摘要:

Chemical Society Reviews Vol 7 No 4 1978 Page HAWORTH MEMORIAL LECTURE Human Blood Groups and Carbohydrate Chemistry By R. U. Lemieux, F.R.S. 423 Photophysics of Molecules in Micelle-forming Surfactant Solutions By K. Kalyanasundaram 453 Synthetic Pyrethroids -A New Class of Insecticide By M. Elliott and N. F. Janes 473 MELDOLA MEDAL LECTURES I Molecular Shapes By J. K. Burdett 507 II Fe(C0)4 By M. Poliakoff 527 1978 Indexes 541 The Chemical Society London Chemical Society Reviews Chemical Society Reviews appears quarterly and comprises approximately 25 articles (ca. 500 pp) per annum. It is intended that each review article shall be of interest to chemists in general, and not merely to those with a specialist interest in the subject under review.The articles range over the whole of chemistry and its interfaces with other disciplines. Although the majority of articles are intended to be specially commissioned, the Society is always prepared to consider offers of articles for publication. In such cases a short synopsis, rather than the completed article, should be sub-mitted to The Managing Editor, Books and Reviews Section, The Chemical Society, Burlington House, Piccadilly, London, W1 V OBN. Members of the Chemical Society may subscribe to Chemical Society Reviews at €6.00 per annum; they should place their orders on their Annual Subscrip- tion renewal forms in the usual way. Non-members may order Chemical Society Reviews for 1E16.00 ($33) per annum (remittance with order) from: The Publications Sales Officer, The Chemical Society, Distribution Centre, Blackhorse Road, Letchworth, Herts., SG6 IHN, England. 0Copyright reserved by The Chemical Society 1978 ISSN 0306-0012 Published by The Chemical Society, Burlington House, London, W1V OBN Printed in England by Eyre & Spottiswoode Ltd, Thanet Press, Margate

ISSN:0306-0012    

DOI:10.1039/CS97807FP009

出版商:RSC    

年代:1978

数据来源: RSC

摘要:

Human Blood Groups and Carbohydrate Chemistry By R. U. Lemieux, F.R.S. DEPARTMENT OF CHEMISTRY, THE UNIVERSITY OF ALBERTA, EDMONTON, ALBERTA, CANADA TCG 2G2 It is a truly outstanding privilege to present the Haworth Memorial Lecture for 1978 and it is particularly gratifying to receive such high distinction outside of my own country and especially here in the United Kingdom. Therefore, I would like first to thank all of those concerned with the decision to grant me this honour on the occasion of this, the IXth International Symposium on Carbohydrate Chemistry, where I am among many friends and ex-colleagues. The achievement of such recognition has of course required understanding and devoted assistance from many sources-governmental, academic, colleagues, co-workers, and family.By honouring me, The Chemical Society honours all these-a favour for which I am deeply indebted. My interests in basic chemical research, especially since my appointment to the University of Alberta in 1961, were highly demanding in terms of facilities, collaboration, and especially in the time available for effective engagement. These were achieved primarily through the support and trust provided to me and our Department of Chemistry by both the University of Alberta and the National Research Council of Canada. Since my work has been judged highly significant, then these organizations are to be particularly commended and applauded. It is a happy circumstance, I believe, that I could come here today with a lecture on aspects of the carbohydrate chemistry of the human blood-groups.This subject is particularly appropriate for a Haworth Memorial Lecture of The Chemical Society because of the rich history of serology and haematology in Britain starting with the discovery of blood circulation by Harvey in 1616, going through the first human-to-human blood transfusion by James Blundell in 18 18, and eventually leading to the pioneering and monumental accomplishments on the chemical structure of the blood-group determinants made through the superb collaboration of Walter Morgan and Winifred Watkins at the Lister Institute of Preventive Medicine. In the first Haworth Memorial Lecture presented by Maurice Stacey in 1971,l he made reference to the great importance of the work on deoxysugars by the Haworth school of carbohydrate chemistry to the field of nitrogen-containing * Delivered at the IXth International Symposium on Carbohydrate Chemistry on I1 April1978, at the Institute of Education, University of London.M. Stacey, Chem. SOC.Rev., 1973,2, 145. Human Blood Groups and Carbohydrate Chemistry immunopolysaccharides. He mentioned that while with Haworth his own dis- covery of L-fucose residues in blood-group substances, ‘has had quite remarkable consequences in elucidating the specialist sub-groups and in stimulating research generally in this field.’ Thus, it seemed fortunate that I could, because of research in recent years in my laboratory, speak on this occasion on our syn-theses of immunodominant parts of oligosaccharide antigenic determinants related to certain important human blood groups and to comment on the results of our conformational analyses of these complex structures.Since Haworth was, in my estimation, the father of conformational analysis in carbohydrate chem- istry, I consider this latter subject also to be highly pertinent to a lecture in his memory. My first encounter with blood-group chemistry was in the reading of a chapter entitled, ‘Chemistry of the Mucopolysaccharides and Mucoproteins’ by Maurice Stacey in 1946.2 That was the year that I gained the Ph.D. degree under the supervision of Professor Clifford B. Purves who had been a graduate student with Professor E. L.Hirst at St. Andrews, and it is through him that my con- nection with the famous British school of carbohydrate chemistry was made. The discovery at the turn of this century by Landsteiners of the ABO system was a turning point in the science of haematology.This was a matter of particular significance to blood-transfusion science. It was demonstrated that the serum of a person of either A or B group agglutinated the red cells of the other group, and that the sera of 0group people agglutinated cells of both A and B people. The cells of a fourth group of people, termed AB, were found to be agglutinated by the serum of both A and B people but the serum of these people did not agglutinate either A or B cells. Agglutination in vivo gives rise to serious patho- logical conditions referred to as blood-transfusion reactions and can involve extensive lysis of red cells.Its avoidance by proper typing in the ABO system was then a major step toward the modern situation wherein some 20 million litres of blood are collected annually in the western developed countries for transfusion purposes. A substantial proportion of the blood collected is dedicated to the preparation of testing reagents for blood typing and for the blood- fractionation industry to extend blood usage by providing a broad range of fractions, mainly of interest to clinical problems concerned with blood coagula- tion. With Landsteiner’s discovery and the general growth since then of the chemical and biological sciences, the science of haematology rapidly grew to the point that over 160 different immunological specificities are now recognized for human red cells.At least 13 independent and well-defined blood group systems are known and some 50 specificities are of clinical importance. At least five blood- group systems are known to possess oligosaccharide determinants. This list may grow since carbohydrates as oligosaccharidic structures, offer a wide assortment of conformationally rigid structures to serve as recognition sites at cell surfaces. My lecture is restricted to our syntheses of determinants for the ABO and Lewis a M. Stacey, Adv. Carbohydrate Chem., 1946,2, 161. K. Landsteiner, Biochem. Z.,1920,104,280. Lemieux systems, how the products of these and similar syntheses may become of medical interest, and some comments on their conformational properties.The blood group determinants are inherited according to the Mendelian genetic laws and arise in the individual as the result of the person possesshg genes, which gives a code for the enzymes, which are necessary to build the oligosaccharide determinants. Substances possessing human blood-group activities occur as oligosaccharides in milk and urine, as complex water-soluble glycoproteins in body secretions and tissue fluids and on the surfaces of cells and tissues, and in the form of water- insoluble glycosphingolipids mainly on the surfaces of red cells and tissues. Substances possessing human blood-group specificities are also found in certain animal tissues, plant extracts, and in many bacteria.The glycosphingolipids occur hydrophobically bonded to the surface of cells and tissues. Although these structures have been studied extensively for over 30 years, it has only been within the last decade that a large number of their structures have become known in detail. This knowledge4 was acquired in several laboratories but mainly through the efforts of KoScielak and co-workers in Warsaw and Hakomori and his associates at the University of Washington. The work was strongly handicapped by the great difficulty in the isolation of these substances. For example, starting with 50 kg of packed red cells, Hakomori was able to isolate only about 2 mg of a pure glycosphingolipid. These studies based on highly sophisticated modern methods of separation and instrumentation for structural analysis have now produced structures for over 13 blood-group specific glycosphingolipids, an example of which is presented in Figure 1. The B-group glycosphingolipid is presented in such a way as to illustrate the strong hydrophobic bonding which can occur with the lipid bilayer of a cell membrane from penetration of the ceramide portion of the glycosphingolipid into the lipidic membrane.As indicated, the oligosaccharide determinants appear to all begin with a p-lactosyl group attached to the l-oxygen of the ceramide portion. The structures of blood-group specific glycoproteins which are found in secretions such as saliva, gastric juices, milk, sweat, and tears are illustrated in Figure 2.Although saliva represents a readily accessible source of these glyco- proteins (also known as blood-group substances), this secretion contains only 10-130 mg of active material per litre. On the other hand, ovarian cysts can accumulate fluids for long periods and several grams of purified blood-group substance can often be isolated from a single cyst. Being available in substantial quantity for several decades, the structures of the blood-group substances drew widespread attention and were intensively studied in many laboratories. A review of this extensive effort is outside the scope of this lecture and I can only refer you to the excellent reviews by Dr. Winifred Watkin~.~ The fist stage of J. KoScielak, in ‘Human Blood Groups’, Proceedings of the 5th International Convocation on Immunology, Karger, Basel, 1977, p.143; S. Hakomori and A. Kobata, in ‘The Antigens’, Vol. 11, ed. M. Sela. Academic Press, New York, 1977, Vol. 11, p. 79. W. M. Watkins, in ‘Glycoproteins: Their Composition, Structure and Function’, ed. A. Gottschalk, Elsevier, Amsterdam, 1972, p. 830; and also in Biochem. SOC.Symp., 1974,40, 125. Human BIood Groups and Carbohydrate Chemistry 8 426 Lemieux (N-acetyl tactosaminyl) I no I Pmcvxw Protein no Blood-Group Specific 40-45 mob percent Oligosaccharido Determinant (several sugar residues) -0 OH of amino acids are serine (R=H)ad threonim(R=CYwhich 80-90X carbohydrab 10 -2OX protein Occur in tissue fluids, in secretions and at cell and tissw surfacer Figure 2 Illustration of the general structure for blood-group specific glycoproteins, also known as blood-group substances, which occur in tissue fluids, in secretions, and at cell and tissue surfaces these studies was based on the observation by Landsteiners in 1920 that a simple substance with a structure closely related to that of the antigenic determinant can combine with the antibody and thereby competitively inhibit the reaction between the antibody and the antigen. A large number of oligosaccharides isolated from human milk and characterized by Kuhn and co-workers at Heidelberg in the 1950’s were particularly useful in revealing the structures of serologically active units in the blood-group substances.This led to studies which involved the use of enzyme specificities for the destruction of serological activities and the detection of inhibition of the destruction by specific sugars and certain derivatives. The final stage involved partial acid and base degradations of the glycoproteins to provide serologically active oligosaccharide fragments which subsequently were subjected to structural analysis. It is these studies, mainly performed in the laboratories of Morgan and Watkins at the Lister Institute of Preventive Medicine, and of Kabat and co-workers6 at Columbia University, that yielded the detailed structural information which put synthetic chemists, like myself, ‘into business’-so to speak. As indicated in Figure 2, the blood group specific glycoproteins are 80-90% carbohydrate.Some 40-45 of the amino acid units per 100 amino-acid units are the hydroxy amino-acids, serine and threonine, and the oligosaccharide units are attached to these hydroxyl groups by way of an N-acetyl-a-D-galactosamine unit. It is of interest to note that the first disaccharide unit appears to be the 3-O-(/?-~-galactosyl)-a-~-N-acetylgalactosaminylgroup. This disaccharide unit is substituted in part by an N-acetyl-lactosamine group at the &position of the a-D-galactosamine residue. The normal blood-group oligosaccharide determin- ants then extend from the 3-position of the /?-D-galactosyl group. The chemical structures of the terminal groups responsible for the A, B,O(H) specificities are shown in Figure 3.It is seen that the O(H)determinant is the precursor for both the A and B determinants. It may be noted that 0 was K. 0.Lloyd, E. A. Kabat, and E. Licerio, Biochemistry, 1968,7,2976. 427 Human Blood Groups and Carbohydrate Chemistry GROUP 0(HI .c-~-Fuc-(1-+2)-0-D-Gal.... R-D-Glc-UAc-(l-+31-~-D-GaI.,.1 c(1-,3)A oc-L-Fuc-11-.2)-8-~Gal.... Type 1 chain ~-O-GalWAc-(l+ 31 OR (1-41 B d-L-Fuc414 4-0-Gal 41 31 Figure 3 me A, B, and O(H)human blood-group determinants initially assigned to designate red cells that were not agglutinated by either anti-A or anti-B sera; that is, had zero activity. Since then the cells were found to have the specific determinant indicated in Figure 3.The structure, a-~-Fuc-(1+2)- p-~-Gal-( 4 or 4)-/?-~-GlcNAc-is now termed the terminal trisaccharide 1units for H-activity and this is why the designation O(H) is used. As indicated, the p-~-Galunit of the terminal trisaccharide for the H deter-minant is linked either to the 3-or to the 4position of a /~-D-G~cA?Acresidue. The (1-3) linkage provides what has been termed the Type 1 chain and the (1-4) arrangement the Type 2 chain.' From a stereochemical point of view, this difference imposes a very substantial difference in structure close to and perhaps included in the immunodominant part of these antigenic determinants. We have examined this matter in some detail in recent years and I wish now to outline briefly some of our findings.Our approach to these matters is based on n.m.r. spectroscopy, both 13Cand 1Hn.m.r., and in molecular modelling with computer assistance. However, prior to serious involvement in such studies, it seemed mandatory to examine in detail the influence on the conformational preference for glycosidic linkages of the bonding phenomena which I have termed the exo-anomeric effect. These studies began with the establishment of a relation between the torsion angle defined by neighbouring lH and 13Catoms.* Once a Karplus-type relation- ship was established, a number of appropriately 13Cenriched model glycosides were synthesized so as to allow accurate measurement of the change in coupling constant between the aglyconic carbon and the anomeric hydrogen with changes in both the structure of the aglycon and the configuration at the anomeric centre.9 These and related studies led to the conclusion that the exo-anomeric effect must definitely play a dominating role in the determination of the orienta- tion of an aglyconic carbon relative to the anomeric hydrogen.This orientation is provided by the torsion angle as defined in Figure 4.lO The conclusion was reached that in the absence of truly exceptional steric encumbrances, glyco- 'V. P. Rege, T. J. Painter, W. M. Watkins, and W. T. J. Morgan, Nature, 1963,200, 532. OL. T. J. Delbaere, M. N. G. James, and R. U. Lemieux, J. Amer. Chem. Soc., 1973, %, 4501. @ R. U. Lemieux, S. Koto, and D. Voisin, 'Advances in Chemistry Series', 1978, in press.lo R. U. Lemieux and S. Koto, Tetrahedron, 1974,30, 1933. Lemieux 2R3H III Ill c-2 c-2 Q-0or p-L Figure 4 Definition of the #H and t,P torsion angles about glycosidic linkages pyranosides in solution can be expected to possess +H angles in the range f50" to -t 60°, the sign of the torsion angle depending on the absolute cofiguration of the sugar. The +H angle for a-glycosides appears to be a little larger than that for the p-anomers both for reasons of 13C to IH coupling constantsg and for theoretical reasons, as recently published by Jeffrey, Pople, and co-workers.ll A good compromise appears to be to set at _+ 55" for an a-glycoside and f50" for a p-glycoside. On this basis, the prefeqed conformation for a glycosidic linkage is expected to result from rotation about the aglyconic carbon to glyco- sidic oxygen bond only.These rotations are said to change the value of the #H angle. As will be seen later, our procedure is to maintain 'normal' angles unless it becomes apparent from molecular modelling that exceptional non- bonded interactions about the anomeric centre can only be favourably relieved by a change in the +H angle. Judging from the ab initio molecular orbital calcula- tions performed by Jeffrey, Pople, and co-workers,ll changes of +H within the range of k 15" from 'normal' values are not highly demanding in energy. In our work, we do not change the t$H angle from the 'normal' values unless this appears to lead to a relief of a non-bonded interaction of near 1kcal mol-1.This approach is undeniably arbitrary but as we shall see appears well justified as a useful working hypothesis. l1 G. A. Jeffrey, J. A. Pople, J. S. Binkley, and S. Vishveshwara,J. Amer. Chem. SOC.,1978, loo, 373. Human Blood Groups and Carbohydrate Chemistry The results obtained on subjecting the Type 1 and Type 2 disaccharides to conformational analysis, using standard hard-sphere calculations1°J2 based on the best available atomic parameters for the constituent structures as determined by X-ray crystallographic analyses of appropriate model compounds and setting c$~ = 50" (the 'normal' p-glycoside value), are presented in Figure 5. On this 3.96 (ro=3.56i) Figure 5 Conformations for the Type 1 and Type 2 disaccharides as estimated by Jiard-sphere calculations following the procedure described by Rao and co-workers and setting the i$H torsion angles at +-SO".The close proximity of the 2'-hydroxyl group to a group on the neighbouring sugar is to be noted basis, #H angles of + 18" and + 8" are predicted for the Type 1 and Type 2 disaccharides, respectively. It is at once seen that these are vastly different molecular structures. Of particular importance from the point of view of blood- group determinants is that the 2-hydroxyl groups of the P-D-Gal units are in very different environments. In the Type 1 chain this hydroxyl is in Van der Waal contact with the carbonyl carbon of the acetamido group, whereas in the Type 2 chain, this hydroxyl is in near Van der Waal contact with the methylene group at C-5 of the P-D-G~cNAc residue. Clearly, the two disaccharides would present very different substrates to the enzymes responsible for the conversion of these structures into the Type 1 and Type 2 H-determinants.In all likelihood, the enzymes are different. Watkins and Morgan13 have suggested that the /~-D-GIcNAc residue is involved as part of the determinant for the H-glyco- protein, If so, it can be expected, I believe, that the cross-reaction between these antibodies and the alternate H-structure is very weak. Is V. S. R. Rao, F. R. Sundararajan, and G. N. Ramachandran, in 'Conformations of Biopolymers', ed. G. N. Ramachandran, Academic Press, New York, 1967, p. 721. W. M. Watkins and W. T.J. Morgan, Vox Sangidinis, 1962, 7, 129. Lernieux In order to gain experimental evidence for the conformations shown for the Type 1 and Type 2 disaccharides, we investigated the effect of change in pH on the chemical shifts of the 13C-atoms in the aminodisaccharides presented in Figure 6. We have shown that protonation of the amino groups in such structures 4.4 5.2 -1.8 HO Ho% HO -0.4 4.5 9.0 4.1 Figure 6 The shielding of lSC-atoms which are /? to amino groups which is observed on protonation of the amino groups.@ The exceptionally large shiJis observed for both the anomeric and aglyconic carbons of the latter compound are attributed to the close proximity of the two amino groups give rise to remarkable p-shifts which are highly useful in the structural analysis of such c0mpounds.1~ Normal /%shifts involve the shielding of a 13C-nucleus which is to the amino group by about 4.5 p.p.m. It is seen that the shifts observed for both the aglyconic and anomeric carbons in the disaccharide that is expected to have two amino groups in close steric relationship are truly anom- alously high.This result would be in accord with the hydration of the ammonium groups (relative to that for the free amino groups) causing an increased demand for space and thereby affecting a change in conformation about the glycosidic bond. Regardless of the reason, these data require the two amino groups of the l4 R. U.Lemieux and S. Koto, Abstracts of Papers, Amer. Chem. SOC.,1973, 165, Medi 022.43 1 Human Blood Groups and Carbohydrate Chemistry Type 1 disaccharide to be close enough to interact, whereas those of the Type 2 disaccharide are not. Therefore, the data lend support to the conclusions reached by the hard-sphere calculations regarding the conformations of the Type 1 and Type 2 chains, As was seen in Figure 3, the A, Byand H determinants involve (1-3) and (1-4) attachments to fl-~-GlcNAc units both in linear and in branched struc- tures. The branched structures have been detected both in glycosphingolipids and in glycoproteins. The indication appears to be that the Type 1chain is more prevalent in the glycoproteins than in the glycosphingolipids.4~5 The essentially complete lack of cross-reactions between A and B specificities is indeed remarkable when one considers that the only difference between the determinants is the difference between an acetamido and a hydroxyl group.How- ever, this is not surprising if one examines molecular models in the conformations provided by hard-sphere calculations while assuming 4 angles in accord with the exo-anomeric effect. These conformations are approximately displayed both for Type 1 and Type 2 chains by way of conformational drawings in Figure 7. These conformational formulae attempt to show that the a-D-GalNAc and clu-D-Gal residues of the A and B terminal tetrasaccharide units are expected to be far removed from the P-D-GIcNAc residues in both the Type 1 and Type 2 forms. Since the acetamido and hydroxyl groups of the CX-D-G~NAC and CX-D-G~residues of the A and B determinants, respectively, play such a dominat-ing role in determining these immunological specificities, it could be expected that the combining sites for anti-A and anti-B antibodies would be directed mainly, if not entirely, toward the terminal trisaccharide units.In other words, it could be expected that syntheses of the terminal trisaccharides in the form of trisaccharide haptens such as displayed in Figure 7,would provide structures, depending on the R substituent, which would combine at least extensively with natural anti-A and anti-B antibodies regardless of whether or not these were derived from antigenic determinants related to Type 1 or Type 2 chains. Indeed, this was the case.The use of the 8-methoxycarbonyloctyl alcohol as starting material for the synthesis of these structures was based on the need of such a residue in the final structure to serve as a bridging arm to form immunoadsorbents and artificial antigens.15 This choice of bridging arm proved useful for other reasons as well16 but time does not allow the presentation of data in this regard. The main challenge in the syntheses of the A and B determinants was to achieve the establishment of the two a-linkages in high yield. A number of approaches have been evident for over 20 years for the establishment of a-fucosyl and a-galactosyl linkages but none of these were considered likely to produce the a-anomer in substantially greater yield than the fl-form and, perhaps more importantly, the total amount of glycoside formation could not be expected to be high.However, a promising method became apparent in the mid-1960's as a result of our systematic investigations of reactions at the anomeric centre and 16 R. U. Lemieux, D. R. Bundle, and D. A. Baker, J. Amer. Chem. SOC.,1975,97,4076. la R. U. Lemieux, D. A. Baker, and D. R. Bundle,Canad. J. Biochem., 1977,55,507. Lemieux OH Synthetic Hopten Figure 7 Projection formulae for the tetrasaccharide terminal units for the A (R = NHCOCH,) and B (R = OH) human blood-group determinants in the Type 1 and Type 2 chains and related trisaccharide determinants (see Figures 9 and 11) aimed at illustrating the con formations provided by hard-sphere calculations afer setting appropriate +H torsion angles which I have termed the 'halide-ion catalysed a-glycosidation reaction'.l' This reaction played a central role in the first syntheses of blood-group active tri- saccharides by Hugues Driguez.laJ g The method involves guiding the reaction between an appropriately blocked glycosyl halide and an alcohol under solvolytic conditions by way of the @halide to form the a-glycoside. R.U. Lemieux, K. B. Hendriks, R. V. Stick, and K. James, J. Amer. Chem. Soc., 1975,97,4056. R. U. Lemieux and H. Driguez, J. Amer. Chem. Soc., 1975,97,4063. l9 R. U. Lemieux and H. Driguez, J. Amer. Chem. Soc., 1975,97,4069. Human Blood Groups and Carbohydrate Chemistry Because of the anomeric effect,20 /%halides are thermodynamically much less stable than their a-anomers and, therefore, exist in very low concentrations when in equilibrium with their a-forms.21 However, it was discovered that /3-halides have a much greater reactivity relative to their a-anomers than could be expected from their relative thermodynamic stabilities.Thus, it became apparent that an a-glycosyl halide could be used to prepare an a-glycoside should the rate of formation of the &halide from the a-halide be substantially greater than the rate of the reaction of the a-halide with the alcohol to form fl-glycoside. Under these conditions, the low equilibrium concentration of the p-halide would become insignificant to the overall course of reaction. We had established that the a+P equilibration of a glycosyl halide can be made extremely rapid by the presence, in the reaction medium, of a soluble halide salt in sufficient concentration.22 We have proposed an explanation for the high reactivity of /%halides compared with their a-anomers, which is based on stereoelectronic demands for the forma- tion of reactive intermediates." As seen from Figure 8, the formation of a glyco-side from a glycosyl halide and an alcohol under solvolytic conditions is expected to proceed by way of ion-pair to alcohol triplets.The more rapid formation of a-glycoside is then attributed to a more ready decomposition of its precursor triplet than of the triplet that leads to fl-glycoside formation. This situation is rationalized on the basis that the formation of the /i?-glycoside requires the achievement of a boat-like intermediate so as to allow an anti-periplanar arrange- ment in the transition state between the glycosidic bond being formed and the electron pair on the ring oxygen being recovered by the ring oxygen from its contribution to the reacting centre in the formation of the triplet intermediate. That the halide-ion catalysed a-glycosidation reaction worked very well for the preparation of the B-trisaccharide determinant is displayed in a highly abbreviated fashion in Figure 9.23 It may be noted at this point that the problems of blocking and deblocking attendant to this work with multifunctional substrates is not trivial.Considerable planning is required in terms of choice of blocking groups with regard to both a maintenance of the hydroxyl group to be glycosidated in as reactive a form as possible and the keeping of access to the positions to be glycosidated in the order necessary for overall success.However, modern organic chemistry is rich in blocking-deblocking methodologies and, with care, it is normally possible to plan a multistage process while avoiding, so to speak, 'falling between stools'. The main problem normally involves the optimization of a reaction for the particular application at hand. The advents of thin-layer chromatography and high-field Fourier-transform p.m.r. spectroscopy as analytical tools are particularly indispensable in this regard. As seen in Figure 9, optimization of the halide-ion catalysed reactions enabled R.U. Lemieux, in 'Molecular Rearrangements', ed. P. de Mayo, interscience, New York, 1964, p. 709. I1 R. U. Lemieux and J. Hayami, Canad.J. Chem., 1965,43,2162. Is R. U. Lemieux and A. R. Morgan, Canad.J. Chem., 1965,43, 2205. as R. U. Lemieux and Y.Fouron, to be published. Lemieux OBn OBn Bi Sbw -Br-Fast -Br-I I OBn \-ti*I+* OBnOBn BnO BnO O,R Figure 3 A sationalizotion of the CONYS~of'the broniide-ion cataljsed a-galactosidation of an alcohol the establishment of the two a-glycosidic bonds in the B-determinant in excellent yield using only slight excesses of the reacting glycosyl bromides.23 Such high yields greatly facilitate isolation and purification of the product as well as to make possible efficient large-scale processes.The lack of a highly stereoselective method for reducing 2-oximino-a-~-lyxo- Human Blood Groups and Carbohydrate Chemistry pR = (CH2),COOCH3 Figure 9 Use of the halide-ion cataIysedgIycosidation reaction in the course of the synthesis of the terminal trisaccharide unit for the B human blood-group determinant hexopyranosides to 2-amino-2-deoxy-a-~-galactosidesled us to abandon our so-called oximino-chloride method24 for the preparation of 2-amino-2-deoxy-a-~-galactopyranosides.~~The success reported by PaulsenZ6 in the preparation of 2-azido-2-deoxy-a-glycopyranosidesby reaction of the alcohol with 2-azido- 2-deoxy-~-glycopyranosylchlorides in the presence of silver salts led us to con- sider this route.However, to be practical, it seemed necessary to find a simpler route to the desired 2-azido-2-deoxy-~-glycopyranosylchlorides than the multi- step processes used by Paulsen and co-workers. The azidonitration of alkenes using ceric ammonium nitrate and sodium azide reported by Trahanovsky and Robbins2' in 1971 seemed promising in this regard. Indeed, Murray Ratcliffe in his first trials, as seen in Figure 10, obtained a near 80 % yield of tri-O-acetyl-2-azido-2-deoxy-~-galactosylnitrate as an approximately 2:l mixture of the 8-to a-anomeric forms.28 This was ac- complished by reaction of the readily available tri-0-acetyl-D-galactal in aceto- nitrile at -25 "Cwith 2 mole equivalents of ceric ammonium nitrate (CAN) and one mole equivalent of sodium azide.Replacement of the 1-nitrates to afford tri-O-acetyl-2-az~do-2-deoxy-a-~-galactopyranosylhalides is readily ac-complished. The iodide is particularly reactive and was therefore chosen for the s4 R. U. Lemieux, K. James, and T. L. Nagabhushan, Conad.J. Chem., 1973,51,42. Is R. V. Stick and R. U. Lemieux, Austrol. J. Chem., 1978, 31, 901. H. Paulsen, C. KolBT, and W. Stenzel, Angew. Chem. Internat. Edn., 1976, 15,440. l7 W. S. Trahanovsky and M. D. Robbins, J. Amer. Chem. SOC.,1971,93,5256.R. U. Lemiew and R. Murray Ratcliffe, Canad. J. Chem., submitted. Lemieux ZCAN + NoN~+ CH3CN AAc c o sN3 o 2 AcO -25' 80% LiI CH,CNI EtrN*CI-CI -C H3 CN AcO N3 60% overoll (no? purified ) Figure 10 The azidonitration of tri-0-acetybgalactal in the course of the preparation of $4, 6-tri-O-acetyl-2-azido-2-deoxy-~-~-gaZactopyranosylchloride preparation under kinetic control of the desired tri-O-acetyl-2-azido-2-deoxy-/I-D-galactopyranosyl chloride.As can be seen from Figure 1 1, the tri-O-acetyl-2-azido-2-deoxy-/I-~-galacto-pyranosyl chloride was indeed very useful for the preparation of the terminal trisaccharide for the A human blood-group determinant.29 Having accomplished the establishment of the a-linkage in high yield, it was a relatively trivial matter to reduce the azide to amine for N-acetylation and then to remove the blocking groups to provide the desired A-hapten. At this point, I think it appropriate to ask and answer the question 'Why synthesize these complex haptens? In fact, it can be strongly contended, I believe, that advances in immunochemistry have for many years rendered $ear that such syntheses would not only be desirable but indeed necessary for con- tinued progress in the improvement of health care.The supply of antigenic determinants from natural sources is completely inadequate both as to the range of structures desired and as to the amounts available. The glycosphingolipids that occur on red cells are in extremely low natural abundance. Furthermore, these occur in extremely complex mixtures of closely related structures-the problem of obtaining even milligram amounts is formidable. The natural abundance of blood-specific glycoproteins is rather substantial. However, these are both chemically and immunologically hetero- geneous structures.Their degradation and procedures to isolate the products in pure chemical form is very costly and the range of products available is highly *# R. U. Lemieux, D. A. Baker, and R. Murray Ratcliffe, Canad. J. Chem., submitted. 437 Human Blood Groups and Carbohydrate Chemistry R = (CH2)B COOCH3 CO HO h O RO + 0 N3 B% H3 Bn0 OBn OAc AcO Figure 11 The synthesis of on inlernrediute in the course of the synthesis of the terminal trisaccharide unit for the A human blood-group determinant limited. The isolation of pure oligosaccharides with structures related to blood-group specificities from human milk and urine is possible.Nevertheless, the supplies are rather limited; the procedures are difficult and, at best, are amenable to the provision of only gram amounts of a limited range of structures. On the other hand, with the advent of appropriate synthetic methodologies, the supply of any given oligosaccharide would be limited only by the scale of operation. The foreseen range of products which are desirable and which can be made available in substantial amounts by synthesis is already large and will continue to grow. The haptenic structures themselves are of interest to effect changes in biological equilibria by inhibiting specific antibody-antigen interactions. This is useful for the characterization of the specificities of either antibodies or antigens in biological systems.By immobilizing the haptenic structures on solid supports, monospecific immunoadsorbents can be prepared which almost certainly will find a number of important uses because these immunoadsorbents allow the collection and purification of specific antibodies from sera and plasma. Thus, the use of these immunoadsorbents can be expected, in many instances, to replace the use of red cells for the removal of an unwanted specificity in the preparation of a typing serum. The preparation of artificial antigens by attachment of the hapten to a suitable carrier molecule allows the immunization of animals to raise antibodies specific 438 Lemieux to the carbohydrate determinant. The immunoadsorbent then allows the isola- tion of these antibodies from the animal serum.Such monospecific antibodies can then find a wide range of applications such as the detection of antigens in body fluids and the establishment of antigenic sites on tissues and cells. The tests can involve precipitin and agglutination reactions or involve the labelling of the antibody for radioimmunoassays, immunofluorescence assays, or with assays based on electron spin-labelling, etc. Of course, the monospecific immuno- adsorbents also allow the isolation of natural antibodies specific for the carbo- hydrate determinant used and this technique of affinity chromatography based on synthetic haptens can be extended to the isolation of lectins from plants and also enzymes concerned with the synthesis of the carbohydrate structure in viva. Thus, it can be appreciated that the availability of synthetic oligosaccharide determinants can have an important impact on many aspects of medical practice such as in the preparation of typing reagents of interest to blood transfusion, tissue transplantation and diagnostics for cancer and autoimmune diseases.Indeed, one can imagine a number of therapeutic as well as diagnostic applica- tions, Also, as will be seen later, the synthesis of these complex oligosaccharides provides these materials in sufficient quantity to allow studies of their con- formational properties and to examine structure-activity relationships and thereby contribute significantly to progress in the fundamental science for these important biological processes.Because of the foregoing possible uses and because of the limitations, in terms of the work that can be accomplished in one laboratory, I have established the general procedure, outlined in Figure 12, for our synthetic goals. We build the oligosaccharide in glycosidic union to the 8-methoxycarbonyloctyl alcohol which HOCH2(CH2)7COOCH3 J"ULTISTEP SYNTHESIS OLIGOSACCHARIDE-0-CH2 (CH2)7COOCH3 IH2NNHz 1HOIiO OLI GOSACCHARI DE-O-CH2 (CH2) 7CONHNH2 OLIGOSACCHARIDE-FI-CH2 (CH2 )7CON3 AHINE CARRIERMOLECULEI ,AMINATED SOLID SUPPORT I CROSS REACTION 1IHMUN I ZATION 7-ANTISERUM ICROSS REACTION 1 ANTIBODY Figure 12 A general procedure for the prepnrntion of artificial ailtigeris arid iini~unio-adsorbents Human Blood Groups and Carbohydrate Chemistry later serves as a bridging arm.15 Normally, the procedure which is used to prepare an artificial antigen or immunoadsorbent involves the preparation of the hapten acyl azide by way of the acyl hydrazide.The acyl aide is then allowed to react with an aminated solid support to prepare the immunoadsorbent or with a suitable amine carrier molecule to prepare the artificial antigen.16 The hapten, immunoadsorbent and artificial antigen can then be used to examine cross-reactions with natural systems. The procedure, which is outlined in Figure 12, can be illustrated by way of the preparation and properties of immunoadsorbents for the human A and B anti bodies.As seen in Figure 13, we normally employ aminated gIass beads as solid support for the preparation of an immunoadsorbent. An immunoadsorbent prepared in this way and which contains 0.5 micromoles of hapten per gram can substitute for over a hundred times its weight of packed red blood cells. Thus, we can imagine the day when rather laborious and uncertain procedures involving adsorptions with red cells will be replaced by fully automated procedures based on affinity chromatography. At this point, I would like to acknowledge a grant-in-aid for my research made by the Canadian Medical Research Council which rendered possible avery fruitful collaboration with the Canadian Red Cross Transfusion Service. As judged by saline agglutination tests, the immunoadsorbent prepared from the A-trisaccharide determinant removed all of the anti-A antibodies from a human anti-A serum.The use of the similar immunoadsorbent but possessing only the a-~-GalNAc-( 1-+3)-/3-~-Gal disaccharide component of the A-tri- saccharide resulted in adsorption of only about 85 % of the antibodies which are collected by the trisaccharide-immunoadsorbent. When the size of the A- determinant was reduced to the simple a-D-GalNAc structure, no discernible amount of anti-A antibodies was adsorbed. These results illustrate the desirabil- ity, at least for certain purposes, to synthesize the determinant as completely as possible. The Lewis human blood-groups were not in the past of primary importance to blood transfusion since the sera of humans do not normally contain antibodies with these specificities although over 22 % of people possess Lewis-a determinants on their red cells and tissues and 72 % possess Lewis-b antigens.However, typing for the Lewis groups has become of major importance because a mismatch in the Lewis system in the course of one transfusion leads to immunization against the foreign antigen. Thus, a second transfusion of cells carrying this Lewis specificity can lead to a serious transfusion reaction and this can affect about 6% of the population. Thus, the modern blood-banking industry is now in great need of a secure supply of reliable typing reagents for the Lewis system of which the Lewis-a and Lewis-b groups appear to be of most immediate importance.As seen in Figure 14, the Lewis-a and Lewis-b determinants are synthesized from the Type 1 chain. The introduction of an a-L-fucopyranosyl group at the 4-position of the F-D-G~CNAC residue provides the terminal trisaccharide of the Lewis-a determinant. a-L-Fucosylation of the 2-position of the P-D-Gai residue Lemieux Human Blood Groups and Carbohydrate Chemistry O-D-Gal-(1--3)-O-&Gl~lAc .... Type 1 precursor chain O-D-Gal-(l-3)-O-D-GlcWAc ..... O-D-Gal-(1-3)-O-D-Glc~A~ w-L-Fuc-(~-+~) Lewis-A 8 /’”\ Le gene B gene Fuc-( 1-4 1 1 O-D-Gal-(l-+3)-O-D-GlcUAc .... OC-L-FUC-(~-2) J Lewis-B (Gene interaction product) Figure 14 The relationshr’p between the A, B, Hand Lewis human blood-group determinants of the Lewis-a trisaccharide would lead to the terminal tetrasaccharide for the Lewis-b group.However, the Lewis-b determinant is a gene interaction product, and is actually derived by a-fucosylation of the H-determinant. The syntheses of the Leaand L.eb determinants provided very interesting synthetic challenges.15J0 Of course, these are multistep processes and a detailed consideration of the various stages in these syntheses does not seem warranted on this occasion. Figure 15 simply presents a key intermediate which can be used to synthesize either the H, the Lea, or the Leb determinant, CH ),,C 00CH p-02NBrO A~NHIH and Leb Ac=ocetyl, En= benzyl, Br zbenzoyl, Ph =phony1 Figure 1sA synthetic precursor to the H, Lewis-a and Lewis-b determinants R.U. Lemieux and D. A. Baker, Cunud. J. Chem., submitted. Lemieux Hydrolysis of the p-nitrobenzoyl group followed by a halide-ion catalysed glycosidation using tri-0-benzyl-a-L-fucopyranosylbromide as reagent intro- duced the tri-0-benzyl-a-L-fucopyranosylgroup at this position. Catalytic hydrogenolysis then provided the desired H-trisaccharide hapten.30 On the other hand, instead of the hydrogenolysis, the 4,6-O-benzylidene group could be selectively removed by mild acid hydrolysis. The monoacetylation of this product introduced the acetyl group at the less hindered primary position in high yield. This product then possessed a free hydroxyl at position 4 of the /~-D-G~cNAc- residue which was availablz for a-L-fucosylation as previously described for the preparation of the H-determinant.The product of this reaction is shown in Figure 16. Figure 16 The blocked synthetic intermediate which on hydrogenolysis provided the terminol tetrosacchnride unit for the Lewis-6 human blood-group determinant I felt it desirable to point out through such a complete drawing that, because of the extensive use of abbreviated formulae, carbohydrate structures, to the uninitiated, often appear much simpler than these really are. First of all, it may be noted that the blocked penultimate intermediate in the preparation of the Lewis-b determinant is an oily substance of very high molecular weight. The separation of this substance from appreciable amounts of diasteroisomers as could arise in the fucosylation reactions would present a very serious problem.The avoidance of such problems by the utilization of highly stereospecific glyco- sidation reactions is not only desirable but virtually indispensable as is the characterization of the products encountered in these syntheses by Fourier- transform n.m.r. at the highest possible magnetic field. The production of monospecific antibodies from artificial antigens is expected to become of major importance both to medical research and practice. Figure 17 illustrates the preparation of an artificial antigen using bovine serum albumin 443 Human Blood Groups and Carbohydrate Chemistry HoOHbvOH 7fN3 OH n~'w'' 0 Bovine krum Albumin (carrier molecule) 0 1.3 &'-Gal -GlcNAc *O-CH2 a-L -F uc Freund'r complete adiuvant I Vaccine Test animalI Anti-W Serum Figure 17 The preparation of an artificial antigen possessing the terminal trisaccharide unit for the Lewis-a human blood group as antigenic determinanP as the carrier molecule and the trisaccharide determinant related to the Lewis-a human blood group.15 The antibodies raised in animals against this antigen show good promise as a source of anti-Lewis-a antibodies both for tissue and red cell typing and for the detection of Lewis antigens in body fluid and secretions, and this matter promises to be a major development in these regards.An interesting contrast between the use of an artificiaI antigen and a natural antigen in immunization studies is provided by our experience using the Lewis-b specific human blood-group substance, a highly purified glycoprotein provided by Professor E.A. Kabat and termed the HLeb blood-group substance because of the close relationship between the H and Leb determinants. As s&n in Figure 18, the HLeb blood-group substance used in the immuniza- tion of rabbits led to the precipitation of 375 pg of protein per 50 pl of crude antiserum. However, our artificial Leb antigen precipitated only about 45 %of this amount.30 Thus, the natural antigen raised more antibodies which do not recognize the Leb tetrasaccharide determinant than those that do. It is seen that our H and Lea artificial antigens also precipitated protein from the crude anti- HLeb serum.However, as seen in Figure 19, the H, Lea, and Leb antibodies were completely adsorbed from the serum using our Leb immunoadsorbent. As Lemieux Precipitating Antigen C 0 10 20 30 40 50 pg Antigen/50 PIof Serum Figure 18Precipitin data on the crude antiserum from rabbit immunized against natural Lewis-b human blood-group substance and using both the natural antigen and art@cial antigens to @feet the precipitationao expected from the precipitin curves, shown in Figure 18, only about half of the antibodies which were precipitated from the serum by the immunizing antigen passed through the column. When the antibodies that were adsorbed were de- sorbed and isolated, as expected, these were precipitated as well by the artificial antigen as by the immunizing HLeb blood-group substance.80 We do not know the specificities of those antibodies which were raised to the natural antigen but which do not combine with the J&-tetrasaccharide determinant. It is evident, however, that this glycoprotein has more than one immunologically important determinant.Furthermore, it is evident that a precipitationof an antigen by this Humair Blood Groups and Carbohydrate Chemistry Antibodies not adtorbed Antibodies adsorbed 100r r--40t! Leb -BSAtl/ A H -BSA I Id L 0 10 20 30 40 50 0 10 20 30 40 50 pg AntigenBOpI of Serum pg Antigen/= pl of Serum (a) (bJ Figure 19 Precipitin data using the antigen shown to efect precipitation from serum described in Figure 18 (a) after adsorption with a Lewis-b active glass-bead immuno- adsorbent and, (b) on the anti-Lewis-b antibodies which had adsorbed on the columnJo antiserum would not necessarily indicate Leb activity in terms of the Leb tetra-saccharide structure.A definite conclusion in this regard could only be reached by examining whether or not the precipitation is inhibited by the Lebtetra-saccharide and this illustrates a possible use for the synthetic determinants as inhibitors. We expect that such studies will help to clarify the multiple immuno- genicities of such glycoproteins-a matter which could well prove, I think, to be of substantial importance. In closing, I would like to say a few words about the conformational properties of human blood-group determinants by using the Lea, Leb,and Hdeterminants as an example.Our approach in this re~pect,~1 as discussed earlier with regard to the Type 1 and 2 chains, is to make hard-sphere calculations based on the em-anomeric effect to estimate what may be the sterically most plausible con-formation. Once indications in this respect are obtained, we examine the proton and carbon-13 n.m.r. spectra to see whether or not the conformations predicted 31 R. U. Lemieux, S. Koto, and V. S. Rao, Rec. Trav. chim., submitted. 446 Lemieux by the molecular modelling experiments are in reasonable accord with the observed n.m.r. parameters. The total non-bonded interactions present at various t,bH angles are plotted against the $H angles for the oligosaccharide structures as is shown in Figure 20.$7 degrees Figure 20 Hard-sphere calculations, based on the $= torsion angles expected because of the exo-anomeric efect, to estimate the preferred conformations for the terminal Lewis-a trisaccharide and its two component disaccharides Thus, a plot of the change in conformational energy with change in t,bH is obtained. We term these plots #-energy profiles. The valence angle for the glyco- sidic oxygen, termed the T angle, was set as 117" for all of these calculations-a value often found in the crystal structures of disaccharides. These calculations were made using the Kitaygorodsky formula32 which involves the use of both attractive and repulsive terms between the various atoms in the molecules treated as hard-spheres.In fact, an inspection of these contributions shows that a A. I. Kitaygorodsky, Tetruhedron, 1961,14,230. Human Blood Groups and Carbohydrate Chemistry the attractive terms have little influence on the preferred #H angle. That is, nearly the same #H angle would be predicted on the basis of the repulsive interactions only. Nevertheless, it is of interest to note that the total attractive interactions are greater than the total repulsive interactions at the most favourable #H angle for the three oligosaccharides shown. Certainly, the accumulation of near 7 kcal mol-l of attractive interactions versus about 2 kcal mol-1 repulsive inter- actions in the Lewis-a determinant with the c$H and #H angles shown well displays the large net attractions that can arise from a large number of small Van der Waalattractions+ matter of great importance to antibody-antigen combination including, I believe,33 carbohydrate determinants.It is seen from the $-energy profiles for the two disaccharides that the /?-linkage appears to offer a broader range of conformations of near equal conformational energy than does the &-linkage. For this reason, the #H angle for the CX-L-FUC-(1-+4)-/?-~-GlcNAc portion of the Lewis-a trisaccharide was set at the 25" value estimated for the disaccharide itself. Therefore, the $-energy profile shown for the Lewis-a trisaccharide is that arising through variation of the #H angle for the /?+Gal glycosidic linkage.On this basis, the most favourable value for this $=angle appears to be +20". Having thus arrived at a conformation for the Lewis-a determinant, the most favourable orientation for an CX-L-FUCresidue placed at the 2-position of the /?-D-Gal unit to form the Lewis-b determinant was estimated. As seen from $-energy profiles plotted in Figure 21, this CX-L-FUCresidue encounters severe repulsive non-bonded interactions when the c$H angle is set at the 'normal' value of 55". The major contribution arises from van der Waal conflict between the H-1 of this a-L-fucosyl group and 0-3 of the /?-D-galactosyl unit-a repulsion of near 3 kcal mol-l. However, a change of the dH angle from 55' to 40°, a change which is not expected to be highly demanding in terms of the exu-anomeric effect'll lowered this interaction to 0.3 kcal mol-1 without introducing substantial other destabilizing interactions.Therefore, the t$H angle for this ~-L-Fucresidue is assumed to be 'abnormal' with a value of near 40". A comparison of the #-energy profile for the H-determinant with that for the Lewis-a determinant at once shows that the strongly repulsive interactions found in the H-determinant (and consequently in the Lewis-b determinant) are inter- actions between the (II-L-FUCgroup attached to the 2-position of the gal and the ~-~-Gal-(l-*3)-~-~-GlcNAcdisaccharide. Figure 22 provides a list of internuclear distances and van der Waal inter- actions which help to better describe the conformations of the H,Lewis-a, and Lewis-b determinants.Also, some of these interactions appear highly pertinent to the interpretation of the p.m.r. spectra for these structures. First of all, it may be noted that the two CX-L-FUCresidues touch each other over the p-side of the @-Gal unit. That is, the methyl group of the c-fucosyl unit is within van der Waal interaction with the ring-oxygen and the methyl group of the d-fucosyl unit. *$ R. U. Lemieux, P. H. Boullanger, D. R. Bundle, D. A. Baker, A. Nagpurkar, and A. Venot,Nouveau J. Chim. 1978,2,321. Lemieux H Lewis b HO OH -OH T ~117' r ~117' r 5-P W 4-C 0.-c 3-U cE 2-C ? 1-0 ? C 0z" t -1 -24' -2 \ 22't 11111111111 -20 0 20 40 60 qH (degrees) Figure 21 Hard-sphere calculations to estimate the preferred conformations for the H trisaccharide and Lewis-b tetrasaccharide determinants and to illustrate the eflect of changing the $H torsion angle from 55" to 40"for the a-L-fucosyl group attached to the 2-position of the fi-D-galactosyl residue Secondly, H-5c is seen to be strongly interacting with both 0-lb and O-Sb. These repulsive interactions could be expected to strongly deshield H-5c and it will be seen that in fact this hydrogen is strongly deshielded both for the Lea and Leb determinants.Thirdly, it is seen that H-5d is very close to 0-lb. Although the interaction appears weak, deshielding of H-5" relative to its position in the spectrum for methyl a-L-fucopyranoside must be expected. Finally, it is seen that H-ld and 0-3" appear in a repulsive interaction. As noted above, this interaction was strongly relieved by changing the 4Hd torsion angle from 55" to 40".This residual interaction between, H-ld and 0-3b would be in accord with the occurrence of the p.m.r.signal for H-ld at an unusually low field. Human Blood Groups and Carbohydrate Chemistry Interoc ting Internudeor Non-bonded Atoms Distance Interaction li /kcal mol-' no 3.86 -0.07 4.29 -0.07 n 2.3 1 +0.67 2.40 +0.21 2.75 -0.04 $0 2.42 +0.34 Figure 22 Internuclear distances for the Lewis-b tetrasaccharide detertninant involving atoms whose signals are readily identified in the proton magnetic resonance spectrirtn (Figure 23).The conformation is rhat depicted in Figure 21 The p.m.r. spectra in DzO for the Hand Lea trisaccharide determinants and for the Leb tetrasaccharide determinant taken at 360 MHz are presented in Figure 23. These spectra display well the great promise offered by these high- field instruments to obtain information, both structural and conformational, about these complex structures. As already inferred, the spectra provide excellent support for the conformations of these structures as derived by hard-sphere calculations based on the operation of the exo-anomeric effect. First of all, the spacings observed are in accord with the chair conformations shown for all of the sugar residues.34 Note, also, that an addition of the spectra for the Lea and H determinants provides an excellent approximation of the spectrum for the Leb determinant-as is required by the procedure used to make the calculations. Because H-ld of the H and Leb determinants interacts strongly with 0-3b of the galactosyl residue, this hydrogen should be to lower field than H-lCof the other fucosyl group in the Leb determinant and of H-1C in the fucosyl group of the Lea determinant-and it is to lower field by 0.13 p.p.m.€3-Yinteracts strongly with both 0-lb and 0-5b and should be strongly deshielded. Infact, the signal for this hydrogen is 0.94 p.p.m. to lower field than that for the corresponding hydrogen in the model methyl a-L-fucopyranoside and, indeed, it is over 0.3 p.p.m. to lower field than either one of the p-anomeric hydrogens of the Lea trisaccharide.This remarkable observation appears defi- nitely to require that the conformation of the Leadeterminant be very close to that predicted by molecular modelling after assuming the influence of the exo-anomeric effect. It is seen that H-5d in both the H and Leb determinants is 0.42 p.p.m. to lower field than H-5 of methyl a-L-fucopyranoside and this deshielding can be attri-buted to the interaction with Glb. 34 G.Kotowycz and R.U.Lemieux, Chem. Rev., 1973,73, 669. 450 Lemieux Lewis-o determinant H-5C I i3 n-id ,,-,c II Lewis-b determinant I1.51 .5 3H-Sd n.lb H-10 H determinant HO-Figure 23 360 MHz proton magnetic resonance spectra for the synthetic Lewis-a, Lewis-b, and H determhants [R= (CH&COOCH dissolved in D 2O Furthermore, the occurrence of the signals for the two C-methyl groups in the Leb determinant to lower field than those for C-methyl groups of the parent Lea and H determinants is in accord with the close proximity of the two fucosyl residues in the Leb determinant. 451 Human Blood Groups and Carbohydrate Chemistry The general agreement between the calculated model and the p.m.r.spectra is in a way surprising since the molecular modelling assumes no influence what- soever from an environment, and the proton magnetic resonance spectra are for the structures dissolved in water. This correspondence clearly suggests a high degree of conformational rigidity for the structures and, of course, to be most effective as a determinant, a structure should be conformationally well specified.Otherwise, the energy required to organize a determinant into the conformation demanded by the combining site will oppose the driving force for combination. In conclusion, the objective of my lecture today has been to attempt to display, mainly through recent research in my laboratory, the state of a body of know- ledge-the roots of which can be traced back to the work by Haworth. I hope I was able to show that the leading edges of synthetic and structural carbo- hydrate chemistry are now meeting leading edges in biology and that this meeting augurs well for the improvement of the knowledge required to deal with important human problems. As pointed out by Angya135 in his review of conformational analysis in carbo- hydrate chemistry, Haworth predicted in 192936 with regard to the various possible shapes of sugar molecules that, ‘these considerations open up a large field of inquiry into the conformation of groups as distinct from structure or configuration’.Considering that there existed no experimental data to guide this speculation, this was a remarkable prediction indeed. 56 E. L. Eliel, N. L. Allinger, S. J. Angyal, and G. A. Morrison, ‘Conformational Analysis’, Interscience, New York, 1965, p. 362. a’ W. N. Haworth, ‘The Constitution of Sugars’, Edward Arnold & Co., Landon, 1929, p. 90.

