orbitals. The lowest IP band relates to two degenerate z--orbitals distinguished by their different nodal charac- teristics (Figure 6). The introduction of a substituent atom will lift the degeneracy since only one of the orbitals has a node at the point of substitution. Thus, a clear splitting of the band near 9 eV can be seen in the spectra of many benzene derivatives (e.g.C6H6Cl, Figure 6). The magnitude of the splitting and the shift of the band (from that in benzene) reflects the nature of the substituent. Similar results have been reported for halogenoacetylenes.16 The spectra of isomers and other structurally similar compounds often show important differences. For example, Betteridge et aZ.17918 have demonstrated this effect in the spectra of cis-and truns-1,3-dichloropropeneand of 2-and 3-bromothiophen. Sometimes, differences in the spectra of similar molecules may be related to steric effects. For example, Brundle and RobinlB found that the p.e.s. spectra of butadiene and hexafluorobutadiene indicated that the interaction of the two ethylenic groups was three times as great in the former as in the latter.They concluded on the basis of this that the carbon skeleton of hexafluorobutadiene is non-planar. In a similar manner, Baker et ul.l6 showed that steric effects have an effect on the p.e. spectrum of t-butyl phenyl ether. It has occasionally been observed that corresponding bands in spectra obtz’lned by using different energy vacuum-u.v. sources are not the same.1~20~21 The reason for this is that if the incident quantum, hv, is equal to the energy needed to l4 A. D. Baker, D. Betteridge, N. R. Kemp, and R. E. Kirby, Analyt. Chem., 1971, 43, 375. l6 A. D. Baker, D. P. May, and D. W. Turner, J. Chem. SOC.(B), 1968, 22. H. J. Haink, E. Heilbronner, V. Hornung, and Else Kloster-Jensen, Helv. Chim. Acra, 1970, 53, 1073. A.D. Baker and D. Betteridge, Analyr. Chem., 1970, 42, 43A. A. D. Baker, D. Betteridge, N. R. Kemp, and R. E. Kirby, Analyr. Chem., 1970,42, 1064. lS C. R. Brundle and M. B. Robin, J. Amer. Chem. SOC.,1970, 92, 5550. ‘O J. Berkowitz and W. A. Chupka, J. Chem. Phys., 1969, 51, 2341. ‘I W. C. Price, Proc. 4th Conf. Molecular Spectroscopy, ed. P. Hepple, Inst. Petroleum, 1968, p. 221. Electron Spectroscopy promote an inner electron into an unoccupied orbital, autoionization (spon- taneous ejection of an electron to give an ion) can then occur as a secondary step if hv exceeds one of the orbital IP’s of the molecule. The ionized state thereby produced may differ from the corresponding ionic state resulting from a direct electron ejection in that there may be greater probabilities of forming it in higher vibrational states.This will result in the fine structure being modified.20 Photoelectron spectra of solids have been reported.22 Such studies, usually on metals, are often referred to as ‘photoemission studies’. Whereas gaseous studies give spectra showing discrete bands attributable to the discrete molecular orbitals of free atoms or molecules, solid-state studies are used to give information about the band structures of the materials con~erned.~~~~~ Most studies of this type have been carried out using an LiF window to separate the solid from the photon source (usually a continuum or many-lined source in conjunction with a monochromator), but this limits studies to hv < 11.6 eV.4 X-Ray Photoelectron Spectroscopy The experimental conditions and fundamental principles of ESCA are identical with those of p.e.s. (Section 3), except that the excitation energy consists of soft- X-rays rather than vacuum-u.v. photons. Therefore, many of the previous com- ments concerning p.e.s. are also applicable to ESCA. The use of soft X-rays allows study of core- as well as valence-shell electrons, although for the latter ESCA is inferior to p.e.s. because of the greater linewidths of the X-rays (N 1 eV) as opposed to vacuum-u.v. photons (a few meV). This causes correspondingly broader bands in ESCA spectra, resulting in loss of fine structure and a merging of the closely situated levels in the valence-shell region. Bands due to core electrons, however, are generally well separated so that solid-phase as well as gas-phase ESCA spectra frequently show completely resolved bands in the core electron region.Thus, solid samples examined by ESCA routinely yield meaning- ful results, making it a more versatile technique than p.e.s2 Vapour-phase ESCA studies do nevertheless provide sharper bands and are accordingly sometimes desirable, despite a loss in count-rate.2 Small shifts in band maxima, or changes in bandshapes may occur on going from gas- to solid-phase spectra. This is because the former relate to free atoms and molecules, whereas the latter are influenced by factors such as hydrogen-bonding, crystal lattice effects, and by the Fermi level of the irradiated material.2b Unlike p.e.s., ESCA can often give the atomic composition of the substance being investigated.This is because the core electrons of different atoms have quite distinct binding energie~.~~~~ For example, the binding energies of the Is electrons of the atoms of the first two rows of the Periodic Table are, in electron volts: H, 14; Li, 50; Be, 110; B, 190; C, 280; N, 400; 0,530; F, 690; Ne, 867; D. E. Eastman, ‘Photoemission Spectroscopy of Metals’, to appear in ‘Techniques in Metals Research VI’ ed. E. Passaglia, Interscience. (a) C. N. Berglund and W. E. Spicer, Phys. Rev. (A), 1964,136,1030, 1044; (b)N. V. Smith and W. E. Spicer, ibid., 1969, 188, 593; (c) W. F. Krolikowski and W. E. Spicer, ibid., 1969, 185, 882; Phys. Rev. (B), 1970, 1,478; (d)H.Kanter, ibid., p. 2357. a4 K. Siegbahn, Phil. Trans. Roy. SOC.,1970, A268, 33. Baker, Brundle, and Thompsori Na, 1070; Mg, 1305; Al, 1560; Si, 1840; P,2150; S, 2470; C1, 2823; Ar, 3203. Of all the elements, only hydrogen uses its 1s orbital to form multicentred molecular orbitals in its compounds. The 1s electrons of the remaining elements retain their 'atomic' character in their compounds; therefore, the binding energies of these elements do not alter very much from one compound to another. Thus, a peak in the ESCA spectrum of an unknown compound near 280 eV would indicate the presence of a carbon atom in that compound. In many cases, other inner-shell orbitals, e.g. C12p, S 2p, may be as useful as the 1s orbital for identi- fication purposes.Some small perturbations of the core electrons of an isolated atom do never- theless occur when the atom becomes part of a molecular system, e.g. an alloy or a chemical compound. The origin of such a perturbation lies in the electro- static interaction between the valence and core electrons and gives rise to 'chemical shifts' of core-electron bindins energies. The magnitude of the chemical shift observed by ESCA provides evidence as to the way in which the atom concerned is bonded, e.g. whether a nitrogen atom is in an amino- or a nitro- group. An example of chemical shifts in an inorganic compound is seen in the ESCA spectrum of sodium a~ide.~" The two terminal nitrogen atoms of the azide anion, N3-, are in a different chemical environment from the middle I I 1 I a I I I I 396 400 404 408 el 198 400 402.404 406 el ORBITAL IP Figure 7(a) N Is ESCA spectrum of sodium azide. Peaks due to positively and negatively charged nitrogen are clearly distinguished; (b) N 1s ESCA spectrirm of sodium oxyhyponitrite. The two peaks are due to non-equivalent nitrogen atoms Electron Spectroscopy nitrogen atom, and this causes the binding energies of the Is electrons to be different. The result is that in the part of its ESCA spectrum near 400eV (i.e. the N 1s region, see above), two peaks in the intensity ratio equal 2 :1 can be seen [Figure 7(a)]. ESCA studies have already solved many chemical structural problems. One example is the structure of the oxyhyponitrite anion, N2032-.26 Three possible structures (1)-(3) had been suggested before the ESCA studies; 0--O=N-O-N-O-O=N-N / -O-N=N-()-O-\ 0-(2) (3) the N Is part of the ESCA spectrum [Figure 7(b)] clearly shows the presence of structurally non-equivalent nitrogen atoms, and this rules out the symmetrical structure (1).MO calculations and considerations of the actual binding energy values observed further showed that only structure (2) was compatible with all the observations. A second example is the structure of cystine S-dioxide.2u Of two possible structures (4) and (3,only (5) was compatible with the ESCA spectrum, which showed two distinct sulphur peaks. 0 t R-S-S-R R-S-S-R $4 .1 00 0 (4) (5) More complex structural elucidations have been reported by Hedman et aZ.26 These workers deduced the structures of the products resulting from the reactions between H,S and pentane-2,4-dione, and between H,S and a-angelica lactone.Carbon ESCA chemical shifts are of obvious interest to organic chemists. However, the C Is peak is only shifted 11 eV on passing between the extreme examples of CH4 and CFp.27 This shift range is sufficient to allow the observation of discrete peaks from carbon atoms in very different environments in fairly small molecules; e.g., the four different carbon atoms of ethyl trifluoroacetate, CF,CO,CH,Me, all show up as separate peaks in its ESCA spectrum.2a How- ever, for larger molecules, or even for small molecules containing a few carbon atoms in similar environments, separate peaks due to the different carbon atoms 85 J.M. Hollander and W. L. Jolly, Accounts Chem. Res., 1970, 3, 193. 26 J. Hedman, P. F. Hedtn, R. Nordberg, C. Nordling, and B. J. Lindberg, Spectrochim.Acta, 1970, 26A, 761. D. W. Davis, J. M. Hollander, D. A. Shirley, and T. D. Thomas, J. Chem. Phys., 1970,52, 3295. 368 Baker, Brundle, and Thompson are not resolved. This is illustrated by the ESCA spectra of the sodium salts of some aliphatic carboxylic acids (Figure S).2a Although the carbon atom attached i 280.0 285.0 290.0 -IP/eV -Figure 8 C Is ESCA spectra of the sodium salts of some aliphatic carboxylic acids. Carbon peaks correspond to hydrocarbon and carboxyl carbon, respectively to oxygen (CO)stands out as distinct from the carbon atoms of the alkyl chain (CH), the individual carbon atoms of the alkyl chain do not appear as separate peaks.However, peaks in complex spectra can be sometimes resolved. For example, Barber and Clark2* have reported determining the N 1s and C 1s binding energies for all the different nitrogen and carbon atoms in compounds as M.Barber and D. T. Clark, Chem. Comm., 1970, 22, 23, 24. IIp +I I I I I I I I1 I I. I I g 285 286 287 288 289 290 399 400 401 402 n* Cls Nls-4 B -Binding Energy/ev -3 W Baker, Brundle, and Thompson complex as the nucleic acid bases, adenine, thymine, and cytosine. Their results are shown in Figure 9. The assignments of different bands in the spectra to particular carbon or nitrogen atoms were accomplished by comparison with quantum mechanical calculations of orbital energies.Br~ndle~~ has questioned the validity of these results and, in general, curve-resolving procedures should be used with caution. The identification of non-equivalent heavy-metal atoms may prove to be more difficult in many cases than might at first be expected. The study of heavy-metal compounds by ESCA is an important area because of the great variety of oxida- tion states involved. There are numerous cases where the technique has worked straightforwardly (e.g. the distinction between Eu2+ and Eu3+ in complexe~~~), but there are cautionary examples also. For example, sodium dichromate has the structure (6), and one might reasonably expect two distinct lines in the 0 region of the ESCA spectrum in a ratio 1 :6 representing the two different types of oxygen present.Only one line is observed.8d Prussian Blue, KFe,(CN),, contains iron in the Fe3+ and Fe2+ states in a 1 :1 ratio. At first sight, the Fe 3p region of the ESCA spectr~m~~~~~ (two components, Fe 3p+ and Fe 3p), com-pare spin-orbit splitting in p.e.s. Section 3) indicates only one type of iron since there is no 1 :1 doubling of the peaks. There has been much peculation^^^^^ on the reasons for this, but it now seems likelyZg that the observed Fe 3p+ and Fe 3pp peaks represent only the Fe2+ state, the Fe3+ being represented by a collection of small peaks almost merging into the background and each other.This ‘multiplet’ splitting of what naIvely should be a single peak has been dis- .~~cussed by Fadley et ~1in relation to other cases. Considerable attention has been directed toward the development of methods suitable for predicting the binding energies of core electrons in any given mole- cular structure. The success of such a method would clearly have far-reaching implications on the future of ESCA as a tool for structural elucidations. A match between the predicted ESCA spectrum for a structure proposed for an unknown material, and the experimental spectrum for that material, would confirm the structure. So far, correlations between ESCA chemical shifts and parameters derived from Pauling electronegativities, and from semi-empirical MO calcula-*9 C.R. Brundle, Appl. Spectroscopy,1971, 25, 8. ‘O C. S. Fadley, S. B. M. Hagstrom, M. P. Klein, and D. A. Shirley, J. Chem.Phys., 1968,48, 3779. a1 G. Wertheim and A. Rosencwaig, personal communication. 32 C. S. Fadley, D. A. Shirley, A. J. Freeman, P. S. Bagus, and J. V. Mallow, Phys. Rev. Letters, 1969, 23, 1397. 371 Electron Spectroscopy tions have been reported. Jolly et aZ.33have also used thermochemical parameters to calculate ESCA chemical shifts. In addition, a scheme for calculating the actual count-rate for a given peak in an ESCA spectrum has been 5 Penning Ionization Spectroscopy The ionization of gaseous atoms or molecules by electronically excited neutral species is known as the Penning effect.35 Such processes occur if the IP of the target atom or molecule is lower than the excitation energy of the neutral particle.Unlike the ionization caused by electron or photon impact, collisions occur between uncharged particles; therefore, the force field is small and the collision time increased with the consequence that collision complexes between the particles are favoured in certain cases. Much of the work in this area has been concerned with the mass spectrometric investigations of positive ions produced by Penning ioni~ation.~~ However, CermAk and Herman3sb suggested the measurement of the kinetic energies of released electrons, and later investigated the use of He 2lS and 23S metastable atoms as ionizing particles for e.s.3p37 Experimentally, the He metastables were produced by bombardment of He with an electron beam.38 The information obtained from pis.in these experiments can be illustrated by the examples of N, and NO.37The p.i.s. spectrum of N2exhibits six peaks, three due to ioniza- tion by 2% atoms (20.61 eV) and three by z3Satoms (19.81 eV). As in Section 3, the basic pattern of three peaks corresponds to the ionic states of Ng+, x2cg+,A2& and B2ZU.ilthough no fine structure is seen, the narrowness of the peaks of the x2Zg+and B2Zustates (relative to those of the A2nUstate) is indicative of the excitation of vibrational levels in the A2nustate. These results are identical with those obtained by p.e.s. With NO, the absence of peaks due to the states lC+and A3Z+ has been taken as evidence that a collision complex HeNO is formed, and that autoionization of the complex determines the populations of the various states of NO+ ions.Additionally, there is a suggestion that trans- formation of the internal energy of the HeNO complex into kinetic energy of He and NO+ takes place. Clearly, pis. gives information similar to that derived from p.e.s. ;however, it is also apparent that the technique is important for studying unusual short- lived collision complexes. 6 Auger Spectroscopy In an Auger spectrometer a beam of electrons strikes the sample and electrons a3 (a) W. L. Jolly and D. N. Hendrickson, J. Amer. Chem. SOC.,1970, 92, 1863; (b)W. L, Jolly, ibid., p. 3260. s4 G. F. Crable and H. D.Seaman, unpublished work. See also U. Gelius, Uppsala Uni- versity, Institute of Physics, 1971, UUIP 753; A. D. Baker and D. Betteridge, ‘Photoelectron Spectroscopy-Chemical and Analytical Aspects’, Pergamon, Oxford, 1972. s6 F. M. Penning, Z. Physik, 1928,46, 335; 1929,57, 723; 1931, 72, 338. s* (a) W. P. Scholette and E. E. Muschlitz, J. Chem. Phys., 1962, 36, 3368; (b)V. CermAk and Z. Herman, Nature, 1963, 199, 588; (c) Coil. Czech. Chem. Comm., 1965, 30, 169. 87 V. CermBk, J. Chem. Phys., 1966,44, 3781. V. CermAk, J. Chem. Phys., 1966,44, 3774. Baker, Brundle, and Thompson leaving are energy-analysed in an analyser of the type described in Section 2 or, more usually for solid samples, by using a retarding potential grid analy~er.~~.~~ The Auger process follows the ejection of an inner-core electron.The resultant hole is filled by an electron from a less tightly-bound level, releasing sufficient energy for another electron (the Auger electron40) to be ejected (processes 1,l' and 2,2' in Figure 10). The energy of the Auger electron 1,l' is given by EA~ ~~2: EW -2Ex where W and X are inner-core levels; therefore EA is charac- ~ Free Electrons(Auger) L-0 Vacuun 7Lew 2' 13' T IP He v[ IHe' Ion 1' wF/ X Y W Figure 10 Energy level diagram showing three types of Auger process; these are the 1,l' and 2,2' processes, and the i.n.s. process induced by Hef bombardment, 3,3' .X, Y, and W levels are inner-core levels. V is the valence region and consists of discrete levels only forgases.(Seealso D.S. Urch, Quart. Rev., 1971, 25, 343) N.J. Taylor, Vacuum, 1969, 19, 575. 40 P. Auger, J. Phys. Radium, 1925, 6, 205. 