摘要:

Chemical Society Reviews Editorial Board Jean-Pierre Sauvage (CNRS, Strasbourg) [Chair] Vicenzo Balzani (Bologna) Ed C. Constable (Basel) Chris Elschenbroich (Marburg) Tim C. Gallagher (Bristol) Editorial Office Martin Sugden (Managing Editor) David Bradley; Peter Whittington (Production) Debbie Halls (Editorial Secretary) http://chemistry .rsc.org/rsc tel: +44 (0)1223 420066 Chemical Society Reviews publishes concise, succinct and lightly referenced articles that provide an introductory overview to topics of current interest in chemistry. The articles appeal to the general research chemist as well as to the expert in the field and provide an essential starting point for further reading. Advanced undergraduates, postgraduates and experienced re- searchers should all benefit from reading Chemical Society Reviews. Chemical Society Reviews (ISSN 0306-0012) is published bimonthly by the Royal Society of Chemistry, Thomas Graham House, Science Park, Cambridge, UK CB4 4WF.1997 subscription rate: El30 (USA $234). Customers in Canada will be charged the sterling price plus a surcharge to cover GST. Individuals can subscribe for &45 (USA $80) providing their institutional library takes a full price subscription. All orders accompanied by payment should be sent directly to The Royal Society of Chemistry, Turpin Distribution Services Ltd, Blackhorse Road, Letchworth, UK SG6 IHN. (NB Turpin Distribution Services Ltd., distributors, is wholly owned by the Royal Society of Chemistry.) Payment should be by cheque in pounds sterling payable on a UK clearing bank or in US dollars payable on a US clearing bank.Second class postage is paid at Zdenek Herman (Prague) Horst Kunz (Mainz) John P. Maier (Basel) D. Mike P. Mingos (Imperial) Jeremy K. M. Sanders (Cambridge) Royal Society of Chemistry Thomas Graham House Science Park Cambridge UK CB4 4WF csr@ rsc .org fax: +44(0) 1223 420247 The Editorial Board commissions articles that encourage international, interdisciplinary dialogues in chemical research. The Board welcomes any suggestions for new articles. A guide for authors and synopsis form can be found in the first issue of this year’s volume or on the RSC’s World-Wide Web home page (URL above).Alternatively, they can be requested from the Managing Editor, in paper or electronic form (postal and e- mail address above). Jamaica NY 1141-9998. Airfreight and mailing in the USA by Publications Expediting Services Inc., 200 Meacham Avenue, Elmont, NY 11003 and at additional mailing offices. US Postmaster: send address changes to Chemical Society Review, c/o Publication Expediting Services Inc., 200 Meacham Ave- nue, Elmont NY 11003. All dispatches outside UK by bulk airmail within Europe and Accelerated Surface Post outside Europe. 0The Royal Society of Chemistry, 1997 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, recording, or otherwise, without the prior permission of the publishers. Typeset and printed in Great Britain by Black Bear Press Limited.

ISSN:0306-0012    

DOI:10.1039/CS99726FX001

出版商:RSC    

年代:1997

数据来源: RSC

ISSN:0306-0012    

DOI:10.1039/CS99726BX003

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Tilden Lecture: Shining light on metal catalysts John Evans Department of Chemistry, University of Southampton, Southampton, UK SO17 1BJ X-Ray absorption spectroscopy can provide local structural information about the reaction centres in metal catalysts. Developments in this technique are illustrated with the chemistry of oxide supported metals e.g. Rh(COh/titania and by studies on some homogeneous catalysts (rhodium- catalysed carbonylation and nickel catalysts for alkene catenation). Energy dispersive EXAFS promises the oppor- tunity to probe the structures of short-lived reaction intermediates. 1 Introduction While the development of a high performance catalyst may be the Holy Grail for most scientists engaged in catalytic research, providing a molecular level understanding of the chemical events at that reaction centre is tantalising to many.In my previous review in this journal,' I investigated the relationships between metal carbonyl cluster complexes and oxide-supported heterogeneous catalysts. One of these, the use of cluster complexes to provide a spectroscopic database for interpreting the spectra of adsorbates in heterogeneous catalysis and surface science, has proved to be of substantial benefit. The other was the attempted synthesis of a uniform array of metal particles on an oxide surface to provide molecular type heterogeneous catalysts. However, in the succeeding years it proved very difficult to maintain low oxidation state cluster complexes under the relatively alien environment of many oxide surfaces (typically silica, alumina and titania). While stabilising inter- stitial or bridging ligands retarded cluster breakdown, they did not prevent it under catalytic reaction conditions.It was apparent that a richer vein would be to probe the inorganic chemistry of metals on oxide surfaces, again taking the synthetic strategy from organometallic chemistry, but that would require improved characterisation procedures. In this review, I shall discuss the development of an array of techniques to follow this chemistry. The problem of characterising metal centres on disordered surfaces is not very distinct from that of elucidating solution structures, and we shall also see how John Evans obtained a BSc in chemistry in 1970 from Imperial College London and then moved to Cambridge to carry out re-search towards a PhD with Lord Lewis and Brian Johnson.After a year as a postdoctoral assistant at Princeton University with Jack Norton, he returned to Cam-bridge holding an ICI and then a Royal Society Pickering Re-search Fellowship. He moved to the University of Southampton in 1976, and was appointed to the Chair of Inorganic Chemistry in 1990. similar combinations of spectroscopic techniques can be used to investigate homogeneous catalysts. 