ISSN:0306-0012    

DOI:10.1039/CS9780700423

出版商:RSC    

年代:1978

数据来源: RSC

摘要:

Photophysics of Molecules in Micelle-formhg Surfactant Solutions By K. Kalyanasundaram DAVY FARADAY RESEARCH LABORATORY OF THE ROYAL INSTITUTION, 21 ALBEMARLE STREET, LONDON W1X 4BS 1Introduction Amphiphilic molecules containing both hydrophobic and hydrophilic moieties associate in water above a certain critical concentration to form aggregates of colloidal dimensions called ‘micelles’. The architecture of a micelle is such that the interior contains the hydrophobic alkyl chain part of the amphiphiles and the charged headgroups are located at the surface forming a charged electrical double layer (interface) in contact with the bulk water. Detailed structural and dynamical aspects of these organised multimolecular assemblies have been the subject of intense research activity using various physical methods.Recent advances on the many facets of micellar chemistry have been reviewed in several p1aces.l Though not a pre-requisite for this review, readers are well advised to consult a recent reviewl‘ in this series for an up-to-date account and for an explanation of the terminologies used in this field. Among the various physical methods that have been used, photophysical methods stand unique for their simplicity, wide scope, and extreme sensitivity at very low solute (probe) concentrations. Also the time scales spanned by phdo- physics-from few picoseconds to several seconds-enables one to study both the fast and the slow dynamical processes associated with the aggregates. The advantages and potentialities of photophysical studies in aqueous micellar media are manifold. The peculiar make-up of the micelle enables one to organize the reactants on a molecular level.By comparison of the data in micelles with similar data in homogeneous solvent systems, one learns more about the molecular details of a given reaction, picks up conditions which favour one pathway over another, and at the same time is able to comment on the intricate details of micellar structure and dynamics. The random, statistical distribution of the solute amongst the micelles, coupled with the presence of a charged interface nearby, often lead to significant differences in the rates and efficiency of the reactions undergone by the solute. The methodology of the technique has lac.Tanford, ‘The Hydrophobic Effect’, Wiley, New York, 1973; J. H. Fendler and E. J. Fendler, ‘Catalysis in Micellar and Macromolecular Systems’, Academic Press, New York, 1975; P. H. Elworthy, A. T. Florence, and C. B. Macfarlane, ‘Solubilisation by Surface Active Agents’, Chapman and Hall, London, 1968. lb‘Micellisation, Solubilisation and Microemulsions’, ed. K. L. Mittal, Plenum Press, New York, 1977, vols. 1 and 2. ICL. R. Fisher and D. G. OakenfulI, Chem. SOC.Rev., 1977,6,25. 453 Photophysics of Molecules in Micelle-forming Surfactant Solutions advanced to such a level in micelles that these applications can be easily carried over to studies of similar bioaggregates such as lipid vesicles, liposomes, poly- mers, and proteins.The scope of this review is to outline some of the various photophysical processes that have been studied in aqueous micellar solutions and to indicate their applications in several areas. The field is still very much in its infancy and is experiencing a rapid growth. Except for those studies referred to in the section on ‘reversed micelles’, all references are to the micelles formed in water as the medium. Forlack of space the various photophysical processes as such will not be discussed at any length, and readers are referred to the excellent monographs available.2Also,the review is more illustrative in nature than a comprehensive discussion of all the reported work. In studies of photophysical processes in micelles there are a few cautionary notes worth mentioning.In multiphase heterogeneous systems such as micelles, the high local electric fields present near the surface fall off quite rapidly as one moves deeper into the inner core. So for any generalization of a set of results using different probes it is useful, and even mandatory, to talk about the exact solubili- zation or binding site of the probe in the aggregate. A probe can reside solely in the inner hydrocarbon phase, sandwich at the surface with the polar headgroups, or just adsorb at the surface by electrostatic interactions. Depending on the solubility characteristics, the reactants (the probe and the quenchers) can be dispersed primarily in the micellar pseudophase or in the bulk water, or partition between the two phases with an associated distribution coefficient.In the latter case, one has a situation in which a reaction can occur simultaneously in more than one phase with very different features in each phase. When condensed aromatic hydrocarbons whose dimensions compare favour- ably with the overall dimensions of the micelle itself (radius 20-25 &are used, assignments to the dynamic solubilization sites are qualitative in nature. With large size probe molecules it is also likely that the solubilization perturbs the micellar structure creating water channels. To overcome some of the above problems it is advantageous to use a built-in chromophore, or even pick up the components of the surfactant themselves to be the reactants (functional surfact- ants) whose size is quite small.If a highly polar group is built into a hydrophobic alkyl chain, there may be a perturbation of the micellar structure by the intrinsic property of the probe to seek polar environments. Thus, to provide confidence in the usage of photochemical probes, it is advantageous to employ other compli- mentary physical methods to ascertain the average, dynamic solubilization sites and on the pertubations, if any, due to the introduction of the solutes. 2 Fluorescence The basic idea behind the use of a fluorescence probe is that certain types of molecules display a selective affinity for a unique site on a macromolecule and the * J. B. Birks, ‘Photophysics of Aromatic Molecules’, Wiley, New York,1970; C.A. Parker, ‘Photoluminescence of SoIutions’, Elsevier, New York, 1968;‘Organic Molecular Photo-physics’, ed. J. B. Birks, Wiley, New York,1976, Vols. 1 and 2. Kalyanusundaram nature of the probe environment is reflected in their emission properties. The various fluorescence parameters that are used in this context are the fluorescence excitation and emission spectra, presence of vibrational fine structures and their intensities, shifts in the position of emission maxima, quantum yields, lifetimes, and the polarization of the fluorescence. The success and the ambiguities associated with the fluorescence probe analysis are very much dependent on to what extent the actual solubilization site can be specifiedand how well the medium effects on the above fluorescence parameters are characterized. A.Solvent Effects on the Fluorescence Spectra.-One simple and seemingly rather straightforward application is that based on the solvent effects in the emission spectrum of a probe molecule. When excited states of a molecule are created in polar solvents like water or acetonitrile either by continuous or flash excitation, depending on their polarity, the excited states interact to a varying degree with the solvent molecules before the molecule returns to the ground state. Such solute-solvent interactions in the excited state are often reflected in the fluorescence spectral position, shape, and lifetimes. Milder interactions lead either to blurring or to variations in the relative intensities of the vibrational fine structures of the emission spectrum.In the case of stronger reactions, the Franck- Condon envelopes of the excited state themselves shift to give red or blue shifts in the emission maxima. A case where the solvent interactions perturb mainly the relative intensities of the vibrational fine structures is the so-called ‘Ham-effe~t’.~ In aromatic mole- cules such as benzene or pyrene (with minimum D2h symmetry) the absorption and fluorescence spectra show mixed polarizations owing to the vibronic coupling between the first (S1)and the second (SZ)singlet excited states. The first singlet absorption (So-+Sl)is symmetry forbidden and is weak. In the Ham effect, the forbidden vibronic bands in weak electronic transitions show marked intensity enhancements under the influence of solvent polarity.In pyrene, for example, if one numbers I to V the principal vibronic bands observed in the room temperature fluorescence in solution, peak I11 (0-737 cm-1 band) is strong (allowed) and shows minimal variations in intensity. Peak I (0-0 band) shows significant intensity enhancements in polar solvents. Thus the peak intensity ratio (III/I) in the normal fluorescence spectrum serves as a measure of the polarity of the medium. Quantitative studies3p4 indicate that the solvent dipole moment as well as the dielectric constant contribute to these relative intensity enhance- ments. The peak ratio (III/I) has been used recently 596 as a probe in micelles to determine critical micelle concentrations (CMC) and the extent of water penetra- a J. S.Ham, J. Chem. Phys., 1953,21,756; A. Nakajima, Bull. Chem. SOC. Japan, 1971, 44, 3272; Spectrochim. Acta, 1974, A30, 860; J. Mol. Spectroscopy, 1976, 61, 467. K. Kalyanasundaram and J. K. Thomas, J. Amer. Chem. SOC., 1977, 99, 2039. A. Nakajima, Photochem. Photobiol., 1977, 25, 593; J. Luminescence, 1977, 15, 277. * R. C. Dorrance and T. F. Hunter, J. C. S. Faraduy I, 1977,73,1891; D. A. N. Morris and J. K. Thomas, in ref. 16; Th. Proske, Ch. H. Fisher, and M.Grtitzel, Ber. Bunsengesellschaft Phys. Chem., 1977, 81, 816; W. Schencke, M. Gratzel, and A. Henglein, ibid., 1977, 81, 821. Photophysics of Molecules in Micelle- forming Surjactant Solutions tion in the micelles.In studies of lipid vesicles it has been used to monitor changes associated with lipid phase transitions and to determine the rather lower CMC values for the micelles formed by lysolecithins. A more familiar example of solvent effects is the solvent-induced red shifts in the fluorescence maximum of molecules of the type aryIaminonaphthalenes7**[e.g. l-anilino-%naphthalene sulphonate (ANS), N-phenylnaphthylamine (NPN)], indoles,g and aromatic aldehydesfo (e.g. pyrene-3-carboxaldehyde).In this class of compounds fluorescence lifetimes, emission maxima, and the quantum yields vary markedly with the solvent polarity. Though the exact photophysical proces- ses involved in these intense solvent effects are not well understood and are still under active investigation,ll several useful linear correlations of the emission maxima with the bulk solvent dielectric constant have been demonstrated and these correlations find increasing use as a rough measure of the polarity of the probe binding sites.Except with the non-ionic micelles, studies with charged molecules of ANS type have not been satisfactory. It is not clear whether these negatively charged probes bind to anionic micelles. In cationic micelles there is frequent interaction of probes with monomeric surfactants at surfactant concen- trations well below the CMC. Nevertheless, estimates for polarity of probe bind- ing sites in various micelles using these probes are available. In very early fluorescence probe studies,l2 changes in the quantum yields and lifetimes at a given wavelength were used to probe micellar structure.For studies of this type, ideal probes are those which do not carry appreciable charge either in the ground or in the excited state. A probe under this category is pyrene-3-carboxaldehyde (PyCHO), which shows large red shifts due to the solvent-induced mixing of (n,n*)and (~,n*)excited states. With PyCHO near the micelle-water interface, the fluorescence spectral shifts have been used to estimate polarity at this water interface. The polarity estimates are in good agree- ment with similar estimates from electrophoretic measurements. Among the heterocyclics, indole fluorescence shows solvent-induced spectral shifts and several 1,3-dialkyl indoles with the indole moiety built into the alkyl chain have been examined.9 Time-correlated single photon counting allows resolution of the indole fluorescence into those from aqueous and micellar components in the vicinity of CMC.The relative intensity of the ‘normal’ to the ‘anomalous’ long wavelength fluorescence of dimethylaminobenzonitrilel3~has M. T. Flanagan and S. Ainsworth, Biochim. Biophys. Acta, 1968,168, 16; H-C. Chiang and A. Lukton, J. Phys. Chem., 1975,79, 1935; R. C. Mast and L. V. Haynes, J. Colloid Inter-face Sci., 1975, 53, 35. e. G. A. Davis, J. Amer. Chenr. SOC., 1972, 94, 5089. N. E. Schore and N. J. Turro, J. Amer. Chem. SOC.,1974, 96, 306; ibid., 1975, 97, 2488. lo K. Bredereck, Th. Forster, and H. G. Oeirstein, in ‘Luminescence of Organic and Inorganic Materials’, ed.H. P. Kallman and G. M. Spruch, Wiley, New York, 1960; K. Kalyanasun-daram and J. K. Thomas, J. Phys. Chem., 1977, 81,2176. l1 E. M. Kosower, H. Dodiuk, K. Tanizawa, M. Ottolenghi, and N. Orbach. J. Amer. Chem. Soc., 1975,97, 2167; G. R. Fleming, G. Porter, R. J. Robbins, and J. A. Synowiec, Chem. Phys. Letters, 1977, 52, 228. For a review see, M. Gratzel and J. K. Thomas, in ‘Modern Fluorescence Spectroscopy’, ed. E. L. Wehry, Plenum Press, New York, 1976, Vol. 2, p. 169. 13a0.S. Khalil and A. J. Sonnessa, Mol. Photochem., 1977, 8, 399. Kalyanasundaram been used as a probe. Solvent effects on the relative ratio of cyclization to cleavage in Norrish Type I1 photoreaction~l~~ also serve to monitor the local solvent properties of micelles.B. Fluorescence Quenching.-The diffusion-controlled process of fluorescence quenching has been used to study various dynamical properties of aggregated systems of micelles and lipid vesicles. A fluorescence probe such as pyrene solubi- lized in the micellar interior is excited by a short nanosecond light pulse. In the presence of substances which act as quenchers the decay of fluorescence is enhanced. The rate at which the quenchers enter the micelle and/or the probe diffuses in the micellar interior determines the kinetics of the quenching process. Consequently, a kinetic analysis of the fluorescence decay curves and yields provides information on the permeability of the micelle or the vesicle to the quenchers and on the movement of the probe inside the aggregate.Several studies14 based on this concept of fluorescence quenching have led to a variety of information on the properties of micelles: the CMC, distribution coefficients for the case of partitioning of the probe or the quenchers between the micellar phase and the bulk water, extent of counterion binding to the micellar surface, oxygen penetration, and the influences of additives on the permeability properties of the aggregate. In cases where there is a single quenching process involved, e.g. probe dispersed primarily amongst the micelles and the quenchers restricted to the bulk aqueous phase, or vice versa, the fluorescence decay is exponential and the quenching process adequately described14 by the well known Stern-Volmer kinetics scheme.Deviations from a single exponential decay are observed when there is a significant partitioning of the probe, e.g. naphthalene,l5or the quencher, e.g. methylene iodide,lga between the bulk water and the micellar phase. If the overlapping quenching processes have very different rates and/or the partitioning coefficients are fairly large, the fluorescence decay can be approximated by the sum of two exponentials. Several kinetic mode1sl6J7 for the analysis of such types of complex decays have been proposed. Complications also arise in cases where one uses electrically charged water-soluble probes and/or quenchers. For example, the charged probe can distribute itself in the two phases or more than one charged quencher molecule preferentially bind to the micellar surface.The latter case leads to quasi-static distributions in which there is locally high concentrations of the quencher on the micellar surface. Cu2+ quenching of pyrene l3bN,J. Turro, K. C. Liu, and M. F. Chow, Photochem. Photobiol., 1977,26,413. l4aM. Grltzel, K. Kalyanasundaram, and J. K. Thomas, J. Amer. Chem. SOC., 1974,96,7869. 14bM. Grltzel and J. K. Thomas, J, Amer. Chem. SOC., 1973, 95, 6885. lUS. C. Wallace and J. K. Thomas, Rad. Rcs., 1973, 54, 49; H. J. Pownall and L. C. Smith, Biochemistry, 1974, 13, 2594; L. K. Patterson and E. Vieil, J. Phys. Chem., 1974, 96, 306. lsR. R. Hautala and N. J. Turro, Mol. Photochem., 1972, 4, 545; R.R. Hautala, N. E. Schore, and N. J. Turro, J. Amer. Chem. SOC., 1973, 95, 5508. leap. P. Infelta, M. Grltzel, and J. K. Thomas, J. Phys. Chem., 1974,78, 190. lsbP. P. Infelta and M. Grltzel, J. Chem. Phys., 1978, in the press; M. Tachiya, Chem. Phys. Letters, 1975, 33, 289. l7 M. A. J. Rodgers and M. F. de Silva e Wheeler, Chem. Phys. Letters, 1978, 53, 168. Photophysics of Molecules in Micelle-forming Surfactant Solutions fluorescence17 and I-quenching or pyrenel-butyrate fluorescence,lB both in anionic micelles, illustrate these cases. Detailed kinetic analysis assuming a two- phase model, in favourable cases, has led to the determination of the distribution coefficients. By comparison of the fluorescence lifetimes of a probe such as pyrene-l- sulphonate (PSA) (which binds on the micellar surface) in cationic micelles of cetyltrimethylammonium halides with different halide counterions, it is possible to estimatelk the local concentration of bound halide ions.Studies with the quencher bromide and non-quencher chloride as counterions give local bromide concentration of N 3M.A very rapid drop in this high local concentration with increase in distance into the inner core is inferred from comparative analysis of lifetimes of probes, PSA, pyrenebutyric acid (PBA), and pyrene, which penetrate the micelle to varying degrees. Similarly, the different fluorescence lifetimes for a given probe19 under aerated, de-aerated, and oxygenated conditions, give a measure of oxygen penetration in micelles.The quenching rate constant for a given probe-quencher-micelle system has been used as a probe to monitor changes in the permeability properties of the aggregates when other non-quencher additives such as Mg2+ and benzyl alcohol are present,14b and also to study20 processes such as electrolyte-induced phase transitions from spherical micelles to larger rod-shaped aggregates. Quenching of indole fluorescence, which occurs via both static and dynamical quenching processes in homogeneous solvents, has been examined21 in anionic micelles in an attempt to gain further insight into the mechanisms involved in the quenching process. Dynamics of fluorescence quench- ing has also been used extensively in studies of bile acid micelles22 and in lipid vesicles23 to monitor lipid phase transitions.Recently there has been some discussion in the literature24 as to the exact region where the fluorescence quenching occurs; in the non-polar interiors with water-insoluble quenchers entering through water channels created by the intro- duction of the probe, or the excited probe diffuses out into the bulk aqueous phase. For water-insoluble probes, such as pyrene solubilized in ionic micelles, preferred mechanisms25 require the quenchers to enter the micelle rather than the excited pyrene exit into the aqueous phase. With regard to the polarity of the average quenching site, it appears to be non-polar. Arguments based on the emission maxima of exciplexes have been advanced. Processes such as micelle- monomer exchange, micelle complete dissolution, and exit rates for aromatic loF.H. Quina and V. G. Toscano, J. Phys. Chem., 1977,81, 1750. lS M. W. Geiger and N. J. Turro, Photochem. Photobiol., 1975,22, 273. loK. Kalyanasundaram, M. Gratzel, and J. K. Thomas, J. Amer. Chem. SOC., 1975,97,3915.M. R. Eftink and C. A. Ghiron, 1. Phys. Chem., 1976, 80,486. M. Chen, M. Griitzel, and J. K. Thomas, Chem. Phys. Letters, 1974, 24, 65; J. Amer. Chem. SOC., 1975,97, 2052. laS. Cheng and J. K. Thomas, Rad. Res., 1974,60,268; S. Cheng, J. K. Thomas, and C. F. Kulpa, Biochemistry, 1974, 13, 1135; M. Wong, J. K. Thomas, and C. F. Kulpa, Bio-chim. Biophys. Acta, 1976, 426, 71 1. M. A. J. Rodgers and M. F. de Silva e Wheeler, Chem. Phys.Letters, 1976,43, 587; B. B. Craig, J. Kirk, and M. A. J. Rodgers, ibid., 1977, 49, 437. J. K. Thomas, Accounts Chem. Res., 1977, 10, 133. solubilizates all occur at very slow rates (microseconds, or longer) and so on nanosecond t ime-scales of fluorescence quenching, micelles with solubilized probes can be considered a rigid system. C. Excimer Kinetics.-Another diffusion-controlled photo-physical process, which has received wide attention and application in micelles and lipid vesicles, is the formation of intermolecular excited dimers, often abbreviated as 'excimer'. In micelles, time-resolved fluorescence studies of excimer formation kinetics have provided a clear cut demonstration of the random (statistical) manner in which water-insoluble molecules distribute themselves amongst the micelles.In lipid vesicles similar analysis provides a means of monitoring lateral diffusion of probes in the lipid bilayer of membranes and also follow changes occurring dur- ing the lipid phase transitions. Following the initial work of Forster and Selinger,26 the formation of excimers of pyrene and other molecules in micellar media has been investigated by several groups.20~27-2QIn homogeneous solvents like cyclohexane, the yields and the rate of formation of excimers are dependent on the probe concentration, the tempera- ture and the viscosity of the medium, and the process is adequately described by the familiar Forster-Kasper Scheme. In micellar media, for water-insoluble solutes such as pyrene, the probability of the excited singlet state leaving one micelle and finding another ground state pyrene (from another micelle) within its excited state lifetime is very low (estimates for the exit rate of probes from micel- les, based on triplet state studies discussed later, are of the order of milliseconds) and hence the intermolecular formation of excimers is essentially an intramicellar process. Only those micelles which have more than one pyrene molecule incor- porated at the instant of flash excitation alone give rise to excimers.Given the bulk concentration of the probe (pyrene) and the concentration of the micelles, the probability of finding one, two, or more probe molecules in a given micelle can be computed assuming a random distribution of solute amongst the micelles present.The simplest, and also a fairly reasonable model, is that based on Poisson-Boltzmann statistics (P-B). According to the Poisson distri- bution, the probability Pnof finding n solute molecules in a given micelle is given bY mne-mPn = -n! where m is the mean (average) number of solute molecules per micelle. The micelle concentration at various bulk surfactant concentrations (surf.) can be computed from the aggregation number and the CMC (Micelle) = [(surf.) -(CMC)]/Agg. No. (2) Since micelle-monomer exchange and solute exit rates from the micelle are quite as Th. Forster and B. K. Selinget, 2.Narurforsch., 1964, 19, 38. R. C. Dorrance and T. F. Hunter, J.C.S. Faraday I, 1972, 68, 1312; ibid., 1974, 70, 1572.a* M. Hauser and U. Klein, 2.Phys. Chem. (NF.),1972, 78, 32; Actu Phys. Chem., 1973, 19, 363. aeW.Khuanga, B. K. Selinger, and R. McDonald, Austral. J. Chem., 1976,29, 1. '@W. 1976,101,209.Khuanga, B. K. Selinger, and R. McDonald, 2.Phys. Chem. (NF.), Photophysics of Molecules in Micelle-forming Surfactant Solutions slow, in the Poisson-Boltzmann distribution micelles are considered as rigid boxes in which the solutes are dispersed. Dorrance and HunterY2’ however, prefer to treat the micelles as an open system (with a finite probability of micellar col- lapse) and use a slightly modified distribution Pn = mn/(l + m)l+n (3) which reduces to P-B statistics when n is large. Hauser and Klein2* propose that the distribution is more like that of Bose-Einstein (RE).However, when m < 1, both B-E and P-B statistics predict roughly the same type of distribution. Experimental verification^^^^^^-^^ for a random distribution hypothesis come from time-resolved fluorescence studies on the monomer, excimer growth and decay, and from their relative yields for various probe-to-micelle ratios. Using a Poisson distribution of pyrene amongst the micelles, micellar aggregation num- bers and diffusion rates have been determined. In studies of microviscosities o€ micellar core using the relative monomer-to-excimer yield~,3~ failure to take this random distribution effects into account has resulted in abnormally high ‘7’ values for the inner core. The dynamics of excimer kinetics coupled to the mono- mer fluorescence quenching has been used to distinguish the lateral diffusion of the probe as against the vertical diffusion in larger rod-shaped micellar aggre- gates. For solutes such as 2-methylnaphthalene or 1-cyanonaphthalene, which form excimers at relatively high concentrations owing to low enthalpy changes, the statistical restrictions on the excimer formation are much less severe.With these solutes solubilized at high occupation numbers, one is dealing virtually with a dispersed lipophilic ‘normal’ solution. In larger unilamellar bilayer vesicles formed by the lecithins, the hydrophobic volume over which the pyrene molecules are dispersed is considerably large and in these systems excimer formation can be described by the normal diffusion- controlled kinetics.31-34 At temperatures well below the lipid phase transitions, the local viscosity is fairly high and the probe diffusion is very much lateral.Attempts have been made to describe this lateral diffusion of probes 32b,34as well as the reactions between two reactants, both adsorbed on the micellar surface36 as reactions occurring topologically in two-dimensional surfaces, as against the normal three-dimensional diffusional processes in bulk solvent systems. There have been several studies of lipid phase-transitions using pyrene excimers. Intramicellar, intermolecular formation of phenyl excimers between built-in ao H. J. Pownall and L. C. Smith, J. Amer. Chem. SOC.,1973, 95, 3136.31 H. J. Galla and E. Sackmann, Ber. Bunsengeseilschaft Phys. Chem., 1974, 98, 949; Bio-chim. Biophys. Acta, 1974, 339, 103; P. Sengupta, E. Sackmann, W. Kuhlne, and H. P. Scholtz, ibid., 1976, 436, 839. saaJ. M. Vanderkooi and J. B. Callis, Biochemistry, 1974, 13, 400; J. M. Vanderkooi, S. Fischoff, B. Chance, and R. Cooper, ibid., 1974, 13, 1589. snbJ. M. Vanderkooi, S. Fischoff, M. Andrich, F. Podo, and C. S. Owen, J. Chem. Phys., 1975, 63, 3661. a* A. K. Soutar, H. J. Pownall, A. S. Hu, and L. C. Smith, Biochemistry, 1974, 13,2828. a4 D. A. N. Morris, Doctoral dissertation, University of Notre Dame, 1977. m A. J. Frank, M. Gratzel, and J. J. Kozak, J. Amer. Chem. Soc., 1976,98,3317; A. J. Frank, M. Griltzel, A. Henglein, and E. Janata, Internut.J. Chem. Kinetics, 1976, 8, 817. Kalyanasundaram phenyl (or phenoxyl) groups has been reported.36 Studies of intramolecular phenyl excimers in compounds such as biphenyl alkanes, dibenzylether and dibenzyl- amines in mi~elles~~ provide another elegant way of probing dynamics of intra- molecular excimer-forming systems. D. Excited State Charge-Transfer Complexes (Exciplexes).-Formation of charge-transfer complexes (exciplexes) in the fluorescence quenching of aromatic molecules by quenchers such as amines have been observed in the laser photolysis studies in homogeneous solvents. In non-polar solvents the exciplex is quite stable, luminesces and, in polar solvents, rapidly dissociates into molecular ions. Studies of the exciplex formation kinetics in micellar aggregates,3*939 with either one or both the donor-acceptor pair solubilized in the micelle, provide an elegant method of probing heterogeneities in the micellar structure and their effect on the dissociation of the exciplex.Features of intermolecular exciplex of pyrene-dimethylaniline (Py/DMA) with pyrene and several of its derivatives and of the intramolecular exciplex Py-(CH&-DMA have been investigated recently in various ionic and non-ionic micellar systems. Singlet excited states of pyrene are efficiently quenched by DMA by a charge-transfer process to form the ionic exciplex (Py- -DMA+)* whose fate depends critically on the nature of the micelle. Stern-Volmer plots for the pyrene fluorescence quenching are nonlinear due to multiple binding of DMA to the ionic micelles.In cationic micelles, following the quenching, the DMA+. cation is expelled from the micellar surface while Py-*is retained (stabilized) leading to a long life- time for Py-..(Similar solute ejection mechanisms have been proposed40 earlier for the ejection of duroquinone anion (DQ-*)from anionic micelles following its electron-transfer quenching of the chlorophyll u singlets.) In anionic micelles, on the contrary, the micellar surface traps DMAf. ions leading to an enhanced geminate ion-combination. Because of the trapping of DMA+- at the surface some of the Py-* ions escape the recombination and decay with lifetimes much longer than those observed in homogeneous solvents.Earlier transient absorp- tions due to the exciplex have been reported14b in the pyrene fluorescence quench- ing in the mixed micelles of laurylamine and sodium lauryl sulphate. However, this has been questioned4' as this report implies the presence of free base at pH of the solutions of well below the pKa of the amine. In the case of Py-(CH&- DMA, the emission from the intramolecular exciplex as well as formation of Py-* have been observed to varying degree in various micelles. The exciplex yield and lifetime decrease as one goes through the series: hexane, neutral micelle 3saS.J. Rehfeld, J. Colloid Interfuce Sci., 1970,34,518. sebK.Kalyanasundaram and J. K. Thomas, in ref. Ib, Vol. 2, p. 569. 37 B.Selinger and K. Zacharaisse, unpublished work, quoted in ref. 29b;K.Kalyanasundaramand J. K. Thomas, unpublished results. 38 B. Katusin-Razem, M. Wong, and J. K. Thomas, J. Amer. Chern. Soc., 1978,100, 1679. 3s H. Masuhara, K. Kaji, and N. Mataga, Bull. Chern. SOC.Japan, 1977,50,2084;Y.Waka, K. Hamamoto, and N. Mataga, Chern. Phys. Letters, 1978,53, 242. Ch. Wolff and M. Gratzel, Chem. Phys. Letters, 1977,52, 542. 41 B. K. Selinger, Austral. J. Chem., 1977,30, 2087. 461 Photophysics of Molecules in Micelle-forming Surfactant Solutions (Igepal CO-630),methanol, cationic micelle (CTAB), and anionic micelle maw. E. Fluorescence Depo1arization.-Studies of the depolarization of fluorescence from solubilized probes in macromolecular systems provide information concern- ing the mobility of the probe and its orientation as well as the microviscosity of the probe environment. When a fluorescent molecule is excited by a plane polarized light, its emission will be maximally polarized if, during its excited state lifetime, the probe does not change its position as in a viscous medium.If the molecule is not rigidly held, Brownian motions of the probe will tend to remove the orientation imposed by the polarized excitation. The theory associated with the depolarization of fluorescence due to this random Brownian motion, has been determinedg2 and the observed polarization p is given by the Perrin’s equation. A fluorescence probe, loosely bound in a micelle, probes the molecular motions in its immediate environment.The ‘7’ thus derived is termed ‘microviscosity’ in order to distinguish it from the bulk viscosity of the medium in which the micelles are present. Molecules such as perylene, 2-methylanthracene, and diphenylhexatriene (DPH) have been used in the steady state fluorescence depolarization studies43 to measure microviscosities for the inner hydrophobic regions of aggregates of micelles and lipid vesicles. For micellar systems the measured microviscosities are of the order of 15-30 cP. Although these values are high compared with 1-2 CP observed for pure hydrocarbon liquids, they nevertheless stfess the fluid nature of the micellar core. N.m.r. relaxationg4 and laser Raman scattering studies45 of the segmental mobility of various units in micelles indicate a gradient in the motional freedom of the hydrocarbon chains with the last three-four carbon atoms at the end of the chain (in the core) behaving as though they are in neat hydrocarbon liquids. In micelles, formed by the bile acids,22 the microviscosities are comparatively high (r) > 100 cP) and in lipid vesicles, at temperatures below the lipid phase transition, q is again of the order of a few poises.Recently an extension of the above steady state method has been introduced wherein the dynamical aspects of the depolarization are examined on the nano- second time scales. In the dynamic polarization experiments, the probe is excited by a short (nanosecond) polarized light pulse and the fluorescence decay of (Ill and IL) the components are directly monitored separately.The time-dependent fluorescence depolarization anisotropy r(t) thus measured provides additional (more direct) information on the degree of anisotropy of the medium and on the type of rotational diffusion the excited probe executes inside the aggregate. There 4a G. Weber, Ann. Rev. Biophys. Bioengg., 1972, 1, 553. 