373 Electron Spectroscopy teristic of a particular atom, as in ESCA e.g. an Auger peak near 164 eV is characteristic of tantalum. Chemical shifts can be used for bonding studies, but are more complex than for ESCA because shifts in both W and X are involved. EAuger is independent of the energy of the incident electron beam, meaning that the beam need not be monoenergetic. The only requirement is that the incident energy, Eo,is greater than Ew. In practice it is found that maximum intensity is achieved when Eo is about three times Ew.~~ The Auger peaks in the spectrum of electrons leaving a sample represent only a fraction of the total number of electrons being analysed, particularly when solid samples are involved (solid studies are of a surface nature-see Section 9).A hypothetical solid spectrum is given in Figure ll(a). Small Auger peaks are superimposed on a high background. The major contributor is the incident beam elastically scattered from the surface. There are also numerous energy- loss peaks (see Sections 7 and 8), Auger peaks being distinguished from these because they fall in a different energy region and also, since their energy is independent of E,, the Auger peaks will appear at the same kinetic energy if E,, is changed. The high background represents incident beam electrons multiply- scattered in their progress through the solid sample.The small Auger peaks are made more conspicuous by differentiating the spectrum. An example is given in Figure ll(b) (titanium). Peaks not corresponding to titanium Auger lines allow the identification of impurity elements pre~ent.~@ The majority of Auger transitions are 2,2’ rather than the 1,l’ type, i.e. a valence-shell region (V) is involved. EAuger is then given by EW -2Ev. For 2,2’ Auger electrons there will be no real chemical shift behaviour because valence region changes cannot be related to individual atom~.~b Since EW is so much larger than EV the energy region of the transition will still be characteristic of an atom; e.g. an Auger peak at approximately 250 eV is characteristic of a carbon 2,2’ transition.For solids, 2,2’ peaks can be quite broad because of the broad valence-band structure. Though no true chemical shift behaviour occurs, changes in the valence-band structure will result in changes in the shape of the Auger peak which may be used to identify chemical changes in a sample. In this fashion, Chang has been able to demonstrate the presence of SiOz on the surface of a silicon ~ample.~b*~l With gases many discrete peaks are obtained, covering approximately the same energy spread as a broad solid 2,2’ peak, representing transitions involving all the discrete valence region MO’s instead of the band structure of a solid. Vibrational structure may be present (compare p.e.s. spectra). CO and CO, have many 2,2’ peaks stretching from 220 to 270 eV42 that are characteristic of carbon, but the detailed structures are characteristic of the individual molecules.Similarly there are 2,2’ transitions in the charac- teristic oxygen region (460-510 eV) but the detailed structures are again charac- C. C. Chang, Surface Science, 1970, 23, 283. W. E. Moddeman, T. A. Carlson, M. 0. Krause, and B. P. Pullen, J. Chem. Phys., 1971, 55, 2317. Baker, Brundle, and Thompson (a) I-Elastically scattered incident beam including plasmon, multiple plasmon,and surface plasmon losses I I I 0 200 400 600 800 1000 Electron EnergyjeV 1 I I f I 200 100 600 800 Electron Energy lev Figure 11 (a) Hypothetical Auger spectrum from a solid.Also shown are energy loss features. (b) Diferential spectrum of a titanium sample teristic of CO and C02.42Thus we have both an elemental and a molecular analysis. Much of the work on gaseous molecules has been performed using X-rays 375 Electron Spectroscopy rather than an electron beam to form the inner-core hole. A disadvantage with X-rays is that they are less intense than electron beams and cannot be focused to small spots. An advantage, particularly for solids, is that without an incident electron beam one has a much lower background of multiply-scattered elec- tron~.~~1,l' transitions and chemical shifts have been studied using X-rays, e.g. the Auger peaks from the two different sulphur atoms in solid sodium thio- sulphate are separated by a shift of 4.7 eV.2a When using X-rays to study Auger spectra one of course also obtains a normal ESCA spectrum (Section 4) and so both studies can be carried out simultaneously.2a 7 Electron Impact Energy Loss Spectroscopy Electrons, like photons, when traversing an array of atoms or molecules may induce excitation phenomena.Photons, however, usually transfer all their energy and are therefore annihilated, whereas electrons continue with a fraction of their initial energy. Conservation of energy requires that the energy loss suffered by an impacting electron (i.e. the energy of the incident electron less that of the continuing or scattered electron) is exactly equal to an excitation potential of the bombarded species. In e.i.s., a monochromatic beam of electrons is passed through a gaseous sample (or directed on to a solid surface) and the energy spectrum of the in- elastically scattered electrons recorded.The spectrum reveals peaks attributable to the different excitation energies of the target atoms or molecules. The same information is also obtained from optical absorption spectroscopy, but in e.i.s. the entire excitation spectrum from the i.r. to the far U.V. is covered in one instru- ment, admittedly with worse resolution than optical instruments in the visible and i.r. regions. A further distinction between e.i.s. and optical spectroscopy is that excitations forbidden by the selection rules of the latter may be observed in the former under certain conditions; for example, under optimized conditions of impacting electron energy and scattering angle.In particular, electrons are effective in causing transitions between states of different spin-multiplicity through electron- exchange mechanisms if their energies are within approximately 25 eV above the threshold for such an excitation. For example, Trajmar et a1.44 have com- pared the gas-phase e.i.s. spectra of ethylene and acetylene with the correspond- ing optical spectra and discussed the importance of singlet-triplet transitions in the former. Spectra of other gaseous atoms and molecules, mostly simple ones, have also been reported and discussed in terms of the electronic or vibrational transitions that OCCU~.~~~~Recent work describing results for formaldehyde is of interest because it reveals structured bands indicative of autoionizing Rydberg states 2-3 eV above the ionization threshold.45 There is undoubtedly considerable scope for further studies on chemically more interesting molecules, and the 43 C.R. Brundle, Surface Science, 1971, 27, 681. 44 S. Trajmar, J. K. Rice, and A. Kupperman, Adv. in Chern. Phys., 1970, 18, 15. 45 M. J. Weiss, C. E. Kuyatt, and S. Mielczarek, J. Chern. Phys., 1971, 54, 4147. 376 Baker, Brundle, and Thompson possibility of developing e.i.s. as a complementary tool for structural and analytical work. In this regard, it is interesting to note that Lindholm et aL4‘ have made use of e.i.s. results to substantiate orbital sequences suggested by p.e.s. E.i.s.has been used extensively to study solids.47 Promotion of electrons from filled to empty energy levels (bands) are termed band-to-band transitions. Of perhaps more interest are plasmon excitations, which may be thought of as the collective oscillations of the Fermi gas, induced by interaction of the electron beam with the solid. Plasmon and multiple plasmon losses can be seen in Figure 1l(a). Since their energies are dependent on solid structure, plasmon losses may be used for chemical studies, e.g. alloy proper tie^.^^ In practice, the virtual surface nature of the technique (Section 8) has caused much experimental dis- agreement, because contaminated surface layers were inv01ved.~’ Ionization brought about by electron bombardment of energy, E, results in two electrons leaving the collision site, the scattered, El, and the ejected electron, Ez.The excess energy of the process, E -IP, is shared between the two electrons, unlike photon impact (Section 3) where it is completely transferred to the ejected electron.Therefore, in e.i.s. a weak continuum rather than a peak starts at the energy loss equal to the IP since the two resultant electrons may take any values provided E -IP = El + Ez. (Compare vacuum-u.v. absorption spectroscopy where band-to-band transitions give discrete peaks but ionizations produce continua.) By using co-incidence techniques to record the spectrum for only a fixed value of El,a discrete peak spectrum giving IP values from measured Ez values becomes 8 Electron Spectroscopy and Surface Studies Electrons travelling out from deep within a sample lose energy through collisions and so do not appear at their expected energies in the electron spectrum, which is therefore characteristic of only a surface slice.Factors controlling electron ‘escape depths’, d, have been discussed d is dependent on the kinetic energy,E, of the escaping electron and the nature of the solid. For low E( < 10eVj do! l/Eafor high E (< 200 eV) d a E; in between d is fairly constant, and can be as little as 5-50 A. Materials of high atomic number have low d values. In ion neutralization spectroscopy (i.n.s.),6 He+ ions strike a solid sample, an electron is transferred to the ion, neutralizing it, and an Auger electron is ejected by the energy released (process 3,3’, Figure 10).The important difference from a 2,2’ Auger process is that since the He+ ions cannot penetrate the sample the phenomenon is entirely a surface one. 1.n.s. has been used to study the surface state band structure of rnetal~,~ and to study the electronic structures of adsorbed 46 E. Lindholm, 0. Edqvist, L. E. Selin, D. L. Asbrink, C. E. Kuyatt, S. Mielczarek, J. A. Simpson, and I. Fjsher-Hjalimars, Physica Scriptu, 1970, 1, 172. p7 0. Klemperer and .I.P. G. Shepherd, Adv. Phys., 1963, 12, 355. 4a B. M. Hartley and J. B. Swan, Austral. J. Phys., 1970, 34, 655. 49 (a)U. Amaldi, A. Egidi, R. Marcomero, and G. Pizzeita, Rev. Sci. Insfr., 1969, 40, 1001; (b)E. Ehrhardt, M.Schulz, T. Tekaat, and K. Willman, Phys. Rev. Letters, 1962,22, 89. C. R. Brundle, ‘The Application of Electron Spectroscopy to Surface Studies’, in ‘Surface and Defect Properties of Solids’, ed. M. W. Roberts and J. M. Thomas (Specialist Periodical Reports), The Chemical Society, London, 1972, Vol. 1, p. 171. Electron Spectroscopy gases on metals.51 In some cases narrow peaks superimposed on the metal band structure seem to indicate the discrete MO’s of ‘surface molecules’ e.g. H,Se on Ni(100) may form an Ni,Se array in C,,symmetry with the Se atoms above the Ni plane.61 For Auger transitions in the intermediate energy range, escape depths of €50 A can be obtained. As. is therefore used routinely to detect elements present at a s~rface;~~~~*~~~ e.g.the titanium Auger spectrum of Figure ll(b) shows surface contamination. The phosphorus comes from ‘cleaning’ by etching with acid. There are many applications in the area of thin film technology where < 1% monolayer is dete~table.~, Cleaning procedures can be evaluated, surface and grain boundary segregation studied, doping followed, etc. Hass and GrantS3 demonstrated the applicability of Auger chemical shifts to surface work by showing that different monolayer oxide phases on Ta(100) had different shifts, which were also different from the bulk oxide shift. Detection of surface SiO, by shape changes in the 2,2’ Si peak was also mentioned in Section 5. Surface carbide can be similarly distinguished from adsorbed C0.54 Shape changes in 2,2’ Auger peaks are equivalent to changes in i.n.s.spectra. In e.i.s. plasmon losses and the 0-2 eV loss region which relates to molecular vibrational excitations (compare i.r.) are of surface importance. Electrons with low dvalues should be studied (easily arranged by varying incident beam energy). ‘Surface’ plasmon losses may be distinguished from bulk losses and used to follow surface conditions. The intensity of surface plasmons can be sensitive (reduced) to as little as 0.04 monolayers of an Propst and PiperS6 studied the first 1 eV loss region under high resolution for the adsorption of gases on to tungsten and related the losses to the vibrational modes of the surface species formed. This would seem an area of potential which has not been further investigated.P.e.s. studies on solids have conventionally used energies below 11.6 eV (Section 3), and it has been considered that the band structures obtained were bulk properties. Recent studies indicate that photoemission may be primarily a surface effect.67 When using higher photon energies (e.g. He1 at 21.2 eV) the ejected electrons have lower d values and definitely come from the surface layers. Apart from variation in escape depth the results are similar to i.n.s., yielding information on the bonding of adsorbed layers to substrates. Bordass and Linnett5* attempted to obtain the p.e. spectrum of methanol on tungsten, and Eastman has observed the superimposition of a broad band, attributable to surface nickel oxide, on the band structure of The chemisorption of CO on to nickel has also been studied.Ss 61 H.D. Hagstrum and G. E. Becker, J. Chem. Phys., 1971, 54, 1015. b2 W. E. Weber, Solid State Technol., 1970, Dec., 49. 63 T. W. Hass and J. T. Grant, Phys. Letters (A), 1969, 30, 272. 5d T. W. Hass and J. T. Grant, Appl. Phys. Letters, 1970, 16, 172. 58 G. W. Simmons, J. Colloid and Interface Sci., 2970,34, 343. 56 F. M. Propst and T. C. Piper, J. Vuc. Sci. Technol., 1966, 4, 53. 57 N. V. Smith and G. B. Fisher, Phys. Rev. (B), 1971, 3, 3662. 58 W. T. Bordass and J. W. Linnett, Nature, 1969, 222, 660. 5B D. E. Eastman, private communication. Baker, Brundle, and Thompson Siegbahn et a1.2a estimated the probing depth of ESCA by monitoring a marker peak (Br 3d)while covering a surface with dilayers of stearic acid.Their estimate of 80 8, is likely to be greater than for non-organic compounds, par- ticularly metals, but again the values will depend on the energies of the electrons concerned. E.s.c.a. instruments in operation are not of ultra-high vacuum and so a full appraisal of surface applicability has not been possible. Delgass et aLsO have made preliminary studies of chemical shifts for nitrogen compounds adsorbed on to zeolites; for the dispersion of active metals on a support (a common method of increasing catalytic activity); and from crystalline oxides before and after catalytic use. Fadley and Shirleys1 demonstrated that the two Fe 3p peaks present for an iron sample were due to bulk iron and surface iron oxide.9 Analytical Aspects Auger spectroscopy will not be discussed here as its use as a powerful tool in surface analysis was described in Section 8. The potential of p.e.s. and ESCA in analytical chemistry has recently been cited.l'~~~ As the p.e.s. spectra of structur- ally similar compounds are often quite different,14Js it is clear that the technique can be used with some success to give qualitative or 'fingerprint' information. For example, the spectra of phosphorus-containing pesticides have been investigated with a view to their identification, and with later developments quantitative estimation, in materials causing public concern.63 In principle, quantitative measurements are distinctly possible as electron count-rates are functions of the numbers of molecules.Furthermore, the analysis of simple mixtures of compounds is a possibility, and perhaps with the aid of a g.1.c.-linked system more complex mixtures could be studied. The main problems of quantitative measurement are, in fact, those associated with any analytical instrument, viz. the problems of sample handling and introduction, memory effects, and output data treatment. These problems will undoubtedly be solved by future improvements in instrumental design. Many of the above comments also apply to other e.s. techniques. At the present time, the main use of ESCA lies in the mapping of elements in solid surfaces, with the advantage that information can be obtained non-destructively on a small amount of sample (<1 mg).In a qualitative sense, Jack and recently studied the ESCA spectra of a number of quaternary nitrogen and phosphorus compounds in an attempt to test the feasibility of a one-atom correlation (quaternary nitrogen or phosphorus). The authors pointed out that once sufficient information is available to do multiple-atom correlations, ESCA will become a complementary tool to i.r., n.m.r., and mass spectroscopy. With regard to gas analysis, Siegbahn et UZ.~~have shown that the 0.9%of argon in air is easily detectable by ESCA. In addition, the N Is binding W. N. Delgass, T. R. Hughes, and C. S. Fadley, Cuta!wis. Rev., 1971, 4, 179. C1 C. S. Fadley and D. A. Shirley, Phys. Rev. Letters, 1968, 21, 980.6p D. M. Hercules, Analyt. Chem., 1970, 42, 20A. c3 D. Betteridge, M. Thompson, A. D. Baker, and N. R. Kemp, Analyt. Chem., in the press. 64 J. J. Jack and D. M. Hercules, Anulyr. Chem., 1971, 43, 729, 1066. Electron Spectroscopy energies of N2and NH3were clearly distinguished, in a mixture of these gases. Similarly, a mixture of CO, COB,and CHI could be analysed via the appro- priate 0 1s and C 1s binding energies. E.i.s. appears to have considerable potential as a technique for the analysis of gases and vapours, and in particular for the determination of trace contami- nants in the atmo~phere.~~ In this regard, Rendina and Grojeans6 were able to detect a ‘trace’ of CO introduced into a sample of air of pressure 0.1 Torr. The authors also suggested that argon peaks can be used as an internal standard for accurately measuring concentrations of trace gases in air. IXJ. A. Simpson and C. E. Kuyatt, Amer. Lab., 1968, Oct. J. F. Rendina and R. E. Grojean, Appl. Spectroscopy,1971,25, 34.