2 Surface organometallic chemistry (SOMC) 2.1 Surface organometallic chemistry on high surface area oxide surfaces The parallels between the chemistry of metals on oxide surfaces and in solution have been developed by many groups, with those led by Basset,2 Gates,3 Ichikawa,4 Iwasawa,s Marks,6 Ozin,7 Schwartz,g Ugo and Psaro9 and Yermokov'o having been the most prominent.In many instances the chemistry on the oxide surface can be understood using organometallic concepts. An oxide surface might typically provide Bronsted or Lewis base (02-), Bronsted acid (-OH) and Lewis acid (M"+) sites. For example, the labile ether ligand in [RuC12(CO),(thf)] (thf = tetrahydrofuran) can be understood to undergo substitu- tion by a surface silanol of a highly hydroxylated silica surface acting as a Lewis base in this 18-electron Ru" centre (Fig. l).ll A more complicated example is found from the reaction of [OsH2(CO),] with the more basic oxide MgO, which has been dehydroxylated at high temperatures (800 "C).The 0s" hydride is deprotonated by the strong Bronsted basic oxide ligands to form the 18-electron [OsOH(C0)4]- anion.12 There is a low frequency v(C0) absorption in the IR spectrum of this material typical of those caused by a Lewis acid interacting with the carbonyl oxygen (Fig.2). Under these activation conditions, surface magnesium centres are formed which can fulfil that role. Accordingly, this band is lost on exposure to thf vapour, which preferentially complexes with the cation, so forming a local surface ion pair. 0r' Fig. 1Proposed reaction product from [RuC12(CO),(thf)] and silica Taking a more difficult example, the grafting of [Rh(y3- C3H5),] onto silica can be considered to include the electroph- ilic cleavage of a Rh-ally1 bond by a silanol group, leading to the evolution of propene.13 The surface can then furnish a Lewis base (siloxide) site to coordinate the metal.However, this by itself would provide a 16-electron coordination sphere, the four- electron y3-allyl anion being displaced by a two-electron siloxide (assuming little n bonding from the siloxide). An Chemical Society Reviews, 1997 11 l--1-1900crn Fig. 2 Proposed surface species from the interaction of OsH2(C0)4 with MgO (activated at 800 "C) (left) and that on subsequent exposure to thfl2 alternative structure would involve the interaction of a second oxygen, probably involving a longer M-0 bond length from a neutral surface site than that typical of that to an anion Lewis base site.However, observing these is not easy. Mass balance and IR spectroscopic studies provide the surface stoichiometry, and evidence of the q3-allyl group. We have attempted to locate these distances by using Rh K-edge EXAFS (extended X-ray absorption fine structure). l4 Analysis of this data, however, is consistent with either of these structural proposals since in the presence of the six carbon atoms it is difficult to assess the coordination number of minor light atom shells with any degree of certainty. identified at a distance typical of a zirconium(1v)-siloxide group. The zirconium atom, as an eight-electron centre, is highly electron deficient, and this is probably the basis of its high catalytic activity. An additional back-scattering compo- nent was also evident, and this suggested that the unsaturation is partially alleviated by a weaker Zr-0 interaction (Fig.4). One unit which occurs very frequently in oxide-supported rhodium chemistry is the gem-dicarbonyl, Rh(C0)2. This was identified very early in the use of IR spectroscopy in conjunction with CO as a chemisorption probe. Its nature was rather contentious, with differing techniques suggesting the rhodium atoms were either isolated (by IR) or on the fringes of two-dimensional rafts (by TEM). This was settled in favour of the former by elegant Rh EXAFS studies by Koningsberger and Prins, which enabled them to probe the metal structure under similar conditions to those of the chemisorption experiments.16 Not only did they demonstrate that the ancillary ligands were solely oxygen, at distances typical for a RhI-0 bond, they showed that these centres were formed from the corrosive chemisorption of metal particles. Hence, the use of CO Fig.3 Proposed surface species from the reaction of [R~(Y~-C~H~)~] chemisorption to measure rhodium surface area with a pre- with sumed surface Rh :CO stoichiometry of 1 :1 was flawed.silica More promising cases for identifying metal-surface interac- tions will be provided by centres with lower ancillary ligand coordination spheres. One such centre is the silica supported zirconium hydride formed after the hydrogenation of [(SIL- O)Zr(CH2CMe3)3].This hydride, which catalyses the cleavage of the C-H and C-C bonds of alkanes, has been characterised by IR, NMR and EXAFS measurements.l5 Three Zr-0 bonds were 2.!t ' 1.945 Fig. 4 Proposed structure for a silica supported zirconium hydride catalyst for C-C and C-H activation 12 Chemical Society Reviews, 1997 Interestingly, thermolysis of these dicarbonyl units reformed metal particles. These Rh(C0)2 units have been formed by many groups from molecular precursors, e.g. [Rh(~-Cl)(C0)~1~and [Rh4(y-CO)3(CO)9] or by reaction of other organometallic centres with CO { e.g. [Rh(q3-C3H5)2(O-SIL)].The precursors can either be } introduced from solution or by vapour phase deposition (MOCVD). This latter process can be more readily adapted to ultra-high vacuum conditions of the type required by surface science experiments.That opens up the possibility of removing the vagueness implicit in all of the figures above about the oxide binding site since single-cry stal supports may be employed. 2.2 A surface organometallic chemistry approach to heterogeneous catalysts The aim of the approach, derived in conjunction with Professor Hayden in our Department, has been to establish a fundamental understanding of the chemistry associated with oxide-supported transition metal chemistry by using surface science techniques to approach the structural detail now commonplace in molecular organometallic chemistry. This is outlined in Fig. 5. Vapour phase deposition can be used on to both high-area and single- crystal oxide surfaces and monitored by a library of techniques to follow the chemistry occurring during the interaction of the metal with the oxide and its subsequent reactivity and upon exposure to catalyst substrates, promoters and poisons.Some of the techniques can only readily be applied to one regime or the other, but other linking techniques are required for cross-referencing. The first extended study with this approach has been on the reaction of [Rh(p-Cl)(C0)2]2 with titanium dioxide. As might be expected, the Rh(C0)2 units can be formed from MOCVD onto high area titanias. The observation of the symmetric and antisymmetric v(C0) IR bands is not diagnostic. However, by using C160/Ci80 mixtures, the six bands from the three possible isotopomers have been identified.14 Analysis of the EXAFS data is consistent with the rhodium centres being like that in 1.A surface rhodium dicarbonyl has also been formed from [Rh(r3-C3H5)(CO)2], showing that the chlonne is not essential. co CI-Rh-CO I0 1 Thermolysis of 1 under mild conditions appears to maintain the Rh-C1 bonds, but after heating to 525 K the EXAFS data indicated all the detectable