4s M. Shinitzky, A. C. Dianoux, C. Gitler, and G. Weber, Biochemistry, 1971, 10, 2106; M. Shinitzky, Israel J. Chem., 1974, 12, 879; R. C. Dorrance and T. F. Hunter, J.C.S. Faraday I, 1977, 73, 89. 44 E. Williams, B. Sears, A. Allerhand, and E. H. Cordes, J. Amer. Chem. SOC.,1973,95,4871; R. T.Roberts and C. Chachaty, Chem. Phys. Letters, 1973, 22, 348. 46 K.Kalyanasundaram and J. K. Thomas, J.Phys. Chemistry, 1976, 80, 1462; H. 0. Ashi, M. Okuyama, and T. Kitagawa, Bull. Chem. SOC.Japan, 1975,48,2264. have been few studies46 of this type in lipid vesicles. Analysis of the decay profiles of r(t) indicate that the orientational motion of molecules such as DPH in the lipid phase can be described by a wobbling diffusion restricted by a certain aniso- tropic potential and the wobbling diffusion confined to a cone with a uniform diffusion constant. F. Excitation Energy Transfer.-Transfer of excitation energy under suitable conditions between the excited electronic states of two different chromophores find application in the biophysical studies as a spectroscopic ruler in the deter- mination of interchromophore distances. In micellar media, with proper choice of conditions, one can construct a model system in which the donor-acceptor pairs are placed in well-defined geometry and proximity and also set up con- ditions wherein there is a fairly high local concentration of the solutes inside the micelle.The ability to solubilize chlorophyll a in non-ionic micelles at concentrations close to the in vivo level in chloroplasts (-0.1M) has enabled a study4' of the process of energy transfer between two Chl a molecules by concentration depolarization of the fluorescence. By appropriate choice of solutes to micelle ratio, it is possible to study energy transfer under various multiple occupancy conditions. These studies, in addition to demonstrating the localization of the solutes, also confirm the operation of the Forster type of inductive resonance. Self energy transfer between the built-in naphthalenes has also been examined48 in the micelles formed by cetylaminonaphthalenesulfonates.When both the donors and the acceptors are localized inside the micelle, the local concentration of solutes is high giving very efficient energy transfer. Such enhanced efficiency in the energy transfer has been demonstrated between various types of laser dyes49 such as Rhodamine 6G and between a thionine-methylene blue pair.50 Recently there have been several studies which indhte that desegre- gation of the hydrophobic dyes in micellar media enhances considerably the CW lasing of dyes such as Rhodamine 6G and also leads to superior temporal stability for polymethine dyes compared with that in the non-aqueous solvent systems which are normally employed.While there is no energy transfer between naphthalene and the heavy metal salt, terbium chloride, in homogeneous solvents, very efficient energy transfer has been demonstrated 51 in aqueous anionic micelles. Here again the role of micelles is to allow compartmentalization of no more than one donor per micelle and at the same time concentrate a large number of acceptors at the micellar surface. In 46 S. Kawato, K. Kinoshita, and A. Ikegami, Biochemistry, 1977, 16, 2319; K. Kinoshita, S. Kawato, and A. Ikegami, Biophys. J., 1977,20, 289; J. H. Easter, R. P. DeToma, and L. Brand, ibid., 1976, 16,571; L. A. Chen, R. E.Dale, S. Roth, and L. Brand, J. Biol. Chem., 1977,252,2163. 47 K. Csatorday, E. Lehoczki, and L. Szalay, Biochim. Biophys. Acta, 1975, 376,268. 48 M. Shinitzky, Chem. Phys. Letters, 1973, 18, 247. IrnG. A. Kenney-Wallace, J. H. Flint, and S. C. Wallace, Chem. Phys. Letters, 1975, 32, 71. O0 G. S. Singhal, E. Rabinowitch, J. Hevesi, and V. Srinivasan, Photochem. Photobiol., 1970, 11, 531. b1 J. R. Escabi-Perez, F. Nome, and J. H. Fendler, J. Amer. Chem. SOC.,1977,99,7749. Photophysics of Molecules in Micelle-forming Surfactant Solutions homogeneous media, triplet-triplet annihilation rapidly deactivates naphthalene triplets before they can transfer their excitation energy. Efficient transfer of excitation energy from the built-in phenyl group in surfactants such as phenyl undecanoate to solubilized aromatic molecules such as naphthalene and pyrene has been advanced36be52 as evidence for the solubilization of these aromatics inside the miceIle close to the phenyl group.A recent applica- tion using micelles as a medium to study photoreaction of water-insoluble solutes involves53 studies of reactions of singlet oxygen produced by triplet energy transfer from sensitizers. In these studies singlet oxygen is produced by energy transfer from the triplet state of methylene blue or 2-acetonaphthone and its reactions studied indirectly by monitoring the concentration of dibenzofuran with which it reacts. G. Excited State Acid-Base Equilibria.-In Section 2A reference was made to those compounds whose fluorescence properties are dependent on the solvent polarity (dipole moment and dielectric constant).There is another class of compounds, such as aromatic amines and phenols, whose fluorescence is pH dependent and there has long been an interest54 in the use of these fluorescent pH indicators as probes for micellar surface. Most of these compounds have two PKa values, one for the ground' state protonation (PKa) ROH G+ RO-+ H+ ;RNHa + H+ + RNH,+ (4) and another for the excited state (p&*) ROH* + RO-* + H+ ;RNH2* + H+ + (RNH,+)* (5) The fluorescence from these molecules at a given temperature is thus dependent on (i) the relative magnitudes of PKa, pKa* with respect to the pH of the medium, (ii) how efficiently the equilibration occurs in the excited state within its lifetime and, (iii) how efficiently the solvent or other quenchers quench each of the two fluorescent species.Thus, 2-naphthol in water, in the pH range pKa-pKa* fluoresces from both ROH* and RO-*due to inefficient equilibration in the excited state while l-naphthol fluoresces only from RO-*. Studies of ground and excited state acid-base equilibria for various molecules have sho~n~~s55 that micelles have a pronounced influence on both PKa and pKa*. For coumarins (which are stronger acids in the excited state and hence relative fluorescence intensity is a measure of ground state dissociation) changes in PKa can be monitored either by absorption or by fluorescence. For amines, most M.Almgren, Photochem. Photobiol., 1972, 15, 297. 63 A. A. Gorman, G. Lowering, and M. A. J. Rodgers, Photochem. Photobiol., 1976.23, 399; A. A. Gorman and M. A. J. Rodgers, Chem. Phys. Letters, 1978,55, 52; I. B. C. Matheson, J. Lee, and A. D. King, ibid., 1978,55,49; Y. Usui, M. Tsukada, and H. Nakamura, Bull. Chem. SOC. Japan, 1978, 51, 379. 66 L. K. J. Tong and M. C. Gleismann, J. Amer. Chem. SOC., 1957,79,4305; P. Mukerjee and K. Banerjee,J. Phys. Chem., 1964,68,3567; M. Montal and C. Gitler, Bioenergetics, 1973, 4, 363; M. S. Fernandez and P. Fromherz, J. Phys. Chem., 1977, 81, 1755. 66 B. K. Selinger, Austral. J. Chem., 1977, 30, 2087; B. K. Selinger and A. Weller, ibid., 1977, 30,2377; U. Khuanaga, R. McDonald, and B. K. Selinger, 2. Phys.Chem. (NF.), 1976, 101,209; J. R. Escabi-Perez and J. H. Fendler, J. Amer. Chem. SOC., 1978, 100, 2234. Kalyanasundaram often the free base is an efficient quencher while the protonated form is not. Thus a fluorescence-quenching titration as a function of pH in compounds of the typc anthracene-(CH&-DMA provides a direct measure of the pKaof the amine. In all cases, micelles (both ionic and neutral) alter the PKa by 1-2 units. The PKa of acid-base reactions in micelles is influenced, firstly, by the effective dielectric constant at the solubilization site and, more predominantly, by the effect of the charge dissociation of the counterions at the micellar double layer. (Estimates of local electric field strengths at the micellar surface are several kV per cm.) Micellar effects on the excited state acid-base equilibria in 1- and 2-naphthol and pyrene-1-amine have been recently investigated.1-Naphthol and pyrene-l- amine, which show complete equilibration for excited state reactions in homo- geneous solvents, show only partial equilibration in micelles; 2-naphthol was found to go from partial equilibration to complete lack of reaction. This ‘suppres- sion of pKa* effect’ has been attributed to the higher micellar viscosity. Increased efficiency of some dyes as laser media when solubilized in the micelles has also been attributed to this micdar effect. 3Triplet State Studies All the processes described in Section 2 are singlet state reactions taking place at nanosecond time scales or less.On these time scales, the micellar aggregate can be considered as a rigid (permanent) specie and micelles dispersed in water can be treated conveniently as a two-phase system. There are, however, several much slower processes connected with the micellar association equilibria, processes such as exchange of monomer with the micelle, the complete collapse of the micelle (‘dissolution equilibria’), and exit and re-entry of the solubilizates in and out of the micelle. These slower (micro or millisecond) processes are conveniently probed by studies with the triplet excited states. A. Phosphorescence and the Triplet State.-The rare observance of phosphor- escence emission from aromatic molecules in fluid solutions is often attributed to the impurity quenching of the excited states.Studies on singlets, discussed earlier, indicate that the micellar environment tends to shield or screen the excited state of a probe located within the lipid phase from reactions with molecules located in the bulk aqueous phase; it is thus reasonable to expect sufficient protection of the triplet state in micelles that phosphorescence may be observed at room tempera- ture. Recently, phosphorescence emission from a variety of aromatic molecules has been observed56 in anionic sodium lauryl sulphate micelles. Molecules such as 1 -bromonaphthalene and 1 -bromopyrene emit phosphorescence quite strongly in fluid aqueous micellar solutions at room temperature. With non-halogenated aromatics such as pyrene or naphthalene, intense phosphorescence was observed in the presence of thallous (TI+) ions which bind strongly to the negatively charged micellar surface.The success of these experiments is partly due to the intra/intermolecular heavy atom effects and partly due to the micellar protection K. Kalyanasundaram, F. Greiser, and J. K. Thomas, Chem. Phys. Letters, 1977, 51, 507. Photophysics of Molecules in Micelle-forming Surfactant Solutions of the triplet state from the aqueous quenchers and from the triplet-triplet annihilation process. Each of these effects by themselves leads only to extremely weak emission. The successful observation of phosphorescence enables one to monitor some of the slower processes mentioned earlier. Quenching studies on 2-bromonaphthalene emission with water-soluble quenchers such as I-indicate that the solute leaves a NaLS micelle in 2 msec and re-enters with a rate constant of about 1 x 109 M-l sec-1.There have been few studies of reactionsof the triplet state by direct monitoring of the triplets by laser flash photolysis.lB Quenching of anthracene triplets by Cu2+ ions in cationic CTAB micelle give the rate constant for anthracene exit to be of the order of 2 x 102 sec-l. In all cases, the triplet lifetimes (either by phos- phorescence or by T-T absorption) in micelles are much larger compared with that in homogeneous solvent systems. For water-insoluble solutes with very low exit rates, one can produce and use fairly high concentrations of the triplets without appreciable deactivation by triplet-ground state and triplet-triplet quenching mechanisms.This is very important, if one wants to utilize all the triplets efficiently in triplet-photosensitized reactions, as will be discussed later. B. Photoionization.-Photoionization of molecules and subsequent electron transfer reactions are being investigated in a wide variety of systems because of their importance in our understanding of primary photophysics, solar energy storage, and their relevance to biological electron-transfer processes. In the photo- lysis of aromatic and heterocyclic molecules in polar solvents, depending on the light intensity, one observes, in addition to the triplets, their ionization products, solute cations, and solvated electrons.The photoionization occurs by one or two photon absorption processes. The relative efficiency of the two channels- photoionization versus triplet-is dependent on the nature of the medium. Micelles have been found57958 to have a pronounced influence on these reactions. The efficiency of photoionization is greatly influenced when molecules are photolysed in anionic micelles. For tetramethylbenzidine, for example, the ratio of the yields of solute cation to the triplet is 6.0 in anionic NaLS micelles com- pared with 0.17 in methanol. This is due to the increased probability of electron escape to the bulk water, effective stabilization of the cation, and prevention of the re-entry of the solvated electron by the negatively charged micellar surface. A photoejected electron with an excess energy > 1.1 eV is capable of escaping the micellar charge and is solvated in the bulk water.The range, energy, and the reactivity of the photo-ejected electron prior to thermalization and solvation and also of the hydrated electron, have been examined in detail. In cationic micelles, as with the exciplex dissociation case mentioned earlier, the probability of b7 S. C. Wallace, M. Grtitzel, and J. K. Thomas, Chem. Phys. Letters, 1973, 23, 359; M. GrBtzel and J. K. Thomas, J. Phys. Chem., 1974, 78, 2248; D. J. W. Barber, D. A. N. Morris, and J. K. Thomas, Chem. Phys. Letters, 1976, 37, 481 ;P. Picuolo, Doctoral Dis- sertation, University of Notre Dame, 1977. E.II S. A.Alkaitis, M. Gratzel, and A. Henglein, Ber. Bunsengesellschaft Phys. Chem., 1975,79, 541; S. A. Alkaitis, G. Beck, and M. Gratzel, J. Amer. Chem. SOC.,1975, 97, 5723; S. A. Alkaitis and M. GrBtzel, ibid., 1976, 98, 3549. 466 Kalyanasundaram geminate ion-recombination is enhanced and hence the photoionization efficiency is low. The very low yields of ions and high yields of excited states in the photolysis in homogeneous non-polar solvents are also attributed to the very efficient recombination of the geminate ion-pair. Studies on the mechanisms of photo- ionization indicate that the thresholds for photoionization are also significantly reduced in aqueous micellar solutions in comparison with that in non-polar alkane liquids or in the gas phase.In micellar solutions, the ionization potentials for solutes are estimated to be at least 2-3 eV less than those in the gas phase. 4 Photoredox Reactions Photoredox reactions, in which an electron is transferred from a low energy donor to a high energy acceptor using visible light, are currently receiving wide attention as a possible means of solar energy conversion and storage, and also as simple models to simulate photosynthetic electron-transport. A heterogeneous system, such as micelles containing a strongly absorbing photo catalyst, offers several advantages over homogeneous solvent systems. Firstly, most of the water- insoluble sensitizers can be used. By keeping the solute to micelles ratio fairly low, it is possible to use high concentrations of the sensitizer without appreciable loss in the overall efficiency.Secondly, the low ionization thresholds in micelles enables usage of visible light. In the third place, the rate of geminate ion- recombination can be kept low in anionic micelles. In energy-storing redox reactions, a major cause for the overall inefficiency in homogeneous solvent systems is the very fast, thermodynamically favourable back reactions of the redox products in the dark. Studies of electron transfer reactionss9 in micelles, using triplet excited states of molecules as donors or as acceptors and also those involving hydrated electrons and solutes outlined below, indicate that, with proper choice of conditions, these undesirable back reactions can be reduced to some extent.A. Reactions of Hydrated Electrons.-Micellar effects on the reactivity of the hydrated electron, ezj (produced in the bulk water by pulse radiolysis) with solutes solubilized perferentially in the micellar phase have been investigated for a wide variety of solutes60 in different micelles. Electron transfer reactions of the tY Pe etq + s+ s- which occur at diffusion-controlled rates in the homogeneous solvent systems, are For a detailed review of these studies, see A. Henglein and M. Gratzel in ‘Solar Polar and Fuels’, ed. J. R. Bolton, Academic Press, New York, 1977,p. 53; M.Gratzel in ref. lb,p.531 ;A. J. Frank in ref. Ib, p. 549. “OnK.M. Bansal, L. K. Patterson, E. J. Fendler, and J. H. Fendler, Infernat.J. Rad.Phys. Chem., 1971,3, 321 ;J. H.Fendler, H. A. Gillis, and N. V. Klassen,J.C.S. Faraday I, 1974, 70, 145;M.Gratzel, J. K. Thomas, and L. K. Patterson, Chem. Phys. Letters, 1974,29, 393;L.K.Patterson and M. Gratze1,J.Phys. Chem., 1975,79,956;A. J. Frank, M. Grltzel, A. Henglein, and E. Janata, Ber. Bunsengesellschafr Phys. Chem., 1976,80,547;A. J. Frank, M. Gratzel, and A. Henglein, ibid., 1976, 80, 593. *ObM. Gratzel, J. J. Kozak, and J. K. Thomas, J. Chem. Phys., 1975,62, 1632. Photophysics of Molecules in Micelle- forming Surfactant Solutions subjected to large retardation or enhancements if the solute is solubilized in an ionic micelle. The large positive charge on the cationic rnicelles attracts the eG to the micelle, giving rise to abnormally high rate constants (> 5 x 1011M-l sec-l).Anionic micelles similarly repel the ez and reduce the rate. Cases are also known where the micelles promote electron-transfer reactions such as coa-+ Py+ col + Py-’ (7) 3DQ* + CO:--+DQ-* + CO,-* (8) (Py = Pyrene and DQ = Duroquinone) which do not occur in homogeneous solutions. For micelles with reactive headgroups, as in cetylpyridinium chloride, the net positive charge on the micelle catalyses the rate of the reaction of ez with the headgroup leading to rate constants as high as 1.5 x 10l2M-1 sec-l. It is to be noted that these electron transfer reactions are complimentary to the photoionization studies where an electron is ejected into the bulk water. The behaviour of the neative ions such as esr;; in the presence of highly charged ionic micelles are governed largely by the sign and the relative magnitude of the electric field (‘zeta potential’) at the micellar surface.The high surface potential (in the range 50-200 mV) present over the few angstroms thickness of the Stern- layer decreases rapidly with an increase in distance in the Gouy-Chapman layer. The surface potential-distance profiles have been computed60b from the numerical solutions of the Poisson-Boltzmann equation and the rate constants for the various ez reactions have been correlated in terms of the drop in the micellar surface potentials. Mechanistically, the reactions of ea, with acceptors sohbilized in ionic micelles have been treated61 as tunnelling processes. Under these mechanisms, whether or not a given electron-transfer will occur under a given set of conditions depends on the extent of the overlap in the estimated distributions of the occupied and unoccupied redox levels of the redox systems eZ/e and A-/A.B. Electron-Transfer Reactions of the Triplets.-Micellar effects on the triplet excited state redox reactions have been investigated under conditions wherein the donor-acceptor pair is spatially separated with a charged electrical interface introduced between the two. Under such conditions, significant differences in the electron-transfer rates have been observed58~62~63 for a diverse class of molecules such as pyrene, nitroanthracene, tetranitromethane, phenothiazine, tetramethyl- benzidine, and duroquinone.Instructive among these studies are the intramicellar electron-transfer between the triplet state of solubilized aromatic molecules and ionic acceptors adsorbed strongly on the micellar surface. Consider, for example, the electron transfer from 61 A. Henglein, Ber. Bunsengesellschaft Phys. Chem., 1974, 78, 1078; ibid., 1975, 79, 129; M. Gratzel, A. Henglein, and E. Janata, ibid., 1975, 79, 475. OP A. J Frank, M. GrLtzel, A. Henglein, and E. Janata, Ber. Bunsengesellschaft Phys. Chem., 1976, 80, 294. m R. Scheeret and M Gratzel, J. Amer. Chem. SOC.,1977, 99, 865; Ber. Bunsengesellschaft Phys. Chern., 1976, 80, 979; M. Gratzel, A. Henglein, R. Scheerer, and P. Toeffl, Angew. Chem., 1976, 98, 690. Kalyanasundaram tetramethylbenzidine (TMB) triplets to Eu3+ ions absorbed on the surface of anionic (NaLS) micelles.3TMB* + Eu3++ Eu2+ + TMB+ (9) In a homogeneous solvent system, as in methanol, the rate constants for the forward and back transfer are 6.4 x lo9sec-1 and 1.4 x lo7M-1 sec-1, respec-tively. In anionic micelles, in the absence of acceptor cations, the triplets decay very slowly (first ti for 3TMB* is about 800 psec). In the presence of small amounts of Eu3+ (3 x lO-3M) the triplets decay extremely rapidly (t, 30N nsec) giving rise to the redox products TMB+*and Eu2+*. In homogeneous solvents, following the electron transfer the products back react by second order, equal concentration kinetics. In micelles, however, there are isolated ion pairs and the back transfer can be considered as a summation of intramicellar events occurring between the donor (D+*)and acceptor (A-*) pair on the micellar surface. Considering the micelle as a macromolecule, such back reactions should follow first-order kinetics, as has been observed experimentally.Such types of very fast intramicellar electron transfer followed by a pseudo first- order back reaction has been demonstrated for a variety of redox pairs. If the acceptor is a neutral hydrophobic molecule, e.g. duroquinonein anionic micelles, following the intramicellar electron-transfer, part of the redox pair recombines efficiently while some of the solute anions (DQ-*)escape from the anionic micelles by solute ejection mechanisms referred to earlier (see p.39). A phenomeno-logical modeP4 which takes into account the influence of the compartmentaliza- tion, as well as the statistical distribution of reactants, has been developed to describe the redox kinetics of fast intramicellar redox reactions. The rate laws derived differ significantly from those in homogeneous kinetics. In cases where the back reaction between D+*and A-. is reduced as in the micelles, it allows build- up of the redox products on steady state irradiation. C. Photosensitized Redox Reactions.-An extension of the direct photoredox reaction between a donor-acceptor pair is the photo-sensitized electron transfer in which a third component (sensitizer) receives the visible light and sensitizes the electron transfer.An advantage of the three-component system over the two is that it allows the build-up of considerable amounts of the redox products, much more than the concentration of the compound that receives the light. In function- alized micellar systems, such three-component electron transfer can be carried with a proper organization of the reactants at the molecular level. One study where a comparison has been made on the overall efficiency in micelles, as against the homogeneous solvent system, is the chlorophyll u sensitized reduction of methylviologen in non-ionic micelles. (Sensitized reduction of methylviologen is of interest as a simple model of photosystem I and hydrogen gas can be 44 M. Maestri, P. P. Infelta, and M. Gratzel, J. Chem. Phys., 1978, in the press.e6 K. Kalyanasundaram and G. Porter, Proc. Roy. SOC.(Lond.), 1978, in the press; K. Kalyana-sundaram,J.C.S. Chem. Comm., 1978,628; Y. Moroi, A. Braun, and M. Gratzel, J. Amer. Cliem. SOC.,1978, in the press. K. Kalyanasundaram, J. Kiwi, and M. Griitzel, Heiv.Chim. Acra, in the press. 469 Photophysics oj*Molecules in Micelle-forming Surfactant Solutions released from reduced viologen through the use of enzymes or metal catalysts.) Here, the water-insoluble sensitizer is solubilized in the neutral micelle and the D/Apair (both water-soluble) randomly dispersed in the bulk aqueous phase. Such spatial separation of the sensitizer leads to significant differences in the redox kinetics. With respect to the overall efficiency, the reduction was found to be very efficient in methanol for low D, A concentrations and under conditions where high concentrations of the sensitizer are used (to maximize the yields at short exposure times) reactions in micelles provide better efficiency.The micellar surface charge and also the binding of either the donor or the acceptor to the micelle have been found to play a major role in controlling the overall efficiency in similar reductions in anionic micelles with tris-bipyridylruthenium(I1) as the sensitizer. N-methylphenothiazine and di-indole derivatives have been used in similar studies. 5 Photophysics in Reversed Micelles A. General Featuresof the Reversed Micel1es.-Certain types of surfactants such as dialkylsulphosuccinates (Aerosols) form aggregates in non-polar organic solvents and these are termed66 'reversed' or 'inverted' micelles.In reversed micelles, the polar headgroup of the amphiphiles constitute the core and the hydrophobic tails extend into and are surrounded by the bulk apolar solvent. Reversed micelles formed by surfactants such as Aerosol-OT solubilize relatively large amounts of water. The water is present in the polar centres where it forms spherical pools, the sizes of which are controlled by the surfactant-to-water ratio. Studies of reversed micelles have been of interest from their industrial importance as in dry cleaning and also as simple model systems to simulate the water pockets often found in various bioaggregates. The state of the solubilized water, interactions, and reactions of various solutes are being investigated by a variety of physical methods.The physical properties of the solubilized water have been found to be quite different from that of the bulk water. 'H,23Na n.m.r. studies, for example, on the sodium di-iso-octylsu'lphosuc- cinate-heptane-water system indicates' that until there is sufficient water molecules for the solvation of all the sodium counterions (H20:Na+ ca. 6) water protons behave as co-ordinated water and only at higher water concentrations behave like normal hydrogen-bonded water. B. Fluorescence Probe Studies in Reversed Micell-.-The nature of the inner aqueous core and various substrate-surfactant interactions have been examinedss 66 J.H. Fendler, Accounts Chem. Res., 1976, 9, 153. 6T M.Wong, J. K. Thomas, and T. Nowak, J. Amer. Chem. SOC., 1977,99,4730. 6saM. Wong, M.Griitzel, and J. K. Thomas, Chem. Phys. Letters, 1975, 30, 329; M.Wong,J. K. Thomas, and M. Grltzel, J. Amer Chem. SOC., 1976,98, 2391 ;D. J. Miller, U. K. A. Klein, and M. Hauser, J.C.S. Faruday I, 1977, 73, 1654; U. K. A. Klein, D. J. Miller and M. Hauser, Spectrochim. Acra, 1976, 324, 379. rebG. D. Correll, R. N. Cheser, F. Nome, and J. H. Fendler, J. Amer. Chem. SOC., 1978, 100, 1254. secM. Wong and J. K. Thomas in ref. lb, p. 647. Kalyanasundaam recently by fluorescence probe analysis. The emission properties of 1,&anilino-naphthalene sulphonate m the reversed micelles were found to be extremely sensitive to the size of the solubilized water clusters.The quantum yields and life- time for the fluorescence decrease with increasing radius of the core while the position of the emission maximum shifts to a longer wavelength. At low water content the fluorescence from probes such asRhodamine B are strongly polarized, indicating a very rigid core (7 > 40cP). Under these conditions,.the quenching of fluorescence of water-soluble probes, such as py~ene-1-sulphonate (solubilized at the interface) by ionic quenchers, is also very inefficient. Steady state fluorescence depolarization results on 8-hydroxy-1,3,6-pyrenetri-sulphonate (pyranine) at various water contents in the dodecylammoniumpro- pionate @AP)-cyclohexane-water system have been interpretedssb in terms of the number of water molecules involved in the solvation of the surfactant head- groups.Intramicellar prototropic changes in the fluorescence of pyranine ROH" + Ha0 + RO-* + H*O+ (10) has also been examined69 in reversed micelles. In the DAP-cyclohexane-water system, efficient triplet energy transfer between solubiliid pyrene-1 -butyrate and terbium chloride (which does not occur in the absence of rnicelles) has been demonstrated. C. Electron-Transfer Reactions inReversed Miceiles.-Effects due to the charge on the donor, the availability of the acceptor, the microenvironment around the acceptor or the electron, and energy transfer from a biphenyl anion and triplets (produced by nanosecond pulse photolysis and radiolysis) to acceptors located at Werent sites, have been investigatedaSC in the reversed micelles Aerosol-OT- heptane-water system.Cu2+, H30+and pyrene-1-sulphonic acid were used as electron-acceptors and several pyrene derivatives were used as energy acceptors. Increasing the micellar size and the water content tend to increase the rate of these reactions if the two reactants are hydrophilic and are in the micelle, e.g., the electron transfer from biphenyl anion to Cu2+. Here, increase in water content also increases the mobility of the two solutes. If one reactant is hydrophobic (and hence located in the alkane phase) and the other hydrophilic, then increase in the water content decreases the rate of the reaction. For non-charged reactants, if one is located in the micelle, the rates decrease slightly due to the clustering of this reactant in one phase.6 Concluding Remarks Studies of the photophysics of molecules, reviewed here, continues to be a very fruitful area of research. As indicated in several places, these studies have provided more direct information on several dynamical aspects of the micellar association:permeability, counterions binding, surface charge and its variations, solute entry and exist rates, etc. Studies in micelles also have clearly indicated the variations/complications that can arise when one attempts to use some of the 6@ U.Klein and M.Hauser, 2.Phys. Chem. (NF.),1974, 90, 215. Photophysics of Molecules in Micelle-forming Surfactant Solutions well-defined photophysical processes as probes for biological macroaggregates.With studies in the simpler micellar-model system, one is better equipped for the study of larger aggregates using these methods. In various places it has been pointed out how the solubilization of a solute molecule in the micelle alters the photoreactions undergone by the solute. Organization of the reactants at the molecular level with ease is something peculiar to the micelles. Advantages in our ability to desegregate the solutes from each other and at the same time use high concentrations of photo-sensitizer solute are only now beginning to be appreciated and one can definitely expect several useful applications based on this to be developed. Applications in the area of solar energy conversion and in the usage of laser dyes have been indicated. The number of studies of slower processes with the triplet state have been few compared with those using fluorescence. One can anticipate extensive applications of phosphorescence in the near future, especially on the dynamics of micellar association equilibria. As mentioned in the introduction, only in photophysical methods has one a very wide range of time scales to work with, from a few picoseconds to several seconds. The author wishes to express his deep appreciation and gratitude to Professor Sir George Porter for his constant encouragement, and to Professors J. K. Thomas and M. Gratzel for sharing their wide experience and expertise in this area.