ISSN:0306-0012    

DOI:10.1039/CS9720100355

出版商:RSC    

年代:1972

数据来源: RSC

摘要:

Chemicals in Rodent Control By N. J. A. Gutteridge LILLY RESEARCH CENTRE LTD., ERL WOOD MANOR, WINDLESHAM, SURREY 1 Introduction For centuries rodent pests have deprived man of his food and given disease and death in return. In many areas of the world, this menace has had to be accepted as a part of the environment since rodent control measures were either ineffective or too expensive. Early attempts at disinfestation were often hampered by man’s own ignorance of rodent behaviour; however, modern techniques have now evolved so that highly efficient control of rodent pests is often possible. A number of general acc~unts~-~ of the problem and specialized reviews of e.g. rodent behaviour with respect to controlf5 rodenticides,* 6-g repellants,1°-12 chem~sterilants,~~-~~etc., are available, but a review devoted solely to the contribution made by chemicals has not appeared hitherto.The objective of this article is to describe the chemical background surrounding the control of rodent pests and to stimulate interest in chemicals, both those in use and those of potential usefulness in rodent control. * The term rodenticide in this article covers only the chemical poisons that bring about the death of the rodent pest directly, rather than the broad interpretation used elsewherels which includes chemosterilants, repellants, etc. R. A. Davis, ‘Control of Rats and Mice’, Ministry of Agriculture, Fisheries, and Food Bulletin No. 181, 1967. a A. S. Strivastava, Labdev. J. Sci. Tech., 1966, 4, 207. * T.J. Gray, World Health, 1967, 3. M.A. C. Hinton, ‘Rats and Mice as Enemies of Mankind’, British Museum (Natural History), Economic Series No. 8, 1918. D. Chitty and H. N. Southern, ‘Control of Rats & Mice’, CIarendon Press, Oxford, 1954, 3 vols. a J. H. Krieger, Agric. Chem., 1952, 7, 46. ‘I E. Enders, ‘Chemie der Pflanzenschutz und Schadlingsbekampfungsmittel’, Springer-Verlag, Berlin, 1970, p. 601. D. H. Frear, ‘Chemistry of the Pesticides’ ,Van Nostrand, New York, MacMillan, London, 1955, p. 437. E. M. Mills, Pest Control, 1955, 23, 14. lo J. F. Welch, Agric. Food Chem., 1954, 2, 142. l1 H. V.Thompson, Forestry Abstracts, 1953, 14, 129. l* J. F. Welch, Proceedings of the Third Vertebrate Pest Conference, California, ed.M. Cummings, 1967, p. 36. l3 J. E. Brooks and A. M. Bowerman, Soap, 1969,45, 58. l4 W. E. Howard, ‘Pest Control’, Academic Press, New York and London; Biocontrol and Chemosterilants, 1969, 10, 343. l6 R. E. Marsh and W. E. Howard, Proceedings of the Fourth Vertebrate Pest Conference, California, 1970, p. 55. l6 ‘Webster’s 7th New Collegiate Dictionary’, G. Bell & Sons Ltd., London, 1969, p. 745. Chemicals in Rodent Control No apology is given for including brief references to non-chemical procedures, since integrated programmes are essential for successful control. Particular reference is made to rodents of the U.K. that are commensal, i.e. rodents dependent on man for food and shelter, but examples of procedures used to combat other rodent pests are included.2 Rodent Pests One of the largest groups of animals in the animal kingdom in the Class MAM- MALTA is the Order RODENTIA, which contains upwards of 3000 species.17 In the rodent classification (see Table) rats and mice are grouped together in the same family MURIDAE. (Contrary to popular belief, the rabbit is included in the Order LAGOMORPHA and hence it is not strictly a rodent.) The name rat may be correctly applied to about 500 species of rodent, but only two species (Rattus norvegicus and Rattus rattus) are of worldwide signifi- cance, and both these species appear in Britain. R. norvegicus (Berkenhout), (the common rat, brown rat, etc.) infests most habitats provided by man and has the capacity to adjust to almost any environmental condition, although it is mainly a burrowing and water-loving animal of the temperate zone.R. rattus (Linnaeus), (black rat, ship rat, etc.)exists in three subspecies (see Table), which in Britain and some other countries interbreed freely and so are ecologically indistinguishable.l* R. rattus is more of a climbing or arboreal species and is particularly widespread in the tropics. R. rattus has been called the plague rat for it was a vector in the plagues of the Middle Ages. It is now rarely observed away from seaports and dockyards in Britain. At least 130 species of mice exist and four types are found in Britain, although it is only the house mouse, Mus musculus (Linnaeus)that is a common urban pest. 3 Need for Control A.Damage.-In common with other rodents, the rat has incisor teeth which grow throughout life. The outer enamel of the incisors has a value of 5.5 on the Moh scale of hardness, so that lead pipes, metal-sheathed cables, insulated electrical wirings, plastics, hardwoods, etc., are all open to attack by rodents. It has been estimatedlO that in Britain some fifty million rats exist, causing E50-60 million worth of damage per year. B. Food Losses.-Food losses due to rodent attack can be severe, the food being taken from the field, granaries, stores, and domestic properties. It has been estimated3 that the total annual world loss of stored cereals and rice for which rats are responsible exceeds 33 million tons. J. Z. Young, ‘The Life of Vertebrates’, Clarendon Press, Oxford, 1964, p.652. E. W. Bentley, ‘Biological Methods for the Evaluation of Rodenticides’, Ministry of Agriculture, Fisheries, and Food, Tech. Bull., No. 8, 1958. lS P. L. G. Bateman, ‘Rats’, Advice and Action Ltd., Public Relations Consultants, East Grinstead, Sussex. Table Classijication of Rodents* CLASS MAMMALIA I ORDER LAGOMORPHA RODENTIA I etc. FAMILY etc.kptc.it..;. GENUS SPECIES SUB-SPECIES w-~ * Assistance from J. M. Ingles, Mammal Section, British Museum (Natural History), London, S.W.7, is gratefully acknowledged. Chemicals in Rodent Control C. Disease.-Rats and mice are known to transmit at least thirty-five diseases, and carry many different kinds of lice, fleas, ticks, and mites.2 One disease known as the plague was responsible for the death of twenty-five million people during the fifteenth century.This disease, which is still found in many parts of the world, is caused by the bacterium Pasteurella pestis, and is spread from rats to man by a flea (Xenopsylla cheopis). Many other serious diseases are spread by rats and mice, e.g. Leptospiral Jaundice (Weil’s Disease), ‘Rat bite fever’ (Soduku),and Trichinosis. In control measures it is important to aim for total extermination, as the very existence of rodent pest populations in and around human habitation is a potential health hazard. 4 Control of Rodent Pests Although shrouded in superstition and folklore, a number of old-fashioned methods were partly effective since they were based, like modern techniques, on careful observation of animal pests and their behaviour.Skilled ‘rat-catchers’ employed in medieval days knew much about these habits and one such person hired by a German city probably gave rise to the legendary tale of the highly successful Pied Piper of Hamelin. Present day control tackles the problem from both the offensive and defensive standpoints. Mechanical control is valuable in integrated control procedures and includes the use of traps,20 barriers, and general rodent-pr~ofing.~~~~ A number of biological control methods are of interest. Introduction of predators to destroy rodent pests was one of the first recorded extermination rnethod~,~ but incomplete disinfestation and disturbances of the ecological balance restrict their value.22 An infectious disease pathogenic only to the rodent pest has also been con- sidered.Incorporation of cultures of Salmonella enteritidis in rat baits is effective but non-specific. Danger to man and domestic animals2s has resulted in the cessation of this practice. A specific virus infection, myxomatosis, was more successful in limiting rabbit population~.~~*~~ Specific non-pathogenic diseases, which could render animals more susceptible to chemical poisons, may have their place, e.g. parasitaemia in the canefield rat (Holochilus sciureus) of British Guiana2s increases its susceptibility to anti-coagulant poisons. The essential step in any ideal control operation is the elimination of the rodent’s two basic living requirements, namely food and she1ter.l Even if this is not practicable, however, merely the combination of good hygiene, tidy storage, and frequent refuse disposal is a great aid to subsequent extermination work.Nearly a11 modern extermination procedures depend on chemical methods. 2o ‘Trapping Rats and Mice’, United States Dept. of the Interior Fish & Wildlife Service, Leaflet No. 320, 1961. 21 ‘Controlling Rats & Mice, Fundamentals of Rodent Proofing’, United States Dept. of the Interior, Fish and Wildlife Service, Leaflet No. 313, 1961. 23 Ref. 12, p. 137. 23 J. Taylor, Lancet, 1956, 1, 630. 24 H. V. Thompson, Ann. Appl. Biol., 1953, 41, 358. 25 F. Fenner, Brit. Med.Bull., 1959, 15, 240. 28 J. F. Bates, Proceedings of the 11th Congr. I.S.S.C.T., Mauritius, 1962, p. 695. Gutteridge The rodenticides are accepted as the main eradication tool, but other chemicals such as chemosterilants are useful in supporting roles. The main factors that need to be kept in mind when using chemicals are the safety precautions necessary to protect man, his livestock, and other animals. In order to counteract possible outbreaks of resistance, a continual check must be made on rodenticidal performance. 5 Rodenticides Rodenticides are normally employed in solid baits or in dust (p. 396) or liquid form while suitable volatile chemicals have found use as fumigants (p. 397). Although toxicity (conveniently expressed as the median lethal dose, L&, in mg/kg, p.0.) is an essential pre-requisite of an effective rodenticide, it is not the only criterion upon which an ideal rodenticide is based.Additional features6-8 of an ideal rodenticide are set out below: (i) Toxic action slow, to allow animal to consume a lethal dose. (ii) The poison should not be unpalatable, and preferably odourless. (iii) Symptoms of acute poisoning should be absent; no bait shyness. (iv) The poison should be specific to the species to be controlled. (v) The manner of death, preferably humane, should not arouse sus-picions in surviving animals. (vi) No difference in susceptibility due to age, sex, or strain should be present. (vii) There should be no danger of secondary poisoning through animals eating poisoned rodents.(viii) No immunity or build-up of tolerance to the poison should develop. (ix) The chemical compound in the bait should be stable under varied environmental conditions. (x) To allow easy removal of corpses, the animals should preferably die in the open. Since these requirements are numerous and difficult to achieve in practice, a high toxicity and palatability with one or more safety features is the usual aim. The chemical poison should be of constant composition within a fixed particle size rangels (previously determined for optimum toxicity) and be easily available in a pure state. The effects of possible impurities which might be present in the large scale preparation of the rodenticide should also be tested on the pest species and other animals.The carcinogenic effects of one impurity sometimes found in the rodenticide antu (a-naphthylthiourea) has led to the removal of this rodenticide from the market in the U.K.27 The bait chosen and other additives (p. 398) greatly contribute to the success or otherwise of a particular poison, but as yet a poor rodenticide has not been transformed into a good one by changes in formulation. From the foregoing it can be seen that the search for potential rodenticides is more difficult and complex than might at fist appear. One approach, using 27 Anon. Lance?, 1966, 2, 1183. Chemicals in Rodent Control anti-metabolites, is essentially based on careful studies of the target animal’s biochemical make-up.It is hoped that firstly, an essential metabolic pathway could be discovered not present in related species, and secondly, that a chemical compound could be designed selectively to block this route. The compound so synthesized, even if it could reach the active site and in the form required, must possess the correct stability, palatability, and onset of action necessary for an efficient rodenticide. The anti-metabolite 6-amino-nicotinamide is current- ly being studiedz8 as a candidate rodenticide. The biological evaluation of rodenticides is similarly a difficult task, and a clear account of the problems has been given by Bentley.ls The rodenticides used in baits may conveniently be divided into organic and inorganic compounds; the latter are usually considered as acute poisons while the former require subdivision into both acute and chronic poisons.A. Bait Poisons.-(i) Organic Compounds. (a) Acute rodenticides. The acute rodenticides are those in which a lethal quantity of poison is ingested in a single dose in the food or drink of the rodent. Unfortunately, animals often consume a sub-lethal dose which, although insufficient to kill, still produces disturbing side effects. The animals associate these unpleasant symptoms with the poisoned bait and ‘bait-shy’ animals result which are unlikely to be killed with the same poison and bait combination. However, in some circumstances, e.g. where outbreaks of disease necessitate immediate control, acute poisons are preferred to the second type of rodenticide, the chronic kind.Most of the acute rodenti- cides require prebaiting techniques, for rodents need to be conditioned in order to overcome their shyness towards new objects. The unpoisoned bait is first presented to the rodent until the animal feeds regularly and then it is replaced by bait containing the poison. Red squill is probably the oldest known r~denticide.~~ A detailed account of its historical and botanical origin and its toxicological properties has been pre~ented.~Red squill may be extracted from the bulb of the lily-like plant Urginea maritima, common to the Mediterranean coastal area. A toxic principle, named scilliroside8 (LD5,,= 0.70 mg/kg, male white rats) has been isolated from the plant extract and assigned the structure (1).Personal communication, Ministry of Agriculture, Fisheries, and Food. 29 A critical review of the currently used acute rodenticides is given by N. G. Gratz. ‘Seminar on Rodents and Rodent Ectoparasites’, Geneva, 1966. (W.H.O. Vector Control, 66.217.) Gutter idge The main disadvantage30 of red squill as a rodenticide is the variation in potency of the extracted materials, which has necessitated the setting up of biological standardization tests based on rodenticidal activity.2@ Good control of R. norvegicus but only moderate control of M. muscuZus and R. rattus has been claimed,31 using 0.5 % stabilized scilliroside in baits. The violent nature of rodent deaths caused by red squill poisoning has brought about the banning of this poison in the U.K.on humanitarian Strychnine (2) (LD60= 50 mg/kg, R. nor~egicus)~has been used as a vertebrate pesticide since the seventeenth century. The bitter taste of the alkaloid seems to interfere with the success of rodent campaigns.33 No advantages have been evident in employing strychnine Salkss The use of this compound in rodent control was banned3a in 1935 in the U.K. although it is still employed for mole extermination. 34 NHCS-NHz Antu, a-naphthylthiourea (3), which was the first synthetic organic rat poison,36 may be prepared3s by treating a-naphthylamine with ammonium thiocyanate. Particle size has an interesting effect on for an unknown reason, larger particles (50-55p) are more toxic than smaller particles (5p).Antu is primarily 3O A.Mallis, ‘Handbook of Pest Control, Rats and Mice’, MacNair-Dorland Co., U.S.A., 1945, p. 13. 31 D. R. Maddock and H. F. Schoof, Pest Control, 1970, 38, 32. D. C. Drummond, Chem. and Ind., 1966, 1371. s3 W. A. McDougall, QuoenslandJ. Agric. Sci., 1944, 1, 1. G. S.Hanley and T. F. West, ‘Chemicals for Pest Control’, Pergamon Press, Oxford and London, 1969, p. 139. $5 C. P. Richter, J. Amer. Med. ASSOC.,1945, 129, 927. 36 S. B. Alvarez, Rev. quim. farm. (Santiago, Chile), 1947, 4, 2. s7 E. W. Bentley, Y. Larthe, and A. Taylor, J. Hyg. (Cambridge), 1955, 53, 328. Chemicals in Rodent Control effective against R. norvegicus (LD50 = 7 mg/kg) and considerably less lethal3* to R.rattus and M. musculus. Sub-lethal doses cause a definite tolerance which is even evident a few hours after ingestion of the poison. Antu has now lost favour2’ as a rodenticide in the U.K. NMe’ ‘Me Castrix, 2-chloro-4-dimethyIamino-6-methylpyrimidine(4),39 developed in Germany during the Second World War, is a powerful convulsive agent (LDs0= 1 mg/kg, albino rats), for which fortunately, there is an effective anti- dote, sodium pentobarbital. The poison is well accepted by in baits at a concentration of 0.25-1.0% and against mice in grain baits it has proved most effective.29 Preliminary trials against Hulochilus sciureus have given promising results,2s but field use against R. norvegicus was not satisfactory.29 Monofluoroacetic acid derivativesQo have been screened by research workers of the United States Fish and Wildlife Service, following a lead from Polish chemi~ts.~~.~~Number 1080 in their series was sodium fluoroacetate and 108 1 fluoroacetamide. Independent led to the discovery of the potassium salt of monofluoroacetic acid as a component of the South African plant Dicha-petdhm cymosum, well known to be poisonous to livestock.Sodium fluoroacetate is exceedingly toxic to man and all animals, especially as well as to rodent pests (LD50= 3-5 mg/kg, R. norvegicu~).