rhodium was in large, ordered fcc particles. However, in the chlonde-free system, the rhodium particles appeared to be extremely small (CNRh-Rhca. 2 and CNRh0 ca. 0.9) and could be readily disrupted by exposure to c0.14 To try to establish the nature of the surface sites adopted by the rhodium on to titania, deposition on to a single-crystal plane of rutile was attempted. The (1 10) plane is one of the best studied and is the most stable low-index plane of rutile (Fig.6).'7 This can be prepared as an ordered, stoichiometric surface. Fig. 6 Structure of the (1 10) surface of rutile Small circles are Ti, and the cross-hatched shading of the oxygen atoms form the top-most layer Deposition of [Rh(p-C1)(C0)2]2 onto this surface at room temperature generates a chemisorbed species shown by XPS to have very similar Rh binding energy to the precursor, and hence is likely to be rhodium(r).l8 Identifying it as an Rh(CO);! centre was confirmed by reflection-absorption IR spectroscopy (RAIRS) recorded with an incident angle of 83" and detecting radiation polarised perpendicular to the crystal surface.Under this arrangement the symmetric v(C0) band appeared as an apparent emission, while the antisymmetric band was a much weaker absorption. This effect will be manifest at near-grazing incidence at a semiconductor surface if these bands are polarised perpendicular and parallel to the surface, respectively. Two possible orientations of the Rh(CO):! are presented in Fig. 7. In the first of these, (a), the polarisations of the two modes are as observed, while in the second both modes would be polarised at approximately 45" to the surface. Hence the former model is preferred. A remaining difficulty is to establish the fate of the chlorine. XPS shows the rhodium attains a binding energy more like that of surface-bound chlorine after 3Methodolgy for the chemistry of metals on oxides Single crystal surfaces MOCVD or MVD Techniques [ Mass spectrometry (Metal Chemisorption r Mass spectrometry 7 RAIRS LEED SEXAFS Metal reactivity F)( Adsorption on the metal ) Transmission IR EXAFS STM fl TEM o-adsorption and catalysis XPS fl NMR Promoter effects Fig.5 Methodology for studying the chemistry of transition metals on oxide surfaces Chemical Society Reviews, 1997 13 Fig. 7Surface models for Rh(C0)2 on rutile(1 lo). Model (a) is consistent with the IR observations. the initial chemisorption, and distinct from that of the Rh-C1-Rh site. It is not yet clear whether the chlorine is still coordinated to the rhodium or whether a second oxide substitutes it.It is intended that Rh K-edge SEXAFS measurements made on a UHV chamber presently being commissioned will solve this problem. Unfortunately, there is insufficient order in the rhodium carbonyl overlayer to form a LEED pattern. Thermolysis (800 K) of this species also seems to form large rhodium particles. Under a narrow range of milder conditions the rhodium can be completely decarbonylated but the Rh(CO)2 unit can be partially regenerated. The metal particles which are formed absorb CO in an atypicaI way for rhodium metal. For comparison, MVD of rhodium was used to form overlayers. These adsorbed CO in a manner very similar to a Rh(ll1) surface, although the saturation coverages were reduced to ca 0.33 and only the terminal (q) CO site could be identified {a p-CO site is also observed on Rh( 1 1 1) } .The frequency of the IR band for this site increased with coverage, as is normal. However, the Rh sites formed by thermolysis (resulting from either MOCVD or MVD initially) required about 106-107 larger exposure of CO to allow observation of the v(C0) bands in the IR, and then only displayed the frequency for saturation coverage. This implies a rate-determining step before the adsorption of CO on the metal surface. This suppressed CO adsorption behaviour is reminiscent of the SMSI effect (strong metal-to-surface interaction). Various models for this have been proposed, including electronic effects for reduced titanium centres and migration of the oxide surface over the metal.Our evidence confirms the presence of reduced titanium, but also suggests that islands of rhodium sites become available after reaction with CO and the unprotected metal can then rapidly adsorb CO to achieve saturation.'* Migration of oxygen from titanium dioxide over the rhodium would be consistent with this. It is our intention to characterise the particle growth process in much more detail by in situ SEXAFS and STM studies. In one system, the reaction between [Rh(@-C3H&] and Ti02, some differences in behaviour have been observed between experiments carried out on both oxide surface types. In both cases, there is evidence for the reaction of surface hydroxyl groups and the rhodium-ally1 bonds, forming [(Ti-O)Rh( q3- C3H5)2]; this was shown on titania by difference DRIFTS spectra and by O(1s) XPS on hydroxylated rutile (110).Thermolysis of the single-crystal sample under UHV was not clean, but led to decreasing binding energies for both the Rh(3d) and C(1s) XPS peaks, indicative of carbonaceous metal formation.14 However, related in situ experiments using a DRIFTS cell allowed the formation of the Rh(CO):! unit again. Presumably, the carbonyls emanate from oxidation of the ally1 ligands. As yet, we cannot say whether this is due to the higher base pressure in the DRIFTS cell or due to more reactive surface sites in the anatase-rich titania. We aim to distinguish between these using a transmission IR UHV for powdered oxides developed from a design reported by Yates;I9 this will radically reduce the pressure gap between these types of experiments.Metal vapour deposition onto rutile( 110) has also been extended to palladium.*O An interesting feature of this work is that, on annealing, CO adsorption indicates that the predomi- nant metal plane is Pd( 1 1 1). At intermediate metal loadings, the LEED pattern from the surface shows reflections due the hexagonal structure of Pd(ll1) aligned with that of the underlying rectangular net of rutile( 110). Consistent with this, STM images show that rectangular Pd clusters are formed which are mutuaIly aligned (and also with a very narrow size distribution). Clearly these two layers are not structurally well matched, and it may be that the interfacial strain limits the potential for metal particle growth.As yet, these studies have shown some insight into the early stages of the interaction of organometallics with oxide surfaces and begun to show some of their subsequent chemistry. The use of X-ray absorption spectroscopy (XAS) has been an important component in these studies. 