ISSN:0306-0012    

DOI:10.1039/CS9780700453

出版商:RSC    

年代:1978

数据来源: RSC

摘要:

Synthetic Pyrethroids -A New Class of Insecticide By M. Elliott and N. F. Janes DEPARTMENT OF INSECTICIDES AND FUNGICIDES, ROTHAMSTED EXPERIMENTAL STATION, HARPENDEN, HERTS., AL5 254 1 Introduction Pyrethroid insecticides have evolved in a classical sequence: activity observed in a natural extract, compounds responsible isolated and identified, increasingly active analogues synthesized. Recent synthetic pyrethroids are among the most potent pesticides known, and at present are being evaluated for many applications and as possible replacements for some of the organophosphate, carbamate, or organochlorine insecticides now considered unacceptable. Few classes of bio- logically active compound have such great potential for structural variation with retention or enhancement of potency.The insecticidal properties of the powder from pyrethrum flowers (Chrysan-themum cinerariaefulium)were being exploited in Europe by the 19th century’ when few effective insecticides were available. Therefore as soon as the nature of the active constituents was known2 synthetic analogues were investigated2 in attempts to elucidate the principles governing their activity and to discover simpler or more potent insecticides. New compounds have been discovered with greater insecticidal activity or faster knockdown than the natural esters and, in some cases, enhanced photostability and diminished mammalian toxicity. This survey traces the development of the present wide range of synthetic compounds, and the growing comprehension of the principles which govern their activity.It reviews most relevant publications up to Spring 1978; the profusion of information, especially in patents published in the past three years, has made detailed coverage of all topics impracticable. Previously, the chemistry of the natural estersY3s4 the relationship between structure and activity5-8 and the C. B. Gnadinger, ‘Pyrethrum Flowers’. McLaughlin Gormley King Co., Minneapolis, ’H. 1936. Staudinger and L. Ruzicka, Helv. Chim. Ada, 1924, 7, 177, 201, 212, 236, 245, 390, 448. a L. Crombie and M. Elliott, Fortsrhr. Chem. org. Nafursfofle, 1961, 19, 120. M. Elliott and N. F. Janes, in ‘Pyrethrum-the Natural Insecticide’, ed. J. E. Casida, Academic Press, New York, 1973, p. 56.ti M. Elliott, Pyrethrum Post, 1951, 2 (3), 18. M. Elliott, Chem. and Ind., 1969, 776. M. Elliott, Bull. World Health Organ., 1971, 44, 315. M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, and D. A. Pulman, in ‘Mechanism of Pesticide Action’, ed. G. C. Kohn, ACS Symposium Series No. 2, Americ’an Chemical Society, Washington, DC., 1974, p. 80. Synthetic Pyrethroids-A New Class of Insecticitte potential of pyrethroids as economic insecticidesg-11 have been reviewed. Proceedings of recent symposia on ‘Synthetic Pyrethroids’ and ‘Newer Appli- cations of Pyrethroids’ have been published.12J3 Two valuable alerting services cover the subject.14~15 Large areas of pyrethrum are cultivated in high altitude regions of Kenya, Tanzania, and Ecuador, for commercial extraction of the natural insecticide.The structures and absolute configurations (Figure 1a) of the six insecticidal esters in the extract have been fully confirmed by physical techniques.16-19 R‘ R’ CHa=CH- -CHI PyrethrinI CH,- -CHI CincrinI CHs-CHa- -CHI JasmolinI CHa=CH- --COSCH, Pyrethrin I1 CH,- -CO,CHs Cinerin I1 CHs-CHa- -COpCHa Jasmolin I1 (a) natural esters (b) most active isomer in fenvalerate Figure 1 (a) TIte six natural esters; (6) a recent synthetic pyrethroid 2 Definition Although it is accepted that pyrethroids interfere with nerve action, the precise M. Elliott, in ‘The Future for Insecticides: Needs and Prospects’, ed. R. L. Metcalf and J. J. McKelvey, jun., Wiley, New York, 1976, p.163. lo M. Elliott, N.F. Janes, and C. Potter, Ann. Rev.Ent., 1978,23,443. l1 M. Elliott, Env. Health Persp., 1976, 14, 3. l* ‘Synthetic Pyrethroids’, ACS Symposium Series No. 42, ed. M. Elliott, American Chemical Society, Washington, DC., 1977. la Pesticide Sci., 1977, 8, 236-330. (sX~L\ l4 Bibliography of Insecticide Materials of Vegetable Origin, Tropical Products Institute, London. Is Research Service Bibliographies, Series 4, ‘Pyrethrins and Pyrethrum Insecticides’, Public Library of South Australia, Adelaide. l6 A. F.Bramwell, L. Crombie, P. Hemesley, G. Pattenden, M.Elliott, and N. F. Janes, Tetrahedron, 1969, 25, 1727. l7 L. Crombie, G. Pattenden, and D. J. Simmonds, J.C.S. Perkin I, 1975, 1500. G. Pattenden, L.Crombie, and P.Hemesley, Org. Mass Spectrometry, 1973, 7, 719. l* M. J. Begley, L. Crombie, D. J. Simmonds, and D. A. Whiting, J.C.S. Perkin I, 1974, 1230. Elliott and Janes system attacked in insects is not known,neither is their mode of action well enough understood to provide a basis for recognising an insecticide as a pyre-throid. When developments since 1974are considered, basing a definition on structural affinities is also problematical, for, with the exception that they are both esters, little superficial connection is apparent between pyrethrin I and a recent important active compound, fenvalerate20I2l (Figure 1). However, strong evidence for a definite relationship (to be discussed) suggests that fenvalerate and pyrethrin I should both be considered members of the same class.3 Structural Variations and Insecticidal Activity Almost all active pyrethroids are esters. The constituent acids and alcohols, and simple derivatives of them, are practically inactive, as Staudinger and Ruzicka2 demonstrated in their remarkable pioneering work. Much evidence suggests that high insecticidal activity depends on the overall shape of the molecule,22 with certain key structural features appropriately disposed; other properties such as electron density and polarizability are of secondary importance. Almost every part of the parent molecule has now been replaced by a unit of analogous struc- ture without losing insecticidal activity; yet other changes, apparently no more drastic, produce inactive compounds.Because of this strong dependence of the activity of pyrethroids on structural shape, the effects of structural variation are analysed in relation to the segmented structure ofpyrethrin I as shown in Figure 2. In the following sections different structures are represented as combinations Figure 2 Segmentation scheme for pyrethrin I of units directly comparable to those in pyrethrin I, and the most active natural ester, and the importance of each unit is indicated approximately by a one- to three-star rating of its overall performance. This modular approach to systematize the discussion of structural variations reflects a practical basis for designing 2o N. Ohno, K. Fujimoto, Y.Okuno, T. Mizutani, M. Hirano, N. Itaya, T.Honda, and H. Yoshioka, Pesticide Sci., 1976,7,24I ;Jap. P. 73 06 528. 21 A. N. Clements and T. E. May, Pesticide Sci., 1977, 8, 661. 22 M. Elliott, in ref. 12. 475 Synthetic Pyrethroids-A New Class of Insecticide synthetic pyrethroids which has led to a succession of potent in~ecticides~3-~7 and helped to establish the principles, reviewed here, underlying activity.28 As in other applications of additivity principles to interpret the results of variations assumed to be independent, conclusions must be qualified by recog- nizing that effects of altering one segment of the molecule may be influenced by the nature of the other groups present and may differ markedly between species of insect. Relative activities are often difficult to assess because many bioassay procedures emphasize knockdown rather than kill, and many patents lack data useful for external comparisons.Segment A.-A centre of unsaturation at this site in the molecule is essential for high activity, but the structures of the natural esters (I-111), all active insecticides, show that variation is possible. Synthetic analogues with vinyl (IV) or ethynyl (VI) groups here have extended the range, but substituents on them (V, VI) do not improve activity. Rating' Ref: Variation Rating Ref: V1"I111 ,111, 111 * 30, 32-34 natural IN***Iesters (Fig. la) ** * * 23, 29 * 30,31 23 M.Elliott, N. F. Janes, K. A. Jeffs, P. H. Needham, and R. M. Sawicki, Nature, 1965,207, 938. M. Elliott, A.W. Farnham, N. F. Janes, P. H. Needham, and B. C. Pearson, Nature, 1967, 213, 493. p5 M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, and D. A. Pulman, Nature, 1973, 244,456. a6 (a) M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, D. A. Pulman, and J. H. Stevenson, Nature, 1973, 246, 169; (6) 'Proceedings of the seventh British Insecticide and Fungicide Conference (Brighton)', 1973, p. 721. M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, and D. A. Pulman, Nature, 1974, 248, 7 10. M. Elliott, N. F. Janes, and I. J. Graham-Bryce, 'Proceedings of the eighth British Insecticide and Fungicide Conference (Brighton)', 1975, p. 373. M. S. Schechter, N. Oreen, and F. B. LaForge, J. Amer. Chem. Soc., 1949, 71, 3165. *O W.A. Gersdorff and N. Mitlin,J. Econ. Entomol., 1951,44, 70. 31 P. D. Bentley and N. Punja, in ref. 12. 32 M. Nakanishi, T. Mukai, S. Inamasu, T. Yamanaka, H. Matsuo, S. Taira, and M. Tsurada, Butyu-Kngaku, 1970, 35, 87. a3 H. Ogami, Y.Yoshida, Y. Katsuda, J. Miyamoto, and T. Kadota, Bcfyu-Kagaku, 1970, 35,45. J4 C. Corral and M. Elliott, J. Sci. Food Agric., 1965, 16, 514. 35 M. Elliott, N. F. Janes, and B. C. Pearson, J. Sci. Food Agric., 1967, 18, 325, 476 Elliott and Janes The most important unsaturated unit identified so far is phenyl (VII), present in all recently discovered potent pyrethroids (see Table 1 in Section 4) as a phenoxy or benzyl group (0or CH2 in segment B); substitution on ~henyl~~-~* or its replacement by a hetero-aromatic rings9 usually diminishes activity.Segment B.-This unit is methylene in the natural esters and in many active synthetic compounds (see Table 1). Its function is steric rather than chemical, for replacement by 0 generally produces a favourable change of properties of great practical importance when segment A is pheny1.7~40 Other replacements 011-VI) usually diminish activity. Segment B Variation Rating Ref. Variation Rating Ref. I I * * see text IV *y ** 7 I1 y’ * * * see text v 0 * 37,41 I11 7’ * 40 * 42,43 e-g-J ,o When segments A and B are combined as a cyclopentenyl (~yclethrin,~~) or a penta-lY3-dienyl (isopyrethrin I,45) side-chain, activity is also less. Segment C.-Recognition of the significance of this structural unit has been very important in the discovery of the newer synthetic pyrethroids. The methyl group on C-3 of the cyclopentenone ring (a consequence of the biosynthetic route, which may involve acetate46) apparently affects activity little, for one normethyl compound was more potent than the parent (benzyl sub- stituted in segments A and B).Apart from this variation, no pyrethroids in which segment D is incorporated in the same ring as segment c show significant activity. However, with segment D outside the ring, there are many effective variations (III-WII) with planar or near planar aromatic heteroaromatic rings or acyclic M. Elliott, N. F. Janes, and M. C. Payne, J. Chem. SOC. (0,1971,2548. M. Elliott, A. W. Farnham, N. F. Janes, and P.H. Needham, Pesticide Sci., 1974, 5, 491. T. Matsuo, N. Itaya, T. Mizutani, N. Ohno, K. Fujimoto, Y. Okuno, and H. Yoshioka, Agric. Biol. Chem., 1976, 40,247. M. Matsui, F. B. LaForge, N. Green, and M. S. Schechter, J. Amer. Chem. SOC., 1952,74, 2181. I0 K. Fujimoto, N. Itaya, Y. Okuno, T. Kadota, and Y. Yamaguchi, Agric. Biol. Chem., 1973,37,268 1. W. A. Gersdorf€ and N. Mitlin, J. Econ. Entomol., 1954, 47, 888. Fr. P. 2043019/1971.M. Elliott, A. W. Farnham, N. F. Janes, M. M. Petersen, and P. H. Needham, unpublished results. I4 H. L. Haynes, H. R. Guest, H. A. Stansbury, A. A. Sousa, and A. J. Borash, Contrib.. Boyce Thompson Inst., 1954, 18, 1. M. Elliott, J. Chem. SOC.,1964, 888. Ref. 4 p. 108. 477 Synthetic Pyrethroids-A New Class of Insecticide units.By finding that an ester of piperonyl alcohol had insecticidal activity, Staudinger and Ruzicka2 established a precedent for replacing cyclopentenonyl by benzyl. An increase in activity when an unsaturated substituent was placed at position 4 3923 confirmed the structural analogy. Later, some 3-substituted benzenes (IV)were shown to be even more acti~e.~~~~ Heteroaromatic replace- ments, especially furan, close in size and shape to cyclopentenone, also have activity, which is greatest when 3,5-subst i t uted.5~240ther heterocyclic variations such as thiophene,47 and rings with two heteroatoms, are generally less insecticidal. Segment C Variation Rating Ref. Variation Rating Ref. **. natural esters *** see text x=o,s ** 36 VI ,&’ ** 48 ** see text VII 4@0 * 49, 50 *** see text esp.R1 =H Ra =C1,CHS Many acyclic compounds have been investigated (VI-VIII) but, although relatively easily synthesized, in general they are less active insecticides than the cyclic compounds. Segments A +B +C.-Some insecticidal esters are derived from alcohols which are not obvious combinations of the segments discussed, yet are clearly pyre- 47 B.P. 1265437/1972. 48 B.P. 1226788/1971. 49 B.P. 1313554/1973.RothamstedAnn. Rep. 1971, Pt. I, p. 188. 61 K.Sota, T.Amano, M. Aida, K. Noda, A. Hayashi, and I. Tanaka, Agric. Biol. Chem., 1971,35,968; 37,1019. aa RothamstedAnn. Rep. 1973, Pt. I, p. 169. Elliott and Janes SegmentsA + B + C Variation Rating Ref.Variation Rating Ref. 0 esp. R1 + R* = (CHJ. throids because they are only active when they incorporate pyrethroid acids. Tetramethrin, the prototype, is a strong knockdown agent, and many alternatives for R1 and Rz are patented, Other variations in this category are based on benzo- furans54 and dihydrofurans.65 SegmentD.-All active pyrethroids reported so far are esters in which the carbon atom joined to the ester oxygen is sp3 hybridized; it is either incorporated in a cyclopentenone ring (variation I) or connects, for example, a benzene ring to the ester oxygen, when it is either primary (11) or secondary (JY-V). Phenyl estm (III) where it is spz hybridized are much less active. Segment D Variation Rating Ref: Variation Rating Ref.* natural esters IV y-= **R =N * * *R 56 27,38 other * 38,57 11 w *** see text 111 -* 6, 23 In the benzene and furan series, esters with an unsubstituted CHz group (variation II) are effective, but especially in 3-phenoxyhnzyl compounds, introduction of cyan0 produces dramatic changes in activity. When the absolute configuration of the -CH(CN)-group is S, activity is increased up to 15-foId2' over the unsubstituted compound (depending on the acid component present), whereas in the opposite configuration activity is depressed by as much as eight times;5* the pure esters required for this study were separated from diastereo- 68 T. Kato, K. Ueda,and K. Fujimoto, Agric. Biol. Chem., 1964,243,914.64 B.P. 1271 771/1972; U.S.P. 3816469/1974. so Ger. Offen. 2108932/1972; 2555581/1974. s* B.P. 1270315/1972. ST Ger. Offen. 2407024/1974; 2609704/1976. M. Elliott, N. F. Janes, D. A. Pulman, and D. M. Soderlund, Pesticide Sci.,1978,9, 105; M. Elliott, A. W. Farnham, N. F. Janes, and D. M. Soderlund, Pesticide Sci., 1978, 9, 112. 479 Synthetic Pyrethroids-A New Class of Insecticide isomeric pairs chromatographically. The C-4 epimers of cyclopentenolone esters apparently differ less in activity (see discussion58). The a-ethynyl compounds (IV) are also active. SegmentsC + D.-If appropriate sectors of the flexible pyrethroid structure could be maintained by suitable additional connections in the conformation adopted at Segments C + D Variation Rating Ref.Variation Rating Ref. X = 0,S, CHI, CO the site of action, particularly active compounds might be produced. In variation (11), several alternative extra connecting units have been examined. Activity was generally small, comparable to that of esters of most other benzyl alcohols with a-substituents (above); the most interesting compound (11, X = 0, R = 7-Me) has moderate activity.sO Segment E.-Even small alterations in this unit at the centre of the molecule would be expected to produce large overall stereochemical differences with consequent effects on potency; the variations listed (11-VIII) do indeed diminish or remove activity. In addition, there is evidence from physical properties such as dipole momentss7 that in esters one of the two conformations in which all four bonds are coplanar is strongly preferred.X-ray analytical evidence for all pyrethroids e~aminedlS,6*,6~ shows this to be a consistent feature, therefore the ester unit in pyrethroids may have properties not reproduced by alternative structures. The relative ease of ester cleavage also exerts an important influence on mammalian toxicity (see below). 6* B.P. 1274595/1972; U.S.P. 3647857/1972; Jap. Kokai, 74 26421-2; M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, and B. C. Pearson, unpublished results. O0 Y. Inoue, S. Ohono, T. Mimno, Y. Yura, and K. Murayama, in ref. 12. 61 P. E. Berteau and J. E. Casida, J. Agric. Food Chem., 1969, 17, 931. 6a M. R. Altamura, L.Long, and T. Hasselstrom, J. Org. Chem., 1962, 27, 594. ea M. H. Black, in ref. 12. e* M. Matsui, K. Yamashita, M. Miyano, S. Kitamuka, Y. Suzuki, and M. Hamuro, Bull. Agric. Chem. SOC. Japan, 1956,20, 89; Belg. P. 852082. O6 Jap. P. 61 8498. J. R. Reid and R. S. Marmor, J. Org. Chem., 1978, 43, 999. O7 L. E. Sutton, in 'Determination of Organic Structures by Physical Methods', ed. E. A. Braude and F. Nachod, Academic Press, New York, 1955, Vol. I. p. 405. J. D. Owen, J.C.S. Perkin I, 1975, 1865. J. D. Owen, J.C.S. Perkin I, 1976, 1231. Elliott and Janes Segment E Variation Rating Ref. Variation Rating Ref. I /O>f0 *** esters NH 0 I1 'Ir * 22, 23, 61 VI JL0, * 63 0 * 61 VII Hob *64 IV * 0 OH 0 It IX *66AOCI OMe Segmq@D + E.-As in the previous section, the evidence available indicates that compounds in which the central ester link is reversed show little or no activity.Segments D + E Variation Rating Ref. Variation Rating Ref. Segment F.-Both methyl groups (I) are present in the most active compounds72 but that cis to segment E has been shown,?* in some cases, to be the more important ;all known cyclopropyl esters with no substituents here are inactive. The function of the methyl groups in the active molecules is probably related more to their steric than to their chemical characteristics, because dichloro-01) 70J. J. K. Novak, J. Farkas, and F. Sorm, Coll. Czech. Chem. Comm.,1961,26,2090. 71 Ger. Offen. 255399111976; 271233311977.70 F. Barlow, M. Elliott, A. W. Farnham, A. B. Hadaway, N. F. Janes, P. H. Needham, and J. C. Wickham, Pesticide Sci., 1971, 2, 115. 7s P. E. Burt, M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, and D. A. Pulman, Pesticide Sci., 1974, 5, 791. 74 T. Sugiyama, A. Kobayashi, and K. Yamashita, Agric. Biol.Chem., 1974, 38, 979. Synthetic Pyrethroids-A New Class of Insecticide Segment F Variation Rating Ref. Variation Rating Ref. y *** '7estersnatural 111 ** 71 and spiro-(111) substituted cyclopropanes show significant insecticidal activity, but esters with larger groups are less active. Inversion of stereochemistry at C-1 (IV) eliminates or greatly diminishes insecticidal activity in all dimethylcyclo- propane esters, except when there is no substituent at C-3.Cyclopropanes with an additional group at C-l,75 dimethyl a~iridines,~~ ~yclopropenes,~7and cyclob~tanes~~have little activity. Segment G.-Many compounds with diverse substituents in this segment are active, showing considerable latitude in requirements; however, certain small changes here can influence activity profoundly. Activity increases with the num- ber of C-3 methyl groups. As with segment F, alternative groups (111, IV) with steric properties similar to (11) are effective. However, only compounds with unsaturation in the substituent at C-3 are highly active. In the homologous series (VI) the but-l-enyl analogue (R1 =H, R2 =Et) with the same number of carbon atoms as the parent chrysanthemate (I), and possibly optimum polarity,85 is most active.Ethano-bridged compounds (VI; R1 +R2=(CH2)4) are also more potent than the corresponding chrysan- themates.86 3-Dienyl substituents (VI; R1 or R2 =alkenyl) give outstandingly active esters,25 the most effective being buta-l,3-dienyl and penta-l,3-dienyl, without a 1'-methyl Compounds with substituents containing hetero- 76 R. G. Bolton, Pesticide Sci., 1976,7,251. 76 M. P. Sammes and A. Rahman, J.C.S. Perkin I, 1972, 344. Jap. P. 71 21373 78 P. J. Crowley, Ph.D. Thesis, University of Manchester, 1974. 'Is M. Matsui and T. Kitahara, Agric. Biol. Chem., 1967, 31, 1143. 8o R. H. Davis and R. J. G. Searle, in ref. 12; U.S.P.3823177/1974. U.S.P. 3962458/1976. 8a M. Elliott, A. W. Farnham, N.F. Janes, P. H. Needham, and D. A. Pulman,Pesticide Sci., 1976,7,492. 83 J. Farkas, P. Kourim, and F. Sorm, Chem. Listy, 1958,52,695. 84 J. Lhoste and F. Rauch, Pesticide Sci., 1976, 7, 247. G. G. Briggs, M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, D. A. Pulman, and S. R. Young, Pesticide Sci., 1976, 7, 236. L. Velluz, J. Martel, and G. Nomind, Compt. rend., 1969, 268,2199. 87 Ger. Offen. 2231436/1973; M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, and D. A. Pulman, Pesticide Sci., 1976, 7, 499. 482 Elliott and Jms Segment G Rating Ref. Rating Re$ *** naturalI ‘I‘ esters VI *** see text I1 *** 61, 72, 79 VII *.+ see text I11 ** 72 VIII ** 84 IV ** 7, 80, 81 Ix ** 82 V ** 81 X Y0 ** 838-” atoms (VI;R1 =CH20Me, COzMe, etc; R2 =Me, halogen) are more polar, and especially active as knockdown agents.88 The activity of both cis-(VII; R1 =R2 = Me) and trans-chrysanthemates indicates the broad steric latitude within which unsaturated groups on C-3 confer activity.Replacing the methyl groups in either isomer with halogens (VIor VII; R1 = R2 = halogen) gives a considerable increase in insecticidal activify25-27,*9,90 and, with appropriate alcohols, the very valuable property of photostability (see Section 6). Variation (VIII) is present in the most powerful known knockdown agent. Of other variations reported, only the methoxyimino ether 0is more active than isobutenyl (I). Substituted ethynylgl and alkenylidene92 groups give esters of low activity.Substitution of methyl groups into otherwise active compounds greatly diminishes potency, a result ascribed to disturbance of the optimum conformation for activity.93 88 Ger. Offen. 2 109010/1971; 2449643/1975. M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, and D. A. Pulman,PesticideSci., 1975,6,537. -> D. G. Brown: 0. F. Bodenstein, and S. J. Norton, J. Agric. Food Chem., 1973,21, 767; 1975,23, 1 15; Botyu-Kagaku, 1976,41, I. M. Yoshimoto, N. Ishida, and Y. Kishida, Chem. Pharm. Bull., 1972,20,2593; Rothamsted Ann. Rep. 1976, Pt. I, p. 163. g* Jap. Kokai 74 80242. 9s M. Elliott and N. F Janes, in ref. 12. Synthetic Pyrethroids-A New Class of Insecticide .~~Segments F +G.-Ohno et ~ 1 recently made the important discovery that acyclic units (11) can function as acidic components of esters with typical pyre- throid alcohols. The most effective compounds were p-substituted 3-methyl-2- phenylbutyric acids (11, R1 = R2 = Me, R3 = H, R4 =p-CI, p-CH3, or 3,4-methylenedioxy). Of the two optical forms of each of these acids, that related Segments F +G Variation Rating Ref.Variation Rating Ref. * * 20,94 II sterically to the (more active) (1R)-chrysanthemate gives the more active esters. The discovery of this variation not only provides significant evidence of the features essential for activity in this group of insecticides, but also considerably increases the potential range of practical insecticides; numerous replacements for the substituted phenyl group have already been described in patents.Variation (111) is particularly interesting because it may indicate a structural connection between DDT-type compounds and pyrethroids. Summary of structure-activity relationships.-The relative insecticidal activities of the many structures summarized in the previous sections are most straight- forwardly interpreted by assuming that the action of pyrethroids involves approach of an intact molecule to a site in the nervous system of the insect; a metabolic activation (comparable to the thion oxon transformation of organo- phosphates) is probably not involved. Greatest potency depends on at least two centres having appropriate chirality. For example, in chrysanthemates the configuration at C-1 must be [R], in 3-methylbutyrates the sterically equivalent [S]and in alcohols, for cyclopentenolones [S]at C-4,and for a-cyano-3-phenoxy-benzyl alcohol [S] at C-a.These conditions imply chirality in the interacting system at an important stage in the process of poisoning. Two centres of un- saturation at the extremities of the molecule (segments A and o) and a gem-@* N. Ohno, K. Fujimoto, Y. Okuno, T. Mizutani, M. Hirano, N. Itaya, T.Honda, and H. Yoshioka, Agric. Biol. Chem., 1974, 38, 881; M. Miyakado, N. Ohno, Y.Okuno, M. Hirano, K. Fujimoto, and H. Yoshioka, Agric. Biol. Chem., 1975, 39, 267; Ger. Offen. 2335 34711974. B5 G. Holan, D. F. O’Keefe, C. Virgona, and R. Walser, Nature, 1978,272, 735. 484 Elliott and Janes dimethyl group or its steric equivalent /?to the ester group are features of all potent pyrethroids so far described.Other segments of the molecule can be replaced by a wide range of sterically equivalent groups whose function may be to influence preferences for the relative conformations between segments, whilst maintaining suitable molecular polarity. 4 Chronological Survey of Effective Combinations The sequence of compounds in Table 1 reflects the progressive advance in under- standing structure-activity relationships and the associated development of commercially important insecticides. Although some compounds may be especially active against one particular pest at one stage in the life cycle (e.g. the 3-methyl-2-phenylbutyratesagainst lepidopterous larvae),20 experience has shown that the levels of activity against the two chosen species of insect in the Table provide a useful general indication of the practical value, where appro- priate, of the compound. By the compounds they synthesized and tested for insecticidal activity, Staudinger and Ruzicka2 showed remarkable insight into the structure-activity relationships of pyrethroids, and provided the foundation for modern concepts of the essential requirements for activity.However, the first major advance towards a commercially important synthetic pyrethroid was the versatile synthesis of cyclopentenolones by Schechter et al.29 who developed allethrin (4J),contain-ing all eight possible stereoisomers. Later one- and two-isomer preparations (3B, 4B) were developed commercially.Combining Chen and Barthel’s observationlOl of activity in various benzyl chrysanthemates with the need for unsaturation in segment A led to 4-ally1 and 4-allyl-2,6-dimethylbenzylchrysanthemates (65 and 75). This investigation was pursued by showing that benzene could be replaced by furan when benzyl was substituted for allyl, the optimum orientation found being in 5-benzyl-3-furylmethyl esters (9). In a parallel development, the chrysanthemate (85) of N-hydroxymethyl-tetrahydrophthalimide, a relatively inexpensive alcohol, was shown to have excellent knockdown action against flying insects, though relatively low insecti- cidal toxicity. 5-Benzyl-3-furylmethyl alcohol was then used to examine the relative activities of esters of novel acids.The tetramethylcyclopropane carboxylate (NRDC 108, 9L) is the most effective pyrethroid with no chiral centre. Ethanochrysanthemates (e.g. 9N) are generally somewhat more active than the corresponding chrysanthe- mates. Inverting stereochemistry at C-3, as in the cis-chrysanthemate (9F), increases activity to some species. The cis thiolactone compound, RU 15525 (9M) 96 L. Crombie, S. H. Harper, and F. C. Newman, J. Chem. SOC.,1956, 3963. g7 W. A. Gersdorff and N. Mitlin, J. Econ. Entomol., 1953, 46, 999. W. F. Barthel, Adv. Pest Control Res., 1961, 4, 33. gs B.P. 1223217/1971. loo M. Elliott, A. W. Farnham, M. G. Ford, N. F. Janes, and P. H. Needham, Pesticide Sci., 1972, 3,25. lol Y.L. Chen and W. F. Barthel, U.S.Dept. Agric. ARS, 33-23/1956. 485 Synthetic Pyrethroids-A New Class of Insecticide Table 1 Relative toxicities of pyrethroids to two insect species Name* Formula? First Pyrethrin I Allethrin ‘Bioallethrin’ ‘S-Bioallethrin’ Dimethrin Tetramethrin ‘ABC’ ‘DMABC’ Resmethrin Bioresmethrin ‘NRDC 108’ Prothrin ‘Ethanoresmethrin’ Proparthr in Cismethrin ‘3BBC‘ Phenothrin ‘Benzylnorthrin’ Bu tethrin ‘Cyan0 pheno thrin’ ‘NRDC 134’ Permethrin Biopermethrin ‘RU 15525’ Fenvalera t e ‘NRDC 167’ Decame t hr in ‘NRDC 173’ Cypermethrin Ref. Syn-thesized 1956 96 1949 29 1949 29 1953 97 1958 98 1964 53 1965 23 1965 23 1967 24 1967 24 1968 61,72 1967 33 1969 86 1970 32 1971 72 1971 7,99 1971 7940 1971 36 1971 51 1973 38 1973 25 1973 26 1973 26 1973 81 1973 20 1974 72 1974 27 1975 92,93 1975 92 Relative Toxicity (Bioresmethrin=100) to Houseflies Mustard beetles 2(+KD) 150 3(+KD) 1 5(+KD) 2 9(+KD) 4 0.3 0.2 2(+KD) 2 7 0.1 7 2 42 37 100 100 74 30 7 1.2 150 180 -6 42 52 15 53 31 72 7 17 14 -180 110 240 280 69 140 86 240 39(+KD) 52 47 100 200 160 2800 5500 390(+KD) 180 260 430 *The name by which the compound is referred to in at least one publication.If not in quotes, it is a proposed or accepted common name; ?Esters are designated by a number-letter combination to indicate the alcohol [formulae (1-12)] and acid [formulae (A-Q)] compo-nents, respectively; $Measured by topical application and probit analysis as described;loO molar basis a-e( f)-cis,frans-chrysanthemates of the following alcohols: a3,4-dimethyl-benzyl ; b5-propargylfurfuryl ; C2-methyl-5-propargy1-3 furylmethyl ; d3-benzylbenzyl ; e3-chloro-4-phenylbut-2-enyl is the most powerful knockdown agent yet described, but the trans isomer, and the corresponding 3-phenoxybenzyl esters, are not comparably active.Of the many mono- and poly-heterocyclic alcohols with a structural similarity Elliott and Janes (4) (RSat (2-4) // y&\ (6)R=H (7) R = CH, 0. R 0 (8) (B)X = Me px(F)X = Mep /wx(C)X = F (G)X=F'* '1 X (D) X = C1 7 (H)X = C1 (A) 0 (lR, trans) (E) X = Br 0 (I R, cis) (I)X = Br (J) X = Me ,p(K)X = CI 'I 0 0 (N)R' + R' = (CHJ,pOyR'(0)R1 = H,R2= MeI Ra (P) R' = H, R2= Et 0 3' 487 Synthetic Pyrethroids-A New Class of Insecticide to 5-benzyl-3-furylmethyl alcohol, only the propargyl compounds are significantly active, especially against flying insects. Butethrin with an acyclic unit for segment c shows useful activity to a limited number of species.In 1969, two research groups independently recognized the significance of the structural similarity between 5-benzyl-3-furylmethyl alcohol and benzyl alcohols with m-substituents such as benzyl and phenoxy. Esters from 3-phenoxybenzyl alcohol (10) were generally less active than those from 5-benzyl-3-furylmethyl alcohol (9) but activity in esters of a-ethynyl alcohols having been detected, a-cyano-3-benzylbenzyl and -3-phenoxybenzyl esters, e.g.(11B) were examined and found to have increased insecticidal activity. Initial indications of the valuable influence of changing the 3-substituent in dimethylcyclopropanechrboxylates(variations in segment G) stimulated synthesis and examination of analogues with a diverse range of groups at this position. Acids with dichloro- and dibromo-vinyl side chains formed exceptionally effective combinations with the three most powerful alcohols, (9A), (lOA), and (11A). The last two were not photolabile, so combining them with the com- parably stable dihalovinyl acids produced the first group of synthetic pyre- throids sufficiently persistent to control insect pests of agricultural and horti- cultural crops in sunlight.Of all the possible combinations in this group, the diasteremisomeric pair of esters (111) from the racemic cyanohydrin of 3-phenoxybenzaldehyde and [1 R,cis]-3-(2,2-di bromovinyl)-2,2-dimethylcyclopro-panecarboxylic acid was exceptionally active insecticidally, due almost entirely to one isomer (decamethrin; NRDC 161 ;121) which was separated by crystal- lization.2'958 Further, decamethrin is one of the few biologically active com- pounds suitable without modification for heavy atom X-ray analysis to establish absolute configuration.s8 Other combinations being developed for practical applications are the (k)-cis-,trans-dichlorovinyl esters of 3-phenoxybenzyl alcohol (permethrin; NRDC 143 ;10K) and of a-cyano-3-phenoxybenzyl alcohol (cypermethrin; NRDC 149; 11K).The [l R, trans]-difluorovinyl ester of 5-benzyl- 3-furylmethyl alcohol (9C)has a unique combination of rapid knockdown action against houseflies and killing power greater than bioresmethrin. The ester of a-cyano-3-phenoxybenzyl alcohol with 2-(4-chlorophenyl)-3- methylbutyric acid (fenvalerate; S-5602; 1 1Q) now being introduced also has valuable potential as an insecticide for agricultural use. The four named com- pounds (lOK, 11K, 121, and llQ), after extensive field trials throughout the world, are at present considered to have the most favourable combination of properties and prospects for practical application.5 Synthesis of Components of Pyrethroid Esters A. Alcohols.