~~Its lethality is due to the blocking43 of the vital mammalian energy-releasing citric- acid cycle, and there is no specific antidote although glycerol monoacetate and other suggestions have been put Sub-lethal doses do not generally appear to lead to tolerance although cases of acquired resistance are rep~rted.~~,~~ Sodium fluoroacetate has found use in the control of rats in sewersQ4 and ships.45 In sodium fluoroacetate has been used to control rabbits and in the United States,*’ to control ground squirrels.In the interests of safetya2 to man 38 M. Lund, World Rev. Pest Control, 1967, 6, 131. 39 K. P. Dubois, K. W. Cochran, and J. F. Thomson, Proc. SOC. Exp. Biol.Med., 1948,67,169. 40 M. B. Chenoweth, J. Pharmacol., 1949, 97, 383. 41 E. R. Kalmbach, Science, 1945, 102,232. 42 J. S. C. Marais, Onderstepoort J. Vet. Research, 1944, 20, 67. 43 R. Peters, R. W. Wakelin, and P. Buffa, Proc. Roy. Soc., 1953,.B140,497. 44 E. W.Bentley, ‘Control of Rats in Sewers’, Ministry of Agriculture, Fisheries, and Food, Tech. Bull., No. 10, 1960. 45 J. H. Hughes, US.Public Health Service Rep., 1950, 65, 1021. 4e C. S. Hale and K. Myers, Int. Pest Control., 1970, 12,12. 47 R. E. Marsh, Proceedings of the Third Vertebrate Pest Conference. California. ed. M. Cummings, 1967, p. 2. 388 Gutteridge and non-pest species, the sale and distribution of this otherwise effective rodenti- cide and its related compounds are now restricted4* in the U.K. The first suggestion for the use of fluoroacetamide as a rodenticide is attri- buted to Chapman and Phillips.4g It is less toxic (LD50= 13 mg/kg, R. norve-gi~us)~Othan fluoroacetate but proved more successful in field trials in sewerss1 at 2 % bait concentration than sodium fluoroacetate at 0.25% or zinc phosphide at 2.5%.Similar restrictions apply to the use of this rodenticide. Many examples of monofluoroacetic acid (3,and monofluoroethanol derivatives (6),which possess similar toxicity, appear in the literature. 7940962-54 FCH2COR R = NHNHPh, NHCH-OCONHPh, (5) I CCI, NHCH-NHPh, NHCH-SR1, or NHCH-NHCONHRf I I I CCl, CC13 CC13 R1= alkyl, aryl, etc. FCH,CH R I OH R = H, CH2F, or CH,Cl (6) Norbormide, 5-(a-hydroxy-a-2-pyridylbenzyl)-7-(a-2-pyridylbenzylidene)nor-born-5-ene-2,3-dicarboximide(7), as prepared commercially, exists as a mixture 48 ‘Use of Fluoroacetamide and Sodium Fluoroacetate as Rodenticides; Precautionary Measures’.Ministry of Agriculture, Fisheries, and Food Leaflet, 1965. 49 C. Chapman and M. A. Phillips, J. Sci. Food Agric., 1955, 6, 231. E. W. Bentley and J. H. Greaves, J. Hyg. (London), 1960, 58, 125. E. W. Bentley, J. Hyg. (London), 1961, 59, 413. Ka L. Karel, J. Pharmacol. Exp. Therap., 1948, 93, 287. K3 B. Y.Falkenshtein and I. P. Ershova, Gigiena i Sanitariya, 1957, 22, 96. 64 C. Fest and G. Hermann, Pjlanzenschufz Ber., 1969, 39, 241. 389 Chemicals in Rodent ControI of geometric and optical isomers66 which collectively possess a highly specific toxicity to rats (LD5,,= 9-12 mg/kg, R. norvegicus).58This material was the first known Rattus-specific toxic agent, for related genera such as Mus~~and Bandi~ota~~are to all intents and purposes immune.Norbormide was fist synthesized5' during a study of potential anti-rheumatic agents: $H t080 The stereoisomers were separated5* by fractionation and chromatographic procedures and shown to vary widely in potency. Norbormide analogues have also been synthe~ized~~ for structure-activity studies. Substitution at any but the dicarboximide ring positions led to compounds less than one-twentieth as active as norbormide while compounds possessing substituents on the imide nitrogen atom displayed potencies ranging from about equivalent to that of norbormide to less than one-twentieth of this activity. Only mediocre results have been obtained in rodenticide field trials, e.g. in New Zealand,5g WalesYG0 This has been attributed to the and elsewhere.2g~s1 rodent's ability to detect the presence of norbormide in the bait and to develop bait-shyness.In a comparative trialso versus zinc phosphide, norbormide was proven somewhat inferior, even when various concentrations, various cereal baits, and direct-baiting and pre-baiting techniques were used. In spite of these disappointing results, norbormide is an interesting development in rodent control and has been recommendedGo for use where risks to livestock are high. 66 A. H. Netherwood, Agri. Vet. Chem., 1965, 6, 115. 56 P. J. Deoras, Current Sci., 1965, 34, 348. R. U. Russell, J. Forensic Sci. SOC.,1965, 5, 80. tis G. I. Poos, R. J. Mohrbacher, E. L. Carson, V. Paragamian, B. M. Puma,C. R. Ras- mussen, and A.P. Roszkowski, J. Med. Chem., 1966, 9, 537. s9 A. E. Beveridge and M. J. Daniel, Proc. N.Z. Ecolog. SOC.,1966, 13, 40. 60 B. D. Rennison, L. E. Hammond, and G. L. Jones, J. Hyg. (Cambridge), 1968, 66, 147. 61 D. R. Maddock and H. F. Schoof, Pest Control, 1967, 35, 22. Gutter idge a-Chloralose (8) is a recently introduced acute poison.s2 It acts by retarding the animal's metabolic processes, so that the animal dies from hypothermia. This substance is thus more effective at temperatures below 15 "C and is more specific to small animals such as mice = 300 mg/kg at 1&18 0C)62 because of their larger surface-area to volume ratio. Restrictions on the place- ment of poisoned baits exists3 since this poison is hazardous to birds. The effects of microencapsulation have been examineds4 and work concerned with devising improved formulations is under way.S Me II( C I O 0-)-P-N=C--NH*I 2 Gophacide, OO-bis-(p-chlorophenyl)acetimidoylphosphoramidothioate (9),a new cholinergic rodenticide, has been found to be of value in the control of deermice(Peromyscusmaniculatus)s6and pocket gophers (Thomomys talpoides, Geomys bursarius, and related species). Field trials versus R. norvegicus, R. rattus, and M. musculus with baits containing the poison at 0.2-0.5% concentration have generally given favourable The acute toxicity and mechanism of action have been described,s8 and atropine and pralidoxine have been suggested as antidotes.ss sa P. B. Cornwell, Pharm. J., 1969, 202, 74.83 'Alphakil-A New Rodenticide for Mouse Control', Rentokil Laboratories Ltd., Tech. Release, 1966, 66/2. O4 P. B. Cornwell, Znt. Pest Control, 1970, 12, 35. 6s M. C. Hoffer, P. C. Passof, and R. Krohn, J. Foresrry, 1969, 67, 158. 66 V. B. Richens, Proceedings of the Third Vertebrate Pest Conference, California, ed. M. Cummings, 1967, p. 118. 67 Anon. Pest Control, 1969, 31, 15. K. P. Dubois, F. Kinoshita, and P. Jackson, Arch. Internat. Pharmacodyn., 1967, 169, 108. 39 I Chemicals in Rodent Control Sila trane, 1-@-chlorophenyl)-2,8,9- trioxa-5-aza- 1-sila bic yclo [3,3,3 lundecane (lo), is another recently reportedss acute poison (LD,o = 1-4 mg/kg, lab. rats). It is claimed to be an effective fast-acting control agent exhibiting no secondary hazards, since rapid detoxification occurs after ingestion.Field studiesss are in progress to assess its usefulness for control of rats, ground squirrels, and mice. (b) Chronic rodenticides. Chronic rodenticides bring about the death of the rodent only after the poisoned bait has been consumed on a number of occasions. The symptoms of poisoning are so delayed that the animal never learns to associate discomfort with bait consumption and continues to feed until a lethal dose has been ingested. The cumulative, slow-acting nature of these materials is characteristic of this type of poison, hence their respective LDso values do not reflect a chronic poison’s potential killing power. For R. norvegicus survived single 50 mg/kg doses of the anticoagulant warfarin, but succumbed to 5 consecutive doses of 1mg/kg taken on successive days.The main compounds possessing a chronic poisoning action are the anticoagulants, which interrupt the synthesis of blood-clotting factors so that poisoned animals die from internal bleeding. Other substances with chronic poisoning properties but with different modes of action are also known, e.g. trifluorobenzimida~oles~~and quinoline disulphides.72 The evaluation of chronic rodenticides has been discussed by Bent ley. CH2COMe OH CHZCOMeaR0 CH2 COMe 8s C. B. Beiter, M. Schwarcz, and G. Crabtree, Soap, 1970, 46,38. 79 W. J. Hayes and T. B. Gaines, Publ. Health Rep., Wash., 1950, 65, 1537. 71 South African P. 8004/1969. 7s Unpublished researches.Lilly Research Centre Ltd., Ministry of Agriculture, Fisheries, and Food. Gutteridge Anticoagulant rodenticides are either coumarin (1 1) or indanedione (12) derivatives. (a) R = CO*CMe3 Some early studies in the United States to discover the cause of sweet-clover disease in cattle led to the isolation of 3,3’-methylene-bis-4-hydroxycoumarin [dicoumarin, (13)].73 This compound was found to make the blood clot more OH OH slowly than normal and was immediately recognized to be of value in human medicine for alleviating conditions such as coronary thrombosis. The synthesis of other, related compounds followed and the 42nd substance described in the by Links’ group was more effective than dicoumarin. This com- pound later became known by its generic name, warfarin; the first four letters being derived from Wisconsin Alumni Research Foundation, to whom the patent rights were assigned.In 1948, a report by O’COII~O~~~ appeared on the merits of the multiple- dose technique that had proven successful with dicoumarin. This discovery added fresh impetus to research efforts in the anticoagulant field. A number of other haemorrhagic agents were tested subsequently and the rodenticidal action of 1,3-indanediones was disc~vered.~~ The near ideal situation in rodent la M. A. Stahmann, C. F. Huebner, and K. P. Link., J. Biol. Chem., 1941,138, 513. l4 R. S. Overman, M. A. Stahmann, C. F. Huebner, W. R. Sullivan, L. Spero, D. G. Doherty,M. Ikawa, L. Graf, S.Roseman, and K. P. Link. J. Biol. Chem., 1944, 153, 5. 16.J. A. O’Connor, Research. London, 1948, 1, 334. H. Kabat, E. F. Stohlman, and M. I. Smith, J. Pharmacol., 1944, 80, 160. Chemicals in Rodent Control control brought about by the introduction of anticoagulants has now changed, however, with the appearance of genetically based re~istance.~~ The anticoagulants possess certain general properties,6 e.g.: (a) No bait shyness; animals ingest bait until death. (b) No prebaiting is necessary as acceptance of poisons is good at lethal concentrations. (c) Low dosages are effective, e.g. warfarin used at 0.005-0.25~,!J in pre- pared baits. (d) They are relatively non-toxic to domestic animals and man, although the view that they are without risks of any kind is erroneous.(e) Accidental poisoning can be controlled by the prompt use of Vitamin K. A number of accounts of the relative merits and demerits of individual anti- coagulants have appeared7 -84 but only a few specific properties of individual rodenticides will be discussed here. Warfarin, 3-(1 -phenyl-2-acetylethyI)-4-hydroxycoumarin(1 la), may be syn- thesizeda5 by a Michael condensation between benzalacetone and 4-hydroxy- coumarin in the presence of a base such as piperidine. The product is a racemic mixture which exhibits reactions typical of its functional groups. Warfarin is the most widely used anticoagulant7’ for the control of R. norvegicus and M. musculus, and satisfactory results have been reported with R.rattus and in trials against other rodent pest~.~~~~~ Dangers to non-pest species, although minimal, are, however, not entirely absent.87 Poisoning techniques involving warfarin have been extensively studied. In locations deficient in water supplies the sodium salt can be effective when pre- sented to rodents in their drinking water.s In solid baits it has been foundlS that smaller particles lower the acceptance. Protection and preservation of baits in wax formulations and paper-wrapped baits is common practice under some adverse conditions.s8 Other poisoning techniques have been described, for example the use of warfarin in contact d~sts,~~ foams,0o and aeros01s.~~ Other important coumarins are coumachlor (11 b), coumatetralyl (1lc), and fumarin (1Id).77 E. W. Bentley, ‘Review of Currently Used Anticoagulants’, Seminar on Rodents and Rodent Ectoparasites, Geneva 1966 (W.H.O. Vector Control, 66.217), p. 89. 78 J. H. Greaves and P. Ayres, J. Hyg. (Cambridge), 1969, 67, 3 11. 79 E. W. Bentley and T. Larthe, J. Hyg. (Cambridge), 1959, 57, 135. F. P. Rowe and R. Redfern, Ann. Appl. Biol.,1968, 62, 355. J. P. Saunders, S. R. Heisley, A. D. Goldstone, and E. C. Bay, J. Agric. Food Chem., 1955, 3, 762. 8a F. P. Rowe and R. Redfern, Ann. Appl. Biol.,1968, 61, 322. 83 E. W. Bentley and M. Rowe, J. Hyg. (Cambridge), 1956, 54, 20. 84 W. J. Hayes and T. B. Gaines, Publ. Health Rep., Wash., 1959, 74, 105. 85 M. Seidman, D. N. Robertson, and K.P. Link, J. Amer. Chem. SOC. 1950, 72, 5193. 86 J. C. Taylor, H. G. Lloyd, and J. F. Shillito, Ann. Appl. Biol. 1968, 61, 312. 87 D. S. Papworth, Roy. SOC. Health J., 1958, 78, 52. R. A. Gillbanks, P. D. Turner, and B. J. Wood, The Planter, 1967, 43, 297. 89 F. P. Rowe and A. H. J. Chudley, J. Hyg. (Cambridge), 1963, 61, 169. go V. G. Zatsepin, Trudy Vses. Nauchn.-Issled. Inst. Vet. Sanit., 1966, 25, 357. Fr.P. 1489 813 (Chem. Abs., 1968, 68, 104 137v.). 394 Gutteridge Coumachlor, 3-(1-p-chlorophenyl-2-acetylethyl)-4-hydrosyin(11b), is similar to warfarin but somewhat less useful against R. norvegicus.7g It has been used effectively as a contact dust. Coumatetralyl, O2 4-hydroxy-3-a-tetralyl-coumarin (1 lc), and fuma~in~~,3-(2-acetyl-l-furylethy1)-4hydroxycoumarin (lld), have proved good alternatives to warfarin for the control of rats and mice.pival, 2-pivalyl-l,3-indanedione(12a), may be preparedg3 by means of a Claisen condensation between diethyl phthalate and pinacolone. It was syn-thesized as part of a study aimed at comparing insecticidal activity with varia- tions in 1,3-indanedione structure. An account of the early development of this compound as a rodenticide has been given by Mil1s.O Studiess3 have indicated that pival is a useful alternative to warfarin against R. ruttus. An advantage over warfarin is the insecticidalg3 and fungistatic action of pival that retards the deterioration of prepared baits. Other indanedione derivatives, diphacinone (2-diphenylacetyl-l,34ndanedione)(1 2b),04 chlorophacinone { 2-[l-(p-chloro-phenyl)-l-phenyl]acetyl-l,3-indanedione)(12c),g5~g6etc., have found use as rodenticides.(ii) Inorganic Compounds. In general these compounds are non-selective in action and for this and other reasons are not frequently used. One poison, however, zinc phosphide, has held its place and proved valuable for the extermination of rats resistant to warfarin. Zinc phosphide (Zn3P2) is a greyish-black powder (LD50= 40 mg/kg, R. norvegicus)lS possessing a strong disagreeable odour which, surprisingly, does not deter rats and is sometimes said to possess certain attractive properties. Nevertheless, the prebaiting technique is still required. The instability of zinc phosphide in the presence of moisture can cause deterioration of poisoned baitsg7 For longer-lasting effects, baits are sometimes wrapped in waxed2 or waterproof paper, or mixed with mineral 0i12g,g7 rather than water. In the U.K., cereal baits such as soaked wheat or medium oatmeal containing zinc phosphide (2.5 %) have been used successfu1ly.l The advantages of low secondary toxicity and low cost together with its fairly good safety record have contributed to the widespread use of this Cases of acquired resistance have been found with the species R.ratt~s~~and B. bengalensis.OS Arsenious oxide (arsenic trioxide, As203), also known as ‘white arsenic’, has a toxicity that is dependent upon the particle size, e.g. for white rats LD5,,= 60 mg/kg at < 5p diameter but 148 mg/kg at > 1Oop.l8 Arsenious oxide was one of the earliest rodenticides, but its use has decreased rapidly of late due to general restrictions on the sale of arsenic-containing and to poor 8a I.F. Thompson, Baywood Courier, 1969, 3, 10. 93 L.B. Kilgore, J. H. Ford, and W. C. Wolfe. Ind. and Eng. Chem., 1942, 34,494. gp R. L. Gates, Pest Control, 1957, 25, 14. 95 J. Tahon, Parasitica, 1969, 25, 167 (Chem. Abs., 1970, 73, 55 009x). 96 R. Moens and A. Ghesquiere, Rev.Agr. (Brussels), 1969, 22, 1089 (Chem. Abs., 1970, 72, 89 249v). 87 H. F. Schoof, Pest Control, 1970, 38, 38. QR A. S. Srivastava, Labdev. J. Sci. Tech., 1967, 5, 168. 395 Chemicals in Rodent Control and erratic levels of acceptance by rodents.Acquired tolerance to this rodenticide has been reported.38 Thallous sulphate (Tl2S04), a cumulative poison which exhibits no warning propertiesto is in some ways a most effective rodenticide (LD,, = 16 mg/kg, R. norvegicur)l* but its use is limited by serious human health hazards. It is dangerous not only as a direct poison, but also because it is absorbed through the skin.e Secondary poisoning is also possible, and sub-lethal doses induce sterilityes and other effects.83 An antidote employing dimercaprol and methionine has been describedyBB but cases of thallium poisoning have been so widespread that, although excellent results can be achieved in con- trolling rodents, it is now banned in many countries for general use.6188 B. Poison Dusts.