3 Spectroscopic characterisation of homogeneoustransition metal catalysts 3.1 Scanning XAS studies of homogeneous catalysts However, the attributes of XAS that make it applicable to disordered heterogeneous catalysts, namely its ability to probe short-range order with element specificity, also make it viable for improving the characterisation of homogeneous catalysts.21 While NMR and IR spectroscopy can achieve higher resolution in solution and thus be more definitive than in heterogeneous catalysts, there are functional groups which are difficult to identify directly by these techniques alone (e.g.M-X bonds when X = C1, Br and I). Cells can readily be constructed which, by substitution of window material, can be used for IR, UV-VIS and XAS spectroscopies. For example, the well-known rhodium catalysed methanol carbonylation catalyst22 can be studied by IR and Rh K-edge XAS in this way.23 The principal rhodium species in the catalyst system, [Rh12(C0)2]- 2 can readily be identified and the bond- lengths established in solution (Fig. 8). It is known that the initial steps in the reaction are the oxidative addition of CH31 and then methyl migration.The resulting acetyl complex has been identified by X-ray diffraction as IRh(COCH3)-(CO)13]22-; the dimer allows the rhodium centres to attain 18 electrons through iodine bridges. In a coordinating solvent, such as methanol, these bridges may be cleaved to a solvated monomer, which may be more important in the catalytic cycle. Rapid-scanning EXAFS studies showed that the dimer can be identified in thf solution at -20 OC, but that it does indeed cleave at 0 "C. The bond lengths obtained on the monomeric acetyl complexes 3 and 4 are fully consistent with the 14 Chemical Society Reviews, 1997 -1-Me1 '\ /co MeOH 2.65 .,Rh ,/1.84 I co /3 I 2.82 2 Me \c I 2.81 4 Fig.8 Interatomic distances established by Rh K-edge EXAFS on the methanol carbonylation catalyst system stereochemistries shown. The acetyl groups exert a strong trans-influence lengthening the Rh-I bond by ca. 0.2 A, and therefore probably labilising it. Mostly though we have studied the activation of transition metals by main-group metal alkyls. One example of this was the activation of [Cu(acac)2] by ZnEt2 (1 :1),24 which forms an ethanol synthesis catalyst.25 The adjacency of these two metals in the periodic table allows the fates of both to be followed readily by XAS. The copper was found to form locally ordered fcc colloidal particles. Estimates of the particle sizes based on EXAFS coordination numbers alone have substantial error bars.However, for a 1 mM solution in benzene, the particles were sufficiently small that the first coordination number is very sensitive to particle size, estimated as ca. 12 A. The zinc appears to form molecular clusters and so the two metals remain separate in the products. Among the most utilised systems of this nature (Ziegler- Natta catalysts apart) are those derived from nickel providing a series of catalysts for catenating alkenes.26 A low temperature solution cell XAS was developed to study these highly reactive solution.27 Activation of [Ni(-@-C3H5>Br(PPh3)] by AlEt, was followed using both the Ni and Br K-edges (Fig. 9). This showed that the Br was predominantly transferred from the nickel to the aluminium (in toluene solution) in the presence of propene, with 6 being a putative structure.Interaction of 5 with AlEt3 at -60 "C was observable in the absence of the alkene, analysis suggesting a Ni-Br-A1 unit was present (Ni-Br 2.31; Ni-Al 3.20 A), as had been previously proposed for the activation process.26 A highly active propene oligomerisation catalyst is formed from the activation of [NiC12(PEt3)2] by A12Me3A13 or A12Et6.26 The EXAFS patterns obtained for these systems indicate a g>Nis Ni-C 2.08, Ni..C 2.94 nu -Brl -40"c Ni-C 1.99 ~ Ki/Br Ni- C2.03 , Ni- P2.23 PPh Ni -Br 2.28 AIEt,, -40°C Ni -C 2.01 Ni-C2.02 HR Ni -P 2.22 'PPh3 6 Fig. 9 Results of EXAFS studies of the activation process from [Ni(q4-C8H for alkene oligomerisation catalysts in toluene solution transmetalation of the alkyl group from aluminium to nickel.28 The loss of the halide from nickel and its transfer to aluminium is confirmed also for [NiBr2(PEt3)2] by monitoring the bromine K-edge EXAFS data.29 The EXAFS data at the nickel edge is more complex than that of a simple single coordination shell, and could be fitted satisfactorily by the model shown as 7.28 This, however, only represents the mean of a family of related structures although it does indicate an adduct of the aluminium reagent with the nickel complex that is part of the transmetala- tion process. The oligomerisation catalysis may be terminated and the products isolated by solvolysis with isopropyl alcohol.Under those conditions the nickel reverts cleanly to [Nix2- (PEt3)21.TEt3 7 These experiments afforded information about the activation processes of these nickel-catalysed reactions, but did not give any insight into the catalytic process. An interesting candidate for this was provided by the mixture of [Ni(cod)2] (cod = cycloocta-l,5-diene) and the bifunctional ligand PPh2CH2C(CF3)20H. Not only is this an allylaluminium-free catalyst system, it also was the first instance of direct observation of a nickel hydride by lH NMR.3O This was taken as an indication that the 14-electron species 8 was the active component. This complex requires the oxidative addition of the hydroxyl group; without the electron-withdrawing CF3 groups this is extremely difficult.H-Ni ' \ 0 cF, CF3 8 However, the multiplicity of the hydride resonance (apparent triplet) is not consistent with the structure 8. It was found that the intensity of this resonance was maximised with a Ni :ligand ratio of 1 :2, and the structure 9 (Fig. 10) was established by a combination of 31P NMR and Ni K-edge EXAFS.31 Essentially, this is a version of the highly unsaturated transient 8 trapped by the second, monodentate phosphine. On exposure to ethene or propene alkene insertion reactions occur at the nickel hydride bond with the remainder of the coordination sphere intact in the predominant species. On warming, p-hydride elimination regenerates the hydride 9. In this example we have observed the apparent sequences of an alkene oligomerisation process: alkene insertion into Ni-H and then Ni-C bonds, followed by the p-hydride elimination to remove a higher alkene from the coordination sphere.However, the reaction rate is maximised not at the Ni :L ratio of 1 :2 but at an equimolar ratio. This is consistent with phosphine loss from 9 being kinetically important in the oligomerisation process. So it is quite possible that a three-coordinate species like 8 is indeed key to the reaction mechanism, and that our experiments have probed the resting form of the catalyst. The structural motif of a unicharged bidentate ligand is also provided by (3-diketonates, and for some time it has been known that activation of [Ni(a~ac)~]~ (acac = pentane-2,4-dionato) by Chemical Society Reviews, 1997 15 I'y2H\ Ni-0 1.91, Ni- P2.16 Ni \ %cF3 Ni ..C 2.84 P 0.Ph2 CF, F,C CF-"YF,C CF, Ph2 cF, Ni -Fig. 10 Results of EXAFS and NMR studies of the activation process from [Ni(y4-CsH12)2] and PPh2CH2C(CF3)20H for alkene oligomerisation catalysis AlEt,(OEt) affords a hex- 1 -ene dimerisation catalyst in toluene s0lution.3~ Interestingly, this system formed a temperature dependent equilibrium, with the green, paramagnetic precursor dominating at low temperatures (e.g.