-Cyclopentenolones. The original route29 (or a variationlo2) to (f)-allethrolone (4A) is still used commercially, despite numerous published alter- lo*Fr. P. 1434224/1966. Elliott and Janes natives, some originating in the prostaglandin field; for reviews, see ref. 103. (S)-allethrolone(3A),obtained by resolving the hemi-succinate104 or -phthalatelo5 is necessary for the manufacture of S-bioallethrin (3B). The (R)-allethrolone can be rccycled by racemization of a derivative,Io6 or more directly, the R alcohol, as its mesyl derivative, undergoes an SN2 reaction with sodium chrysanthemate with inversion to give the required (4s) ester.lo7 N-hydroxyrnethyl Imides. The alcoholic component (8A) of tetramethrin (85) is readily accessible at low cost from condensation of maleic anhydride and butadiene, followed by rearrangement, imide formation with urea, and hydroxy- methylat ion with formaldehyde. lo* Substituted Benzyl Alcohols.The alcoholic components of the benzyl chrysanthe- mates needed for structure-activity investigations were made by reaction of aryl Grignard reagents with formaldehyde, by reducing appropriate aldehydes or acids, or by the sequence -CH3 --CHzhal ---CHZOH.~~The alcoholic function was protected when necessary as the tetrahydropyranyl derivative whilst a bromo substituent was converted into allyl, benzyl, etc. 2,6-Dimethyl-4-allylbenzyl alcohol was also made by a special route109 in which N-allyl-2,6- xylidine was rearranged in xylene in the presence of zinc chloride to 2,6-dirnethyl- 4allylaniline, and then converted into the alcohol by conventional reactions.5-Benzyl-3-furylrnethyl alcohol. Furans with functional groups at the 3-position are relatively inaccessible110 but an established synthesis of 3-furoic acid111 gave the starting material for the route112 to the alcohol (9A)shown in Scheme 1. The second route shown in Scheme 1 was developed later and adapted for commercial production;112 alternatives for reagents iv-vii have been patented.113 The importance of this alcohol (9A) has stimulated development of several altcrnative syntheses114 one of which (Scheme 2) was subsequently adapted to form the insecticidal ester (R = chrysanthemoyl) directly.3-Phenoxybenzyl Alcohols. These are the most important alcoholic components of lo) R. A. Ellison, Synthesis, 1973,7, 397; G. Pattenden, in 'Aliphatic Chemistry', ed. A. McKillop (Specialist Periodical Reports), The Chemical Society, London, 1977,vol. 5, p.231. lo' Ger. OlTen. 2 263 8801 1973. loo Ger. Offen. 2414794/1974. lo' Ger. Offen. 2535766/1976;B.P. 148S082/1977. lo' Ger. Offen. 2740701/1978. loo Jap. P. 65 22658; M. E. Bailey and E. D. Amstutz, J. Amer. Chem. Soc., 1956,78, 3828. loo M.Elliott and N. F. Janes, J. Chem. SOC. (C), 1967, 1780. P. Bosshard and C. H. Eugster, Adv. Heterocyclic Chem., 1966,7, 377. 111 E. Sherman and E. D. Amstutz, J. Amer. Chem. SOC., 1MO,72,219S;F.Kone, R.Heinz, and D.Scharf, Chem.Ber., 1961,94,825. 11' M. Elliott, N. F. Janes, and B. C. Pearson, J. Chem. SOC.(C), 1971,2551; Anon, Chem. Eng. News, 1971 (2), 32. '13 B.P. 1 178897/1970;B.P. 1 196202/1970;U.S.P. 3755368/1973. 11* B.P. 1213850/1970;G. R. Treves and P. A. Cruickshank, Chem. andlnd., 1971,544;Ger. Offen. 1935OO9/1971; 2122661/1972; 2122822-3/1972; U.S. 3781 308/1973; Y. Naoi,T.Nakano, K. Sakai, K. Fujii, and M. Wakaomi, Nippon Kuguku Kaai, 1977.9, 1365. Synthetic Pyrethroids-A New Class of Insecticide ixtiii vii+ Vlll0"'"iv, v vi-o/-eC0,Et Reagents:i, CHaO, HCl; ii, Benzene, AICl,; iii, LAH; iv, NaOEt + (CH,CO,Et),; v, H,O+; vi, EtOH-HCI; vii, H+, (CHaOH),; viii, NaH, HC0,Et; ix, aq, HCl Scheme 1 the recent generation of synthetic pyrethroids.Although esters from 3-phenoxy- benzyl alcohol (1OA) are less active than those from 5-benzyl-3-furylmethyl alcohol (9A)many are photostable and being more readily synthesized, are less expensive. Esters from a-cyano-3-phenoxybenzyl alrahol (1 1A) are among the most powerful insecticides known. Scheme 2 3-Phenoxybenzyl alcohol (10A) is made by several routes (Scheme 3), most of which involve the intermediate, 3-phenoxytoluene (13) originally made115 by condensing potassium cresate with bromobenzene, but more recently by a process116 more suitable for an industrial plant. Oxidation of the methyl group in (13) with either permanganatel15 or oxygen and catalyst1f7 gives 3-phenoxy- benzoic acid, which can then be reduced to the alcohol (1OA).In a more direct route118 the methyl group is halogenated and the monohalide, with the appro- priate acid in the presence of a tertiary amine, gives the insecticidal ester, e.g. pheno thrin. 11* Fr. P. 1394557-8/1965. 11' B.P. 1496821/1975. 11' Jap. Kokai 73 61450; B.P. 1489325/1977. 118 Ger. Offen. 240245711974; 243788211975 Elliott and Janes Jiii viii esters Reagents: i, Cu; ii, thoria (450°C); iii, fractionate; iv, oxidant; v, reductant;vi, halogen; vii, RCOCl; viii, RCOzH + NR', Scheme3 a-Cyano-3-phenoxybenzyl alcohol (1 1A) is made from 3-phenoxybenzaldehyde Reaction(14) available by oxidation of the or by an Ullman reacti011.l~~ of (14) with HCN gives the racemic alcohol; in the presence of D-oxynitrilase one epimer is preferentially destroyed producing predominantly the less active R-form (Scheme 4).27,58 The problem of isolating esters of this alcohol with the more active S-configuration (12) at this centre was first soIved27,5* using the IR,cis-dibromovinyl acid (11) as resolving agent; the required insecticidal enantiomer [(121); NRDC 161; decamethrin] crystallized from hexane leaving the other diastereoisomer in solution (Scheme 4).The configuration at C-ais epimerizedby base120so the inactive diastereoisomer can be inverted to provide more deca- methrin, without cleaving the ester. a-Cyano-3-phenoxybenenzylbromide is a *I* Belg. P. 842 I77/1976; see also A. Bader, Afdrichirnico Acta, 1976, 9,49. la0Belg. P.853 866-7/1977; Ger. Offen.2718038-9/1977. Synthetic Pyrethroids-A New Class of Insecticide potentially useful intermediate for preparing esters of labile acids via their sodium or amine salts.121 Reagents: i, HCN; ii, D-oxynitrilase; iii, acid chloride of (11); iv, crystallization from hexane Scheme 4 B. Acids.-Chrysanthemic Acid and Analogues. Recent elegant syntheses122 have not signifiwntly influenced the commercial production of ( f)cis,rrans-chrysan-themic acid (lC), the most direct route to which remains the addition of ethyl diazoacetate to 2,5-dimethyl-hexa-2,4-diene(for a review of many routes, see ref. 4). The established route to (& )-trans acid by addition of the methyl-propenyl unit (presented as a sulphone) to seneceoic ester has been modified.123 An efficient asymmetric addition of ethyl diazoacetate to the diene in the presence of a chiral copper catalyst gives a product 80:20 truns:cisand predominantly (80%) lx1Ger.Offen. 2619321/1976. lX*B.P.1416804/1975;H.Hirai, K.Ueda, and M. Matsui, Agric. Biol. Chem., 1976,40,153, 161,169;M.J. Devos L. Htvesi, P. Bayet, and A. Krief, Tetrahedron Letters, 1976,3911 ; A. S. Khanra and R. B. Mitra, Indian J. Chem., 1976,14B, 716; A. J. Ficini and J. d'Angelo, Tetrahedron Letters, 1976,2441 ; S. C. Welch and T. A. Valdes, J. Org. Chem., 1977,42, 2108. I** J. Martel and C. Huynh, Bull. SOC.chim. France, 1967, 985; Hung. Teljes 8014f1974. Elliott and Janes 1R.124 Chirality in the alkyl diazoacetate has less influence.125 New procedures separate optical and geometrical isomers126 and racemize less active for recycling.Many of the structural variations for segment G were first introduced128 (cf. ref. 129) by Wittig synthesis with an aldehydoester. A simple ester (e.g. R = Me) is normally the best intermediate but for side chains labile in base, the acid (15, R = H) is obtained easily by using the t-butyl ester and pyrolysing the Wittig product (15, R = But) (Scheme 5). Thence, many analogues with well-defined stereochemistry could be synthesized. Reagents: i, 0,;ii, RIR*C=PPhs Scheme 5 Commercial resolution of (k)-trans-chrysanthemic acid130 gives the (1 R,trans) acid, and thence by ozonolysis the trans aldehyde. The (lS,trans) acid, which gives esters of much diminished potency, can be converted via the (1 R,cis) acid to the cis aldehyde as shown in Scheme 6.13l As discussed below, this aldehyde is very significant commercially in addition to providing variations for structure- activity studies.HO (lS, tram) 0-0 0 (lR, cis) Reagents: i, H,O+;ii, KOBut; iii, MgBr,,6HsO; pyridine; iv, Os Scheme 6 T. Aratani, Y.Yoneyoshi, and T. Nagase, Tetrahedron Letfers, 1975, 1707; Jap. Kokai 74 14448, 102650. 75 137955. T.Aratani, Y Yoneyoshi, and T. Nagase, Tetrahedron Letters, 1977, 2599. Ia6 B.P. 1359968/1972; 1369519/1972; 1369730/1972; F. Horiuchi and M. Matsui, Agric. Biol. Chem., 1973,37, 1713: Ger. Offen. 2356702/1974; Jap. P. 75 34019. I*' Ger. Offen. 2453639/1975. 11* M. Elliott, N. F. Janes, and D.A. Pulman, J.C.S. Perkin I, 1974, 2470. 119 (a) L. Crombie, C. F. Doherty, and G. Pattenden, J. Chem. Soc. (C), 1970, 1076; (b) Fr. P. 1580474-6/1969; Jap. P. 75 33050. Ia0 F. P. 1536458/1966. Belg. P. 746726/1969. Synthetic Pyrethroids-A New Class of Insecticide Dihnlovinyl Acids. The (& )-cis,trans-dichlorovinylanalogue (1 K) of chrysanthe- mic acid, esterified in permethrin (10K)and cypermethrin (1 1K)was synthesized following Farkas et ~1.132 The potential commercial importance of these products has stimulated the search for alternative syntheses. The dichlorodiene (17) can be made by electro- lytic reduction of the acetate of (16),133 by dehydrocoupling of isobutylene and vinylidene chloride with palladous acetate,134 or by dehydration of hydroxy intermediates (Scheme 7).135 The final stage can be operated continuously136 or alternatively the 2-carbon unit is added using manganic acetatels' and the lac- i - If+ CI OH c1 (16) I A-\ /c' -CI Reagents: i, AlCI,; ii, Ac20; iii, Et,O; iv, toluene-4-sulphonic acid; v, CHN2C0,Et + Cu; vi, Mn(OAc),; vii, S0Cl2, EtOH; viii, base Scheme 7 la*J.Farkas, P. Kourim, and F. Sorm, Coll. Czech. Chem. Cumm., 1959,24,2230; J. Collongeand A. Perrot, Bull. SOC. chim. France, 1957, 204. lJSM. Alvarez and M. L Fishman, in ref. 12. la' D. Holland, D. J. Milner, and H. W. B. Reed, J. Organometallic Chem., 1977, 136, 111. la6B.P. 1493228; 1494817/1977. lJ' B.P. 1459285/1976. la' Fr. Demande 36424-5/1976; cf. Ger.Offen. 2707 104/1977. Elliott and Janes tonic product (19) converted with thionyl chloride into the required acid derivative.138 The synthesis Kondo developed from an earlier routel39 and later modified140 uses the simple, though not readily accessible, starting materials dimethylallyl alcohol and ethyl orthoacetate, and proceeds via a Claisen rearrangement, which is also an essential step in a related route141 from the trichloroethane derived from (16) as shown in Scheme 8.yL 'fj=4iii -% (18) EtO EtOOH ro iv1 it OH Reagents: i, CH,C(OEt)3; ii, heat; iii, CCI,, hv; iv, base Scheme 8 Another approach is based on 4,4-dimethylhex-5-en-2-one,available from a variety of reactions including catalysed addition of vinyl magnesium chloride to mesityl oxide.Thence, carbon tetrachloride addition, cyclization, and dehydro- halogenation give the required product (Scheme 9).13* The sequence of the two last steps determines the cisltrans ratio of the product. The cis and trans isomers of the acid (1K) give insecticidal esters of different potency, species specificity, and mammalian toxicity; controlling their ratio in lSEN. Itaya, T. Matsuo, N. Ohno, T. Mizutani, F. Fujita, and H. Yoshoika, in ref. 12. 13$ K. Kondo, K. Matsui, and Y. Takahatake, Tetrahedron Letters, 1976, 4359; Belg. P. 833 27811976. 140 Ger. Offen. 2547510/1976. Ger. Offen. 2542377/1976. 495 Synthetic Pyrethroids-A New Class of Insecticide iii or iv or 9:l Reagents: i, CH,=CHMgCl; ii, CC14, hw; iii, NaOH, then NaOCl; iv, NaOCl, then NaOH Scheme 9 the product is therefore valuable.The cis-rich products from any synthesis can be equilibrated at the acid chloride stage of ester preparation to a 22:78 niixture.142 Although under practical conditions the ethyl diazoacetate route gives a con- stant 45 55 cis:trans ratio, that from the Kondo139 and Kuraray141 routes can be adjusted within limits; the Sumitomo synthesis138 is even more flexible. The biologically active 1R,trans esters are available by resolution of the ( k)-trans acid.73 The outstanding insecticidal activity (see Table 1) of decamethrin (NRDC 161; 121) stimulated interest in commercial production of this single stereoisomer (of eight possible).This is feasible using a practical and extremely elegant route developed by Martel and shown in Scheme 10.131 The (lS,trans) chrysanthemic (2 isomers) 1or + 0 mother (12 1)liquors decamethrin $.OR 0 Reagents: i, PPh,, CBr,; ii, base; iii, acid chloride; iv. hexane Scheme 10 acid available after resolution of the (+)-trans form to provide the 1R acidic component for bioallethrin, S-bioallethrin, and bioresmethrin is used as a 14* M. Elliott. N. F. Janes. D. A. Pulman, L. C. Gaughan, T. Unai, and J. E. Casida, J. Agric.Food Chem., 1976,24,270. Ger. Offen. 2621 83011976. cf. Jap. Kokai. 75 160242. Elliott and Jones convenient source of the required (1R,cis)-caronaldehyde as described above. This, or a bicyclic equivalent12Qb gives with carbon tetrabromide in a Wittig reaction the (lR,cis)-dibromovinyl acid (11) used as summarized above to synthesize the insecticidal ester.2-(4-Chforophenyf)-3-methylbutyricAcid. Isopropyl halides a1 kylatep-chlorobenzyl cyanide in dimethyl formamide or in a phase transfer system,143 then hydrolysis provides the acidic component of fenvalerate. 6 Photochemistry A. Introduction.-The stability of pyrethroids in the presence of air and light has profoundly influenced their development as commercially important insecticides. Rapid decomposition after application of the natural pyrethrins and all com- mercial synthetic analogues developed before 1973 limited them to situations where only immediate kill is necessary. The recent more stable pyrethroids represent a major advance in insect control because their favourable combination of properties renders them appropriate for a much wider range of uses, especially in agriculture.Consequently, interest in synthetic pyrethroids has greatly increased, and the photochemistry of both unstable and stable compounds has been studied intensively (for a recent detailed review see ref. 144). B. Unstable Compounds.-Both oxygen and light are necessary for rapid poly- merization of the natural pyrethrins;* pyrethrins I and I1 (and pyrethrolone acetate) with dienic side chains polymerize more rapidly than the mono-enic constituents.145 The intractibility of the photodecomposition products formed by attack on the alcoholic components of the natural pyrethrins has obstructed detailed study of the rapid reactions by which they are f~rmed.~J~~ Photo-oxidative attack on the acid (chrysanthemate) component involves step- wise oxidation at the trans-methyl group in the side chain [compounds (20)-(22) isolated] for pyrethrin I, allethrin, and tetramethrin, and epoxidation of the olefinic group for re~methrin.l~~J~~ The products of photo-oxidative attack on the alcohol component of resme- thrin146 suggest an intermediate cyclic peroxide (23) (Scheme 11).The bicyclic products decompose further to simple benzene derivatives, including phenyl- acetic acid. The above reactions are rapid, and predominate when both air and light are present, but if oxygen is excluded, as in many laboratory U.V.irradiation studies, other reactions of these unstable compounds are observed.148 149 Jap. Kokai 76 63 145. 144 R L Holmstead, J. E. Casida, and L. 0 RUZO, in ref. 12. 146 M. Elliott, J. Chem. SOC.,1964, 5225; Y. Abe, K. Tsuda, and Y. Fujita, Botyu-Kagaku, 1972.37, 102. Id' Y.-L Chen and J. E. Casida, J. Agric. Food Chem., 1969, 17,208. 14' K. Ueda, L. C. Gaughan, and J. E. Casida, J. Agric. Food Chem., 1974,22,212. M. J. Bullivant and G. Pattenden, Pesticide Sci.,1976, 7, 231. Synthetic Pyrethroids-A New Class oj.Insecticide 0 (20) R = CHBOH (21) R = CHO (22) R = COaH 0-0 -[-0COR mOCOR' Scheme 11 C. Stable Compounds.-In the synthetic pyrethroids developed since 1973, with properties suitable for outdoor applications, the major photo-oxidative routes described above cannot occur.On the acid side, the isobutenyl side chain in chrysanthemates is replaced; similarly, no sites equivalent to those in rethrolones or furan alcohols, vulnerable to oxidative attack, are present in the benzenoid alcohols on which these important esters are based. Even one photosensitive component, in either part of the molecule, induces fast photodecomposition, but if both alcohol and acid are photostable, deposits persist substantially longer.266 Consequently, the photoproducts formed from the more stable compounds are not analogous to those from photolabile esters. The pattern for permethrin in solvents (and incidentally in soiI)149 involves (see Scheme 12) (a) a diradical intermediate similar to that proposed for chrysanthemates,148 leading to epimers, or by decomposition to 3-phenoxybenzyl dimethylacrylate, (b) loss of halogen from the dichlorovinyl side chain, and hydrogen capture to form the mono- 14' R.L Holmstead, J. E. Casida, L. 0.RUZO,and D. G. Fullmer,J. Agric. Food Chem., 1976 26, 590. + monobenzenoid products Scheme 12 chlorovinyl analogue (a minor metabolite), and (c) hydrolysis, followed by further oxidation or decomposition of the alcohol components. Photolysis produ~tsl~~J~0 from two stable a-cyano-substituted pyrethroids, decamethrin and fenvalerate, suggest that reaction pathways for permethrin (especially rnonodehalogenation) apply also to decamethrin, but that the major breakdown pathways on irradiation in solution involve cleavage of bonds at the ester group (Scheme 13).Although much work remains to be done, the important principlc is already established that the photolabile pyrethroids decompose in light by pathways which involve oxygen, whereas the more stable compounds undergo alternative types of reaction. Q loo R. L. Holmstead and D. G. Fullmer,J. Agric. Food Chem., 1977,25,56; L.0.Ruzo, R. L. Holmstead, and J. E. Casida, ibid., p. 1385: R. L. Holmstead, D. G. Fullmer, and L. 0. RUZO,ibid., 1978, 26, 954. Synthetic Pyrethroids-A New Class of Insecticide CN -co, CNI IArCHOCOR ArCHR 69%with fenvalerate 4 %with decamethrin CN CNI IArCH. + -0COR ArCHO. + COR ArCHaCN ArCOCN RH (10% with ArCH(0H)CN RCHO(ArcH--cN), fenvalerate) ArCHOArCH(CN)CH& Scheme 13 7 Structure-Toxicity Relationships of Pyrethroids in Vertebrates In practice, insecticides can at present be applied only relatively inefficiently;151 much of the dose does not reach the target and is potentially available to con- taminate the environment or affect unintended recipients.An important property of the new compounds is therefore their selectivity between target and non-target organisms, the distinction between insect and mammal being especially important. Averaged selectivity factors (Table 2) for four groups of insecticides indicate the relative safety of pyrethroids. Within this class, relative toxicities (see Table 3) are Table 2 Comparison of toxicities of classes of insecticidesa Insectslmg kg-l Ratslmg kg-l Selectivity factor Carbamates 2.8 45 16 Organophosphates 2.0 67 33 Organochlorines 2.6 230 91 Pyrethroids 0.45 2000 4500 Walues given are geometric means of LD,,’s obtained for a series of representative members of each class, against four species of insect, and against rats.Condensed with permission from a table published in ‘Synthetic Pyrethroids’, see ref. 12) related to the ease with which the compounds are metabolized in mammals. The reactions involved, classified as ester-cleavage, oxidation (mostly hydroxylation), and conjugation, are described be10w.l~~ I. J. Graham-Bryce, Chem. and Ind., 1976, 545. J5* For more extensive information, see: J.E. Casida, K. Ueda, L. C. Gaughan, L. T. Jao, and D. M.Soderlund, Arch. Environ. Contam. Toxicol., 197516, 3, 491 ;J. Miyamoto, Env. Health Persp., 1976, 14, 15; L. 0.Ruzo and J. E. Casida, Env. Health Persp., 1977, 21, 285; L.0. RUZO,T. Unai, and J. E. Casida, J. Agric. Food Chem., 1978,26, 918. Elliott and Jan Microsomal esterases, predominantly in the liver, cleave a wide range of pyrethroids at rates153 related to the degree of hindrance at the ester link. Studies with an isolated enzyme system indicate that esters of secondary alcohols (24;A, B # H) (cyclopentenolones; a-cyanobenzyl alcohols) are cleaved more slowly than those of primary alcohols, and 2,2-dimethyl-cyclopropanecarboxylateswith a substituent at C-3 cis to the ester group (24; C # H) [e.g. cismethrin (9F); NRDC 108 (9L)] are hydrolysed less readily than tram-only substituted com- pounds.2-Methyl-3-phenylbutyrates (M) react at rates intermediate between those of the cis and trans cyclopropane analogues. Oxidation at the trans methyl group (cf. photochemical reaction Section 6) of the isobutenyl side chain (CH3 -CHzOH -CHO -C02H) dominates other mechanisms in all chrysanthemates; epimerization at C-3 in some compounds during this process probably involves the aldehyde intermediate.154 The cyclo-propyl methyl groups are attacked (CH3 -CH20H) when pathways to alter- native products are suppressed (for example in the dichlorovinyl analogues of chrysanthemates). Furylmethyl and benzyl alcohols liberated by hydrolysis are oxidized to the corresponding acids (CH20H -COZH).5-Benzoyl-3-furoic acid is formed from resmethrin (CH2 -CHOH ---t CO)l55 and a secondary alcohol derivative [CH2=CHCH2 -CH2-CHCH(OH)-] produced by attack on the side chain of a1letl~in.l~~ The double bonds in the side chains of allethrin and pyrethrins I and I1 give di~ls,*~~ probably via epoxide intermediates.Phenoxy rings are hydroxylated at the 4', and less at the 2', positions. The alcohols, phenols, and carboxylic acids formed by these hydrolyses and oxidations may be conjugated with glycine, glucuronic acid, sulphate, and other groups. The water solubilities of pyrethroid metabolities are thereby increased, facilitating their excretion. The low mammalian toxicity traditionally associated with the natural pyre- thrins extends to some, but by no means to all, synthetic pyrethroids, as indicated by oral toxicities (Table 3).The ease with which pyrethrins 1 and II are oxidized on the diene side chain and pyrethrin II is cleaved at the methoxy-carbonyl group is associated with their low oral toxicities. S-Bioallethcin, with a less reactive monoene side chain, is more toxic. The central ester bond is not hydrolyscd D. M. Soderlund and J. E. Casida. in ref. 12, p. 162. 154 K. Ueda, L. C. Gaughan, and J. E. Casida, J. Agric. Food Chem., 1975. 23, 106. Is5 J. Miyamoto, T. Nishida, and K. Ueda, Prstic,icko Biocheni. Physiol., 1971, 1, 293. IS6 M. Elliott, N. F. Janes, E. C. Kimrnel, and J. E. Casida, J. Agric. Food Cheiir., 1972, 20, 300.Synthetic Pyrethroids-A New Class of Insecticide Table 3 Mammalian toxicities of synthetic pyrethroidsa Compound LD5o to ratslmg kg-1 Selectivity Oral Intravenous factor d Pyrethrin I 2-5 Pyrethrin I1 900b 0.4-1 72 S-Bioallethrin 680 4c 270 Bioresmethrin 8000 340 30000 Biophenothrin 10000 -24000 Cismethrin 100 6-7 NRDC 108 140 4-5 410 RU 11 679 63 5-10 400 NRDC 132 900 11 1-1 30 5400 NRDC 133 800 90-1 30 5000 NRDC 140 400 26-33 1600 NRDC 141 18 1 A-2.8 68 NRDC 173 130 2.0 2000 NRDC 174 14 0.5 150 permet hrin 2000 450 4800 cy per me t hr in 500 50 4200 decamethrin 70-140 2-3 -6OOo fenvalerate 450 75 900 aMuch of this table reproduced, with permission, from the ‘Annual Review of Entomology’, Volume 23, 01978 by Annual Reviews Inc.The remainder is from results (some previously unpublished) by Dr. J. M. Barnes and colleagues, Medical Research Council, Carshalton, Surrey. The data have been collected and averaged for these comparative purposes only, and should not be quoted out of context; bNatural pyrethrins; Cbioallethrin; dcalculated as LD,, to rats (oral)/LD,, to houseflies (topical), each in mg kg-l significantly in these three compounds, but bioresmethrin and phenothrin, easily cleaved primary esters of a trans-substituted cyclopropane acid with an iso- butenyl side chain also susceptible to attack are outstanding in their low toxicity; they are among the safest known insecticides. NRDC 108 and cismethrin, esters of acids with cis-substituents, are more toxic.In NRDC 132 and 133, absence of the trans-methyl group of the chrysanthemates leads to moderate toxicity, not so great, however, as that of RU 11679, where extreme lipophilicity may be sig- nificant. Transition from isobutenyl to dihalovinyl at C-3 increases toxicity to mammals (NRDC 140 and 141 compared with bioresmethrin and cismethrin) especially with the difluoro compounds NRDC 173 and 174, but these changes are offset by replacing 5-benzyl-3-furylmethyl(9)by 3-phenoxybenzyl (lo), giving esters somewhat less active as insecticides but also more susceptible to mam- malian detoxification by hydroxylation. The greater insecticidal activity pro- duced by introducing the a-cyano group (cypermethrin and decamethrin) amply compensates for the increased mammalian toxicity of the compounds associated with hindrance of esterase activity and diminished rate of oxidation.153 Although intravenous toxicities (Table 3) bear little relation to the practical Elliott and Janes application of pyrethroids they provide valuable information for correlation of structure with activity especially where the toxicities per 0s found for many pyrethroids are too low to permit significant deductions.They may provide evidence of intrinsic toxicity at the site of action in mammalian nervous systems, where few comparisons are yet reported. In one study, White et ~1.l~’measured a six-fold difference in brain levels of cismethrin and bioresmethrin in rats just showing lethal symptoms.The pyrethroids so far examined have very low toxicities to birds, but are lethal to fish at low concentrations (for a discussion and references see ref. 10). 8 Other Aspects of Biological Activity A. The Influence of Polarity.-Correlation of biological activity with measured or estimated polarity (expressed, in the Hansch approach158 as P,the octanol/ water partition coefficient) has been attempted in many systems. With pyre- throids, only a broad generalization that potent compounds have log P values near 6 was possible; the measured activity of pyrethroids is necessarily influenced by many factors, such as rate of penetration, detoxification, and potency at the site of action, dependent upon the chemical and physical properties of the compounds.Pyrethroidal activity depends closely on the overall shape of the molecule22 and may respond to small changes in conformational ~reference,~~ properties which are not easily expressed quantitatively; no useful correlations with other parameters have been reported. Nevertheless, typical log P values of pyrethroids and of other insecticides relate well with many aspects of their behaviour.85 Like the organochlorine compounds, e.g.dieldrin and DDT(1ogP also ca. 6) they partition preferentially into the lipoid rather than the aqueous tissues of complex organisms. However, unlike the organochlorine compounds, pyrethroids are readily metabolized (see above) and do not accumulate. Many organophosphate and carbamate insecticides have log P values below 4 and act systemically in plants, which implies some affinity for the moving aqueous phase.In contrast, the known pyrethroids, being extremely lipophilic, show no systemic, nor even translaminar, action. B. Knockdown.-Some pyrethroids paralyse insects remarkably rapidly. If fol- lowed by recovery, the effect is recognized as knockdown rather than kill.159 The two actions appear to be associated with different properties :160 knockdown with the more polar pyrethroids, perhaps because they penetrate more rapidly (but see also ref. 21) and the more prolonged effects that eventually kill the insect85 with greater lipophilicity. Those pyrethroids with more powerful knockdown action 15’ I. N. H. White, R. D. Verschoyle, M.H. Moradian, and J. M. Barnes, Pesticide Biochem. Physiol., 1976, 6, 49 I. C. Hansch, in ‘Drug Design’, ed. E. J. Ariens, Academic Press, New York, 1971, vol. I, p. 271. 15B R. M. Sawicki, J. Sci. Food Agric., 1962, 13, 283. lE0G. G. Briggs, M. Elliott, A. W. Farnham, and N. F. Janes, Pesticide Sci., 1974, 5, 643. 503 Synthetic Pyrethroids-A New Class of Insecticide (indicated by ‘KD’ in Table 1) are mostly less effective killing agents; of the compounds listed, only NRDC 173 (9C)combines the two actions strongly. Knockdown agents are incorporated in many domestic aerosol insect sprays and are therefore significant commercially; they are less important for agricultural applications, where formulations for residual contact are most appropriate. C.Synergism.-Most commercial formulations of the natural pyrethrins include a synergist (usually piperonyl butoxide in 8-10-fold excess). Potency is thereby increased up to 10-fold, despite the inactivity of the additive alone. In such preparations, the natural compounds, though expensive, compete with less well synergized synthetic a1 ter na t ives. For research, synergism is most rationally investigated by applying a constant largo dose of synergist (e.g., 2 pg per housefly) before the insecticide; otherwise, at fixed toxicant :synergist ratios, relatively little additive would be administered with the more potent compounds. Few formulations with synergists are therefore anticipated for the more stable, active compounds suitable for agricultural applications.The mode of action of synergists is not yet adequately understood, but may involve suppression of oxidative and esteratic detoxificationI61 or other mechanisms.162 Methylenedioxyphenyl synergists, such as piperonyl butoxide, are thought to suppress primarily oxidative detoxification within the insect; the high factor of 300 with pyrethrin 1163 is consistent with the many biologically oxidizable sites recognized in this c0mpound.1~~ However, synergists do not appreciably increase the activities of pyrethroids in all insects. Later synthetic pyrethroids, not well synergized even in the ho~sefly,l~~may be less susceptible to detoxification by insects, especially by oxidative routes. 9 Summary and Conclusions: The Present and Future Importance of Synthetic Pyrethroids This survey has indicated the diverse range of insecticidally active compounds related to the prototype, pyrethrin I.Pyrethroids are lipophilic compounds, very active as contact insecticides and possibly as stomach poisons against a wide range of insect species; some members of the group also have useful repellent action. The exceptional potency of some of the compounds discovered shows how well an active natural product (particularly a chiral one) can serve as the parent structure for examining the relationship between biological activity and chemical structure. The first synthetic compounds, although very active and relatively safe, were too unstable for many applications, but development of more persistent com- pounds with many of the favourable characteristics of the earlier esters greatly increased the scope of the group.In addition to understanding of insecticidal 16’ J. E. Casida, Ann. Rev. Biochemistry. 1973, 42, 259. lea A. W. Farnham and R. M.Sawicki, unpublished results. 163 P. E. Burt, M. Elliott, A. W. Farnham, N. F. Janes, P. H. Needham, and J. H. Stevenson, in ‘Crop Protection Agents-Their Biological Evaluation’, ed. N. R. McFarlane, Academic Press, London, 1977, p. 384. 504 Elliott and Janes activity, knowledge is now accumulating of the influence of structure on toxicity to mammals, birds, and fish and on stability in light and in soils. All implications of the anticipated widespread use of the more stable synthetic pyrethroids must be considered.In many respects they have more favourable properties than other groups of lipophilic insecticides such as the organochlorine compounds because, although they persist adequately on crop surfaces, their physical properties restrict migration in solution and as vapour, and they are rapidly decomposed when exposed to metabolizing systems, such as soil micro-organisms. The potential for developing new compounds with properties especially appropriate for many different individual applications or specifically active against particular pests is great. The many types of biological activity against invertebrates (for example repellency and antifeeding action in addition to kill) latent in the structures of the natural compounds have almost certainly not yet been fully exploited.The further development of synthetic pesticides related to the natural pyrethrins is therefore a challenging area for practical application of many aspects of organic chemistry. We acknowledge help, discussion, and disclosure of unpublished results from colleagues at Rothamsted Experimental Station, Harpenden ;Medical Research Council Toxicology Unit, Carshalton; and numerous industrial organizations, and support from the National Research Development Corporation.