-Dust formulations of lethal substances possess properties useful in rodent-control programmes, e.g.the placing of calcium cyanide dust in the holes and burrows of rodents is a useful procedure in fumigation work.34 Another technique involves the use of contact dusts,8 a method loowhich appears to have arisen accidentally from studies with the insecticides D.D.T. and B.H.C. This method overcomes possible idiosyncrasies in feeding behaviour for it depends upon the rodent inadvertently coming into contact with the dust laid in rodent-frequented areas. It is possible for a lethal dose of a poisonous dust to be eventually ingested by a rodent, for any material that has adhered to its feet and fur is transferred to its mouth during normal cleaning and grooming activity.This method therefore requires concentrations of poisons far higher than that used in baits, for the animal can only be expected to consume small amounts during grooming. A typical poison dusts consists of an inert, finely divided material, a suitable poison with sometimes an adhesive, a water-repellant, and a warning dye. The advantages of contact dusts are that rodents do not suspect the source of illness resulting from ingestion and so do not avoid normal travel routes. Further, it is not necessary to persuade animals to change their feeding habits as with poison baiting. There are several disadvantages, which explain why this technique is not in frequent use. Firstly, there is the danger aspect that prevents use near human or animal foodstuffs because of the risk of contamination.Their correct placement is also necessary so as to be away from areas traversed by other animals, e.g. cats and dogs. All the routes which rodents frequent need to be located. The use of poison dusts is also uneconomic, for much material must be laid even though only a small amount will be removed and consumed by the rodent. The dust should also be fine enough to stick to feet and fur, yet not to be so light as to be moved by air currents. Warfarin8 and other anticoagulants, coumachlor , coumate tral yl ,B2*lol e tc . W. Schild and A. Schrader. Nervenarzt, Heidelberg, 1952, 23, 288; J. Amer. Med. Assoc. 1952, 150, 1730. looE. E. Turtle and A. Taylor, Reports Progr.Appl. Chem., 1955, 40, 680. lol N. Dudley, Barer Agro Chem. Courier, 1970, 3, 11. Gutteridge are normally used at ca. 1% concentration for the purposes of rat and mouse control. D.D.T. in micronized form in concentrations ranging from 20 to 50% has been used against M. miiscuZus.102Lindane at a similar concentration has been claimed more effective than either warfarin or D.D.T.lo3Chemosterilants may also be presented to rodents in contact dust formulations.16 C. Fumigants,-Infestations in warehouses, foodstores, and granaries do not always respond satisfactorily to poison baiting, trapping, and other direct control methods. The main problem is the difficulty of getting the rodent to break cover, for sometimes an apparently attractive bait is not a sufficient lure. Situations like these and others, where direct control is impracticable or unsuc- cessful, may often benefit by the application of fumigation techniques. The penetrating properties of fumigants allows rodent extermination to proceed even in inaccessible areas.There are a number of volatile substances and gases that could be suggested as fumigants but the choice is narrowed when toxicity, diffusion, adsorptive characteristics, and possible side effects are considered. For instance, in buildings containing foodstuffs and other stored commodities, fumigation treatment must not produce any permanent deleterious side-effects through absorption of the fumigant. In the U.K.,l the most frequently encountered fumigants are hydrogen cyanide and methyl bromide, to which chlor~picrin,~~~ a powerful lachrymator, is some- times added as a warning agent.Sulphur dioxide,lo4 although cheaper than some other fumigants, has proved inferior because of poor penetrating properties and corrosive effects. Carbon in the form of ‘dry-ice’ is a convenient and safe method but suffers from being more expensive and difficult to apply than alternative fumigants. A number of other gases and volatile liquids have been investigated, e.g., carbon disulphide,lo6 ethylene oxide,lo7 carbon monox- ide,lO* and ~thers.~,~~~,~~~ The extermination of outdoor colonies of rodents is normally carried out with hydrogen cyanide ga~.~,~~~~~ It is customary to blow or inject calcium cyanide in granular or dust form into a burrow so that when it comes into contact with moist air or soil the gas is liberated. Since hydrogen cyanide is lighter than air, greater concentrations of gas collect in higher areas of the burrow network, so for this and other more obvious reasons, all holes need to be rapidly sealed up.loa‘Insecticide Resistance and Vector Control’, W.H.O. Tech. Report Series No. 443, 1970,p, 241. Io3 Rentokil Laboratories Ltd., Tech. Release, 1969, 69/1. lo4 Ref. 34, p. 274. lob R. H. Thompson, Pest Technology, 1959, 2, 7. Io6 E. R. Kalmbach, F.A.O. Agric. Studies No. 2, Rome, 1962, 149. 1°7 R. H. Thompson and E. E. Turtle, Chem. and Znd., 1953, 365. lo8S. W. Porritt, D. V. Fisher, and E. D. Edge, Proc. Amer. SOC.Hort.Sci., 1952, 60,265. loB‘A Critical Appraisal of Rodenticides’, S. K. Majumder, M. K. Krishnakumari, and K. Muktabai, Indian Rodent Symposium, Calcutta, 1966. Chemicals in Rodent Control Methyl bromide has also been widely used in burrow fumigationl10 and one technique employs ampoules containing the volatile liquid which are carefully broken deep in the burrow system. A more recent approach has been the use of fumigant emulsions.1og Injection into the burrow system of emulsions based on ethylene dibromide or chloropicrin, with water acting as the vehicle, has given good results. 6 Baits and Additives However toxic a chemical poison might be, it will not be lethal unless a rodent of its own volition consumes a lethal dose, which can only occur if the animal visits the spot where the poisoned bait is placed.This demands a high ‘rodent appeal’ from a particular bait, great enough to compete successfully with any other attractive food available to the animal. The bait chosen depends upon a number of factors, e.g. the pest species, the environment in which baiting is to be attempted, the bait’s keeping qualities, and convenience in handling. Baits that have been ernployedlll cover the com- plete range of foodstuffs available but in the U.K. cereal baits have found the greatest use, particularly baits based on oatmea1.112 Unfortunately, although the testing of unpoisoned baits on wild rodents can indicate a preferred bait, it is often not the bait of choice when the poison is added.l13 In a poisoned bait, apart from the toxic ingredient and the bait itself, other additives are sometimes included in the formulation to improve performance.The changes in palatability resulting from the inclusion of certain additives may result in their eventual exclusion even though other beneficial properties might otherwise have been imparted. A. Attractants.-Attractants are substances which lure the animal to the poisoned bait. Strictly, attractants have only this property of enticement and do not necessarily increase the uptake of the bait by the animal. Many of these materials, however, have other properties, such as taste enhancement or masking actions and so a certain degree of ambiguity in terminology has arisen. Fresh raw linseed is an example of a simple attractant which attracts a rat but does not result in an increase in bait consumption.Various flavourings, essences, and oils are claimed to have attractant properties, e.g. arachis although some may actually act as repellants,lls e.g. aniseed Certain odourless oils are taste accentuators; for instance it is clairned1l7 that the scent of a wheat bait containing an anticoagulant poison may be improved with mineral oils. u0P. J. Deoras, Current Sci., 1960, 29, 475; ibid. 1962, 32, 163. ll1 E. M. Mills. Pests 1942, 10, 6. 11* P. B. Cornwell and J. 0. Bull, Pest Control, 1967, 35, 15. 113 H. R. Shuyler, ‘The Development of Baits for Rattus norvegicus’, Ph.D. Thesis, Purdue University, 1954. 114 S. A. Barnett and M.M. Spencer, J. Hyg. (Cambridge), 1953, 51, 16. 116 D. C. Drummond, ‘Repellants and Attractants and their role in the control of Rodents’, International Symposium on Bionomics and Control of Rodents, Kanpur, 1968. S. A. Barnett and M. M. Spencer, Brit. J. Anim. Behav., 1953. 1. 32. ‘I7 J. Sims, Pest Control, 1964, 32, 90. Gutteridge Additives that confer their own flavour to a bait may be ‘attractants’ or second- ary foodslll such as sugar, etc. Maltose at a 2-30 % concentration is consideredlla to improve palatability of various bait compositions. Dexide, a carbohydrate with flavour material, has been reportedllQ to increase consumption of warfarin- containing baits. B. Potentiating Agents.-To enable anticoagulants to be toxic to warfarin- resistant rodents, various potentiating agents have been sought. Since Vitamin K competes with warfarin for the same enzyme site, introduction of a Vitamin K antagonist should permit warfarin to be more lethal.Various compounds have been incorporated in baits to fulfil this role; salicylic acid, 2-methoxy- 1,6naphthoquinone, etc.lZ0Antibiotics, e.g. 5-hydroxytetracycline, that destroy Vitamin-K-producing bacteria, have also been includedlZ0 as well as various sulphonamides, e.g. sulphaquinoxaline.llg Anti-Vitamin C compounds, e.g. D-gluco-ascorbic acid, that increase the permeability of the capillaries have been utilized121 to accentuate the action of the anticoagulants. Synergistic effects have been claimed following the addition of hydrofurfuramide to anti- coagulant baiW2 and the combination of thallium salts with various cou- marins or indanedi~nes.’~~ In spite of these researches no breakthrough in the treatment of resistant rats has been made.C. Formulation Additives.-+) Preservatives. Studies have shown that p-nitro- phenoP is a satisfactory mould-inhibitor in oat baits. This chemical, like dehydroacetic acid and its sodium salt, has been re~ornmended~~J~~ as a bait additives in poison baiting of rats in sewers. Sodium sulphate was the best of a number of compounds examined by the U.S. Fish and Wildlife Service for bait-preservative action.lll A bait containing an insecticide could confer distinct advantages on a formulation to be used in tropical climates.D.D.T. and other insecticides have been examined in baits that tend to be infested by insect pests during storage.lZ6 Two rodenticides that have insecticidal properties are the anticoagulant pivalQ3 and sodium fluoroacetate.lZ7 (ii) Binders. A poisoned bait should remain homogenous, and as an aid to main- taining uniform distribution it is the practice to add a ‘binder’ or ‘sticker’ to hold the components together, e.g. water, syrup, or mineral and vegetable oils.111*128To protect baits physically from deterioration, the preparation of baits set in wax has proved rewarding.88 The high melting point of the wax n8B.P. 1 180 005/1970. 11* R. M.Schisla, J. D. Hinchen, and W. C. Hammann, Nature, 1970, 228, 1229. la0S. A. Span, 301 149/1964, (Chem.Abs., 1965, 63,7606~). lal Belg. P. 642 725/1964 (Chern. Abs., 1965, 63,6266~). laa Belg. P. 660 094/1965 (Chem. Abs., 1965, 63,PI8 967k). la3T. Kusano, J. Fac. Agri. Tottori Univ. 1969, 5, IS. (Chern. Abs., 1971, 74, 22 136d). la4 R. E. Doty and C. A. Wismer, The Hawaiian Planters Record, 1949, 2, 65. la6T. Larthe, The Sanitarian, 1957, 65,276. la6R. W. Smith, Research Dept., Coconut Ind. Board (Jamaica), 1970, 68. la’ W. A. L. David, Nature, 1950, 165,493. la*B. F. Bjornsen, H. D. Pratt, and K. S. Littig, ‘Controlof Domestic Rats and Mice’, U.S.D.H.E.W. No. 563, 1969. 399 6 Chemicals in Rodent Control allows these baits to be used in tropical climates and their high resistance to sun and rain ensures a longer period of usefulness.(iii) Safety Additives. To guard against accidental consumption of the poisoned bait by non-target species, it is often the practice to incorporate an emetic agent since rodents are unable to vomit. Tartar emeticlo2 is generally used, but as responses of humans are variable and acceptability of these baits by rodents has been adversely affected in some cases, e.g. zinc pho~phide,~'9~~ these methods are not totally satisfactory. In many countries a colouring matter is required by law, to draw attention to a bait that contains a poison. Dyes such as prussian b1ue,l1l methylene and others12B appear to exhibit no adverse effects on baits, although this is not invariably the case.130 7 Chemosterilants An alternative approach to a solution of the rodent pest problem is through biogenetic control.The size of an infestation may be reduced to the point of virtual extinction when infertile animals are present in that community. This is possible since these animals are still able to assert their claim to territorial rights, food, and social order position, although they cannot contribute to the birth rate. Infertility may be introduced in a number of ways,14 but the only practical way of implementing biogenetic control is through the use of chemosterilants.lSTo deploy chemosterilants effectively, information concern- ing the breeding cycle and reproductive behaviour of the pest species should be known, and, as in other control measures, ecological aspects must also be con- sidered.Introduction of chemosterilants alone without any preliminary control measures, would probably be unsatisfactory on account of their slowness of action, so a combination of a chemosterilant with a selective rodenticide would appear to be a more satisfactory approach. In the female of the species, a number of steroids have been examined. The oestrogen mestranol(14a), once considered to be of promise, was not satisfactory in with R. norvegicus because of the attendant problems of bait shyness. Other derivatives (14b)132u and quinestrol (14~)'~~~~~~ have been claimed to be more effective. lZ9 W. W. Dykstra, Pest Control, 1950, 18, 9. l30 Y. Larthe, J. Mammal., 1958, 39, 450. 141 R. E. Marsh and W. E. Howard,J. Wildlife Management, 1969, 33, 133.l32 (a) U.S.P. 3 496 272/1970; (b) U.S.P. 3 655 88911972. Gutteridge Some non-steroidal compounds able to terminate pregnancy are derivatives of clomiphene, e.g. MER-25 (15)133 and di~heny1indene.l~~" Et2N.CHzCH20 I In practice it is more convenient to deal with the male animal, where the main work has been directed towards anti-spermatogenic agents. Alkylating that only exert specific reproductive effects include compounds containing the ethyleneimine and methanesulphonate functional groups, for which compounds (16) and (17) serve as examples. Triethylenemelarnine (16) has been examined in trials with rats,136 but has recently lost favour13 as a chemosterilant. Certain heterocyclic compo~nds~~~b exhibit anti-spermatogenic effects and a nitrofuran derivative, furadantin (18), when combined with colchicine, has been successfully used in field studies against B.bengalensis.l3' CH2CH20S02MeCN 3 1CH2CH20S02Me (17) 133 S. J. Segal and W. 0. Nelson, Proc. SOC.Exp. Biol. Med., 1958,98,431. 13* (a) H. Jackson, 'Antifertility Compounds in the Male and Female', C. C. Thomas, Illinois, U.S.A., 1966, p. 176; (b) ibid., p. 100. H. Jackson and A. W. Craig, Ann. New York Acad. Sci., 1969, 160,215. 136 D. E. Davis, Trans. North Amer. Wildlge Conference, 1961, 26, 160. 13' A. S. Srivastava, Labdev J. Sci. Tech., 1966, 4, 178. Chemicals in Rodent Control Another recent advance has been the discovery13* that chlorohydrins, e.g. (19), induce sterility in the male rat.The advantages of relatively fast effects with non-toxicity to other forms of wildlife have been claimed although the precise mode of action has not yet been ascertained. 8 Repellants An alternative form of rodent control is one based on repellency effects, which, although generally less satisfactory than other methods, is particularly useful where rodent damage is the central problem. The main draw-back in the use of repellants lies in the fact that rodents are not destroyed and at best are only diverted elsewhere. Repellency effects created by physical stimuli have been described,l16 e.g. U.V. and high-intensity but it is chemical stimuli that have received the most attention. It is well known that rodents are particularly sensitive to odours and tastes and it has been ~ho~n~~s~~~-~~~ that a number of substances found to possess repellent properties exhibit structure-activity relationships, i.e.repellency may be correlated with specified functional groups attached to certain cyclic and acyclic systems. For the purposes of simplification, three main problem areas may be dis- tinguished, i.e. (A) agriculture, forestry, and open areas, (B) packaged materials and stored products, and (C) wiring and cables. These sections are briefly des- cribed below, together with a few examples of repellants found useful in these situations. A. Agriculture.-The destructive activities of rodents, namely gnawing, burrow- ing, and the search for food, cause much damage12 to agricultural crops, seed- lings, and trees.Taste repellants are particularly useful where a part of a plant or seedling is actually consumed. The properties that need to be associated with these repellants are : effectiveness throughout the whole season, no difficulties in application, no damage to plants or trees, and further, no toxicity to non- pest species. S S I1Me2N-C -S -S-CII -NMe2 The historical development and usefulness of thiram, bis(dimethy1thiocarba- myl) disulphide (20), as an animal repellant has been reviewed.144 Experiments 138 R. J. Ericsson and V. F. Baker, J. Reprod. Fert., 1970, 21, 267. 138 E. J. Wilson, Parasitica, 1960, 16, 119. 140 C. M. Sprock, W. E. Howard, and F. C. Jacob, J. Wildrife Management, 1967,31, 738. 141 E.Bellack and J. B. Dewitt, J. Agric. Food Chem., 1954, 2, 1176. 142 J. E. Fearn and J. B. Dewitt, J. Agric. Food Chem., 1965, 13, 116. 14* J. E. Fearn and J. B. Dewitt, J. Pharm. Sci., 1964, 53, 1269. 