-70 "C). The nature of the active yellow-brown form was not established. By monitoring this reaction at various temperatures by Ni K-edge EXAFS, we gained evidence for a structure consistent with that shown as 11 in Fig.11.33 The alkene could be readily displaced by a phosphine to afford complex 12, which has a similar coordina- tion sphere to 10 in the system derived from the bifunctional phosphine. It is therefore plausible that a derivative of 11 may well play a key role in that catalytic cycle also. So these results lead to a generalised catalytic cycle for alkene dimerisation as shown in Fig. 12. Extensions of this with repeated alkene insertions into Ni-C bonds will lead to oligomer and polymers. This scheme has close parallels with the cationic nickel- and palladium-diazabutadiene systems recently reported by Brookhart et. al.34 and the intermediates follow the results of density functional calculations by Ziegler and coworkers.35 Versions of three of the species in this scheme, 13, 14 and 15 have been observed by EXAFS.Two of these 13 and 14 are stabilised forms of the catalyst precursor or an intermediate in the cycle and are therefore external to the cycle. Our proposal for a complex comprising [Ni(R)(alkene)(acac)] 11 corresponds to species 15 within the catalytic cycle, and is closely related to some of the catalyst precursors with diazabutadienes as auxiliary liga11ds.3~ However, the DFT calculations of Ziegler suggest that the agostic hydrogen interactions in 17 outweigh the n-bonding stabilisation in the nickel-hydride-ethene complex, and also the y-H interaction in 16 will render it more stable than 15 by over 40 kJ mol-1.35 More stable again is predicted to be the (3-agostic species 18, by an additional 40 kJ mol-1 and might therefore be expected to predominate in solution.In 18, the two Ni-C distances were 5 oc [Ni(acac), 1, -+ -AIEtz (OEt) -70 OC + hex-1 -ene Fig. 11 Results of EXAFS studies of the activation process from [Ni(acac)2]3 and AlEt,(OEt) for hexane dimerisation catalysis 16 Chemical Society Reviews, 1997 C/O 2.00, Ni -P 2.18 Ni.. C 2.86 calculated as Nix, = 1.86 and Ni+ as 2.06 A, while the EXAFS data for the species assigned as 11 refined as a shell of 3.1(4) carbon atoms with Ni-C = 2.025(4) A. So differentiation between these structures is dependent upon the estimation of the coordination numbers. While this is not the most precise aspect of EXAFS analysis, it must be noted that a structure like that of 18 requires an error of 30.So the initial proposal of the alkyl- alkene complex 11 provides a better, but not definitive, account for experimental observations. Therefore trying to reconcile this with the results of the DFT calculations is difficult, but we must note the longer alkyl groups in both the P-diketonate and hydrocarbon ligands used in the experiments. However, the results of these DFT calculations were used to suggest that the Ni-H NMR resonance observed by Keim et aL30was due to an intermediate of the type [NiH(alkene)2(E--E)]35 which is inconsistent with our EXAFS and NMR res~lts.3~ 18 3.2 Energy dispersive EXAFS (EDE) Even in a rapid scanning mode, the time required to record an analysable length of EXAFS data (500 eV) is of the order of minutes, while, for a dilute sample, several hours might be taken to obtain optimised data.So such experiments can only be used to investigate the structures of the dominant species stable for those time periods. Clearly, to be able to observe some of the intermediates in a catalytic reaction, these must be generated in high proportion and identified prior to their decay. An 3 Ni -C 2.03 2 Ni- 0 1.92 2 Ni..C 2.90 R' 11 lPEt3/ 3 Ni -C/O 1.89 1 Ni-P 2.11 Et3P 2 Ni..C 2.82 12 L E 13 E 16 15 Fig. 12Generalised cycle for alkene dimerisation by nickel catalysts with a bidentate auxiliary ligand alternative method of acquiring X-ray absorption spectra is to expose the sample to the spectral range and to disperse this across a multi-element detector.This can be achieved by taking the white radiation from a dipole or wiggler magnet on a synchrotron source (as at the SRS at Daresbury Laboratory) or by tuning a harmonic of an undulator to cover the spectral range. The band spread is then obtained by a curved crystal monochromator, which can be in either a Bragg (reflection) or Laue (transmission) geometry (Fig. 13). A slightly different incident angle is experienced at different points on the monochromator, and the spread of wavelengths so formed is focused onto the sample whence it defocuses onto the detector, typically either a photodiode array (PDA) or a CCD camera. Photodiode array Fig. 13Schematic layout of anenergy dispersive EXAFS (EDE)experiment with a Bragg-geometry monochromator.(The bend and Bragg angle are exaggerated to emphasise the ray pathways of different X-ray energies). The experiment gains temporally by removing the need to move any part of the optical system during the data acquisition and by the synchronous acquisition of all data points (the multiplex advantage). The difficulties arise from the needs to attain very sensitive, high output linearity X-ray stable detectors and a high optical purity and stability. The geometry constrains the detection to a transmission mode, and so the technique of choice for very dilute samples, fluorescence, cannot be employed. Recent advances in these technologies indicated that it should be possible to acquire spectra in times of the order of seconds, and a likely goal of milliseconds was feasible.So experiments were carried with modified versions of the variable temperature cells described previ~usly,~~ fitted with a pair of syringe drivers to allow continuous flow or stopped flow. Depending on the volume of the cell employed, perfect plug flow would give residence times of 1-10 s, although the real mixing times were somewhat longer.3' Very recently an ambient temperature cell with a mixing time of 5 ms has also been employed.29 An example of EXAFS data from one of these experiments is shown in Fig. 14.33 The total acquisition time for this spectrum was 2 s on a solution 70 mM in nickel. This spectrum, of the reaction of [Ni(a~ac)~]~, hex-1-ene and AlEt,(OEt), is inter- mediate between that of [Ni(acac),]3 and that of the activated solution, assigned to complex 11.The feature evident in the Fourier transform near 3 %, is best fitted as the Ni.