ISSN:0306-0012    

DOI:10.1039/CS9780700473

出版商:RSC    

年代:1978

数据来源: RSC

摘要:

MELDOLA MEDAL LECTURES* Molecular Shapes By J. K. Burdettt DEPARTMENT OF INORGANIC CHEMISTRY, THE UNIVERSITY OF NEWCASTLE UPON TYNE, NEWCASTLE UPON TYNE, NE1 7RU 1 Introduction For many years chemists have explored structural aspects of simple main group compounds guided by several simple theoretical tools that have proved invaluable. The Valence Shell Electron Pair Repulsion (VSEPR) model, devised by Sidgwick and Powell and consolidated by Nyholm and Gillespie, is a qualitative predictor of the angular geometry of an AHn or AXn system with a main group (A) central atom.’ The ideas of WaIsh,2 published twenty-five years ago, provided a simple molecular orbital rationale of these structures and, in addition, were able to predict the geometries of excited states which VSEPR could not do.One interest- ing feature of the two methods is that whereas the VSEPR scheme emphasizes electron4xtron interactions, and ignores central-atom-ligand interactions, the opposite is true for Walsh’s molecular orbital approach, which is just concerned with the changing magnitudes of central atom orbital-ligand orbital overlap on distortion. A linking piece in this structural jigsaw was provided by Bartell’s adaptation3 of the second-order (or pseudo) Jahn-Teller effect to structural main group chemistry. Shortly afterwards Pearson published4 his symmetry rules for the prediction of molecular geometry, which included and extended Bartell’s work. We shall find, however, that these well proven methods for looking at main group structures need to be replaccd when rationalizing the shapes of transition-metal complexes.Steric effects are often very important in influencing reactions and structures. Recently Glidewell5 has widely applied the ‘hard sphere’ ideas of BartelP to this area and the interplay of steric and electronic controls on geometry is one that we shall return to. Many sets of quantitative molecular orbital calculations have been performed at varying levels of sophisti- cation in efforts to calculate bond angles. It is, however, the purpose of this *These lectures were delivered in April 1978 at the Annual Chemical Congress, University of Liverpool.?Present address: Chemistry Department, University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, U.S.A.R. J. Gillespie, ‘Molecular Geometry’, Van Nostrand-Rheinhold, London, 1972. ‘A. D. Walsh, J. Chem. Soc., 1953, 2260, and following papers. L. S. Bartell, J. Chem. Educ., 1968, 45, 754. R. G. Pearson, J. Amer. Chem. Soc., 1969, 91, 1252, 4947. C. Glidewell, Znorg. Chim. Acfa, 1975, 12, 219; 1976, 20, 113.’L. S. Bartell, J. Chem. Phys., 1960, 32, 827. I Molecular Shapes lecture to review methods which lead to an understanding of molecular shapes at a basic level. One may recall that in Hoffmann’s view ‘. . . to understand an observable means being able to predict albeit qualitatively the result that a perfcctly reliable calculation would yield for that observable’.’ 2 Shapes of Main Group Molecules VSEPR and Walsh’s Scheme.-The angular geometries of simple main group molecules are well matched by the predictions of the theoretical tools we have just mentioned.(The exceptions are of interest in themselves.) For the AH3 and AX3 molecules (A = B, C, N; X = halogen etc.) the VSEPR method correctly predicts BH3 to be trigonal planar (three pairs of electrons) and NH3 to be pyramidal (four pairs of electrons). The number of electrons which we use in the VSEPR count is all the valence (ns + np) electrons on the central atom plus (usually) one from each of the ligands. Where double bonding is possible between A and X (e.g. X = 0)only the electron from the (J part of the inter- action is included. In some cases two electrons come from each of the ligands.Thus C(PR3)2 contains two filled shell ligands (PR3) which contribute two electrons to the VSEPR count. With the four carbon valence electrons, a total of four ’electron pairs are included in the scheme, which rationalizes the non-linear structure* of the molecule (isolectronic with OF2). The methyl group with three and a half pairs provides a problem since how does half an electron pair behave? The Walsh diagram for the AH3 system is shown in Figure 1. (For AX3 the situ- ation is similar.) It shows how the valence orbitals of the unit qualitatively change in energy as the molecule distorts. Walsh arrived at the angular depend- ence of the orbital energies simply by considering in qualitative terms how the ligand-central atom overlap integrals changed on distortion. (This may be put on asemi-quantitative basis by applying to the main group case9 the ideas we describe below for transition-metal systems.) Parr has shown10 how valence bond methods arrive at similar results.For BH3 with two electrons in the la’l and four in the le’ orbital bending is obviously unfavourable. For NH3 with two electrons in la”2 an overall stabilization on bending is possible. With only one electron in this orbital (CH3), is the stabilization energy afforded this electron on bending sufficient to overcome the opposirigeffect of the lower energy elec- trons? Jordan and Longuet-Higginsll suggcsted that the radical would be planar, whereas Linnett and Poe12 suggested that it would be pyramidal. In fact the result of gas phase electronic spectral studies13 and e.s.r.resuItsl4 on matrix ‘I R. Hoffmann, Accounts Chem. Res., 1971, 4, I. a A. T. Vincent and P. J. Wheatley, J.C.S. Dalton, 1972, 617. J. K. Burdett, Structure and Bonding, 1976, 31, 67. lo G. W. Schnuelle and R. G. Parr, J. Amer. Chem. SOC.,1972,94, 8974. l1 P. C. H. Jordan and H. C. Longuet-Higgins, Mol. Phys., 1962, 5, 121. la J. W. Linnett and A, J. Poe, Trans. Faraday SOC., 1951, 47, 1033. G. Herzberg, Proc. Roy. SOC.,1961, A262, 291. l4 R. W. Fessenden and R. H. Schuler, J. Chem. Phys., 1963, 39, 2147. 508 Burdett . . ...... ... . .. . E \"A. 0 e-+ 35 Figure 1 Walsh diagram for an AH3 molecule within the C,,distortion co-ordinate isolated CH3 suggest that it is, or is very close to being, planar; the second row analogue SiH3, however, is pyramidal.l5 Matrix studies14916~1~ also show that substituted methyl radicals are pyramidal (e.g. CF3, CHF3, cc13). Thus on the VSEPR model three and a half electron pairs behave differently accord- ing to the substituents attached to the main group atom. But the vibrational data on matrix isolated CH3 are intrinsically very interesting. The radical was made initially in two ways [reactions (1)18 and (2)19]. vac U.V. CH, ___+ CH3 + H M + CH3X -+CH, + MX (MX = alkali halide) (2) When made by reaction (1) the out-of-plane bending mode (YZ) of the radical at 611 cm-l was associated with an unusual ratio of vz(H)/vz(D) (Table 1). This could be rationalized either by a bond angle smaller than that in NH3 in its R.L. Morehouse, J. J. Christiansen, and W. Gordy, J. Chem. Phys., 1966, 45, 1751. R. W. Fessenden and R. H. Schuler, J. Chem. Phys., 1965, 43, 2704. I' L. Andrews, J. Chem. Phys., 1968, 48,972; J, Phys. Chem., 1967,71, 2761. la D. E. Milligan and M. E. Jacox, J, Chem. Phys., 1967, 47, 5146. Is L. Andrews and G. C. Pimentel, J. Chem. Phys., 1967, 47, 3637. Molecular Shapes Table 1 Vibrational data for CH3 andperturbed CH3 radicals CH3 * * LiBr 730 1,288 normal positive anharmonicity CH3 * LiI 730 CH3 NaBr 700 CH3 -* NaI 696 I .305 CH3 * KI 680 negative an harmonici ty CH3 611 1.319 al.291 for harmonic oscillator electronic ground state (which is unlikely) or by a large negative anharmonicity of a planar structure.This type of anharmonicity is well documented for a small number of systems. (Amongst these is the out-of-plane bending mode of the first excited state of NH3 [(le’)*(la”~)~(2a’l)~],which is also planar20 and closely related to the present problem.) Intriguingly the radical formed in reaction (2) (MX = LiI) showed a higher value of v2 and a small (normal) positive anhar- monicity (Table 1). In order to understand this behaviour we need to look at the third approach to molecular geometry. CH3 and the Second-order Jahn-Teller Effect.-The strategy of this method uses the perturbation expansion of the energy of a molecule3~4~21-23 on distortion along a co-ordinate, Qi.If we write the perturbed Hamiltonian as equation (3) then from first- and second-order perturbation theory for the electronic ground state (10)) The first term in this energy series is the first-order Jahn-Teller term.24 It will be non-zero for (i) any electronic state if Xi is associated with a totally sym- metric mode, and (ii) an orbitally degenerate electronic state if ZZis associated with a mode which reduces the molecular symmetry.We usually ignore (i) and focus on the predictions for degenerate electronic states where the distortion 2o A. D. Walsh and P. A. Warsop, Trans. Faraday SOC.,1961, 57, 345. 21 R. F. W. Bader, Mol. Phys., 1960, 3, 137. H. C. Longuet-Higgins, Proc. Roy. SOC.,1956, A235, 537. 43 J. K. Burdett, Appl. Spec. Rev., 1970, 4, 43.2p H. A. Jahn and E. Teller, Proc. Roy. SOC.,1937, A161, 220. Burdett removes this degeneracy. A tabulation of the permitted distortions Qi for given geometries and electronic state is given by Jotham and Kettle.25 The second term (of order QP) in equation (4) is the one which will mainly concern us here and represents the force constant associated with the distortion. It consists of two parts, a ‘classical’ force constant, (g),andarelaxationpart-describing how the electronic charge distribution changes’or relaxes so as to reduce the overall force constant. If the summation is truncated at the first excited state In) then the force constant is given by equation (5). If there is a small Lk [control-led by the size of the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) separation] then the relaxation term may be large and overwhelm the classical force constant.The resulting negative force constant implies that the molecule will spontaneously deform away from that geometry along the co-ordinate Qf, the actual choice of which is regulated simply by the symmetry properties of the ground and first excited electronic states. An alternative approach is the following. We need to find that distortion co- ordinate which will result in the HOMO and LUMO having identical symmetry properties (i.e. belong to the same symmetry species in the distorted molecule). As this distortion progresses the HOMO and LUMO will heavily mix together and the two energy levels will ‘repel’ one another.The lower energy component (HOMO) which contains one or two electrons will be stabilized by such an inter- action as shown in Figure 2. If the dynamics of the system are controlled by the energetic behaviour of the HOMO, then the molecule as a whole will be stabilized by such a distortion. From group theory we can determine the symmetry of Qi such that the inte- grand l(Ol#iln)12 may be non-zero. We may express the numerator in terms of the transition density+o*#n, where 40is the orbital in the ground state and #,, is the orbital in the excited state which hold the ‘excited’ electron. Figure 3(a) shows schematically how the symmetry species of Qt is determined for AH3 molecules (A = B or N) and also for ClF3. The direct product of the symmetry species of & and 9.must contain either a”2 or e’ for the molecule to distort, as shown in Figure 3(b). Hence the planar structure of BH3, pyramidal structure of NH3, and T-shape of ClFs are neatly rationalized. (It may be noted here that the latter geometry was one not mentioned by Walsh.) The same method can be used to reproduce the geometries of CF4, SF4, XeF4 etc., and usually similar predictions to those from VSEPR are obtained. However, this method does require that we have a knowledge of the MO structure of the symmetric geometry before we can begin. Note that in Figure 3(a) it is the lowest energy ‘transition’ which deter- mines the geometry. A higher energy transition (le’ +2a’l) would give rise to a transition density (and Qi)of species e’ for BH3, which in practice does not give rise to any static distortion.A manifestation of this contribution does however ** R.W.Jotham and S. F.A. Kettle, Inorg. Chim. Acra, 1971, 5, 183. 511 I Molecular Shapes A A€ t E I symmetric distortion co-ordinate- geometry Figure 2 The stabilization of the HOMO brought about by the distortion co-ordinate which causes the HOMO and LUMO to have identical symmetry properties turn up in the vibrational force field of the planar molecule.21 The stretching bond-bond interaction force constant is positive, which shows that the relaxation term of equation (4) is not zero but not large enough to overcome the classical constant.The result of variation of ligand electronegativity can be seen by its effect on the size of the energy gap dc. For the NXs case this will be largely set by the energy difference between la”2 and h’1. The 1a”a orbital remains approximately unchanged in energy but the orbitals involved in u interactions (e.g. &’I) drop in energy and dc becomes smaller. The driving force away from planar for NX3 species should then be larger as X becomes more electronegative. An alter- native way of looking at the increasing tendency for AX3 molecules to pyrami- dalize as the electronegativity of the X ligands increase is provided26 by the theory of isovalent hybridi~ation.~~ Briefly, the more electronegative the ligand X the more polarized the AX bond.In MO language this means that the AX bond will contain more A atomp-character. Increasing central atomp-character in a hybrid leads to smaller X-A-X angles (recall sp, 180”;sp2, 120”;sps, 109”28’;ps, 90”) and thus the molecule should be driven further away from planar as the total ligand electronegativity increases. CH3 has similar HOMO-LUMO properties to NH3 and a distortion from the trigonal planar geometry is predicted but with a value for the relaxation term of half2892Q that for NH3 (half the number of a”2 electrons). The radical is perhaps loJ. H. Current and J. K. Burdett, J. Phys. Chem., 1969,73, 3505. R. S. Mulliken, J. Phys. Chem., 1937, 41, 318; 1952,56,295. J. K. Burdett, J. Chem. Phys., 1970, 52, 2983. J. K. Burdett, J. Mol.Spec., 1970, 36, 365. Burdett CIF,BH3 e' e' ....6; a; -a: a:'+-.'## a: e'$0 X 9"-e" distortion none pyramid T-shape Figure 3 (a) Second-order Jahn-Teller approach to AH8 geometries; (b) the routes bywhich the and e' bending vibrations ofa trigonal planar AHSmolecule lead to pyramidaland T-shape structures rather tenuously planar with a vibrational frequency (VZ = 61 1 cm-l) much less than in BH3 (1 125 cm-l). As the ligand eiectronegativity increases (e.g. to CF3) the molecules become pyramidal in accord with the ideas described above for NF3. By means of the fourth-order perturbation term in the expansions of equations (3) and (4) we may tackle the problem of the anharmonicity of the planar radical (and that of planar NH3 in its first excited state).The anhar- monicity may be shown*s to consist of a 'classical' term and a relaxation term. I Molecular Shapes The latter is simply given by equation (6), which suggests that the larger the I<Ol*rln>l* .<nl&rrln> (6)A4 second-order ‘softening’ of the vibrational force constant, the larger the positive contribution to the quartic term in Qz which gives rise to the negative anhar- monicity. By a mechanism29 which we will not discuss here the effect of perturba- tion by alkali halides is to reduce the relaxation term and thus increase the vibrational force constant and frequency v2 with a commensurate replacement of the negative anharmonicity by a normal (small) positive one (Table 1).A molecule approachable along similar lines which also has a large second- order softening is XeFs, a fluxional molecule in the gas phase with a large ampli- tude and highly anharmonic flu bending mode.30 The VSEPR scheme would give the molecule (seven pairs) a much larger distortion than that actually observed. Steric Effects.-The importance of steric effects is illustrated by a single example. For many years the pyramidal structure of N(CH3)3 but planar geometry of N(SiH3)3 has been ascribed to .rr-bonding between the p,-orbital on the N atom and a Si d-orbital. However, recently Glidewell, using the ideas developed earlier by Bartell of intramolecular van der Waals forces6 and applied especially to hydrocarbon structures, has convincingly argued5 that the non-bonded repul- sions of the large SiH3 groups are large at the pyramidal geometry but are relieved at the planar. In support of this view is the fact that P(SiH3)3 is pyra- midal.The longer P-Si bonds compared with those of N-Si result in a less tightly packed environment. N(SCF3)3 also has a planar NS3 skeleton31 but with shortenedN-S bonds, which are suggested to arise throughn-bonding. The inter- play between steric and electronic controls on molecular geometry is clearly an interesting one. Summary.-The use of several different approaches leads to quite a good appreciation of the factors determining main group geometries and it is possible in some cases (e.g. CH3) to understand very simply rather subtle features of the potential energy surface associated with angular deformations. We have con- centrated on the geometries of covalently bound species. Structures which do not fit into the VSEPR scheme are also found for the more ionically bound members of the MX2series (M= Ca-Ba).In order to understand this behaviour and also some of the basic dynamics behind the operation of the Walsh diagrams, we refer the reader to a recent study by 3 Shapes of Transition-metal Complexes The Failure of Existing Models.-In contrast to main group chemistry, the struc- L. S. Bartell and R. M. Gavin, J. Chem. Phys., 1968, 48, 2466. 31 C. J. Marsden and L. S. Bartell, J.C.S. Dalton, 1977, 1582. 3a M. B. Hall, J. Amer. Chem. SOC.,1978. 100, 6333; fnorg. Chem., 1978, 17, 2261.514 Burdett tures of relatively few transition metal complexes are known in the gas phase. Most of the available ones are either octahedral [Cr(CO)s, MFs] or tetrahedral (vc14, TiC14). The structures of complexes in crystals should be interpreted with care since the influence of the medium is not well understood, and an observed geometry in the solid may not represent the lowest energy configuration of the free molecule. It is also probably true that transition metal structures are more susceptible to distortion in the solid state so that a wider variety of structures are found. For example, CuC142- may adopt the D2d or square planar geometry depending upon the counterion. Pressure also reversibly converts one into the other.A significant advance in the range of available transition-metal systems with a variety of co-ordination numbers and d-electron configurations was the production in low temperature matrices of binary M(CO), and M(N& com-plexes.33 Most of the quantitative structural determinations on these molecules have been performed in laboratories in Newcastle upon Tyne and Toronto. Some of this work is described by Poliakoff in the next article (see p. 527). The matrix does not seem to exert a strong force influencing the geometry of the molecule, and in many ways we may regard them as being pseudo gas-phase structures. Fe(CO)3 (1) and Cr(C0)3 (2) are both pyramidal molecules with bond angles determined using the band intensity method. They were both made by the careful matrix photolysis of the parent molecules Fe(c0)~~~ and Cr(CO)s.35 Ni(C0)3 (3) is a trigonal planar molecule.3~ Fe(C0)3 is probably a triplet species .,....... . . .. . . ... .. . . . . . . . ..... .. . ... . ...\A,,yfi,, -\ Fe Cr Ni [magnetic circular dichroism studies on Fe(C0)4 (see p. 531) show it to have S = 11 and we shall refer to its electronic configuration as hs d8(hs = high spin); Cr (co)3 is certainly 1s d6 (Is = low spin). With three ligand (T pairs the molecules Cr(C0)3, Fe(C0)3, and Ni(C0)3 have a total of six, seven, and eight pairs sur- rounding the central atom, respectively. It is possible to find VSEPR polyhedra to rationalize their shapes (octahedron for six pairs, CsVcapped octahedron for seven pairs, and distorted square antiprism for eight pairs) but these polyhedra may not be used to rationalize other transition-metal structures; CI(CO)S also with eight pairs is a square pyramid3' which does not fit into the square anti- 33 J.K. Burdett, Cuurd. Chem. Rev., 1978,27, 1. M. Poliakoff, J.C.S. Dalton., 1974, 210. s6 R. N. Perutz and J. J. Turner, J. Amer. Chem. SOC.,1975,97,4800. s6 R. L. DeKock, Inorg. Chem., 1971, 10, 1205. ST R. N. Perutz and J. J. Turner, Inorg. Chem., 1975, 14, 262. I Molecular Shapes prism concept. Gillespiel suggested that with these carbonyls the d-electrons should be neglected and just the number of ligand CJ pairs included. Although this correctly predicts Cr(C0)a to be octahedral and Ni(C0)4 to be tetrahedral, all three tricarbonyls should be trigonal planar according to this model, which is not the case.The Jahn-Teller theorem may often be used to rationalize the observed geometries of transition metal complexes, although as a predictor of molecular shape it is usually not very specific. One area where this approach fails is for those cases where a distorted geometry is found but the highest symmetry structure is not orbitally degenerate and therefore is Jahn-Teller stable. Examples of this type are found in both Cr(C0)3 and Fe(C0)3. For application of Jahn-Teller arguments we need a MO diagram for the D3h structure. Two extended Huckel calculations38J9 have derived slightly different results as to the order of the energy levels in the trigonal planar structure [Figures 4(a) and 4(b)].We note that both a Is d6and hs d8 system on the scheme of Figure 4(a) would be Jahn-Teller unstable, but distortion to a T-shape (not to a pyramid) is predicted on group theoretical arguments.25 On the scheme of Figure 4(b) both molecules would be Jahn-Teller stable. On both schemes a pyramidal (CsV)geometry is unlikely for the low spin d8 Fe(C0)3 molecule since here it would be Jahn-Teller unstable. On either scheme the Cr(C0)3 and Fe(C0)3 molecules are predicted to be unstable on second-order Jahn-Teller grounds. The distortion co-ordinate is of species e’ which predicts a distortion to a T-shape, which is patently not the case. The higher energy transition d‘ -e’ does give rise to a transition density of species a”2 for the Cr and Fe examples but the rule discussed in Section 2, p.508 required that the lowest energy transition was most important. Here the structural predictions of the second-order Jab-Teller effect are not reliable. This does not mean, of course, that the perturbation approach to the analysis of MO energy changes on distortion is in general invalid. It does mean, however, that the energy changes associated with a group of valence orbitals on distortion must be considered rather than that associated with one orbital in particular. For Ni(C0)3 the e” e’ transition is not allowed since the 4 d manifold is full (dlo). Figure 4 also shows some quantitative calculations of the orbital energy changes on distortion.We can readily see that double occupation of the 4’1 orbital in both Is d6 and hs d8 molecules strongly encourages pyramidalization. The smaller distortion for Fe(C0)3 away from the trigonal planar geometry com- pared with that for Cr(C0)3 is simply understood since here there is double occupation of the e’ orbital which is destabilized on distortion. In Ni(C0)3, four electrons in this orbital ensure planarity. Figure 4(c) shows that distortion to a T-shape from the trigonal plane is also favoured for the electronic configurations Is d6, hs d8.Do we need then to rely on quantitative calculations in order to pre- dict molecular geometry? The most comprehensive sets of calculations on these angular geometries have used the extended Huckel method.In general these reproduce the observed geometries with remarkable fidelity. Both sets of 38 J. K. Burdett, J.C.S. Furaday fI, 1974, 70, 1599. 3s M. Elian and R. Hoffmann, Inorg. Chern., 1975, 14, 1058. 516 ...... . . . . . .. . . . eA88 e' e" 0 120 H-'Figure 4 MO energy level diagrams for bending within; (a) C,,co-ordinate, from ref. 39; (b) C,, co-ordinate,from ref. 38 ;(c) C,,co-ordinate, i&fromref. 38 Cr 4 .x I Molecular Shapes calculations predict a D2d geometry for the d9 M(C0)4 species but with a CaV geometry close in energy. Both forms have been made in low temperature matrices. Similarly although (hs d8)Fe(C0)4 is predicted and observed to have a CZ,structure, a CsV or Csgeometry lies close in energy above it.As described in the following article, laser i.r. photolysis experiments confirm a thermal re- arrangement pathway via a transition state of this symmetry. For the tricarbonyl series 8is predicted to be: 30", 33", [obs. 25" for Mo(CO)3]; 17", -, [obs. 18" in Fe(C0)3]; 0,8", [obs. 0"in Ni(C0)3] from the two sets of calculations described in refs. 38 and 39, respectively. There is clearly a need for a simple model with which to view these structures. The Angular Overlap Approach.-Our simple molecular orbital approach is based on the angular overlap model (AOM),40-42 which has been used mostly in the past in the interpretation of the electronic spectra and magnetic properties of transi- tion-metal complexes. Basically it provides the energies of the (mainly) transition metal d orbitals in an MLn complex of given geometry in terms of two para- meters, one describing cr-and the other v-type interactions.[Similar to the d or Dq of the crystal field theory (CFT).] Once these energies have been obtained then the weighted sum of the d-orbital energies (weighted by the number of electrons in these orbitals) as a function of the molecular geometry provides the oppor- tunity to explore the configurational potential surface and find the most stable geometry demanded by metal d-ligand interactions for a particular electronic configuration. The AOM is based on an approximation involving the inter- action energy between two orbitals (42, +,) on different atoms. Here +t rep-resents a metal d-orbital and +* a single ligand orbital or symmetry-adapted combination.The stabilization energy E of the bonding component may be written as a perturbation sum [equation (7)] where k is a constant, Sij is the overlap integral between~$iand +j, and deij their unperturbed energy separation. Inthe following discussion we shall concentrate on the leading term in the expansion with an occasional reference to the others. The stabilization of the bonding combination becomes E = /3,Sij2, where PA is k21Aej (A = CT, T,etc.). In our simple model it is also assumed that the destabilization energy of the antibonding orbital is equal to the stabilization energy of its bonding partner. The tremendous power of the model lies in the fact that the SZ~are, in general, dependant on simple geometric expressions as the angular metal-ligand geometry is adjusted while maintaining the same bond length. This means that the following calculations may be simply performed using 'back-of-envelope' computations.Table 2 gives functions for overlap of a ligando orbital (located at the polar position 8,#)with the d-orbitals, *O J. K. Burdett, Adv. Znorg. Chem. Radiochem., 1978, 21, 113. Q1 C. E. Schaffer and C. K. Jerrgensen, Mol. Phys., 1965, 9, 401. rsC.E. Schaffer, Struct. Bonding, 1973, 14, 69. 518 Burdett Table 2 Angular dependance of ligand a-metal d-orbital overlap integral as a junction of the polar co-ordinates of the ligand d-orbital S 1-(3H2 -l)Su2 3+ x2 -y2 -(F2 -G2)Su2 xz 3*FHS, YZ 3*GHS, XY 3+FGS, F = sinOcos4, G = sinOsin4, H = cod and shows some of the overlap integrals which are particularly useful.Thus the interaction energy of a ligand a orbital with the z2orbital is given by the function 1 E = /3,Su2 -(3cos28 -1)2, where 18, is introduced as the proportionality 4 constant describing a-type interactions. The notation used is that of Kettle;43 a simpler way of expressing these values is to put puSa2 = eu, see for example ref. 41. V-Type interactions are described by analogous equations but we will concentrate on a-type interactions in our discussion since these are generally considered to be of large magnitude. We are thus in a position to be able to write the interaction energy of a pair of orbitals as E = hBuSg2,where h is a calculable number and the product &Sa2 the AOM parameter.One way of evaluating the interaction energy is to write down a symmetry-adapted ligand CT combination and calculate its overlap integral Stj with the relevant d-orbital. A quicker method of calculation for an MLn complex is to use the ligand additivity [equation (8)] over all n ligands co-ordinated to the central metal atom. The total a stabilization energyC(a) is then very simply given by equation (9),wherehi is the number of electron holes in the ith d-orbital. Equation (9) arises simply because 43 S. F. A. Kettle, J. Chem. SOC.(A), 1966, 420. I Molecular Shapes when filling d-orbitals with electrons we are filling metal-ligand antibonding orbitals. It is only the empty d-orbitals that have filled metal-ligand bonding counterparts which contribute to the stabilization energ~.4~,~5 An interesting sum rule [equation (lo)] applies to the orbital energies derived from equation (8), CEi = n&,s,Smz (10)i where n is the number of (5 orbitals (ligands) surrounding the central atom.This can be used to check the arithmetic involved in evaluating orbital interaction energies. An exactly analogous prescription applies to the evaluation of .rr-bonding interactions. Care must be taken here to distinguish betweenv-donors (the mainly ligand located components are ML bonding but the mainly metal d-orbitals are ML antibonding) and n acceptors (the mainly metal d-located orbitals are ML bonding and the mainly ligand-located orbitals, which are usually empty, ML antibonding). The d-orbitals are destabilized in the former but stabilized in the latter case.The AOM is then much easier to apply than the crystal field method, especially in lower symmetry environments. The CFT also differs from the drawback that (T,Tbonding, which are vital concepts in modern inorganic chemistry, cannot be included in the model. Another problem with the CFT is that in lower than cubic environments two parameters, Dq and Cp are needed to describe the energy levels. The two are related via a parameter p. In most places where the CFT is used in low symmetry situations a value of p = 1 is arbitrarily used.46 From spectroscopic measurements larger values are probably more accurate but the factors governing the exact choice of p in different environments is far from clear.Figure 5 shows the d-orbital energy levels of geometries of interest obtained from simple calculations involving the overlap integrals. (A slight complication occurs in the T-shape geometry where two d-orbitals have the same symmetry, and allowance for mixing of these orbitals needs to be made.47) Geometries of Complexes.-We have shown elsewhere that the variation in the heats of hydration of the M2+ ions across the first row transition-metal series, one of the classic successes of the CFT, is similarly described by our molecular orbital mode1.46 The forces contributing to are the metal nd-ligand interaction augmented by contributions from ligand interactions with metal (n + 1) s,p-orbitals.These observations suggest that the observed angular geometry will be a balance between that demanded by s,p interactions and that by the d-orbital interactions with the ligands. In general an MLn complex contains no pairs of electrons which are involved in s,p (and d) interactions. 44 J. K. Burdett, Inorg. Chern., 1975, 14, 375. 4bJ. K. Burdett, Znorg. Chem., 1976, 15, 212. p6 J. K. Burdett, J.C.S. Dalton, 1976, 1725. 47 D. S. McClure, in ‘Advances in the Chemistry of the Coordination Compounds’, ed. S. Kirschner, Macmillan, New York, 1961, p. 498. 520 Burdett 22, x2 -y2 x2-Y2 3 x2-y'Z22.75 22 x2 -y21.125 1 22 5, &h5,c4v '22' 2.5 Z2 2.37 Z?X2 -y* xy, yz, xz 1.5 XY 1.5 1.33 'x2 -y2'0.63 4,c2v 3,c2v 3,C3" Figure 5 A40 diagrams in the d-orbital region for some geometries of interest (energy units #luSoaor eu).The co-ordination number and molecular point group are given under each diagram. In the geometries with an angular degree offreedom (e.g. 4, C2v)the n ligands are placed at the vertices of an octahedron such that LML angles are either 90"or 180" Using the VSEPR method (which often dealt successfully with the shapes of molecules with s,p-orbitals alone on the central atom) the geometry demanded by interactions with these higher orbitals will be trigonal planar (&I,) for ML3 and tetrahedral (Td)for ML4 etc. We note that in these molecules the VSEPR geometry is the one with minimum ligand pair repulsions (Pauli avoidance) and also the one containing minimum non-bonded repulsions between the ligands themselves.We call these combined forces, ligand-ligand terms. From Figure 5 we can readily calculate the d-orbital stabilization energy for the various three-co-ordinate geometries which we include here as a function of d-electron configuration. For Is de, Is d8, hs d8, and d10 the results are given in Table 3. There is of course no d-orbital stabilization for Ni(CO)3 at any geometry since all bonding and antibonding orbitals are filled. For the two other mole- cules the T-shape and 'octahedral fac trivacant' (& pyramid) geometries have the same d-orbital energy. We need to turn to the fourth-order term in equation (7) to resolve them.The general result is that the structure with the largest number of cis ligands is more stable. (If the ligands are tl acceptors, tl stabiliza-tion is also maximized at this geometry.) The driving force away from the D3h geometry is larger for Cr(CO)3 (1.5pAc2) Cr (C0)3 than for Fe(C0)3 (0.75/?uSu2). has the structure which is most distorted (0 = 25") from trigonal planar. Ni(C0)3 521 4 Molecular Shapes Table 3 d-Orbital stabilization energies for some three-co-ordinate structures (unitsP# or e,) d-electron configurationa C3Ub D3A CZV" example Is d6 (22200) 6.0 4.5 6.0 Cr(CO)3 hs d* (22211) Is d8 (22220) 3.O 3.O 2.25 2.25 3.O 4.73 Fe(CO)3 Rh(P Ph3)3+ d9 (22221) 1.5 1.125 2.37 d1O (22222) 0 0 0 Ni( C0)3 ad-Orbital occupation numbers in parentheses, lowest energy orbital first; bLML angles 90" (octahedral fac 'trivacant'); CLML angles 90°,180"(T-shape) has no driving force away from the D3h geometry and thus remains planar, held there by ligand-ligand forces.Recently the T-shaped structure predicted for the three-co-ordinate Is d8 ML3 system has been observed48 in a crystallographic environment for Rh(PPh&+. All the observed geometries are in encouraging agreement with those predicted. Of course all we have done really is to calculate, using a simple model, the relative energies of the e and a1 orbitals shown in Figures 4(a) and (b) compared with those of the orbitals of Figure 4(c).Similar arguments may be used to understand the geometries of four-co- ordinate molecules,44 using Table 4. Cr(C0)g with a larger driving force away Table 4 d-Orbital stabilization energies for some four-co-ordinate structures (units &SUBor e,) d-electron configuration Dela Ta c2va example 1s d6 (22200) 8.O 5.3 8.O Cr(C014 Is d8 (22220) 6.0 2.67 5 .O Ni(CN)d2-hs d8 (22211) 4.0 2.67 5 .O Fe(C0)4 d9 (22221) 3.O 1.33 2.5 cuc142-d10 (22222) 0 0 0 Ni(C0)g aLML angles 90",1SO" (octahedral cis 'divacant') from tetrahedral than Fe(C0)4 gives the more distorted geometry [the cis-divacant is more stable than the square planar for this configuration by consider-ing the fourth-order terms of equation (7)]. Ni(CN)42- is found as the square planar molecule but the d9 system CuC1g2- has a smaller driving force from tetra- 4aY.W.Yared, s. L. Miles, R. Bau, and C. A. Reed, J. Amer. Chem. SOC.,1977, 99,7076. Burdett hedral and is sometimes found in square planar and sometimes in D2d environ-ments49 (Figure 6). The reluctance of the 1s d8 square planar geometry to add Is d6 hsd6 lSd7+ D4h Isd8 hsd8 d9 4 D4h Figure 6 Observed geometries of four co-ordinate molecules as a frtnctiorl of'd-electron configuration. Examples: ds, Cr(C0)4 (Is), FeC142-(hs); d7 Rh {S2C2(CN)2}22-(Is),COCI,~-(hs); d8 Ni(CN)42-(Is), Fe(CO), (As); ds CUC~,~-(a variety of geometries are found for this electronic configuration); d10 Ni(CO),, two more ligands to complete an octahedron is another structural feature of these molecules that we can view using our method.50 In addition the kinetic behaviour of ligand substitution in this system (trans effect) is another field where this simple parametrized model is succe~sful.~~ For five-co-ordinate molecules, ground state Cr(C0)5 (Is d6)has the largest stabilization energy for the square pyramid compared with trigonal bipyramid geometry.Fe(C0)5 with only a small distortion energy is found as the trigonal bipyramid although it is fluxional, probably via a square pyramid transition state. The trigonal bipyramid is predicted for the first excited state of Cr(C0)5 4s J. R. Ferraro and J. Long, Accounts Chem. Res., 1975, 8, 171. J. K. Burdett, Inorg. Chem., 1975, 14, 931. 51 J.K. Burdett, Inorg. Chem., 1977, 16, 3013. I Molecular Shapes Table 5 d-Orbital stabilization energies for some five-co-ordinate structures (units &Sa2 or e,) d-electron configuration C4v D3n diference example 1s d6 (22200) Is d6(221 10) 10.0 8.0 7.75 7.75 2.75 0.25 Cr(C0)5 Cr(C0)5* 1s d7 (22210) 8.0 6.625 1.375 Mn(C0)5 Is d*(22220) 6.0 5.5 0.5 Fe(CO)5 since the driving force away from this geometry is smaller than for Fe(C0)5. Matrix experiments with this molecule using polarized spectroscopy and photo- lysis, Scheme 1,52 and visible photolysis studies on Cr(C0)4CS, Scheme 253 show that this is very probable. Scheme 1 pseudorotated cs * ;ic =Ahv' axial CS Scheme 2 basal CS Thus the idea of a balance between VSEPR steric and d-orbital demands in controlling the shape of the molecule is a very satisfying one.A general observa- tion is that the larger the d-orbital driving force away from the ligand-ligand determined geometry the closer the observed geometry is to the d-orbital only prediction. Thus Ni(CN)42- (driving force = 3.3 PuS,2) is a regular square plane, Cr(C0)4 (2.25 puSu2)and Cr(C0)5 (2.33 &,2) have bond angles close to 90" 6a J. K. Burdett, J. M. Grzybowski, R. N. Perutz, M. Poliakoff, J. J. Turner, and R. F. Turner, Inorg. Chem., 1978, 17, 147. 6a M. Poliakoff, fnorg. Chem., 1976, 15, 2022, 2892. 5 24 Burdett and 180" but Cr(C0)3 (1.5 pgSg2)is less than two thirds the way to the fac octahedral trivacant structure.Steric Effects.-Table 6 shows the result of calculations designed to reveal the relative stability of a series of eight-co-ordinate geometries.54 Extended Huckel Table 6 geometry electronic stabilizationa steric energy EHMO energyfrom AOMof do results on L& MLs /kcal mol-l dodecahedron 77.2 3.5 square antiprism 76.4 Ob square prism (cube) 85.2 27 hexagonal bipyramid 86.8 97 CsVbicapped trigonal prism 71.4 166 C2, bicapped trigonal prism 75.2 24 %nits are k4Su4(Aqj)-) = yuSu4 from equation (7); *i.e. on steric grounds the square anti- prism is the most stable geometry calculations on the L@-system itself (MLs but without the metal atom) gave the relative steric (a contributor to the ligand-ligand terms above) merits of the various structures.Evaluation of the fourth-order terms of equation (7) gave the electronic advantages for each geometry [since these are included with a minus sign in equation (7) the smaller this contribution the more favourable the structure]. From the sum rule of equation (10) the second-order terms are equal for all geometries if we assume do configurations. The superposition of the two series gives a good description of the popularity of the various structures. There are a large number of dodecahedra1 and square antiprismatic structures-good on both steric and electronic grounds. An increasing number of CzVBTPgeometries are being identified as a result of the use of various crystallographic shape parameters. These geometries and intermediate versions make up the vast majority of eight-co-ordinate examples.The cube and hexagonal bipyramid are not very good on either basis; only three examples of the former are known and a handful of hexagonal bipyramid structures if the special case of U02 containing systems is excluded. The D3h bicapped trigonal prism is a combination of excellent electronic but very poor steric stability. There are no characterized examples with transition metal ions. Steric effects are therefore clearly important in the geometry field, especially with the higher co-ordination numbers, and may often work against electronic factors. The molecular mechanics results of Kepert55 and the existence of small co-ordination number molecules with bulky O4 J.K. Burdett, R. C. Fay, and R. Hoffmann, Znorg. Chem., 1978, 17, 2553. 66 D. L. Kepert, Progr. Znorg. Chem., 1977, 23, 1. Molecular Shapes ligands as demonstrated by Bradley56 also strikingly reveal the importance of these non-bonded effects. Finally we must also mention here Johnson’s intriguing method57 for deter- mining the stereochemistry of Mn(CO)mspecies, the elucidation of the number and position of terminal, doubly, and triply bridging carbonyl groups, and the geometry of the metal skeleton. The spatial arrangement of the CO groups is found to be one of the close packed arrangements of mspheres. The metal atoms are located at positions set by the best arrangement of an Mnpolyhedron within this structure. The resulting geometrical relationships between each M and a given CO determine whether the latter is in a terminal, doubly, or triply bridging position.This essentially steric argument is the first theoretical method which is able to predict polynuclear carbonyl stereochemistry with any success. It remains to be seen if a MO alternative can be developed. I would like to thank my friends and colleagues who, over the years, have provided a stimulating environment in which to work, especially J. J. Turner and M. Poliakoff for a period of particularly exciting interaction in which many new ideas were conceived. 66 D. C. Bradley, Chem. in Britain, 1975, 11, 393; P. G. Eller, D. C. Bradley, M. B. Hurst-house, and D. W. Meek, Coord. Chem. Rev., 1977, 24, 1. 67 B. F. G. Johnson,Chem. Comm., 1976, 211.