144 M. A. Radwan, Forest Sciences, 1969, 15, 439. 402 Gutteridge have shown that this repellant can confer protection from rodent attacks to and to trees e.g. Douglas Fir seedlings may be protected from rabbits,146 hares, and mice.147 The monosulphide de; ivative also shows re- pellent action to rodents.14* OMPA, octamethylpyrophosphoramide(21)148, is a toxic systemic animal repel- lant which can be readily incorporated into plant tissue. The onset of phyto-toxicity to Douglas Fir seedlings is well above the concentration required for repellency.149 A large number of amine complexes with symmetrical trinitrobenzene exhibited high repellency indices in laboratory tests.lso The aniline complex (TNB-A) was one of the most effective and has been used to protect seedlings and Thecyclohexylamine complex of zincdimethyldithiocarbamate,Zn(S,CNMe,),, has been shown to reduce rodent damage to trees, seedlings, and plant~.~~?~*~ An adhesive, polyethylene polysulphide, can be incorporated to prevent losses due to rain.ll Rodents that cause damage by burrowing, e.g.moles, mice, etc., avoid soil contaminated with certain chemicals such as benzene hexachloride.1° Introduc- tion of suitable substances into the soil of ditch-banks as protection from pocket gophers has been found to have possibilities1° whereas calcium carbide is recom- mended151 for repelIing muskrats from embankments. Herbicides can also in- fluence certain rodent populations through the removal of rodent cover.l0 Field mice were to cease injuring apple trees after treatment of the adjacent plant growth with monuron (22a)153 or diuron (22b).B. Packaging.-Damage to packaging materials, boxes, sacks, and stored articles and products are frequently caused by rodents in their quest for cover and food. The established eradication and proofing techniques constitute the best approach, although alternative secondary measures, such as incorporation F. M. Johnson, J. Stubbs, and R. A. Klawitter, J. WildIife Management, 1964, 28, 15. 146 A. C. Hildreth and G.B. Brown, U.S. Dept. of Agric., Tech. Bull. No. 1134, 1955. 14’ J. F. Besser and J. F. Welch, Trans. North Amer. Wildlije Conference, 1959, 24, 166. 148 A. D. F. Toy and E. N. Walsh, Inorg. Synth., 1963, 7, 73. J. H. Rediske and W. H. Lawrence, Forest Science, 1964, 10, 93. 150 J. B. Dewitt, E. Bellack, and J. F. Welch, J. Amer. Pharm. ASSOC., 1953, 42, 695. lS1 ‘Controlling Muskrats’, United States Dept. of Interior, Fish and Wildlife Service, Leaflet No. 306, 1966. lba L.Holm, F. A. Gilbert, and E. Haltrick, Weeds, 1959, 7, 405. lS8 G. L. McCall, Agric. Chem., 1952, 7, 40. 403 Chemicals in Rodent Control fiR(a) R = 4-chloro (b) R= 3,4-dichloro HN. of repellent substances into the packaging material, may deter or retard rodent attacks.A quantitative method has been devisedlS4 for evaluating chemicals as rodent repellants on packaging materials. Apart from repellency, there are rigorous requirements for potential repellent substances.10 These include stability, no objectionable taste or odour, and the absence of toxic properties. The absence of any adverse effects on packaging materials or enclosed articles is especially critical. Some recent advances have been made in this area, particularly where repellant-treated fabrics enclosed between two layers of polyethylene protect both food and handler.lSs Me Actidione, (cycloheximide), 4-[2-(3,5-dirnethyl-2-oxocyclohexyl)-2-hydroxy-ethyl]glutarimide (23), is a very effective rat-repellant.10~166 Under simulated field conditions all rodent attacks upon treated paper board and cartons were repelled.Unfortunately, this repellant is too toxic to be permitted to come into contact with man’s food or with his skin through package handling, which together with its high cost, probably accounts for its scant commercial exploita- tion. Analogues of actidione that bear imide groups141*143 have been synthesized with the object of eliminating toxic properties while maintaining repellent activity. Although glutarimide was found to be inactive, several phthalimides, in particu- lar N-n-b~tylphthalirnide~~~were found effective in deterring rodent attacks. J. R. Tigner and J. F. Besser, J. Agric. Food Chem., 1962, 10, 484. lSK J. R. Tigner, J. Wildlife Management, 1966, 30, 180.lS6R. Traub, J. B. Dewitt, J. F. Welch, and D. Newman, J. Amer. Pharm. Assoc., 1950,39, 552. Gutteridge C Malathion, S-(1,2-dicarbethoxyethyl)-00-dirnethyl dithiophosphate (24), exhibits a high degree of rodent-repellent action. Laboratory tests in India that food sacks stored in a warehouse could be made resistant to attacks by R. rattus for considerable periods using a mixture of malathion and eugenol. Malathion presents a useful bonus since it is also an efficient insecti- cide, e.g. in the control of weevils on stored grain, while being non-toxic to poultry.l5* Useful repellent activity against M. muscuhs with triphenyltin chloride or tributyltin chloride has been described.15g Muslin treated with tributyltin acetate and protected by polyethylene films in the form of bags and tarpaulins gave short-term protection.155 Envelopes made from polyethylene to which tributyltin chloride had been added prior to extrusion were foundlso to retard attacks from rats and mice.Use of tricyclohexyltin hydroxide has been claimedlel to repel R. norvegicus from corrugated paper and expanded polystyrene boards, etc. The corresponding chloride and bis(tricyclohexy1tin) oxide are also claimedlsl to possess rodent repellency. The odours associated with predators are supposedly able to repel their prey. n-Butyl mercaptan (skunk odour) has been investigatedls2 for its ability to repel rats. In one study, honey containing the repellant protected commercial feed- stuffs stored on a farm.Pentachlorobenzyl mercaptan and mercaptides have been ~laimed'~~~~~* to be satisfactory rodent repellants. C. Cables and Wiring.-Important cable and electrical-wiring systems are vulnerable to damage by rodents. Cables situated above the ground can be periodically inspected for damage but it is impracticable frequently to check underground cables which need to remain immune to rodent attacks. Repellent substances may either be incorporated into the cable, etc. or may be applied as a coating, or alternatively they may be dispersed in the soil surrounding the underground cable. Rodent damage to rope, twine, etc. has also demanded efficient counter-measures, in which repellants can play a part. 16'S. K. Majumder, M.K. Krishnakumari, and J. K. Krishna-Rao. Current Sci., 1964, 33, 212. lS8 M. W. McDonald, J. F. Dillon, and D. Stewart, Austral. Vet. J., 1964, 40,358. R. J. Zedler and C. B. Beiter, Soup, 1962, 38, 75. E. E. Kimmel, U.S.P.3 132 992 (Chem. Abs., 1964, 61, 7642~). E. E. Kenaga, U.S.P.3 389 048 (Chem. Abs., 1968, 69, 43 042g). 16* L. A. Ford and D. F. Clausen, Chem. Eng. News, 1941, 19, 783. H. J. Miller, U.S.P. 3 139 379, (Chem. Abs., 1964, 61, 6314e). la*F. E. Lawlor and I. C. Popoff, U.S.P. 3 217 021 (Chem. Abs., 1966, 65, 8825e). Chemiculs in Rodent Control II Me2N-C-S-S-CMe3 R55, NN-dimethyl-S-t-butyl-sulphenyl-dithiocarbamate(25), and similar types of compound are effective rodent repellant~.~~~J~~ Pocket gopher damage to buried telephone cables has been restricted167 by treating the surrounding soil with R55.When formulated in a cable-coating, this chemical produces a convenient barrier to rodent damage.lsa A number of repellant formulations based on tributyltin salts are of interest for protection of cables and wiring. ‘Bio Met 12’,169when formulated in a plastic coating, is an effective repellant which has no adverse effects on other cable properties.Coatings based on tributyltin chloride in chlorinated rubber have been applied to telephone wires to increase their rodent Long-chain aliphatic amines and salts have been claimed1 71 to prevent damage by rats to binder twine. Dodecylamine acetate has been as an effective means of protecting cordage and insulated wires against rodent attacks.Cord or twine treated with quinaldine and naphthenic acid was to show rodent repellence. 9 Resistance to Rodenticides (Warfarin Resistance) There are two kinds of resistance that may develop from the use of r~denticides.~~ The first type is an acquired tolerance to a poison that builds up in the rodent pest during treatment and is not passed from parent to offspring. This acquired resistance may arise from the use of acute poisons, and such instances have been referred to under the individual acute poisons. A more recently encountered type of resistance may appear after frequent use of anticoagulant poisons, e.g. warfarin. It is this latter resistance which can pass from one generation to the next that poses the more serious problem.A. Introduction.-The physiological mechanism of the action of anticoagulants on the clotting capacity of blood and the role which Vitamin K plays in this process are rather involved and are still open to conjecture. It is nevertheless certain that Vitamin K and the anticoagulants act through the same mechanism le6L. D. Goodhue, U.S.P. 2 862 850 (Chem. Abs., 1959,53, P6520c). lS6W. R. Eddy, U.S.P. 3 503 800 (Chem. Abs., 1970, 72, 122 551n). le7T. H. Mailen and R. E. Stansbury, 15th Annual Wire and Cable Symposium, New Jersey, 1966. J. A. Shotton, U.S.P. 3 434 995, (Chem. Ah., 1969, 70, 107 255j). Anon. Chem. Eng. News, 1967, 45, 24. 170 ‘Rodent Resistant Cable Materials’, U.S. Army Applied Entomology Group Tech.Report No.3, 1968. 171 P. Jucaitis, U.S.P. 2 868 674 (Chem. Abs., 1959, 53, 13 500a). 1’* J. P. Barrett and E. W. Segebrecht, U.S.P. 2 822 296 (Chem. Abs., 1959, 53, 1 6263). 173 P. Jucaitis, U.S.P. 2 864 727 (Chem. Abs., 1959, 53, 6520d). Gutteridge and therefore are mutually antag~nistic.~ql~* Vitamin K is vital to the complex blood-clotting scheme of an animal, so that any antagonism shown towards this vitamin could have lethal results. The administration of warfarin therefore interferes with the normal clotting of blood and may further hasten the onset of internal bleeding by causing a breakdown of blood ~esse1s.l~~ The discovery that, on occasions, warfarin and other anticoagulants lose their toxic action to wild rodents has been the subject of much concern.B. Discovery.-The first case of resistance to warfarin in wild animals was disc~veredl~~in 1958 near Glasgow where populations of R. norvegicus were not effectively controlled by anticoagulants. Two years later, an area roughly centred on Welshpool on the English-Welsh border, was also to con- tain R. norvegicus infestations similarly resistant. Since that time small areas in Kent, Somerset, Gloucestershire, Berkshire, Nottinghamshire and Carmarthen- shire have been to harbour resistant rats as well as places in Den- mark,178 Hungary,179 and the Nefherlands.lso Other rat species, Holochilus sciuveus (British Guiana)26 and Bandicota bengalensis (Ceylon)177 have been re- ported to contain anticoagulant-resistant members.In some ways a more serious threat has been recognized in the U.K. by the discovery that many populations of ill. rnusculus have the inborn ability to tolerate anticoagulants.181~182 C.Resistance Mechanism.-A vigorous programme of research was mounted in several laboratorie~~~~~~~~ when resistance had been confirmed. The results of studies on susceptible and normal rats indicated that the genetic pattern in each resistant population could well be different. It was elucidated that although a single gene was responsible in both the Welsh and Scottish areas, it was pos- sibly a different one in each case. The single-gene basis for the resistance accounts for the rapid spread of inherited which was far more rapid than would be expected if several genes were involved. The pattern of resistance in other groups is more complicated, e.g.in Denmark, tests with resistant wild rats showed that no acceptable theory could explain their genetic The position is again complicated with resistant M. muscr~Zus,~~~for resistance 174 I. H. Stockley, Pharm. J., 1970, 205, 167. 175 D. Drummond, New Scientist, 1966, 30, 771. 176 C. M. Boyle, Nature, 1960, 188, 517. 177 J. H. Greaves, Agriculture, 1970, 77, 107. 17* M. Lund, Nature, 1964, 203, 778. W. B. Jackson, Pest Control, 1969, 37, 51. 180 A. J. Ophof and D. W. Langeveld, ‘Rattenbiologie und Rattenbekiimpfung’, ed. K. Becker, G. F. Verlag, Stuttgart, 1969, p. 39. E. W. Bentley, Ref, 180, p. 19. lBaP. B. Cornwell, Municipal Engineering, 1966, 143, 2371.lS3 J. G. Pool, R. A. O’Reilly, L. J. Schneider, and M. Alexander, Amer. J. Physiol., 1968, 215, 627. lE4M. Lund, Ref. 180, p. 27. F. P. Rowe and R. Redfern, J. Hyg. (Cambridge), 1965, 63, 417. 407 Chemicals in Rodent Control may be either under polygenic control or controlled by a single gene influenced by modifiers. D. Treatment.-Initial observations revealed that, as expected, areas containing resistant rats had soon begun to spread. Therefore, the first practical measures introduced were based on containment, to allow eradication procedures to be more effective. In 1966, in the Welsh area an operation was introduced by the Ministry of Agriculture, Fisheries, and Food in which a cordon, approximately three miles wide, was set up around the known perimeter of the resistance area.175All farms in this perimeter zone were inspected by Ministry operators and systematically treated with acute rodenticides to create a virtual ‘rat-free’ zone.Eradication procedures soon indicated that all the better-known anticoagulants were of little value since resistance was shown to both coumarin and indanedione compounds alike. A short-lived hope that one anticoagulant could stem the tide was dismissed when coumatetralyl-resistant animals were discovered.lel No toxic effects were introduced by these anticoagulants; this was suitably demonstrated when anticoagulant-formulated bait-materials afforded useful prebaits for acute poisons.186 The return to acute poisons, together with the supplementary techniques of fumigation and trapping, proved quite adequate, if not convenient, to keep infestations down to tolerable levels.The Welsh containment operation was discontinued in 1969 as monitoring areas outside the zone indicated the existence of resistant rats.177 Conspiring against the success of this scheme were the reluctance of farmers in the area to stop using warfarin and other anticoagulants and the severe epidemic of Foot and Mouth disease which prevented the free movement of Ministry operators. E. Present Situation.-Although the Welsh cordon experiment was apparently unsuccessful, useful information had accrued during the study which showed that the situation was not as desperate as had been widely reported, for: (a) There is basically no abnormal movement of resistant rats although the area of resistance is gradually increasing.(b) Numbers of resistant rats in particular areas seem to have reached a plateau level. The discovery that resistant rats requirelS7 more Vitamin K suggested that these rats had the lowest survival potential. Thus if the use of anticoagulants ceased, the numbers of resistant rats should de- crease.177 (c) The numbers of rats existing currently in infested areas are of the same order as those that existed in these areas before the outbreak of resistance; consequently there is no increase in the spread of rat-borne diseases.lss The treatment of resistant mice, although less publicized, is still a problem, for resistant infestations are on the increase.In dwellings particularly, the use ln6F. P. Rowe and B. Rennison, personal communication. M. A. Hermodson, J. W. Suttie, and K. P. Link,Fed. Proc., 1969, 28, 386. la8Anon.,Lancet, 1970, 987. Gutteridge of acute poisons is limited because of potential hazards of toxicity to man and non-pest species. 10 Future Outlook Research is under way to discover new rodenticides with different modes of action to replace many unsatisfactory poisons commonly in use. In this connec- tion the Ministry of Agriculture, Fisheries, and Food in the U.K. have given a high priority to testing of candidate rodenticide~.~~~*l~~ A request for the CO-operation of chemical industry to make available compounds previously con- sidered of little value owing to toxicity has been made by the Ministry.Progress is also being madeloo in the further understanding of anticoagulant resistance. Since long-term approaches to rodent control might include selective chemo- sterilants, the search for suitable substances is similarly at the outset a chemical problem, Further studies of rodent behaviour would benefit control, especially with regard to repellants and attractants which could be valuable in directing the movement of rodents to baiting areas. Improved baits subjected to new formula- tion procedures, e.g. microencapsulation,g4~1g1would be an additional aid, for it has been that ‘not so much specific poisons but baits that are only attractive to the pest species’ is the requirement for poison baiting.However, in many cases, if improved standards of hygiene together with rodent proofing and removal of food and cover were introduced, the number of rodents would decrease naturally through environmental pressures. The author wishes to thank staff of the Pest Infestation Control Laboratory, Ministry of Agriculture, Fisheries, and Food, for helpful discussions. The time allowed for the preparation of this article at the Lilly Research Centre is grate- fully acknowledged. lS9 F. P. Rowe, J. H. Greaves, R. Redfern, and A. D. Martin, Ref. 15, p. 126. lBoJ. H. Greaves and P. Ayres, Nature, 1969, 224, 284. lo1 J. H. Greaves, F. P. Rowe, R. Redfern, and P. Ayres, Nature, 1968, 219, 402.