-.Ni distances in a retained trimer. It is suggested that the trimer undergoes a transmetalation of the alkyl group from the aluminium reagent at the terminal nickel centres prior to dissociation into the monomeric units of the activated solution. The behaviour of the 1 2 4 6 a 10 R (A) Fig. 14 Ni K-edge EXAFS analysis of the Ni(a~ac)~,A1Et2(0Et) Ni :A1 = 1 :2) and hex-1-ene (Ni :hexene = 1:20) solution after 4.75 min at 0 "C. Average of 100 scans of 20 ms. (a) EXAFS and (b)Fourier transform with (-) experimental and (---) calculated curves.Chemical Society Reviews, 1997 17 UV-VIS spectra of such solutions also suggests that there is a short-lived species. These experiments have demonstrated the viability of EDE for probing the structures of transients during organometallic reactions in the liquid phase. As is evident from section 2.2 of this review, similar experiments might be carried out on supported complexes. Fig. 15 shows a stacked plot of the results of monitoring the reaction of Rh(C0)dtitania with hydrogen by Rh K-edge EDE. l4 Such an experiment is not currently possible at the SRS. The penetrating nature of the X-radiation at these energies (ca. 24 keV) means that there is a spread of effective X-ray source positions through the crystal for a given energy which then diffuses over several elements of the detector array, so reducing the spectral resolution very markedly.This can be circumvented by using a thin single-crystal wafer as the monochromator set up in a transmission (Laue) geometry (carried out using a 100 p thick Si(ll1) crystal on ID24 of the ESRF}. Energy dispersive Rh K-edge EXAFS (EDE) experiments were performed on the thermolysis and hydrogenation of RhI(CO)fliO;? samples with ca. 3 mass% rhodium. EXAFS data for up to 10 A-l could be acquired with typically 250 X 15 ms scans (ca. 6 s acquisition time). These have yet to receive detailed analysis, but the following observations are apparent from qualitative treatments on stacked plots of raw data (e.g.Fig. 15). When Rh1(C0)2/Ti02 was heated in vacuo mbar) as the sample temperature was ramped from ambient temperature to 300 "C, it was apparent that there was a smooth transformation of Rh(CO)2 into metallic rhodium above 220 "C, with no identifiable intermediate. Alternatively, when the sample was heated under a flow of H2 within the vacuum system as the temperature was ramped, reduction by H2 to rhodium particles occurred most rapidly in a period of 1 minute as the temperature passed through the 80-90 "C range. In combination with isothermal experiments carried out near this temperature region, these results suggest that the reduction may be autocatalytic. This might arise if the dissociative chemisorption of hydrogen, possibly the rate-determining step in the particle formation, is more rapid on small rhodium particles than at the Rh(C0)2 centres.4 Concluding comments The two main aims of this research have been to improve the characterisation of homogeneous transition metal catalysts and Fig. 15 Stacked plot of Rh K-edge EDE of the reaction of Rh(C0)Jtitania with hydrogen. Sample heated from room temperature to 100 "C and then maintained at that temperature. 18 Chemical Society Reviews, 1997 to raise the plane of understanding of oxide-supported metal catalysts to that attainable in solution. These have so far been met imperfectly but further progress is in prospect. The current developments in X-ray absorption spectroscopy indicate that in situ studies of intermediates catalysed reactions are viable, once these have been generated by stopped flow (liquid phase) or pulsed-flow (gas-solid reactors).In the next year or two, structural information of species stable only on a millisecond timescale should be achievable. A more distant horizon is provided by photochemically generated transients, requiring sub ps data acquisition. But the ability to establish structures in disordered phases of such primary species is enticing. Poten- tially with stable, third generation synchrotron sources in a single bunch mode it should be possible to reconstitute analysable EXAFS data from a set on time-slices obtained at different X-ray energies. Deriving molecular-level descriptions of the chemistry of oxide-supported metals is still proving to be very challenging. However, we have shown that combining studies on powdered and single crystal oxide surfaces can offer considerable insight the chemistry underlying heterogeneous catalysis.Further in situ techniques-STM and SEXAFS-for studying the struc- tures on single-crystal surfaces are currently being developed and we have every prospect of visualising this chemistry with greater precision in the coming months. 5 Acknowledgements I wish to thank all my coworkers cited in the references below for making this research so enjoyable. I am especially grateful to Norman Binsted, Judith Corker, Brian Hayden and Tony Masters (University of Sydney) for making most of this all possible. The debt we owe to the staff of the Daresbury Laboratory and ESRF is a great one, especially the station scientists most involved with these experiments-Bob Bilsbor-row, Gerd van Dorrsen, Andy Dent and Michael Hagelstein. The financial support of the SERC, the EPSRC, the University of Southampton and the BP group is also very gratefully acknowledged.6 References 1 J. Evans, Chem. Soc. Rev., 1981,10, 181. 2 J. M. Basset, J. P. Candy, A. Choplin, B. Didillon, F. Quignard and A. Theolier, in Perspectives in Catalysis, ed. J. M. Thomas and K. I. Zamaraev, Blackwell, Oxford, 1992, p. 125. 3 B. C. Gates, in Metal Clusters, ed. M. Moskovits, Wiley, New York, 1986, p. 283. 4 M. Ichikawa, Adv. Catal., 1992, 38, 283. 5 Y. Iwasawa, Adv.Catal., 1987, 35, 187. 6 T. J. Marks,Acc. Chem. Res., 1992, 25, 57. 7 G. Ozin, S. Ozkar and R. A. Prokopowicz, Acc. Chem. Res., 1992,25, 553. 8 J. Schwartz, Acc. Chem. Res., 1985, 18, 302. 9 R. Psaro and R. Ugo, in Metal Clusters in Catalysis, ed. B. C. Gates, L. Guczi and H. Knozinger, Elsevier, Amsterdam, 1987, p. 427. 