ISSN:0306-0012    

DOI:10.1039/CS9780700507

出版商:RSC    

年代:1978

数据来源: RSC

摘要:

MELDOLA MEDAL LECTURES* II Fe(CO), By M. Poliakoff DEPARTMENT OF INORGANIC CHEMISTRY, THE UNIVERSITY OF NEWCASTLE UPON TYNE, NEWCASTLE UPON TYNE, NE1 7RU ‘These Figures, although only approximate on account of the very small quantities of the substance .. . make it veryprob- able that the iron compound is iron-tetracarbonyl, Fe(CO)4, analogous to nickel-tetra-carbonyl, Ni(C0)4.’ L. Mond and F. Quinke (J.Chem. SOC., 1891, 604) 1 Introduction The preparation of [Fe(C0)4] was first claimed eighty-seven years ago by Mond and Quinke. Although the compound was later shown to be [Fe(CO)5], [Fe(CO)4] has since been suggested as an important intermediate in photochemical and thermal substitution reactions of [Fe(C0)5] and its derivatives.1 All attempts to detect its transient existence in solution or the gas phase have so far been unsuc- cessful.In particular, the work of the late E. A. Koener von Gustorf and his co- workers indicates that [Fe(C0)4], if implicated, is remarkably reactive in solution.2 Their flash photolysis experiments on solutions of [Fe(C0)5] suggested that the lifetime of [Fe(CO)4] was less than the time scale of their apparatus, 1p. [Fe3(C0)12] was formed rapidly, < 100 ps, via an unidentified intermediate, possibly [Fe2(CO)a]. On the other hand, flash photolysis of Fe(CO)5 in the gas phase leads to the formation of Fe atoms.3 In this lecture I describe the role of matrix isolation in the characterization of [Fe(C0)4] and show that, apart from its formula, it has little in common with [Ni(CO)4].The technique of matrix isolation has been reviewed extensively elsewhere.4 In the form discussed here, unstable species are prepared by photolysis of a stable molecule, trapped in a large excess of inert solid at low temperatures (e.g. solid Ar at 20K).The unstable fragments are usually sufficiently dilute in the * These lectures were delivered in April 1978 at the Annual Chemical Congress, University of Liverpool. M. Wrighton, Chem. Rev., 1974,74,401.* E. A. Koerner von Gustorf, N. Harritt, and J. M. Kelly, unpublished results. 3A. B. Callear and R. J. Oldman, Nature, 1966, 210, 730; Trans. Faraday SOC.,1967, 63, 2888.* See for example ‘Vibrational Spectroscopy of Trapped Species’, ed. H. E. Hallam, Wiley, London, 1973. N Fe(CO)4 matrix to prevent any polymerization.Once prepared, the fragments can be studied spectroscopically. 1.r. spectroscopy has been the most important tech- nique in the case of [Fe(CO)4], although u.v.-visible spectroscopy and magnetic circular dichroism, m.c.d., have also played a significant part. In the following sections, I describe how Fe(C0)4 was prepared and its structure determined, the use of m.c.d. to demonstrate its paramagnetism, and its photochemical reactions induced by u.v., visible, and i.r. radiation. 2 Preparation and Structure of [Fe(C0)4] The pioneering work of Sheline and co-workers demonstrated that U.V. photolysis of [Fe(C0)5] in frozen hydrocarbon solutions at 77K resulted in the formation of unidentified [Fe(CO)J species.5 Rest confirmed that similar results6 could be obtained in solid Ar at 20K, and Newlands and Ogilvie found that [Fe(C0)4(C2Hs)] and [Fe(C0)4(CzH2)] could be produced by U.V.irradiation of [Fe(CO)5] in Ar matrices containing ethylene or acetylene.’ More extensive studies by Poliakoff and Turner showed that U.V. photolysis of [Fe(CO)5] in a large number of differcnt matrices gave rise to molecular CO and an unstable [Fe(C0)4] species which had at least three i.r. bands in the ‘C-0 stretching’ region of the spectrum.* The presence of these three bands eliminates tetrahedral or square planar structures for [Fe(C0)4], as a Ta or D4h molecule should have only one i.r. active C-0 stretching mode. A number of other possible structures, which have more than one i.r.active C-0 stretching mode are shown by structures (1)-43). A recurrent problem in matrix isolation is caused by a series of different pheno- mena, usually called ‘matrix ~plittings’,~ which often result in the presence of two or more closely spaced bands where only one is expected. Unfortunately, the presence of such ‘matrix splittings’ in the spectrum of [Fe(CO)4] meant that there was not enough information in the spectra to prove conclusively which of these I. W. Stolz, G. R. Dobson,and R. K. Sheline, J. Amer. Chem. SOC.,1963,84, 3589; ibid., 1964.85, 1013. A. J. Rest and J. J. Turner, Proceedings of &he4th International Conference on Organo- metallic Chemistry’, Bristol, 1969. M.J. Newlands and J. F. Ogilvie, Canad.J. Chem., 1971,49, 343. M. Poliakoff and J. J. Turner, J.C.S. Dalton, 1973, 1351. Poliakof three structures was correct, There was some circumstantial evidence that [Fe(CO)4] had a C3, structure (l), but more information was required.* This additional information was provided by the use of l3CO isotopic enrich- ment,g a technique which has been described in detail elsewhere.1O The method is based on two observations; (i) that a mixture of [M(12CO),-,(13CO),] mole-cules will have more i.r. active bands than [M(12CO),] itself, and (ii) that although two molecules, [M1(12CO),] and [M2(12CO),] having different struc- tures, may have similar i.r. spectra in the C-0 stretching region, the isotopic mixtures [M1(12C0)z-y(13CO)y] and [M2(12CO)z-y (13CO)y] will have i.r.spectra that differ substantially both in the frequency and the relative intensities of the bands. The prediction of these frequencies and intensities is particularly simple for metal carbonyls as the C-0 stretching vibrations can be treated as if they were totally uncoupled from the other vibrations in the molecule.1° Initial predictions are made using approximate force constants calculated from the frequencies of the unenriched [M(12CO),] molecule and bond angles and rela- tive dipole moment derivatives which reproduce the correct band intensities of [M(12CO),]. Subsequently force constants can be optimized using all of the ob- served [M( 12CO)z-y(13CO)y] frequencies and an appropriate 'least-squares' method.Surprisingly, the spectra of partially substituted molecules, [M(12CO),-, (13CO),], appear to be less affected by matrix splittings than those of the [M(CO),] molecules containing only one i~otope.~ Figure l(a) shows the i.r. spectrum of WO-enriched [Fe(C0)4], obtained by U.V. photolysis of 13C0 enriched [Fe(CO)5] in an SF6 rnatri~,~ and the spectra predicted for a CZ,structure with bond angles 140" and 115" and a C3, structure are shown in Figures l(b) and l(c), respectively. It is clear that the C2, spectrum is in much closer agreement with the observed spectrum than is the CaVspectrum. Similarly the fit for this CZ,structure is better than for a D2d structure or a CZ, geometry with different bond angles.Since a constant linewidth has been assumed for all the bands in the predicted spectrum, there is not a perfect agreement between the intensities in the observed spectrum and that predicted for the C2, structure. Nevertheless the agreement is sufficient to show that [Fe(C0)4] has a CzV geometry. The detailed assignment of bands has been confirmed using i.r. lasers,ll (see below). Bond angles are calculated from the relative intensities of i.r. bands, by assuming that the dipole moment change associated with the stretching of a particular C-0 bond is collinear with that bond and by making the usual double harmonic approximation. The calculated bond angles vary slightly from one matrix to another; SFs (144", 114"), Ar (147", 120"),and CH4 (150", 120") but the differences are within an experimental error of f 5" caused by uncertainties in the measurement of band intensities.9 Although there is the possibility of a M.Poliakoir and J. J. Turner, J.C.S. Dalton, 1974, 2276. lo J. K. Burdett, H. Dubost, M. Poliakoff, and J. J. Turner, in 'Advances in I.R. and Ranian Spectroscopy', ed. R. J. H. Clark and R. Hester, Heyden, London, 1976. B. Davies, A, McNeish, M. Poliakoff, and J. J. Turner, J. Amcr. Chem. Soc., 1977, 99, 7573. x 20 6)0 CtuD x 20BD a XI0 -2075 2050 2000 1975 1950 cm-1 Figure 1 (a) Z.r. spectrum of [Fe(CO),] with 13C0enrichnierit (407,) irr mi SF, matrix at 35K.(-----) Bands due to unphotolysed [Fe(CO),]; (b) calculated ~pectr~irn for a CZr geometry (see 3) with bond angles of 140" and 115"; (c) calciilated spectrum for a C,, geometry (see 1) with a bond angle of-105"between axial and basalgroup.The calculated spectra have been redrawn fLom ref. 9, Figure I, assuming Lorentzian lineshapes and a constant halfwidth of 1.5 cm-' systematic error in the bond angles, it is clear that [Fe(C0)4] is substantially distorted from a tetrahedral geometry. Experiments in Ar matrices suggest that this distortion of [Fe(C0)4] is not caused by interaction with the CO molecule ejected from the parent [Fe(C0)5] molecule during photoIysis.8 If [Fe(C0)5] is irradiated with U.V. light for a few Poliakof seconds, the i.r. spectra show that, for the majority of [Fe(C0)4] molecules, there is interaction with the photoejected CO.After prolonged U.V. irradiation the majority of [Fe(C0)4] molecules no longer interact. Apart from subtle changes in the matrix splittings, there is no difference in the C-0 stretching bands of the interacting and non-interacting [Fe(CO)4] molecules, and hence their structures must be the same. Since [Fe(CO)4] has the same CZ,geometry in a wide range of different matrices, it is unlikely that this structure is imposed on the molecule by the matrix. There can be no direct evidence to show that [Fe(C0)4] has the same structure in solution or the gas phase at normal temperatures, since it has only been detected in matrices. Nevertheless in those cases where unstable molecules, e.g. CH3, have been detected both in a matrix and in the gas phase (see p.507), the structures have been the same. 3 Magnetic Properties of [Fe(CO)4] The observed bond angles of [Fe(C0)4] (-145", N 120") are close to those predicted by Burdett (135", 1 lo") for the minimum energy geometry of [Fe(C0)4] in a triplet ground state.12 Figure 2 is an MO diagram which illustrates the basis of Burdett's argument. [Fe(C0)4] is a d8 system. Tetrahedral [Fe(C0)4], which necessarily has a triplet ground state, is Jahn-Teller unstable, Figure 2(a). Distortion will occur to the minimum energy geometry, Figure 2(b) and, for singlet [Fe(C0)4], the distortion would continue to a square planar geometry, Figure 2(c). If [Fe(C0)4] were a triplet, further distortion of the CZ,geometry, Figure 2(b), would be prevented by the rapid rise in energy of the highest energy d-orbital. Since [Fe(C0)4] has this CZ,geometry, it is predicted to be paramagnetic. This paramagnetism has been established using m.c.d.spectroscopy, a tech-nique which has recently been applied to matrix isolation through the pioneering studies of Thomson and Grinter.14 An m.c.d. spectrum measures the difference in absorption of left- and right- circularly polarized light by a sample placed in a strong magnetic field. The value of m.c.d. for detecting paramagnetic species lies in the fact that a paramagnet has a temperature dependent m.c.d. spectrum, while diamagnetic compounds do not. The m.c.d. spectrum of [Fe(C0)5], isolated in an Ar matrix,15 does not change over the temperature range 5-25 K.U.V. photolysis produces sub- stantial changes in the spectrum, in particular the m.c.d. signal becomes tem- perature dependent with an absorption maximum corresponding to a U.V. absorption band (A,,, = 325 nm)* of [Fe(C0)4]. Thus [Fe(C0)4] is almost certainly paramagnetic. The presence of a broad far-red-near-i.r. electronic transition, 13000 cm-l) is also consistent with a paramagnetic ground state.ll For example, paramagnetic complexes of the isoelectronic Ni2+ ion have la J. K. Burdett, J.C.S. Faraday 11, 1974, 70,1599. l3J. K. Burdett, unpublished calculations. l4 I. N. Douglas, R. Grinter, and A. J. Thomson, Mol. Phys., 1974, 28, 1377. l5 T. J. Barton, R. Grinter, A. J. Thornson, B. Davies, and M.Poliakoff, J.C.S. Chrm. Comm.,1977, 841. eV I I I I I I I I I-7.5 I I I I I I I I I -8.0 i-8.5 Figure 2 The energy ' levels of the d orbitals of [Fe(CO),] in diferent geometries, (a) tetra- hedral, Td; (b) C,,with bond angles of 135" and 110"; and (c) square planar, Dqh. The diagram is drawn to scale from the calculation^,'^ summarized in ref. 12 electronic transitions in the near-i.r., while diamagnetic Ni2+ complexes have no far-red-ncar4.r. absorptions in this region. [Fe(C0)4] is therefore the first binary transition-metal carbonyl not to have a 'low spin' electronic ground state. It would clearly be interesting to know whether [Ru(CO)q] and [Os(CO)4] are similarly paramagnetic.No m.c.d. studies have been madz on these compounds, but rather preliminary i.r. spectra suggest that [Os(CO)4] is neither tetrahedral, nor square planar.9 [Fe(CO)3] (see below) is also predicted to be paramagnetic but unfortunately m.c.d. spectra are not yet available. The paramagnetism of [Fe(C0)4] could also explain many of its reactions in solution, for example rapid dimerization or insertion reactions, l6 similar to those of =CC12. Polymerization of [Fe(C0)4] to form [Fe~(C0)8] and [Fe(C0)1~] can also be observed, when [Fe(CO)a] is photolysed in concentrated mat rice^.^ lo C. S.Cundy, M. F. Lappert, J. Dubac, and P. Mazerolles, J.C.S. Dalton, 1976, 910. Poliakof 4 U.V.Photochemistry-Dissociation U.V. irradiation of [Fe(CO4)], produced photochemically from [Fe(CO)5], leads to further loss of CO and formation of [Fe(C0)3].13C0 enrichment has been used to show that [Fe(C0)3] is a pyramidal CsVmolecule,l7 with a C-Fe-C bond angle of 108". The assignment of the bands has been described in detail N elsewhere10 and the theoretical reasons for this particular structure are discussed by Burdett in the preceding article (see p. 507). A most interesting aspect of this reaction is the difference in yield of [Fe(C0)3] in different matrices. Formation of [Fe(CO)3] is rapid in CH4 or Nz,slow in Ar, and totally absent in SF6. The explanation of these differences is unknown but it may well lie in the addition reactions of Fe(CO)4 with CH4 and Nz matrices. 5 Near-I.R.Photochemistry-Addition Reactions Photochemical addition reactions are found more frequently in matrices than in solution, merely because the photochemistry of co-ordinatively unsaturated molecules cannot be studied in solution. When [Fe(CO)4] is excited by near-i.r. radiation (13000-9000 cm-I), the molecule undergoes a variety of addition reactions depending on the reactants available in the rnatri~.~s119* Recombination [Fe(CO),I + CO +[Fe(CO),] (1) near4.r. Reaction [Fe(CO),] + Q -near-i.r. [Fe(CO),QI (2)(Q = CHI, Xe, Nd The probable structures of the different [Fe(CO)gQ] species are shown in (4)-(6). The geometry of the Fe(C0)4 moiety in [Fe(C0)4CH4] has been confirmed, using I3CO isotope^,^ to be CzVwith bond angles of 173.5' and 125".Unfortunately no i.r. absorptions of co-ordinated CH4 can be detected, because of the large excess of unbound CH4 in the matrix. The most plausible modes of binding CH4 to Fe are either a linear M-H-C bond similar to that found in the room temperature *These reactions were originally thoughts to be caused by near-u.v. light corresponding to the 325 nm absorption of [Fe(CO),J. Later work has disproved this." The near4.r. radiation (13 000-9000 cm-I) corresponds closely to the maximum intensity of the output from the source of an i.r. spectrometer. A filter, usually coated Germanium, is needed to remove radiation of this wavelength from the spectrometer beam to avoid [Fe(CO),] being destroyed while a spectrum is run.8 l7 M. Poliakoff, J.C.S.Dalton, 1974, 210. II Fe(CO)4 H crystal structures of Mo compounds18 or a double H bridge, M’ ‘C,b’ analogous to the bonding19 of BH4- in [Mo(C0)4BH4]-. [Fe(C0)4(alkane)] complexes appear to be thermodynamically more stable than ‘naked‘ [Fe(CO)4] as they are the only species detectable9 after U.V. photolysis of [Fe(CO)5] in hydrocarbon glasses at 77K. The i.r. spectrum of [Fe(C0)4Xe] is so similar to that of [Fe(C0)4CH4] that its structure is almost certainly the same. The com- pound is iso-electronic with the stable anion [Fe(C0)41]-. [Fe(CO)4] does not react with Ar but recent work in NewcastlezO suggests that it may react with Kr. Burdett has suggested13 that the role of the CH4 or Xe in these complexes is to stabilize the singlet state of [Fe(C0)4] but as yet no m.c.d.spectra are available to confirm this. The structure of [Fe(C0)4N2] has not been verified using 13C0 isotopes because the matrix splittings of the bands are too complex to make a detailed analysis po~sible.~By analogy with other [M(CO)zN2] species, the N2 group is almost certainly bonded end-on rather than sideways. Although the original experiments suggested a C3vstructure, both Burdett’s MO calculation^^^ and Timney’s ‘ligand effect’ analysisz1 of the i.r. spectra predict a Czv structure (7). The electronic spectra of [Fe(C0)4] and ‘[Fe(CO)4Q]’ molecules are sub- stantially different. [Fe(CO)4Q] species have bands in the region of 375 nm and no near-i.r. absorptions. [Fe(C0)4] can be regenerated from [Fe(CO)eQ] by photolysis with a filtered Hg arc, h > 375 nm [reaction (3)].The detailed mech- U.V. near-i.r. [WCO)J [FdCO)41 [WCO),QI (3) near-r.r. > 375 nm anisms of all these processes are still unknown. However, sequential i.r. laser and near-i.r. irradiation (see below) suggests that the quantum yield for addition of CH4 to [Fe(C0)4] in a CH4 matrix is considerably higher than the quantum yield for addition of N2 in an NZ matrix.Zz F. A. Cotton, T. LaCour, and A. G. Stanislowski, J. Amer. Chem. SOC.,1974, 96, 754. l9 S. W. Kirtley, M. A. Andrews, R. Bau, G. G. Grynkewich, T.J. Marks, D. L. Tipton, and B. R. Whitlesey, J. Amer. Chem. SOC.,1977, 99, 7154. 2o K. P. Smith, unpublished results. z1 J. A. Timney, Znorg. Chem., submitted for publication.22 B. Davies, A. McNeish, M. Poliakoff, M. Tranquille, and J. J. Turner, J.C.S. Chem. Comm., 1978, 36. Poliakof 6 I.R. Laser Photochemistry 1.r. laser* irradiation at the frequency of a C-0 stretching mode of Fe(C0)4, -1900cm-l, induces a variety of reactions, similar to those induced by near4.r. radiati0n,2~-13000 cm-l [reaction (4)]. When an isotopic [Fe(12C0)4-z(13CO)z] i.r. laser YCO [Fe(CO),l + Q -[WCO),QI (4)(Q = CO, Xe.CHI) mixture is used the difference between the i.r. laser and near4.r. photochemistry becomes clear. With broad band near-i.r. radiation, all of the different [Fe(12CO)4-2(13CO)2] species react. With the highly monochromatic i.r. laser, however, only the particular [Fe(12CO)4-z(13CO)z] molecules, which have absorptions co-incident with the laser emission, undergo reaction and all the other [Fe( 12CO)4-s(13CO)z] molecules remain unaffected.24 These laser-induced reactions involve the absorption of only a single photon of i.r.radiation by an individual molecule. This means that the activation energies for these processes must be < 1900 cm-l or 23 kJ mol-I.? The most interesting laser-induced effects occur with [Fe(C0)4] produced in an Ar matrix by prolonged U.V. irradiation of [Fe(C0)5]. Under these conditions the [Fe(C0)4] and photo-ejected CO molecules are too far apart in the matrix to recombine. 1.r. laser irradiation promotes ligand exchange,ll (Scheme 1);. In solution the two species (7) and (8) would be in rapid dynamic equilibrium but in the matrix at 20K there is insufficient thermal energy for intramolecular re- arrangement.Laser irradiation at the frequency of one of the C-0 stretching absorption bands of (7)converts it into (8). Since molecules of (8) do not absorb at these frequencies, there is no reverse isomerization until the laser is retuned to coincide with the absorptions of (8).The high dilution of the matrix means that this ligand exchange must be intramolecular and the energy of a single i.r. photon, -23 kJ mol-l, is insufficient to cause the breaking of any Fe-CO bonds. A useful spin-off from this experiment is the ability to identify all of the C-0 stretching bands belonging to a particular [Fe( 12C160)4-z(13C1*O)z] molecule. The results are in gratifying agreement with the original a~signrnents.9~~~ It is found that this intramolecular ligand exchange can also be induced by near4.r.radiation,” Scheme 2. U.V. photolysis of [Fe(12C160)5-z(13C180)z] *These experiments used an Edinburgh Instruments C.W. CO laser. *l This produces con-tinuous, monochromatic radiation at one of a series of fixed frequencies, separated by -4 cm-’. The laser is tuned between these emission lines by a diffraction grating at one end of the laser cavity. Tuning is over the region 1950-1650 cm-’. 13Cle0 or 13C180en-richment of [Fe(CO),] is required to bring the absorptions of [Fe(CO),] into the tuning range of the laser. tThe activation energy for recombination with CO is probably extremely low as recombination takes place if the matrix is heated to only 40 K.The activation energy for reaction with CH, is presumably significantly higher because thermal reaction does not occurs up to 40 K. #. In Schemes 1-4 the numbers (in bold) of the isotopic isomers of Fe(CO), correspond to those given in ref. 9. a3 B. Davies, A. McNeish, M. Poliakoff, M. Tranquille, and J. J. Turner, Ber. Birnsensgesell-schaft Phys. Chem., 1978, 82, 121. 21 A. McNeish, M. Poliakoff, K. P. Smith, and J. J. Turner, J.C.S. Clieni. Comni., 1976, 859. 535 II Fe(C0)4 intramolecular rearrangement abe , >;'18821892 a (7) .= 13~180 (8) vco cm-1 2033 2051 1947 1941 1902 1889 1892 1a82 Scheme 1 necessarily produces equal quantities of (7) and (8).Since there are negligible isotopic shifts in the electronic transitions of [Fe(C0)4], (7)and (8) will both absorb near-i.r. radiation and isomerize at the same rate. Thus the isomerization induced by near-i.r. radiation can only be detected after an i.r. laser has been used to alter the relative concentrations of (7)and (8). \ Burdett has provided a simple explanation of how electronic excitation of [Fe(C0)4] could lead to intramolecular rearrangement.l1~l3 The scheme is illustrated in Figure 3. Although the calculations are only approximate, they suggest that all d -d transitions of [Fe(C0)4] should lie in the near-i.r. region of the spectrum. Absorption of near-i.r. radiation will produce electronically excited fFe(C0)4] still with a CZ,geometry, Figure 3(b).* This geometry would have a higher energy than the Td geometry and so distortion would occur to this structure, which has all ligands equivalent, Figure 3(c).The Td molecule is, in turn, unstable with respect to a CZ,geometry in the electronic ground state, and will distort, Figure 3(d).t This scheme is clearly a slight over-simplification since *Figure 3 has been drawn for one particular d 3 d transition, the same arguments can be applied to other transitions. tOf course, the 7'6 structure could also distort back to Figure 3(a). Poliakof c2v c2v F near i.r. / * +=El=+-+ * Figure 3 Suggestedpath way for electronic relaxation and intramolecular Iigand exchange in [Fe(CO),].The d-orbital energies’, are as given in Figure 2 the Td molecule is Jahn-Teller unstable and must represent a local maximum on the potential energy surface. Nevertheless, this single mechanism provides a simple pathway for simultaneous electronic relaxation and intramolecular ligand exchange. Near-i.r. irradiation also promotes addition reactions (4.v.). It is probable that these reactions involve similar mechanisms to ligand exchange. Experiments suggest that reaction and rearrangement are competitive processes.22 The high selectivity of the i.r. laser induced isomerization of [Fe(CO)4] allows us to make a detailed study of the permutational processes occurring during ligand exchange. This approach produces information analogous to that pro- vided by dynamic n.m.r.techniques. The crucial experiment involves the inter- conversion of the three isomers of [Fe(12C160)2(13C180)2], (4), (3,and (6). There are two distinguishable isomerization pathways for these three isomers, as shown in Schemes 3 and 4. If, for a moment, the vacant co-ordination site of [Fe(C0)4] is imagined to be a fifth ligand, then Scheme 3 corresponds to the Berry Pseudo-rotation. By default Scheme 4 is a non-Berry Pseudo-rotation. SF4 which has the same symmetry as [Fe(CO)4] has been shown, by means of d.n.m.r.,25 to undergo thermal ligand exchange via the Berry pseudo-rotation, Scheme 3. The principal difference between Schemes 3 and 4 is that in Scheme 4, (10) isomerizes to (3,while in Scheme 3, (4) isomerizes to (6).The laser experiment illus- *5 W. G. Klemperer, J. K. Krieger, M. D. McCreary, E. L. Muertterties, D. D. Traficante, and G. M. Whitesides, J. Amer. Chem. SOC.,1975, 97, 7023. Berry Pseudo-rotation (4) (5) (5) Scheme 3 non-Berry Pseudo-rotation trated in Figure 4 distinguishes between these two possibilities. Laser irradiation of a band due to (4) causes an increase in the band due to (5)and no change in the band due to (6).The laser-induced ligand exchange in [Fe(C0)4]is therefore the first known example of a non-Berry pseudo-rotation. Unfortunately it is not possible to extrapolate from a permutational mode to a precise mechanism. Nevertheless the results are inconsistent with C4v, D4h, D!M,or Td transition states, which would produce a Berry pseudo-rotation.The rearrangement is consistent with a Cs transition state or CsV intermediate.ll The difference between thc rearrangement modes of [Fe(CO)4] and SF4 has been attributed to the energetic behaviour of the partially occupied metal d-orbitals during dis- tortion of the [Fe(C0)4] fragment.11v13 1.r. laser induced photochemistry has therefore revealed somz very unusual properties of [Fe(C0)4], which are unlikely to have been discovercd by any other technique. 7 Conclusions U.V. photolysis of matrix isolated [Fe(C0)5] produces the rcactive fragment [Fe(C0)4] and molecular CO. A combination of i.r. spectroscopy and lT0 enrichment has been used to show that [Fe(C0)4] has a C2r structure with bond angles of N 145" and N 120".MOcalculations predict that [Fe(C0)4] should have a triplet ground state, and its paramagnetism has been confirmed using m.c.d.It is the first binary transition-metal carbonyl species which does not havc a 'low spin' ground state. [Fe(C0)4] loses CO on U.V. irradiation to form a pyramidal Poliakof 0 I 0-5 1902 1900 1880 cm-1 Figure 4 1.r. spectra illustrating laser isomerization of isomer (4) 0f"Fe('~C~~~),("C~e0),1in an Ar matrix at 20 K (see Schemes2 and 4 for numbering of isomers): (a)beforeand(b)after25 min i.r. laser irradiation at 1902 cm-l, coincident with the band of (4) (Reproduced by permission from J. Amer. Chem. Soc.. 1977,99, 7573.) [Fe(C0)3] fragment. The intuitively unexpected structures of [Fe(CO)3] and [Fe(C0)4] have provided valuable tests of theories for predicting the structures of transition-metal compounds.[Fe(C0)4] has a far-red-near4.r. absorption band A,,, 770 nm due to d -+ d electronic transitions. Excitation of these transitions promotes addition reactions, most importantly with CH4 to form [Fe(C0)4CHg]. This unusual complex has electronic and vibrational spectra which are significantly different from those of [Fe(CO)4]. Although the exact nature of the Fe ---CH4 bonding is still unclear, the strength of the interaction is sufficiently strong to produce substantial changes in the structure of the Fe(C0)4 moiety. Similar addition reactions can be induced by irradiation of the C-0 stretching modes of [Fe(C0)4] using i.r. lasers.1.r. lasers have also been used to promote intramolecular ligand exchange in [Fe(C0)4], and to identify the permutational rearrangement mode involved. [Fe(C0)4] is the first molecule known to undergo a so-called 'non-Berry pseudo- rotation', it is the first binary transition-metal carbonyl to have its rearrange- ment mode established, and it is the first time that such a mode has been identified without the use of dynamic n.m.r. I thank the SRC for generous support and the Society of Maccabaeans for the award of the Meldola medal and prize. I am grateful to all my co-workers, 539 particularly, Dr. R. N. Perutz, and my ‘fellow medallist’, Dr. J. K. Burdett, for their help and criticism and to Mr. R. Graham for his skill and ingenuity in building our apparatus. I am especially grateful to Professor J. J. Turner for all of the help, guidance, and encouragement that he has given to me throughout this work.