ISSN:0306-0012    

DOI:10.1039/CS9720100381

出版商:RSC    

年代:1972

数据来源: RSC

摘要:

Interactions in the Atmosphere of Droplets and Gases By M. D. Carabine DEPARTMENT OF CHEMICAL ENGINEERING AND CHEMICAL TECHNOLOGY, IMPERIAL COLLEGE, LONDON S. W.7 1 Introduction There is an important class of chemical reactions in which initially gaseous substances produce suspended particles or droplets. The first part of this article is primarily concerned with the chemical and physical mechanisms which may contribute to the formation of such aerocolloids, and to the changes in size distribution as they develop or diminish. In the latter part the chemistry and kinetics of some specific aerosol-producing reactions will be considered. Because of their important contribution to particulate air-pollution, most attention will be given to reactions involving sulphur dioxide.In localities where fossil fuels are burned, it is of course a major gaseous pollutant in the atmosphere, and its interaction with other substances can frequently result in smogs, or in droplets of harmful acid. More kinetic studies of gas-particle interactions should be encouraged, and not only because of their relevance to pollution and related problems of waste-gas cleaning. In some manufacturing processes major products are required in the form of fine particles. The ultimate median particle size may outweigh other considerations, as for instance with titanium dioxide pigment, where the radius has to be kept within a distribution close to 0.2 ,um if the light-scattering quality is to be maintained. Again, if particles in the region 0.1 to 10 ,um are to be collected by inertial or electrostatic precipitation, the efficiency will be improved by keeping the median size as high as possible.The incorporation of water into the condensed phase of aerosols will be a major consideration. In humid atmospheres water will tend to condense to form droplets on any hygroscopic solid particle which may be present. For instance, with nuclei such as crystals of sodium chloride and ammonium sulphate, which are common in most atmospheres, rtlative humidities of only 78% and 73% respectively are required for droplets of solution to form. Now droplets of pure water are inherently unstable in that they grow spontaneously at any given relative humidity. This occurs because the vapour pressure at a small droplet falls as its curvature decreases.But droplets containing a solute also exhibit an opposing effect which predominates at smaller sizes. This is the raising, according to Raoult’s law, of the vapour pressure as dilution proceeds. Thus any increment in growth is self-correcting and the droplet reaches a stable, equilibrium size. Of course when growth becomes arrested in this way, droplets can stay suspended indefinitely, and this can be of enormous practical significance. Thus 411 Interactionsin the Atmosphere of Droplets and Gases mists based on soluble air-pollutants may be stable and persistent in ill-ven- tilated atmospheres. Similar stability can be a troublesome feature of mists which are sometimes formed in sulphuric acid manufacture, and which cannot yet be consistently eliminated by design of the plant.These examples should suffice to show that there will be considerable economic importance in understanding the factors which determine size distributions in aerosols, since it may allow effective control of their production and subsequent behaviour. The kinetic processes which aerosol particles undergo can be briefly defined as follows. Nucleation is the initial establishment of a stable condensed phase and may occur either homogeneously, that is by spontaneous aggregation of the condensate, or heterogeneously-by association of the condensate with an already established nucleus of a foreign substance. Growth of particles and droplets is defined as accretion of gaseous molecules at their surface.Unless the number concentration is below about 1O1O particles m-3, growth will be accom- panied to a significant extent by coagulation, the adhesion of particles as a consequence of random or induced collisions. At this level, coagulation would deplete their concentration by about 1 % h-l. After particles of moderate density have exceeded a certain diameter, they will fall in still air with appreciable speeds (about cm s-l for 10pm diameter). Hence as an aerosol develops, removal of larger particles by sedimentation is a process which applies an effective upper limit to the ultimate size distribution in the suspension. In the review which follows of the mechanisms of these processes some recent theories are summarized, and it is intended particularly to stress those cases where chemical reaction accompanies transfer of material across the phase boundary. 2 Mechanisms Theoretical treatments of nucleation and of coagulation include fundamental difficulties and, perhaps as a consequence, have been more numerous than kinetic predictions for growth.In the latter process, the models have necessarily been rather specific, depending on variables such as the diffusion field, the number of components, and their reactivities. A. Nucleation of Particles in Supersaturated Vapours.-The formation of a condensation nucleus in a homogeneous medium depends on fluctuations in the parent phase giving rise to an aggregate or cluster of molecules, and for the cluster to be stable a certain critical size must be exceeded.lY2 In the thermo- dynamic approach to the frequency of such events a free-energy barrier is postulated, and variation of the rate of appearance of stable nuclei with the 1M. Volmer and A.Weber, 2.phys. Chem. (Leiprig), 1926,119,277.* Y.I. Frenkel, ‘Kinetic Theory of Liquids’, Oxford University Press, 1946. Carabine temperature (T) and with the supersaturation ratio (S)is predominantly expo-nential. The exponent FV*may be expressed by where m = mass of molecule, u = surface free-energy, pL = density of liquid, Pvk = Boltzmann's constant, and S = -- vapour pressure at droplet surface Pa vapour pressure at plane surface This follows immediately from consideration of the balance, as a droplet grows, between the free energy expended in the formation of the surface, and the free energy derived from the gas molecules which are condensed. This form of the exponent was also used by Becker and Dori~~g,~and more recent modifications to the theory have been reviewed by Wegener and P~lange.~ The rate of nucleation is positive for all values of the supersaturation ratio, but in practice it increases very sharply around a certain value of S.294In terms of a given experiment, an observable amount of nucleation will occur in a practicable time interval only when this value, S*,is exceeded. Various authors have reviewed the agreement of experiments with these theorie~.~-~Whereas some experiments have been intended to measure the rate directly, others have measured the dependence of S*on temperature.The latter test the rate equation in so far as it predicts that 5(TY". InS* should mu be a constant. Using an expansion cloud chamber, Powells determined S* for water vapour at a number of temperatures, and his results satisfy this relation to within about 6%. So as to avoid significant depletion of the vapour concentration by growth on the nuclei, and to preserve the isentropic nature of the expansion, experiments have usually been designed to produce low concentrations of nuclei in brief experimental times. Typical values in cloud chambers would be 10-lo2 nuclei and 10-1-10-2 s.79g30Besides cloud chamber~,~9~~m-~, devices used recently include rarefaction tubes,ll jet quenching apparatus,l29l3 and supersonic nozzle~.*~~J~With the latter, experimental times are in some cases about low6s.Experiments have nearly always been done with water, and surprisingly the R. Becker and W. Doring, Ann. Physik, 1935,24,719.P.P. Wegener and J. Y. Parlange, Naturwiss., 1970,57,525. B. J. Mason, Discuss. Faraday SOC.,1960,30,20.P.P. Wegener and A. A. Pouring, Phys. Fluids, 1964,7, 352.'L. B. Allen and J. L. Kassner, J. Colloid Interface Sci., 1969,30, 81. C. F. Powell, Proc. Roy. SOC.,1928,A119,553. J. L. Kassner and R. J. Schmitt, J. Chem.Phys., 1966,44,4166. lo B. G.Schuster and W. B. Good, J. Chem. Phys., 1966,44,3132. l1 P. P. Wegener and G. Lundquist, J.Appl. Physics, 1951,22,233. l8 A.G. Sutugin and N. A. Fuchs, J. Colloid Interface Sci., 1968,27,216. l3 W.Higuchi and C. T. O'Konski, J. ColloidSci., 1960,15,14. l4 P.P.Wegener and L. M. Mack, Adv. in Appl. Mech., 1958, V, 301. 413 Interactions in the Atmosphere of Droplets and Gases original work of Volmer and on vapours of several aliphatic alcohols and esters has seldom been repeated.l6J7 Alkyl chloride^^^^'^ and recently some n-alkanesz0 and even metal vapours have been experimentally investigated. Con- tinued attempts are made to compensate for the depletion of available vapour which occurs in the course of rarefaction experiments,21 and to overcome the fundamental problem that neither radius- nor surface-free-energy are well- defined quantities in the clusters of, say, tens of molecules which constitute most critical homogeneous n~clei.~l~~ The latter deficiency is more acute the higher the supersaturation ratio since the number in the critical nucleus is less.2 Solid particles of chemical salts are frequently found in the atmosphere and remain so as long as the relative humidity is low enough. They may originate not by direct transition from gas to solid phase, but either by subdivision of grosser matter or by evaporation of droplets of solution. Data on vapour con- densation to form crystalline nuclei are few; for the interaction of ammonia and hydrogen chloride to form solid ammonium chloride classical nucleation theory appears to apply,z3 and Turkevichz4 has shown from electron micrographs of smokes of metals that the size-distribution curve can be used to deduce the distribution of nuclei formed from the gaseous state.Many forms of heterogeneous nuclei are known, e.g. ions, foreign particles, or even foreign gas-phase molecules, such as the important pollutant molecules SO2, SO3, H2S04,etc.z6 Dunningz6 and MasonK reviewed the agreement of experiments with theory for heterogeneous nucleation. Experiments have been made on hundreds of nucleating substances to examine their propensity for nucleating water droplets and ice particles. The size of the nuclei is only influential in the range up to about 0.1 pm,27928and below pm efficiency is very low. The efficiency of porous particles as nuclei has been shown to be promoted by residual water previously frozen into their capillary pore^,^^^^^ a modification which could occur while particles are at high altitudes. l5 M.Volmer and H. Flood, Z. phys. Chem. (Leipzig), 1934, A170,273. l6 W.G.Courtney,J. Chem. Phys., 1962,36,2009,2018. l7 J. L.Katz and B. J. Ostermeier, J. Chem. Phys., 1967,47,478. la L.Scharrer, Ann. Physik., 1939, 35, 619. lBD. B.Dawson, E. J. Wilson, P. G. Hill, and K. C. Russel, J. Chem. Phys., 1969,51,5389. 2o J. L. Katz, J. Chem. Phys., 1970, 52,4733. 21 L. H. Lund and J. L. Rivers, J. Chem. Phys., 1966,45,4612. 28 J. Lothe and G. M. Pound, J. Chem. Phys., 1962,36,2080. 23 S. Twomey, J. Chem. Phys., 1959,31, 1684. 24 J. Turkevichin, ‘Proceedings of the 3rd Symposium on Fundamental Phenomena in the Materials Sciences’, ed.L. J. Bonk, P. L. de Bruyn, and J. J. Duga, Plenum Press, New York, 1965,p. 195. 25 Y. I. Kogan, L. E. Donetskaya, L. N. Pavlov, and E. N. Rubin, Doklady Akad. Nauk S.S.S.R.,1968,179,1145. 28 W.J. Dunning, Discuss. Faraday SOC.,1960,30,9. 27 N. H. Fletcher, J. Chem. Phys., 1958, 29, 572. a* I. Sano, Y. Fujitani and Y. Maena, Mem. Kobe Marine Obs. Kobe, Japan, 1960,14, 107. 2s K. Higuchi, N. Fukuta, and J. Norihiko, J. Atmos. Sci., 1966,23,187. so N.Fukuta, J. Atmos. Sci., 1966,23,741. Carabine B. Growth and Evaporation of Droplets.-Without Chemical Reaction. Masona1 gives a useful summary of the diffusion equations for mass transfer between a droplet and a surrounding vapour which is stationary relative to the droplet, and in which the concentration of the vapour varies smoothly right up to the interface: (i) In evaporation, the mass, m, is lost at a rate proportional to the radius dm-=-47Tr D(pv,s -pv)dt where r is the drop radius, D is the diffusion coefficient of the vapour, and pv,~ and pV are its densities at the surface and at a large distance.(ii) The rate of decrease of radius is inversely proportional to the radius (iii) The surface area, A, falls off linearly with time (and thus the radius decreases parabolically with time) dA 8nD -=-4pv,s -pv) (3)dt PL These three statements are equivalent and consist in Fick‘s diffusion equation, integrated under the assumption of a distribution of the vapour density which is independent of time.The error due to this approximation is of the order of only a few tenths per cent for water at room temperat~re.~~ With appropriate choices of the value of p. further physical models can be considered: (i) For evaporation into a vacuum (ii) For the growth of a droplet on a nucleus of soluble hygroscopic material where ais the evaporation coefficient of the liquid. pv will be equivalent to the saturated vapour pressure, pm, above a plane surface of the solvent. The Kelvin equationa3 in combination with Raoult’s law leads to the expression wherep’, is the vapour pressure at the surface of the resulting droplet of solution. 81 B. J. Mason, ‘Physics of Clouds’, Oxford University Press, 1971, p.122. 3* N. A. Fuchs, ‘Evaporation and Droplet Growth in Gaseous Media’, Pergamon, Oxford, 1959, p. 63. 33 W. Thomson, Proc. Roy. SOC.Edinburgh, 1870,7,63. 415 Interactions in the Atmosphere of Dropletsand Gases The other properties of the solution are 0’the surface free energy, M the mole- cular weight of the solvent, P’~the density, i the van’t Hoff factor, and nl/nz the mole ratio. Equation (5) can be written as follows, for dilute aqueous solutions with mass m of uni-univalent solute and mass S of solvent Besides diffusion, the other main factor governing the rate of growth is the rate at which latent heat can be dissipated. This dissipation is limited by conduction in the gas phase and is thus expressed by where Ts and Tare the temperatures at the droplet surface and in the surroundings, and K and L are respectively the thermal conductivity of the gas and its latent heat.By combination of equations (l), (6), and (7) with the Clausius-Clapeyron equation for dp/dT, Mason gives the following useful rate expression dr r.-dt As the droplet grows, the curvature and strength of solution become no longer sufficient to affect the value of plS appreciably, and the equation (8) reduces to the reciprocal relation of radius with its rate of increase [equation (2)]. From equation (8) the time can be calculated for growth to specified radii for droplets containing given masses of nucleating material. A typical result, also quoted by Mason, is that under slight supersaturation water droplets will grow on a nucleus of NaCl of mass 10-13 g, to 5 ,urn radius in about five minutes, but will need a further 25 minutes to double this radius.To turn from the growth to considerations of equilibrium between droplet and vapour, it was stated in the introduction that below a certain size droplets containing a solute can differ from those of pure liquid in possessing inherent stability with respect to growth. The transition to spontaneous growth comes when the size is such that the curvature term in (5) or (6),In P’~K l/r, dominates the Raoult’s Law term, which for dilute solutions is of the form In plSK l/r3. The expression (6) can be used to calculate this transitional size, and predicts for instance that with a supersaturation of water of 0.05% and a nucleus of lo-’* g of NaCI, growth is spontaneous only after the radius has exceeded 2 pm.As examples of the size range in which solution droplets are stable, Vohra and 416 Carabine Nair34 quote that aqueous sulphuric acid droplets at 90 % relative humidity will be stable at a radius of 25.4 nm. when the mole fraction is 0.09, whereas at mole fraction 0.33 the equilibrium radius is 2.1 nm. It must be repeated that the expressions quoted above for the growth and evaporation of droplets have all been based on assumptions of control by molecular diffusion in a stagnant gas phase containing no discontinuity of concentrat ion near the surface. This continuum model becomes invalid when droplets are small enough to give values greater than about for the Knudsen number, Kn, which is the ratio of molecular mean-free-path to droplet radius. At atmospheric pressures, this means any droplet of radius below about 7 pm.The consideration of deviations for droplets smaller than this will be limited here to some practical cases. The simplest correction is valid to some limit near Kn= 0.25, i.e. for particles of radius down to about 0.3 pm. In the theory it is assumed that the vapour concentration gradient is continuous only at distances from the surface in excess of some 1-5 gas mean-free-paths. In other words a sharp discontinuity exists at that distance. The consequent ratio of drnldt [equation(l)] in a continuum to that in this ‘slip flow’ regime is The second term depends critically on the evaporation coefficient a, and in fact predominates when the latter is significantly less than unity. Some empirical results for dibutyl phthalate, quoted by Fuc~s,~~ indicate that the correction to equation (1) is nearly linear with Kn,and even at K,, = 0.75 it amounts to only about a factor of two.A different theoretical model with minimal intermolecular collisions is already becoming necessary when Kn has risen to such high values. --(=)correction amounts to Considering now water droplets, the 1 + D brn a factor of two even at radii of about 10 pm if the conventional value of 0.04 is taken for a. Such a low value of a is suspect for pure water but values as low as have been observed for water surfaces where evaporation is in- hibited by contamination.Hence for droplets which contain surfactant con- tamination the discontinuity correction would be vital at a much larger radius than for droplets of pure water. It is not the purpose here to review experimental tests of the above rate equations for single substances, but materials and sizes of droplets tested range from water of diameter about 1 mm (ref. 32) to lead and bismuth at less than 30 nm (ref. 35). Chemically Reacting Aerosols. When chemical reaction at a particle is involved, the rate of its growth or shrinkage may again be limited by diffusion in the gas 34 K. G. Vohra and P. V. N. Nair, J. AerosolSci., 1970,1, 127. 35 M. Blackman, N. D. Lisgarten,and L. M. Skinner, Nature, 1968, 217, 1245.417 Interactions in the Atmosphere of Droplets and Gases phase, or by diffusion inside the droplet. Alternatively, and particularly in the initial stage, some reaction in the interface may be the rate-limiting step. Following the latter model, Cadle and RobbinP give the following upper limit to the initial rate for the general case of gas molecules A, interacting with particles B: where k is a rate constant, and [Ale and [B], are the original concentrations of A and of particles with radius r,. If a steady state of reaction is achieved, which is frequently the case under diffusion control, the time-independent equations for the diffusion are, for the interior of the spherical droplet with a reaction rate q, diffusion coefficient Di,and reactant concentration Ci.Also, for outside the droplet dace + 2dCe---=odr2 r dr and at the interface where r = r, Di-dCi d Ce = De-dr dr Now several predictions of absorption rate can be distinguished: (i) If diffusion in the gas phase is rate-controlling, the solution of the equations for the growth of a stationary droplet is simply equation (1) with reversed sign and p representing the density of the gas A. (ii) When the controlling factors are internal diffusion and the reaction rate, different solutions arise according to the kinetic order of the reaction. For a zero-order reaction with a rate constant k,, the solution for the case where Cistill has a finite value at the centre of the droplet is drn 47~ ----koro8dt 3 If, however, CI falls to zero at some point in the interior where the radius is rl, then drn 47r--= -ko (roa-ria)dt 3 86 R D.Cadle and R. C. Robbins, Discuss. Faraday Sac., 1960, 30, 155. 418 Carabine Consequently if C,is the value at the interface, the concentration falls according to the profile kor13 korI3Ci = Co--k0 (yo2 -ra) --f-601 3Dr, 3Dr A convenient kinetic parameter is the rate of absorption per unit area of drop surface, R= -._ drn 4m02 dt Substitution of this into equation (15) eliminates rl and gives a relationship between R and the other measurable variables If the distance of penetration is small, however, i.e. the reaction is all occurring in a thin outer shell of the particle, dm or -= 4nro2~2CoDik,,dt For a reaction which is first order with respect to A, and has a rate constant kl, Also, when the dimensionless quantity dklro2/Diis large, In the review of experiments which follows the next section, the applications of these solutions will be discussed where they have proved feasible. C.Coagulation of Particles by Brownian Motion.-The most important experi- mental facts of coagulation are simply expressed as follows: (i) A second-order decay is observedS7 in n, the total number of particles in unit volume, dn----KO.n2 dt (ii) The value of KOincreases if the system becomes more polydisperse and ST R. Whytlaw-Gray and H. S. Patterson, ‘Smoke’,Arnold, London, 1932, p. 8. Interactions in the Atmosphere of Droplets and Gases decreases as the particle size increases.Both the effects contribute as coagulation proceeds and the net result is that equation (21) is a good approximation if KO is assumed to be constant throughout. (iii) It is hard to deduce the original population of a decaying aerosol from counts made a significant time after coagulation has commenced. This is because of the reciprocal relationship between n and t, and the magnitudes of KO, generally about 10-15 m3 s-’ for aerosols. The rate of change of concentration as a result of collisions of spherical particles of radii rl and r2 is theoretically predicted38 to be This prediction includes Einstein’s expression for diffusivity in the Stokes regime, together with Cunningham’s correction for the similarity, in aerosols, of the particle size r and the gas mean free path 1. The other variables are: s(rl + r2) = the radius of spheres of influence A = Cunninghani constant (ca.unity) r) = viscosity of the gas. By making the simplification that rl = r2,a comparison between polydisperse and monodisperse coagulation-constants is possible. The two constants are distinguished by containing two different factors which are respectively X = Dlrl (rl + r2)(l/rl+ 1/r2)and Y = 4Dlr1. Hence, since X = D1r1[4+ (drx -,/qr,)2], andtherefore X> Y.Gille~pie~~ haveshown that the difference is never more than 2% for the skewed particle-size distributions en- countered, for instance in atmospheric aerosols. In addition, Gillespie has that the number of collisions induced by shear will be decreased by polydispersity.Since the largest particles disappear from an aerosol suspension by sedimen- tation, there is a tendency for the size distribution to become self-preserving. This will be the practical consequence of the interaction of nucleation, growth, and coagulation. There have been numerous experimental confirmations of this self-preservation rnechani~m.*~-*~Several theoretical approaches have been adopted to model it, and the most comprehensive allow for growth both by coagulation and by single-molecule condensation, and for diminution in size both by splitting into 38 M. Smoluchowski, Z.phys. Chem. (Le@zig), 1917,92,129. 39 T. Gillespie, J.Colloid Sci., 1963, 18, 582. S. E. Devir, J. ColloidSci., 1966,21,9. 41 C. E. Junge, Ber. Deuf. Wetterd., 1952, 35,261. 4a D. K. Swift and S. K. Friedlander, J. Colloid Sci.,1964,19,621. 43 W. E. Clark and K. T. Whitby, J.Atmos. Sci., 1967,24, 677. 420 Carabine smaller aggregates and by evaporation of single rn01ecules.