10 Yu. I. Yermakov and V. Zakharov, Adv. Catal., 1975,24, 173. 11 J. J. Burmeister I11 and B. E. Hanson, Znorg. Chem., 1990, 29,4055. 12 H. H. Lamb and B. C. Gates, J.Am. Chem. Soc., 1986,108, 81. 13 M. D. Ward, T. V. Harris and J. Schwartz, J. Chem. SOC., Chem. Commun., 1980, 357. 14 A. J. Dent, J. Evans, M. Hagelstein, B. E. Hayden, J. F. W. Mosselmans, A. Murray, C. J. Rudkin and N. A. Williams, unpublished results.15 J. M. Corker, F. Lefebvre, C. LCcuyer, V. Dufaud, F. Quignard, A. Choplin, J. Evans and J.-M. Basset, Science, 1996, 271, 966. 16 H. F. J. van't Blink, J. B. A. C. van Zon, T. Huizinga, D. C. Koningsberger and R. Prins, J.Am. Chem. Soc., 1985, 107,5742. 17 The Su$ace Science ofMetal Oxides, V. E. Heinrich and P. A. Cox, Cambridge University Press, Cambridge, 1994. 18 J. Evans, B. E. Hayden, J. F. W. Mosselmans and A. Murray, J.Am. Chem. SOC., 1992, 114, 6912; Su$. Sci.,1994, 301, 61. 19 R. R. Cavanagh and J. T. Yates, Jr., J. Chem. Phys., 1981,75, 1551. 20 J. Evans, B. E. Hayden and G. Lu, Sutf Sci., 1996,360, 61. 21 X-ray Absorption: Principles, Applications, Techniques of EXAFS, SEXAFS and XANES, ed. D. C. Koningsberger and R.Prins, Wiley, New York, 1988. 22 D. Forster, Adv. Organomet. Chem., 1979, 17, 255. 23 N. A. Cruise and J. Evans, J. Chem. SOC., Dalton Trans., 1995, 3089. 24 J. M. Corker and J. Evans, J. Chem. SOC., Chem. Commun., 1994, 1027. 25 M. Simon, A. Mortreuz and F. Petit, J. Chem. SOC., Chem. Commun., 1988, 1445. 26 The Organic Chemistry of Nickel, P. W. Jolly and G. Wilke, Academic Press, New York, 1975,vol. 2; W. Keim, Angew. Chem., Int. Ed. Engl., 1990, 29, 235; G. Wilke, Angew. Chem., In?. Ed. Engl., 1988, 27, 206. 27 P. Andrews, J. M. Corker, J. Evans and M. Webster, J. Chem. Soc., Dalton Trans., 1994, 1337. 28 J. M. Corker and J. Evans, J. Chem. SOC., Chem. Commun., 1991, 1104. 29 J. M. Corker, A. J. Dent, J. Evans, M. Hagelstein and V. L. Kambhampati, J. Physique (C), in the press. 30 U. Muller, W. Keim, C. Kruger and P. Betz, Angew. Chem., Int. Ed. Engl., 1989,28, 1011. 31 P. Andrews and J. Evans, J. Chem. SOC., Chem. Commun., 1993, 1246. 32 J. R. Jones and T. J. Symes, J. Chem. SOC. C, 1971, 1124. 33 D. Bogg, M. Conyngham, J. M. Corker, A. J. Dent, J. Evans, R. C. Farrow, V. L. Kambhampati, A. F. Masters, D. Niles McLeod and C. A. Ramsdale, Chem. Commun., 1996,647. 34 L. K. Johnson, C. M. Killian and M. Brookhart, J. Am. Chem. SOC., 1995,117,6414. 35 L. Fan, A. Krzywicki, A. Somogyvari and T. Ziegler, Inorg. Chem., 1994,33,5287; 1996,35,4003. Received, 2nd September 1996 Accepted 27th September 1996 Chemical Society Reviews, 1997 19

ISSN:0306-0012    

DOI:10.1039/CS9972600011

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Electronic spectroscopy of carbon chains L Carbon chains are of interest in astrophysics and in terrestrial processes, such as fullerene formation. The electronic spectra of a variety of such chains have now been identified in the laboratory using a technique which enables absorption spectra of mass-selected species to be measured in neon matrices. The understanding of their transitions and the trends apparent for these homologous series point out which type and size of carbon chains are relevant for consideration as carriers of the diffuse interstellar bands. 1 Introduction Spectroscopic characteristics of carbon species are desirable not only as basic knowledge, but are necessary in the interpretation of astronomical observations. The availability of laboratory spectra led in the past to the identification of the simple carbon molecules C2and C3 in comets via their electronic transitions as well as to long polycyanoacetylene chains in dark clouds by microwave spectroscopy.' Also in terrestrial chemical proc- esses, such as the formation of fullerenes, carbon chains are postulated as precursors.2 Thus, an understanding of their spectroscopic properties is prerequisite to the study of their reaction mechanisms in the laboratory.This goal to observe and assign the spectra of carbon chains, and their isoelectronic species involving nitrogen and hydrogen, has only recently been realized. It has come about as result of the development of a technique which enables the electronic absorption spectra of mass-selected species in neon matrices to be measured.3 Prior to this, the electronic transitions of only C2,C3, C2- and C2+ in the gas phase had been On the other hand, rotationally resolved infrared spectra of the carbon chains C, in the range n = 3-13 have been obtained in recent years.5 Several studies of carbon vapour condensed in rare gas matrices have John P.Maier received a BSc in chemistry at Nottingham University, and a DPhil in physical chemistry from Oxford University in 1972 with D. W. Turner. He then moved to the Institute of Physical Chemistry, University of Basel, as a Royal Society Postdoctoral Fellow with E. Heilbronner, He remained there as a member of the academic staf and in I992 was appointed to the chair ofphysical chemistry at Basel University.He was awarded the Werner prize of the Swiss Chemical Society (1979), the Marlow medal of the Royal Society of Chemistry (1990),the Chemistry prize of the Gottingen Academy, Germany (1986)and the Latsis prize of the Swiss National Science Founda- tion (I 987). His research inter- ests lie in the development and application of methods for the spectroscopic characterization of ions, ionic clusters and radicals. been reported with some suggested assignments to specific species.6.7 This has been plagued with uncertainty due to the concomitant presence of a number of species. We could circumvent this handicap by conducting such measurements on mass-selected species and this has resulted in the identification of the characteristic x--JIelectronic transitions of a variety of carbon chains, neutral and ionic.These observations allow the relevance of specific species to astrophysical measurements to be discussed and indicate the directions to be pursued in trying to identify the molecules likely to be responsible for the diffuse interstellar bands.8 These are spectral features due to starlight absorption by molecules present in interstellar space, but their identification has remained a mystery for over half a century. It is one of the aims of spectroscopic studies on the carbon chains to establish whether these could be the carriers responsible. Because the electronic transitions in the neon matrix have been observed, measurement of the spectra in the gas phase has become a realistic proposition.2 Approach The difficulties in trying to measure the spectra of transient species in the gas-phase, the ultimate goal, are threefold -their generation in sufficient concentration, availability of a sensitive approach to measure their spectrum and knowledge of the energy region of the transitions are required. We have now developed a technique which combines the virtures of mass- and matrix isolation-spectroscopies.3 Mass-selection alleviates the need to identify the absorbing species, whereas the neon matrix enables sufficient concentrations of ions and radicals to be attained so that direct absorption measurements can be made. The philosophy is then to identify the electronic transitions of a chosen species in the inert neon environment, and with this knowledge in hand to attempt a gas-phase characterization.The studies of the carbon species in the gas phase C2+9and recently C2n-n = 2,3,4,10 were only realised once the electronic transitions were identified in the neon matrix. 