ISSN:0306-0012    

DOI:10.1039/CS9780700527

出版商:RSC    

年代:1978

数据来源: RSC

摘要:

INDEXES Volume 7, 1978 The indexes in this issue cover Volumes 1-7 (Figures in bold type refer to the volume number) Index INDEX OF AUTHORS Aarons, L. J., 5, 359 Ahluwalia, J. C., 2, 203 Allen, N. S., 4, 533 Baker, A. D., 1, 355 Bartlett, P. D., 5, 149 Baxendale, J. H., 7, 235 Beattie, I. R., 4, 107 Bell, R. P., 3, 513 Bentley, P. H., 2, 29 Berkoff, C. E., 3, 273 Bird, C. W., 3, 309 Blandamer, M. J., 4, 55 Blundell, T. L., 6, 139 Boelens, H., 7, 167 Bradshaw, T. K., 6,43 Braterman, P. S., 2, 271 Breslow, R., 1, 553 Brown, I. D., 7, 359 Brown, K. S., jun., 4, 263 Brundle, C. R., 1, 355 Buchanan, G. L., 3,41 Burdett, J. K., 3, 293; 7, 507 Burgess, J., 4, 55 Burrows, H. D., 3, 139 Burtles, S.M.,7, 201 Butterworth, K.R., 7, 185 Cadogan, J. I. G.,3, 87 Carabine, M. D., 1,411 Cardin, D. J., 2, 99 Carless, H. A. J., 1, 465 Cetinkaya, B., 2,99 Chamberlain, J., 4, 569 Chatt, J., 1, 121 Chivers, T., 2, 233 Clark, G. M.,5, 269 Collins, C.J., 4, 251 Colvin, E. W., 7, 15 Connor, J. N. L., 5, 125 Corfield, G. C., 1,523 Cornforth, J. W., 2, 1 Cotton, F. A., 4, 27 CouIson, E. H., 1, 495 Coyk, J. D., 1, 465; 3, 329; 4, 523 Cragg, G. M. L., 6, 393 Cramer, R. D., 3, 273 Crammer, B., 6, 431 Cross, R. J., 2, 271 Dack, M.R. J., 4, 211 Dainton, F. S., 4, 323 de Rijke, D., 7, 167 de Valois, P.J., 7, 167 Dobson, J. C., 5, 79 Doyle, M. J., 2, 99 Drummond, I., 2,233 Elliott, M.,7, 473 Eschenmoser, A., 5, 377 Evans, D.A., 2, 75 Fenby, D. V., 3, 193 Fenton, D. E., 6, 325 Ferguson, L. N., 4, 289 Fisher, L. R.,6, 25 Flygare, W. H., 6, 109 Fry, A,, 1, 163 Georghiou, P. E., 6,83 Gibson, K. H., 6, 489 Goodings, E. P., 5, 95 Gray, B. F., 5, 359 Green, C. L., 2, 75 Greenhill, J. V., 6, 277 Greenwood, N. N., 3,23 1 Griffiths, J., 1,481 Grossert, J. S., 1, 1 Groves, J. K., 1, 73 Guilford, H., 2, 249 Gutteridge, N. J. A., 1, 381 Haines, R. J., 4, 155 Hall, G. G., 2, 21 Hall, L. D., 4, 401 Hall, T. W., 5, 431 Halliwell, H. F., 3, 373 Harmony, M. D., 1, 211 Harris, K. R., 5, 215 Harris, R. K., 5, 1 Martley, F. R., 2, 163 Wartshorn, S. R., 3, 167 Henderson, J.W., 2, 397 Hepler, L. G., 3, 193 Hinchliffe, A., 5, 79 Horton, E. W., 4, 589 Hudson, M. F., 4, 363 Huntress, W. T., Jr., 6, 295 Hutchinson, D. W., 6, 43 Ikan, R., 6, 431 Isaacs, N. S., 5, 181 Isbell, H. S., 3, 1 Jaffe, H. H., 5, 165 Jamieson, A. M., 2, 325 Janes, N. F.,7, 473 Jenkins, J. A., 6, 139 Johnson, A. W., 4, 1 Johnson, S. P.,5,441 Johnstone, A. H., 7, 317 Jotham, R. W.,2,457 Kalyanasundaram, K., 7,453Kemp, T. J., 3, 139 Kennedy, J. F., 2, 355 Kennewell, P.D., 4, 189 Kenny, A. W., 4,90 King, G. A. M., 7, 297 Kirby, G. W., 6, 1 Kitaigorodsky, A. I., 7, 133 Koch, K. R., 6, 393 Kresge, A. J., 2, 475 Krishnaji, 7, 219 Lappert, M. F., 2, 99 Lee-Ruff, E., 6, 195 Leigh, G.J., 1, 121; 4, 155 Lemieux, R. U., 7,423 Leznoff, C. C., 3, 65 Lindoy, L. F., 4,421 Linford, R. G., 1,445 Lipscomb, W. N., 1, 319 Lynch, J. M., 3, 309 McKean, D. C.,7, 399 McKellar, J. F., 4, 533 McKervey, M. A., 3, 479 Mackie, R. K., 3, 87 McNab, H., 7, 345 Maitland, G. C., 2, 181 Manning, P. G., 5, 233 Maret, A. R., 2, 325 Mason, R., 1,431 Mayo, B. C., 2, 49 Meadowcroft, A. E., 4, 99 Menger, H. W., 2,415 Midgley, D., 4, 549 Millen, D. J., 5, 253 Mills, R., 5, 215 Moore, H. W., 2, 415 Morley, R., 5, 269 Morris, J. H., 6, 173 Mulheirn, L. F., 1, 259 Munn, A., 4, 87 Newman, J. F., 4, 77 Nightingale, W. H., 7, 195 North, A. M., 1, 49 Oakenfull, D.G., 6, 25 Page, M. I., 2, 295 Perkins, P. G., 6, 173 Pletcher, D., 4, 471 Poliakoff, M., 3, 293;7, 527 Prakash, V., 7, 219 Pratt, A. C., 6, 63 Ramm, P. J., 1, 259 Rao, C. N. R., 5, 297 Rattee, I. D., 1, 145 Red], G., 3, 273 Richards, D. H., 6, 235 Ritch, J. B., jun., 5, 452 Roberts, M. W., 6, 373 Robinson, F. A., 5, 317 Roche, M., 5, 165 Rodgers, M. A. J., 7,235 Rose, A. E. A., 6, 173 Rouvray, D. H., 3, 355 Rowlinson, J. S., 7, 329 Sanders, J. K. M., 6, 467 Sarma, T. S.,2, 203 Satchel], D. P. N., 4, 231; 6, 345 Satchel], R. S., 4, 231 Schlegel, W., 7, 177 Senthilnathan, V. P., 5, 297 Shorter, J., 7, 1 Simpson, T. J., 4, 497 Singh, S., 5, 297 Smith, E. B., 2, 181 Smith, K., 3, 443 Smith, K.M., 4, 363 Smith, W. E., 6, 173 Stacey, M., 2, 145 Stevens, M. F. G., 7, 377 Suckling, C. J., 3, 387 Suckling, K. E., 3, 387 Sutherland, R. G., 1, 241 Sutton, D., 4, 443 Swan, J. S., 7, 201 Swindells, R., 7, 212 Symons, M. C. R.,5, 337 Takken, H. J., 7, 167 Index Taylor, J. B., 4, 189 Theobald, D. W., 5, 203 Thomas, T. W., 1, 99 Thompson, M., 1, 355 Tincknell, R. C., 5, 463 Toennies, J. P., 3, 407 Tolman, C. A., 1, 337 Truax, D. R., 5,411 Twitchett, H. J., 3, 209 Underhill, A. E., 1, 99 van Dort, J. M., 7, 167 van der Linde, L. M.,7, 167 Vaughan, K., 7, 377 Wain, R. L., 6, 261 Walker, E. R. H., 5, 23 Walker, I. C., 3, 467 Waltz, W.L., 1, 241 Ward, I. M., 3, 231 White, A. J., 3, 17 Whitfield, R. C., 1, 27 Wieser, H., 5, 411 Wiesner, K., 6, 413 Williams, G., 7, 89 Wilson, A. D., 7, 265 Yoffe, A. D., 5, 51 Index INDEX OF TITLES Absorption bands in the specta of stars, a crystal field approach, 5, 233 Across the living barrier, 6, 325 Acylation by ketens and isocyanates, a mechanistic comparison, 4, 231 Acylation, Friedel-Crafts, of alkenes, 1, 73 Adamantane rearrangements, 3, 379 Affinity chromatography, chemical aspects of, 3, 249 Alcohols and amines, conformational analysis of, 5,411 Alkali-metal complexes in aqueous solution, 4, 549 Alkaloids, aconite, synthesis of, 6,413 Alkenes, the Friedel-Crafts acylationof, 1, 73 Aluminium phosphates, the chemistry and binding properties of, 6, 173 Amines and alcohols, conformational analysis of, 5,411 Aphids and scale insects, their chemistry, 4, 263 Application of electrochemical tech- niques to the study of homogeneous chemical reactions, 4,471 Application of research findings to the development of commercial flavour- ings, 7, 177 Aqueous mixtures, kinetics of reactions in, 4, 55 Aqueous solution, micelles in, 6, 25 Aryldiazonium cations, co-ordination chemistry of, 4,443 Atmosphere, interactions in, of drop-lets and gases, 1, 411 Autocatalysis, 7, 297 Azidoquinones and related com-pounds, chemistry of, 2, 415 Azobenzene and its derivatives, photo- chemistry of, 1, 481 Bile pigments, 4, 363 Binding of heavy metals to proteins, 6, 139 Binding properties and chemistry of aluminium phosphates, 6, 173 Biomimetic chemistry, 1, 553 Biosynthesis of sterols, 1, 259 Biosynthetic products from arachi-donic acid, 6,489 -studies, carbon-1 3 nuclear mag- netic resonance in, 4,497Blood groups, human, and carbo-hydrate chemistry, 7, 423 Bond strengths, CH, in simple organic compounds :effects of conformation and substitution, 7, 399 -valences-a simple structural model for inorganic chemistry, 7,359 Bredt’s rule, 3, 41 Brer ns ted relat io n-recen t develop-ments, 2,475 Butadiene, polymerization and co-polymerization of, 6,235 Calciferols, hormonal : chemistry of “vitamin” D, 6, 83 Calorimetric investigations of hydro- gen bond and charge transfer complexes, 3, 193 Cancer and chemicals, 4, 289 Carbohydrate chemistry and human blood groups, 7,423 Carbohydrate-protein complexes, gly- coproteins, and proteoglycans, of human tissues, chemical aspects of, 2,355 Carbon-13 nuclear magnetic resonance in biosyn t hetic studies, 4,497 Carbonium ions, carbanions, and radicals, chirality in, 2, 397 Carbonyl compounds, photo-chemistry of, 1,465 Catalysis and surface chemistry, new perspectives, 6, 373 Catalysis, homogeneous, and organo- metallic chemistry, the 16 and 18 electron rule in, 1, 337 -of the olefin metathesis reaction, 4, 155 CENTENARY LECTURE.Biomimetic chemistry, 1, 553 CENTENARY Light scattering LECTURE. in pure liquids and solutions, 6, 109 CENTENARY LECTURE.Quadruple bonds and other multiple metal to met a1 bonds , 4, 27 CENTENARYLECTURE. Rotationally and vibrationally inelastic scattering of molecules, 3, 407 CENTENARY LECTURE. Systematic development of strategy in the synthesis of polycyclic polysub- stituted natural products :the aconite alkaloids, 6,413CENTENARYLECTURE. Three-dimen- sional structures and chemical mechanisms of enzymes, 1, 319 Charge transfer and hydrogen bond complexes, calorimetric investiga- tions of, 3, 193 Chemical applications of advances in Fourier transform spectroscopy, 4, 569 -aspects of affinity chromato- graPhY, 2,249 --of glycoproteins, proteo- glycans, and carbohydrate-protein complexes of human tissues, 2,355 -interpretations of molecular wavefunctions, 5, 79 Chemicals in rodent control, 1, 381 -which control plant growth, 6,261 Chemistry and binding properties of aluminium phosphates, 6, 173 CHEMISTRY AND FLAVOUR I Molecular Structure and Or-ganoleptic Quality, 7, 167 I1 Application of Research Find- ings to the Development of Commercial Flavourings, 7, 177 I11 Safety Evaluation of Natural and Synthetic Flavourings, 7, 185 IV The Influence of Legislation on Research in Flavour Chemistry, 7,195 V The Development of Flavour in Potable Spirits, 7,201 VI The Influence ‘of Flavour Chemistry on Consumer Accept- ance, 7,212 Chemistry and the new industrial revolution, 5, 317 --a topological subject, 2,457 -of aphids and scale insects, 4,263-of azidoquinones and related compounds, 2,415 -,of dental cements, 7,265 -of dyeing, 1, 145 -of homonuclear sulphur species, 2,233-of the production of organicisocyanates, 3,209-of transition-metal carbene com- Index plexes and their role as reaction intermediates, 2, 99 -of “vitamin” D: the hormonal calciferols, 6, 83 -, some considerations on the philosophy of, 5, 203 Chirality in carbonium ions, car-banions, and radicals, 2, 397 Chlorophyll chemistry, n.m.r.spectral change as a probe, 6,467 Chromatography, affinity, chemical aspects of, 2,249Cis-and trans-effects of ligands, 2, 163 Clathrates and molecular inclusion phenomena, 7, 65 Collisional transfer of rotational energy and spectral lineshapes, 7,219 Complexes, alkali-metal, in aqueous solution, 4, 549 Complex hydride reducing agents, the functional group selectivity of, 5, 23 Conductivity and superconductivity in polymers, 5, 95 Conformation and substitution effects of, on individual CH bond strengths in simple organic compounds, 7,399 Conformation of rings and neighbour- ing group effects, development of Haworth’s concepts of, 3, 1 Conformational analysis of some alcohols and amines :a comparison of molecular orbital theory, rota- tional and vibrational spectroscopy, 5,411 Conformational studies on small mole- cules, 1,293Contribution of ion-pairing to ‘memory effects’, 4,251Contributions of pulse radiolysis to chemistry, 7,235Conversion of ammonium cyanate into urea-a saga in reaction mechanisms, 7, 1 Co-ordination chemistry of aryldiazo- nium cations: arlydiazenato (ary-lazo) complexes of transition metals, and the aryldiazenato-nitrosylanalogy, 4, 443 Corrin syntheis, post-Bl2 problems in, 5.377 Crystal field approach to absorption bands in the spectra of stars, 5, 233 Index Crystals and molecules, organic, non- bonded interactions of atoms in, 7, 133 Cyclopolymerization, 1, 523 Dental cements, chemistry of, 7, 265 Development of flavour in potable spirits, 7,201Dielectric relaxation in polymer solu- tions, 1, 49 Diffusion in liquids, the effect of isotopic substitution on, 5, 215 Difluoroamino-radical, gas-phase kinetics of, 3, 17 Droplets and gases, interactions in the atmosphere of, 1, 411 Drug design, quantitative, 3, 273 Dyeing, chemistry of, 1, 145 Echinoderms, 1, 1 Education, chemical, a reassessment of research in, 1, 27 Education, chemical, review of re-search and development in the U.K., 1972-1 976, 7, 317 Effect of isotopic substitution on diffusion in liquids, 5, 215 Electrochemical techniques, applica- tion of, to the study of homogeneouschemical react ions, 4,471Electron as a chemical entity, 4, 323 -scattering spectroscopy, thres- hold, 3,467 -spectroscopy, 1, 355 Electronic properties of some chain and layer compounds, 5, 51 -transitions, vibrational intensities in, 5, 165 Electrons, solvated, in solutions of metals, 5, 337 Electrophilic aromatic substitutions, non-conventional, and related reactions, 3, 167 -C-nitroso-compounds, 6, 1 Elimination reactions, isotope effect studies of, 1, 163 Enaminones, 6, 277 Energetics of neighbouring groupparticipation, 2, 295 Enumeration methods for isomers, 3,355Environmental protection in the dis- tribution of hazardous chemicals, 4,99 -regulation: an international view, 5,431 Enzymes, immobilized, 6, 215 -in organic synthesis, 3, 387 -, the logic of working with, 2,l -, three-dimensional structures and chemical mechanisms of, 1, 319 Experimental studies on the structure of aqueous solutions of hydro-phobic solutes, 2, 203 FARADAY The electron as a LECTURE.chemical entity, 4, 323 Fe(C0)4, 7, 527 5-Su bstitu ted pyrimidine nucleosides and nucleotides, 6, 43 Fixation, of nitrogen, 1,121Forces between simple molecules, 2, 181 Formation of hydrocarbons by micro- organisms, 3, 309 Fourier transform spectroscopy,chemical applications of advances in, 4, 569 Four-membered rings and reaction mechanisms, 5, 149 Friedel-Crafts acylation of alkenes, 1, 73 Functional group selectivity of com- plex hydride reducing agents, 5, 23 Gas-phase kinetics of the difluoro-amino-radical, 3, 17 Gases, and droplets, interactions in the atmosphere, 1, 411 Glycoproteins, proteoglycans, and carbohydrate-protein complexes of human tissues, chemical aspects of, 2, 355 Growth of computational quantum chemistry from 1950 to 1971, 2, 21 Handling toxic chemicals-environ-mental considerations, 4, 77 HAWORTH MEMORIAL LECTURE.The consequences of some projectsinitiated by Sir Norman Haworth, 2, 145 HAWORTH LECTURE.TheMEMORIAL Haworth-Hudson controversy and the development of Haworth’s con- cepts of ring conformation and of neighbouring group effects, 3, 1 HAWORTH MEMOR~AL LECTURE.Human blood groups and carbo- hydrate chemistry, 7,423 Health hazards to workers from industrial chemicals, 4, 82 Homogeneous catalysis, and organo- metallic chemistry, the 16 and 18 electron rule in, 1, 337 Homogeneous chemical reactions, ap- plication of electrochemical tech-niques to the study of, 4,471 Human blood groups and carbo-hydrate chemistry, 7,423 Hydrocarbon formation by micro-organisms, 3, 309 Hydrogen bond and charge transfer complexes, calorimetric investiga-tions of, 3, 193 -isotope effects, kinetic, recent advances in the study of, 3, 513 Hydrophobic solutes, experimentalstudies on the structure of aqueous solutions of, 2, 203 Imines, photochemistry of, 6, 63 Immobilized enzymes, 6,215Importance of solvent internal pres- sure and cohesion to solution phenomena, 4,211 Inclusion phenomena, molecular, and clathrates, 7, 65 Individual CH bond strengths in simple organic compounds : effects of conformation and substitution, 7, 399 Influence of flavour chemistry on consumer acceptance, 7,212 Influence of legislation on research in flavour chemistry, 7, 195 Infrared and Raman vibrational spec- troscopy in inorganic chemistry, 4, 107 INGOLD LECTURE.Four-membered rings and reaction mechanisms, 5, 149 Inorganic chemistry, bond valences, a simple structural model for, 7, 359 Inorganic pyro-compoundsMa[(X207b], 5,269Insect attractants of natural origin, 2, 75 Insecticide, a new class of: syntheticpyrethroids, 7,473 Index Interactions in the atmosphere of drop- lets and gases, 1,411 -, metal-metal, in transition-metal complexes containing infinite chains of metal atoms, 1, 99 interactions, non-bonded, of atoms in organic crystals and molecules, 7, 133 Introducing a new agricultural chemi- cal, 4, 77 Ion-molecule reactions in the evolu- tion of simple organic molecules in interstellar clouds and planetaryatmospheres, 6,295 Ion-pairing, contribution to ‘memory effects’, 4, 251 Isocyanates and ketens.a mechanistic comparison of acylation by, 4, 231 -, organic, chemistry of the pro- duction of, 3,209Isomer enumeration methods, 3, 355 Isotope effect studies of elimination reactions, 1, 163 Isotopic substitution effects on dif-fusion in liquids, 5, 215 JOHNJEYES Chemicals which LECTURE. control plant growth, 6,261 KELVIN LECTURE. Across the living barrier, 6, 325 Ketens and isocyanates, a mechanistic comparison of acylation by, 4, 231 Kinetics, gas-phase, of the difluoro- amino -radical, 3, 17 Kinetics of reactions in aqueousmixtures, 4, 55 ,%Lactam, synthetic routes to, 5, 181 Lanthanide shift reagents in nuclear magnetic resonance spectroscopy, 2, 49 Laser light scattering, quasielastic, 2, 325 Lasers, tunable, 3, 293 Ligands, cis-and trans-effects of, 2, 163 Liquid, surface of, 7, 329 LIVERSIDGE Recent advances LECTURE. in the study of kinetic hydrogen isotope effects, 3, 513 LIVERSIDGE The surface of aLECTURE.liquid, 7, 329 Macrocyclic ligands, synthetic, trans- ition-metal complexes of, 4, 421 Index Mechanisms, chemical, and three-dimensional structures of enzymes, 1, 319 MELDOLA ChemicalMEDAL LECTURE. aspects of glycoproteins, proteogly- cans, and carbohydrate-proteincomplexes of human tissues, 2, 355 MEDALLECTURE.MELDOLA Fe(C0)4, 7,527MEDALLECTURE.MELDOLA Molecular collisions and the semiclassical approximation, 5, 125 MELDOLA MolecularMEDAL LECTURE.shapes, 7,507MELDOLA MEDAL LECTURE. N.m.r. spectral change as a probe of chlorophyll chemistry, 6,467 Meldrum’s acid, 7, 345 Metal-metal bonding and metallobo- ranes, 3, 231 Metal-ion-promoted reactions of organo-sulphur compounds, 6, 345 Metalloboranes and metal-metal bond- ing, 3,231 Metal-metal bonds, multiple (espec-ially quadruple), 4, 27 -interactions in transition-metal complexes containing infinite chains of metal atoms, 1, 99 Metals, binding to proteins, 6, 139 Micelle-forming surfactant solutions, photophysics of molecules in, 7,453 Micelles in aqueous solution, 6, 25 Molecular collisions and the semi-classical approximation, 5, 125 -orbital theory, comparison with rotational and vibrational spectro- scopy in conformational analysis of alcohols and amines, 5,411 -shapes, 7,507 -structure and organolepticquality, 7, 167 -wavefunctions, chemical inter-pretations of, 5, 79 Monoalkyltriazenes, 7, 377 Motion, molecular, and time-correla- tion functions, 7, 89 Multistability in open chemical reac- tion systems, 5,359 Natural products from echinoderms, 1, 1 --,polycyclic polysubstituted, systematic development of strategy in, 6,413 Neighbouring-group effects and ring conformation, development of Haworth’s concepts of, 3, 1 -participation, energetics of, 2, 295 New perspectives in surface chemistry and catalysis, 6, 373 Nitrogen fixation, 1, 121 C-Nitroso-compounds, electrophilic, 6, 1 Non-bonded interactions of atoms in organic crystals and molecules, 7, 133 Non-conventional electrophilic aro-matic substitutions and related re- actions, 3, 167 Nuclear magnetic resonance and the periodic table, 5, 1 ---,carbon-13, in bio-synthetic studies, 4,497---spectral change as a probe of chlorophyll chemistry, 6,467 ---spectroscopy, lan-thanide shift reagents in, 2, 49 ----: spin-latticerelaxation, 4, 401 Nucleosides and nucleotides, pyrimi- dine, 5-su bstituted 6, 43 NYHOLM MEMORIAL LECTURE.For- ward from Nyholm’s Marchon Lecture, 3,373 NYHOLM LECTURE.MEMORIAL Growth, change, challenge, 5,253 Olefin metathesis and its catalysis, 4, 155 Olefinic compounds, photochemistry of, 3, 329 Organic chemistry of superoxide, 6,195 Organoboranes as reagents for organic synthesis, preparation of, 3, 443 Organoborates in organic synthesis: the use of alkenyl-, alkynyl-, and cyanoborates as synthetic intermedi- ates, 6, 393 Organometallic chemistry and homo- geneous catalysis, the 16 and 18 electron rule in, 1,337 Organo-sulphur compounds, metal-ion-promoted reactions of, 6, 345 Organo- t ransi tion-me tal complexes: stability, reactivity, and orbital correlations, 2,271 PEDLER LECTURE.Porphyrins and related ring systems, 4, 1 Phase boundaries, reactivity of organicmolecules at, 1,229 Philosophy of chemistry, some con- siderations, 5, 203 Phosphates, aluminium, the chemistry and binding properties of, 6, 173 Phosphorus compounds, tervalent, in organic synthesis, 3, 87 Photochemistry of azobenzene and its derivatives, 1,481 -of carbonyl compounds, 1,465 -of imines, 6, 63 -of olefinic compounds, 3, 329 -of organic sulphur compounds, 4, 523 -of the uranyl ion, 3, 139 -of transition-metal co-ordination compounds-a survey, 1,241 Photodegradation and stabilization of commercial polyolefins, 4, 533 Photophysics of molecules in micelle- forming surfactant solutions, 7, 453 Plant growth, control by chemicals, 6, 261 PoIyrner solutions, dielectric relaxation in, 1,49 -supports, insoluble, use in organic chemical synthesis, 3,65 Polymerization and copolymerization of butadiene, 6,235 Polymers, conductivity and super-conductivity in, 5, 95 Polyolefins, commercial, photodegra- dation and stabilisation of, 4, 533 Porphyrins and related ring systems, 4, 1 Post-BIZ problems in corrin synthesis, 5,377 Preparation of organoboranes: re-agents for organic synthesis, 3,443 PRESIDENTIALADDRESS1976.Chemis- try and the new industrial revolu- tion, 5, 317 Properties and syntheses of sweetening agents, 6,431Prostaglandins, tomorrow’s drugs, 4,589 -, thromboxanes, PGX: biosynthe- tic products from arachidonic acid, 6,489 Prostanoids, total syntheses of, 2, 29 Proteins, binding of heavy metals to, 6, 139 Index Pulse radiolysis, contributions to chemistry, 7,235 Pyrimidine nucleosides and nucleo-tides, 5-substituted, 6, 43 Py r o-comp o u n ds , inor g a n i c,Ma[(X207)bI, 5,269 Quadruple bonds and other multiple metal to metal bonds, 4, 27 Quantitative drug design, 3,273 Quantum chemistry, computational, growth of from 1950 to 1971, 2,21 -mechanical tunnelling in chemis- try, 1,211 Quasielastic laser light scattering, 2, 325 Radioactive and toxic wastes: a com- parison of their control and disposal, 4,90 Radiolysis, pulse, contributions to chemistry, 7,235 Raman and infrared vibrational spec-troscopy in inorganic chemistry, 4, 107 Reaction mechanisms, four-membered rings and, 5, 149 --, the conversion of am-monium cyanate into urea, 7, 1 Reactivity of organic molecules at phase boundaries, 1, 229 Recent advances in the study of kinetic hydrogen isotope effects, 3, 513 Research in chemical education: a reassessment, 1, 27 Review of chemical education re-search and development in the U.K.,1972-1 976, 7, 317 ROBERTROBINSON Post-BIZLECTURE.problems in corrin synthesis, 5, 377 ROBERT LECTURE.ROBINSON The logic of working with enzymes, 2, 1 Rodent control, chemicals in, 1,381 Rotationally and vibrationally inelas- tic scattering of molecules, 3,407 Safety evaluation of natural and syn- thetic flavourings, 7,185 Scale insects and aphids, chemistry of,4,263 Silicon in organic synthesis, 7, 15 16 and 18 Electron rule in organometal- lic chemistry and homogeneouscatalysis, 1,337 549 index Small molecules, conformation studies on, 1,293 Solids, surface energy of, 1,445Solute-solvent interactions, spectro- scopic studies of, .5, 297 Solution phenomena, the importance of solvent internal pressure and cohesion, 4,211Solutions of metals : solvated electrons, 5,337Solvent internal pressure and cohesion, importance to solution phenomena, 4,211 Some considerations on the philosophy of chemistry, 5, 203 Some recent developments in chemis-try teaching in schools, 1,495 Spectra of stars, absorption bands in, a crystal field approach, 5,233 Spectral lineshapes, collisional transfer of rotational energy with, '7,219 Spectroscopic studies of solute-solvent interactions, 5,297 Spectroscopy, electron, 1,355 -, Fourier transform, chemical applications of advances in, 4, 569 -, rotational and vibrational, com- parison with molecular orbital theory in conformational analysis of alcohols and amines, 5,411 -, threshold electron scattering, 3,467 Spin-lattice relaxation: a fourth di- mension for proton n.m.r.spectro- SCOPY, 4,401 Stability, reactivity, and orbital cor- relations of organo-transition-metal compIexes, 2,271 Sterols, biosynthesis of, 1,259 Structure of aqueous solutions of hydrophobic solutes, experimental studies on, 2, 203 Substitution and conformation, effects of, on individual CH bond strengths in simple organic compounds, 7, 399 Sulphoximides, 4, 189 Sulphur compounds, organic, photo- chemistry of, 4,523 -compounds, organic, metal-ion- promoted reactions of, 6,345 -species, homonuclear, chemistry, of, 2,233 Superconductivity and conductivity in polymers, 5,95 Superoxide, organic chemistry of, 6, 195 Surface chemistry and catalysis, new perspectives, 6, 373 -energy of solids, 1, 445 -of a liquid, 7, 329 Sweetening agents, properties and syntheses of, 6, 431 Syntheses and properties of sweetening agents, 6,431 syntheses, total, of prostanoids, 2, 29 Synthesis, of corrins, post-Blz prob-lems in, 5,377 -of polycyclic polysubstitutednatural products, systematicdevelopment of strategy in, 6,413 -, organic, enzymes in, 3, 387 -, organic, preparation of organo-boranes as reagents for, 3,443 -, organic, silicon in, 7, 15 -, organic, tervalent phosphorus compounds in, 3, 87 --, organic, use of inorganic poly- mer supports in, 3, 65 -, organic, the use of organoborates as synthetic intermediates, 6, 393 Synthetic pyrethroids, A new class of insecticide, 7,473 -routes to p-lactams, 5, 181 Systematic development of strategy in the synthesis of polycyclic poly-substituted natural products: the aconite alkaloids, 6,413 TATE AND LYLE LECTURE.Spin-latticz relaxation: a fourth dimen- sion for proton n.m.r. spectroscopy, 4, 401 Teaching of chemistry in schools, some recent developments in, 1,495 Tervalent phosphorus compounds in organic synthesis, 3, 87 Three-dimensional structures and chemical mechanisms of enzymes,1, 319 Threshold electron scattering spectro- SCOPY, 3,467 Thromboxanes, prostaglandins, PGX: biosynthetic products of arachidonic acid, 6,489 TILDENLECTURE.Electrophilic C-nitroso-compounds, 6,.1 TILDEN New perspectives inLECTURE.surface chemistry and catalysis, 6,373 TILDEN Valence in transition- LECTURE. metal complexes, 1,431 Time-correlation functions and mole- cular motion, 7, 89 Topological subject-chemistry, 2, 457 Transition-metal carbene complexes, chemistry and role as reaction inter- mediates, 2, 99 -complexes containing infinite chains of metal atoms, metal-metal interactions in, 1, 99 -complexes of synthetic macrocyc- lic ligands, 4,421 -complexes, valence in, 1, 431 -co-ordination compounds, photo- chemistry of, 1,241 Tunable lasers, 3,293 Index Uranyl ion, photochemistry of, 3, 139 Use of insoluble polymer supports in organic chemical synthesis, 3, 65 Valence in transition-metal complexes, 1,431 Valences, bond, a simple structural model for inorganic chemistry, 7,359 Vibrational infrared and Raman spsc- troscopy in inorganic chemistry, 4,107 -intensities in electronic trans-it io ns , 5,165 Vi brat ionally and ro tat ionally inelas- tic scattering of molecules, 3, 407 “Vitamin” D, chemistry of: the hor- monal calciferols, 6, 83 551

ISSN:0306-0012    

DOI:10.1039/CS9780700541

出版商:RSC    

年代:1978

数据来源: RSC