~~-~~ Formally all such steps can be represented as follows : i=cn i= cn Here, in unit time, Nt,j is the number of collisions between i and j clusters which achieve coalescence, and Si,jis the number of splittings into i and j clusters. The older theories of nucleation and coagulation are special cases of (23). For instance, the Volmer and Becker-Doring theories express the process of nuc- leation under supersaturation by selecting only the terms where a single molecule and a cluster are interacting Smoluchowski’s approach to coagulation3* includes only terms such as are represented in equation (221, and Friedlander44 has pointed out that it ought to be extended as follows to take account of the reverse processes, splitting and evaporation: i+j=k i-1 Using the generalized theory, Friedlander et aLi6 have shown that a dimen- sionless parameter can be used to describe the relative rates of condensation and coagulation and to define the point where they compensate one another to produce a surface-area per unit gas-volume which does not vary with time.If the said parameter, which depends on the supersaturation, does not take the unique value mentioned, the supersaturation must vary with time in a specific way for the distribution still to be self-preserving.Numerical evaluations over the whole size spectrum fitted well to this theory and analytical solutions were obtained at the upper and lower ends, which are the influential regions for the preservation mechanism. 44 S K. Friedlander,Phys. Fluids, 1960, 3, 693. 45 S. K. Friedlander and C. S. Wang, J. Colloid Interface Sci., 1966,22,126. 46 J. Pich, S. K. Friedlander, and F. S. Lai, J. Aerosol Sci., 1970, 1, 11 5. 47 S. E. Devir, J. Colloid Sci., 1963, 18,744. 4a G. M. Hidy, J. Colloid Sci., 1965, 20, 123. W. A. Mordy and E. X. Berry, J. Atmos. Sci., 1965,22,340. 50 S. Twomey, J. Atmos. Sci., 1964, 21, 553. 51 V. I. Smirnov, Trudy Tsentr.Aerolog. Observ., 1964,5586 (Ref.Zhur. Khim., 1965,llB1018). 52 M. V. Buikov, Kolloid Zhur., 1967, 29, 42. 63 M. V. Buikov, and A. V. Silaev, Kolloid Zhur., 1967, 29, 34. 50 G. Zebel, Sraub, 1959, 19, 381. Interactions in the Atmosphere of Droplets and Gmes 3 Discussion of Reactions The reactions to be discussed here are classified according to chemical nature without attempting to separate laboratory studies from designed production of aerosols in manufacture, or from their inadvertent production in the atmosphere. In the low-altitude atmospheric chemistry which is relevant to air pollution, certain variables may be hard to measure at the true site of a reaction. Examples of such variables are the intensity of incident sunlight and the concentration of water vapour, or indeed of any reactant in so far as it might be subject to spatial and temporal variations which are not due to chemical conversion.In the laboratory, values of these variables can be set, but there is always some doubt about extending the conclusions to a more general environment. A. Aerosols involving Sulphur Dioxide.-Particles and droplets composed of sulphates form an important part numerically of the atmospheric aerosol. 559 5s For instance, at a site in ‘rural’ England, in a typical sample of all particles in the size range 0.08-1.0 pm, ammonium sulphate formed 90% of the number, and 99 % of the mass. Sulphur dioxide also plays a crucial role in the condensation of the aerosol known as photochemical smog. The chemistry of the involvement of sulphur dioxide in both these aerosols must include its oxidation to sulphur trioxide, and it is useful to distinguish at least three possible mechanisms for this reaction in the atmosphere: (i) in the gas phase, by photochemical oxidation, (ii) in water droplets either with or without catalysis by other solutes which may be present, such as metal or ammonium ions.(iii) on the surface of suspended solid particles. There are recent experimental studies of all these modes of reaction, and a useful summary is given by Urone and Schr~eder.~~ (i) Gas-phase Photochemical Oxidation. (a)Sulphur dioxide photo-oxidation. Few experiments have been carried out in the complete absence of water.observed a rate of conversion to sulphur trioxide of only 8 x lo-*% min-l under sunlight, which is ten times slower than values found in the presence of water vapour. Gerhard and used moist air, illumination equivalent to noon sunlight, and concentrations of sulphur dioxide of the order of 10 p.p.m., and found a rate of 2 x min-1. They detected no marked influence of ambient humidity, foreign nuclei, or of nitrogen dioxide added up to 2 p.p.m. The results of Schuck and Doyleso were two orders of magnitude higher, using only about 0.5 p.p.m. of SOz;even at the lower rate the conversion s6 C. E. Junge and G. Scheich, Atm. Env., 1969,3,423. 68 M.J. Heard and R. D. Wiffen, Atm. Env., 1969,3,337. P. Urone and W. H. Schroeder, EnvironmentalSci.and Technol., 1969,3,436.68 T. C. Hall, jun. Ph.D. Thesis, UCLA, 1953. 68 E. R. Gerhard and H. F. Johnstone, Znd. and Eng. Chem., 1955,47,972. 8o E. A. Schuck and G. J. Doyle, Report No. 29, Air Pollution Foundation, San Marino, California, 1959. Carabine is significant on the time scale of a day, e.g. with a concentration of lo-, p.p.m. SO, the yield of H,SO, in about one hour is lo-&p.p.m., and according to calculations1 the nucleation rate for the condensation of the sulphuric acid would be high at such a partial pressure of acid. Cox and Penketts2 have also estimated about min-1 conversion in moist air using p.p.m. quantities and sunlight. If smog were to form by this means alone, a reduction of visibility to 2 km. would take about tens3 or one hundredK9 hours of bright sunlight.The reaction is generally agreed59g62 to be first order with respect to sulphur dioxide and some rate constants have now been quoted.Ks~60~B2 The mechanism of the photo-oxidation was uncertain in 1961s4 and still is. It has a low, concentration-dependent quantum yield at 313 nm,62 which wave- length of course cannot dissociate SO, but can excite it with a high absorption coefficient to a singlet upper state.6K In view of the strong hygroscopicity of the sulphuric acid produced in the oxidation, it is to be expected that water droplets which are nucleated by it will grow fairly rapidly in diurnal terms. There is some evidence for this in the strong dependence on ambient relative humidity of the optical extinction, which can be correlated with the size distribution of droplets.6s Coutarel et dsshave passed a stream of air containing an aerosol of pure sulphuric acid over a bath of more dilute acid and observed a 3% increase in average radius in a contact time of 10-1 s.After about 100 s sufficient water was absorbed for the sub-micron-sized droplets to reach the size at which their vapour pressure was equal to that of the solution. It could be important in the context of inhalation by mammals of such droplets if their growth in humid conditions is as slow as it appears to be from these results. The author’s ob- servation that the growth rate of the particles (presumably on a volume basis) is proportional to their volume is not discussed, although it implies that water- vapour diffusion to the droplets is not the controlling mechanism [cf.equations (1)-(3) above]. Perhaps the factor giving rise to such slow growth is the raising of the vapour pressure at the drop by the considerable heat of solution which is involved. (b) Sulphur dioxide photo-oxidation in impure systems. The rate of photo- oxidation is greatly enhanced in the presence of other trace gases, notably ammonia, and combinations of olefins with nitrogen oxides. Conversely, it has often been shown in the laboratory that chemical involve- ment of sulphur dioxide is crucial in the production of photochemical aerosol from certain other air pollutants. In particular it enables the formation of such 61 G.J. Doyle, J. Chern.Phys., 1961, 35, 795. 62 R. A. Cox and S. A. Penkett, Atrn. Em., 1970,4,425. 63 J. A. Garland, Atm. Env., 1969, 3, 347. 64 P. A. Leighton, ‘Photochemistry of Air Pollution’, Academic Press, N.Y., 1961, p. 235. 65 J. H. Clements, Phys. Rev., 1935,47,224. 66 L. Coutarel, E. Matijevic, M. Kerlier, and Huang Cheo-Ming, J. Colloid Interface Sci. 1967,24,338. Interactions in the Atmosphere of Droplets and Gases smogs from any olefin, whereas in its absence the effect is limited to cyclo- he~ene,~~other higher cyclic olefins, and diolefins. 67 Even with saturated hydrocarbons, sulphur dioxide at partial pressures of up to 7 kN rn-, is capable of forming dense aerosol~.~~~~~ A copolymer of olefin and sulphur dioxide has been produced in photo- and a tendency has been noted for SO, to form polymers with traces of free radicals in discharges.70 The formation of aerosol from sulphur dioxide- alkane mixtures might thus be a consequence of the production of radicals from the hydrocarbon which, as Ogata69 et al. have suggested, can be effected by excited molecules of SOz which absorb U.V. light with ample energy for fission of a carbon-hydrogen bond. (c) Sulphur dioxide photo-oxidation with nitrogen oxides. Photochemical activation of SO, is not in practice the important primary process in photochemical-smog formation. Nitrogen dioxide is a key component of pollution by automobiles, although the mechanism of its formation from the NO in the exhaust gas is not clearly understood quantitatively.Nitrogen dioxide is much more readily dissociated by photolysis than is SO,, and it has been shown71 that the products can accelerate the oxidation of SO, to SO,. The pattern of the chemical involvement of SO, in the formation of aerosols is complicated. In the above-mentioned aerosols formed in the presence of alkanes, 68*6Qsulphur has been found in the form of sulphonic and sulphuric acids. Even with nitrogen dioxide also present, aqueous sulphuric acid was the major constituent of some aerosols from olefins, 72 and stronger acid, which resulted from lower ambient humidity, altered the proportions of the product in favour of inorganic nitrates. Very little organic material was incorporated and certainly none bonded to sulphur.As Alt~huller~~ has expressed it, the oxidztion of SO, to particulate sulphur compounds is efficiently aided by participation in the smog-forming reactions. (d) The photochemical-smog mechanism. It is still not possible or useful to generalize about the chemical nature of the typical atmospheric smog resulting from photo-oxidation of hydrocarbon-nitrogen oxides-SO,-air mixtures. The constitution depends on conditions such as identity of the hydro- carbon~,~~and the presence of foreign nuclei. Collateral indicators of the level of severity of smog which are commonly used are eye irritation and ozone or 67 M. J. Prager, E. R. Stephens, and W. E. Scott, Ind. and Eng. Chem., 1960,52,521. 68 H. S. Johnston and K. Dev Jain, Science, 1960,131, 1523.69 Y.Ogata, Y. Izawa, and T. Tsuda, Tetrahedron, 1965,21, 1349. 70 D. H. Fraser, personal communication. 7l S. Jaffe and F. S. Klein, Trans. Faraday SOC.. 1966,62,2150. 72 N. Endow, G. J. Doyle, and J. L. Jones, f. Air Pollution Control Assoc., 1963,13, 141. 73 A. P. Altshuller, f. Air Pollution Control ASSOC., 1970, 20, 390. 74 W. E. Wilson, jun. and A. Levy, J. Air Pollution Control ASSOC.,1970,20, 385. 76 A. P. Altshuller, S. L. Kopczynski, D. L. Wilson, W. A. Lenneman, and F. P.Sutterfield, J. Air Pollution Control ASSOC.,1969, 19, 787. 424 Carabirte 'oxidant' c~ncentration.~~-~~ The essentials of a reaction scheme which includes these factors are given by Agnew:76 Nitrogen dioxide can be dissociated by all solar radiation below 390 nm.NO, + hv --+ NO + 0;dH2,,0 = 307 kJ mol-l (1) 0 + O2+ M -O3+ M; dH2980= -96.6 kJ mol-1 and ozone can accumulate as a result of (11) In turn NO may remove O3 0,+ NO -+NOz + O2 (111) but in the presence of hydrocarbon this would suffer competition from RO; + NO 4RO' + NO, Reactions (I), (11), and (111) may comprise the basic photochemical equilibrium, with atomic oxygen then attacking the hydrocarbon: 0 + RH ---t R' + OH' R + 02-ROZ followed by RO, + NO -+ RO' + NO2 RO -k NO2-RONO, The principal eye-irritants are peroxyacylnitrates, of the form R-CO3-NO2, which are in fact mixed anhydrides of nitric and peroxycarboxylic These may be formed as follows: O3 + RIH -R2CO; + R3CH0 R2CO; + NO -NO, + R2C0 R2CO' + 02 + NO2 -+ R2.C03.N02 This scheme is open to two criticisms: (i) Alkyl nitrates are not experimentally and (ii) the molecular singlet 02(ldg)may play a more significant role than atomic oxygen.79-81 Several feasible routes for the photochemical formation of O,(lA,) in adequate yield have been proposed, and its direct addition to olefins would be a simple route to alkenylhydroperoxides : O,(ldg) + CnH2n -+ CnHzn-i00H 76 W.G. Agnew, Proc. Roy. SOC.,1968, A307,153. 77 E. R. Stephens and M. A. Price, Arm. Env., 1969,3,573. 78 E. R. Stephens, Adv. Env. Sci., 1969, 1, 119. 78 J. N. Pitts, jun, A. V. Khan, E. B. Smith, and R. P. Wayne, Environmental Sci.and Technol., 1969, 3, 241. 8o R. H. Kummler, M.H. Bortner, and T. Baurer, Environmental Sci. and Technol., 1969, 3,248. R. P. Steer, P. L.Sprung, and J. N. Pitts, jun, Environmental Sci. and Technol., 1969,3,946. 425 Interactions in the Atmosphere of Droplets and Gases These in turn may be oxidized further and release sufficient energy to effect, for instance, the conversion of nitric oxide to N02.’0The bulk of the nitrogen oxide emitted in the automobile exhaust is NO, but its conversion to NO2 must precede the absorption of the solar-radiation energy. Thus both the schemes, involving atomic and molecular oxygen respectively, will satisfactorily explain the ozone and irritant levels which accompany smog, but neither includes consideration of any of the sulphur compounds referred to in the previous section. (ii) Reactions in Droplets.(a) Chemical oxidation of sulphur dioxide in the droplet phase. It has been mentioned above that ammonium sulphate aerosol is of considerable practical importance in the atmospheric chemistry in geo- graphical areas where substantial amounts of sulphur dioxide and ammonia have been released into a poorly ventilated atmosphere. The particles which would normally remain suspended for an appreciable time lie in the size range 0.2-1 pm,66J+2-86and by this criterion are known in the context of meteoro- logical precipitation as ‘large nuclei’. The proportions of NH,+ and Sod2-generally indicate the presence of NH,HSO, and (NH4)2S04,and the com- paratively small size of the stable particles enables them to spread widely, upwards to reach the stratosphere,86 and outwards over oceans far from the centres of origin.82 Ammonia strongly accelerates the oxidation of SO2in aqueous bulk solutions7 and in macroscopic droplets,88 and so it is probably an important aid to the process in cloud droplets in the appropriate geographical areas mentioned above.84 In laboratory studiess8 of uptake of sulphur dioxide in droplets of diameter 102-1 03 pm the ammonia-catalysed mass-increase was found to be proportional both to droplet surface area and to exposure time.Reference to equation (19) indicates that diffusion in the liquid phase was the overall con- trolling factor. Manganese sulphate in p.p.m. concentrations is one of several salts which have considerable catalytic effect on the solution-phase With droplets go of 500-103 pm diameter Johnstone and C~ughanowr~~ found that equation (18) was obeyed for catalyst concentrations of 500-1000 p.p.m., whereas with only 250 p.p.m.equation (16) was obeyed, and it appeared that oxidation was slow enough for sulphur dioxide to penetrate into the centres of the droplets. C. E. Junge, ‘Proceedings of the Conference on the Physics of Cloud Precipitation’, Wood’s Hole, 1955, p.3. *a E. Eriksson, Tellus, 1952, 4, 215, 280. H. N. Georgii, Umschau, 1968, 68, 565. H. R. Byers, J. R. Sieves, and J. T. Tufts, ‘Proceedings of the Conference on the Physicsof Cloud Precipitation’, Wood’s Hole, 1955, p. 47. 86 J. P. Friend, Tellus, 1966, 18,465.C. E. Junge and T. G. Ryan, Quart.J. Roy. Meteorol. SOC.,1958, 84,46. A. P. Van den Heuval and B. J. Mason, Quart.J. Roy. Meteorol. SOC.,1963, 89, 271. H. F. Johnstone and D. R. Coughanowr, Ind. and Eng. Chem., 1958,50,1169. R. C. Hoather and C. F. Goodeve, Trans. Faraday SOC.,1934,30,1149. 426 Carabine Extrapolation of the observed rates to an atmospheric fog containing 20 ,um diameter droplets of reasonable manganese content and 1 p.p.m. of sulphur dioxide predicted a conversion of 1 % min-l, i.e. 500 times that found in the photochemical oxidation by Gerhard and Johnstone.sB It is interesting that the same reaction, with hydrogen peroxide in the droplets instead of MnSO,, is only some ten times faster, but is controlled by diffusion in the gas-phase rather than internally.Rates of acid formation were measured by Johnstone and Moll,g1 using sub-micron-sized droplets of aqueous manganous sulphate in a fog chamber containing sulphur dioxide-physical conditions which approximate to those in chimney plumes. With the latter practical situation in mind, Fostergz interpreted their results, using a theoretical rate of growth for the droplet radius expressed by Here RH,SO,is the rate of formation and can be represented, at least for low acid concentrations, by a zero-order rate constant. Although the equation is in broad agreement with equation (13), it contains the implication that the acid produced inhibits the oxidation, so that the latter is faster at higher relative humidity where more dilute droplets are concerned.Complexing of the manganese catalyst may be the reason for the inhibition, a question which is further con- sidered by Matteson et aLgSThe conditions on which equation (13) are based are valid for most of Johnstone and Moll's experiments, except at very low partial pressures of sulphur dioxide, and more particularly when an iron salt is the catalyst. Under the latter conditions the rate is dependent on the pressure of sulphur dioxide, which may be due to less complete penetration of the droplets [see equation (14)]. Foster predicted rates of conversion in plumes of about 0.1 % min-l with manganese as catalyst, and 0.15-1.5 % min-l with iron, which is typically ten times the more abundant in pulverized fuel ash.In laboratory experiments, ammonia was found to react rapidly with sulphuric acid aerosol droplets of 0.2-1 pm diameter,g4 and in interpreting the rate of uptake, an empirical modification of equation (9) such as was found adequate. This allows for the departure from the initial rate in terms 91 H. F. Johnstone and A. J. Moll, Znd. and Eng. Chem., 1960,52,861. s8 P. M. Foster, Atm. Env., 1969, 3, 157. ga M. J. Matteson, W. Stoeber, and H. Luther, Znd. and Eng. Chem. (Fundamentals), 1969, 8,677. 94 R. C. Robbins and R. D. CadIe, J. Phys. Chem., 1928,62,469. Interactions in the Atmosphere of Droplets and Gases of x, the fraction of the droplet that has reacted, and F, which is dimensionless and expresses both the diffusion rate of products and the change in surface area.(b)Sulphur dioxide-ammonia reaction at low humidity. The products when two such commonplace chemicals as sulphur dioxide and ammonia react in dry conditions without oxygen are surprisingly not yet identified clearly, but even well below room-temperature they take the form of an aerosol. A yellow solid adduct, formed at temperatures below -10 "Cwith excess sulphur dioxide, was described by Goeringg5 by the empirical formula H3N02S, probably being H-S02.NH2.On the other hand ammonia in excess produces a red adduct H6N20,S,which is probably NH4*SO2.NH2.The i.r. spectra of the products at room temperaturegs indicated gas-phase HNSO and particles of (NH4),S205, formed by the reaction 3SO2 + 3NH3 +HNSO + (NH,),S205 X-Ray and further i.r.identifications of the initial solid aerosolg7 formed at room temperature have been attemptedgs but the results are so far ambiguous. The hygroscopic product(s) progressively change to (NH,),SO in moist air. In the presence of water the possible reactions are more straightforward, although their occurrence in droplets is as yet unconfirmed by experimental proof: NH, + SO, + H20 +NH,.HSO, On the question of the transition from solid particles of (NH,),SO, to droplets, the critical humidity for this, at 15 "C,appears to be about 73%, compared with 78% for sodium chloride. The numerous solid particles of am- monium sulphate found probably result from evaporation of atmospheric dropletsss but the most probable sequence of events is hard to specify in a given case and is obviously under control of meteorological factors.Heard and WiffenS6 found no positive signs of any insoluble nuclei in the particles they collected from the atmosphere. This is not conclusive proof that the ammonium sulphate was not formed in droplets, but it is useful fragmentary evidence, typical of investigations of atmospheric chemistry when performed at ground level. A related reaction of ammonia, with the sulphur trioxide produced by catalytic oxidation, is the basis of a dry methodg9 for cleaning flue gases of their sulphur content. (iii) Oxidation of Sulphur Dioxide on Particles. We have seen89 that the rate of oxidation in fog droplets containing metals such as iron and manganese can be considerable, of the order of 1 % min-l, and hence several tinies faster than the 'J5 M.Goehring and H. W. Kaloumenos, 2. anorg. Cliem., 1950, 263, 137. g6 T. Hata, Bull. Chem. Res. Inst. Non-aqueous Soh. Tohoku Univ., 1964, 14, 5. 97 M. D. Carabine, J. E. L. Maddock, and A. P. Moore, Nature Phys, Sci., 1971,231, 18. g8 M. D. Carabine and A. P. Moore, unpublished work, s9 R. Kiyoura, Staub, 1966, 26, 524. Carabine photochemical o~idation.~g Urone et aZ,loo after confirming the latter photochcm- ical rate at 50% relative humidity, measured the rates over powdered salts and oxides, with and without both U.V. irradiation and water vapour. Substances known to be effective catalysts at high temperature, e.g.V205and Cr,O,, surprisingly produced rates of only about % min-l, which were not greatly enhanced by irradiation or moisture. A key factor may be moisture in the particles themselves; the relative humidity (50 %) employed here was quite insufficient to induce deliquescence in any of the substances, except for calcium oxide which did increase the rate and which was suspected of inadvertent moisture content. When the levels of promotion on albeit relatively coarse particles are so insignificant, it is clear that no substantial measure of atmospheric oxidation can occur on dry airborne particles, the more so since in these experiments the mass ratio of particles to sulphur dioxide was two orders of magnitude higher than typical values in even heavily polluted atmospheres. This assertion must be viewed with reservation until experiments are made with particles of sur-face to mass ratios comparable to those of atmospheric particles: an unex- pectedly high degree of promotion by iron oxide may have been connected with its mode of preparation.ComminslO1 has found interesting correlations between conversion of sulphur dioxide to particulate sulphate and the ambient concentrations of smoke or ash containing traces of various catalytic metals. Let us now summarize the chemical fate of sulphur dioxide in various atmos- pheric environments. In hydrocarbon-polluted atmospheres with intense sunlight, and in laboratory simulations of these, it will predominantly go into the sequence of reactions leading to photochemical smog. In the absence of such radiation, and if droplets are present, oxidative reaction in the liquid phase is bound to predominate.The rate may be greatly increased if iron, or manganese, vanadium, etc. has entered the environment as a component of smoke or ash. Ammonia is a key participant in the global cycle of sulphur reactions. On this scale its emission, mostly from natural sources, relative to that of man-made sulphur dioxide satisfies the stoicheiometry of neutralization to ammonium sulphate. However on the local scale the proportions are frequently vastly disparate, and in any case ammonium sulphate is not entirely innocuous since it can impair visibility by stabilizing mist droplets. The interaction of these two gases in the absence of water may be slow, but could be important in arid atmospheres. In conclusion, it may be said that whereas many examples have been quoted 34~36~88~89of the kinetic study of the growth of particles and droplets which are well above 1 pm in size, studies on particles which are smaller and can hence survive in aerosol suspension are only 97 For observing changes in submicron sizes and their distributions, light scattering with laser sources is one of the more promising current technique^.^^ looP. Urone, H. Lutsep, C. M. Noyes, and J. F. Parcher, Environmental Sci.and Technol., 1968, 2, 611. lol B. T. Commins, M.R.C. Air Pollution Unit, London, personal communication.

ISSN:0306-0012    

DOI:10.1039/CS9720100411

出版商:RSC    

年代:1972

数据来源: RSC