11 3 Experimental considerations Matrix isolation spectroscopy is a well-established technique, and neon matrices show the smallest energy shifts relative to the gas-phase.l2 An experimental advantage compared to tradi- tional matrix spectroscopy where relatively thick matrices tend to be grown on sapphire substrates, and measurements follow as transmission, is the implementation of a waveguide technique. l3 This enables matrices 150 ym thick to be grown in approx- imately two hours and the probing light is propagated through the thin side along the 2 cm length of the matrix.For this purpose the matrices are grown on copper substrates coated with rhodium, providing good reflectivity from the UV to IR. The other half of the instrument provides a mass-selected ion beam. Experience has shown that ion currents of more than 1nA are necessary for the recording of the absorption spectra. Thus, the ion source is a crucial element -hot cathode discharge and a caesium sputter source have been used.14 Electron lenses and a high transmission quadrupole mass-spectrometer steer the ion beam onto the matrix. In Fig. 1 the overall arrangement of the instrument is depicted.Chemical Society Reviews, 1997 21 Codeposition of the mass-selected ions, usually with nominal kinetic energies 50-200 eV, with excess of neon leads to matrix formation with ion densities in the 1015-16 cm-3 range. This is sufficient for the absorption spectra to be discernible. The waveguide approach is used in the 220-1000 nm region, and a reflection method using a Fourier transform instrument, though with an order of magnitude less sensitivity, covers the near IR. 4 Electronic structure considerations The lowest energy, strong electronic transitions encountered in the carbon chains involve the excitation of n electrons. The open-shell species, polyacetylene cations, HC,H+, and the isolectronic chains, C,H, C,-, have the ground state configu-ration n3 and thus X2I-I symmetry.The excited states of relevance are the ones corresponding to n-n electron promo-tion, resulting in 2ILX2I-I electronic transitions. In the case of the bare carbon chains, C,, the species are paramagnetic for n = even but not for n = odd? The former have triplet ground states, X32,-arising from the configuration Matrix Deflector Fig. 1Schematic arrangement of the instrument combining mass and matrix isolation spectroscopies. Mass-selected ions produced in a hot-cathode or caesium sputter source are codeposited with excess of neon to form a matrix at 5 K, and the absorption spectrum is measured by a waveguide technique. HCfjH+ n2.The characteristic transition has 3&--X3Xc,-symmetry, to which configurations arising from both x*-~tand ~t-nexcita-tions contribute.The ones with an odd number of carbon atoms have the electron configurationn4in the ground state and XIZ + symmetry. The n*-n excitation corresponds to the 12,+-X1Z> electronic transition. 5 Polyacetylene chains Polyacetylene cations can be readily produced in a hot cathode source with acetylene or diacetylene as precursor. It is then merely a matter of mass-selecting the appropriate HC,H+ species and codepositioning them with neon. The electronic spectrum of the cation kept under isolated conditions can subsequently be measured, This has so far been carried out for the ion chains with n = 4-16.16 The spectra of the species with an even number of carbon atoms are shown in Fig.2. The polyacetylene cations are open-shell species with 2ll ground state. The transitions observed are of 211-X211 sym-metry and shift monotonically to the red with increasing number of carbon atoms. This is evident from Fig. 3; the energy of the transition is inversely proportional to the length of the species. This trend can be easily modelled by a particle in a ID box where the n electrons are excited. Such an approach also predicts that the oscillator strength of the transition correlates linearly with the number of carbon atoms. This feature is a factor of why the spectra of the longer chains can be detected, even though the attainable current for the mass-selected ion is decreasing. These electronic transitions of the polyacetylene cations HC,H+ with n = 4, 6, 8 have in fact been detected in the gas-phase as their emission spectra.17 They are shifted to higher energies in the gas phase relative to the neon matrix by 79, 135 and 143cm-l, respectively.On the basis of these trends, and the observations in the neon environment, the region for the search of these transitions in the gas-phase for the larger species is predicted sufficiently well to make this feasible. The electronic absorption spectra of the neutral poly-acetylenes, HC,H can be obtained by codeposition of their cationic counterparts with neon, but under conditions such that neutralization is enhanced. This can be achieved by irradiation HC~*H+ 0.1 -0.07-* ' 850 1 0.051 0.00 10.0051 900 950 1000 1050 0.0 800 850 hl nm hl nm Fig.2 The *n-XTI electronic transitions of the polyacetylene cations detected as absorption spectra in neon matrices after mass-selection 22 Chemical Society Reviews, 1997 of the matrix after deposition with broadband UV radiation. specifically the transitions observed are of 3Zu--X32g-This photodetaches electrons from the anions present in the symmetry. The same trend as for the cations manifests itself -matrix which then recombine with the cations. By this means an approximate linear dependence of the wavelength of the spectroscopy on mass-selected neutral species can be carried transition on the number of carbon atoms. This is shown as one out.of the plots in Fig. 3. In Fig. 4 are shown some of the recorded absorption spectra The polyacetylenes with an even number of carbon atoms, for HC,H n = odd.l8 The electron excitation is n-n type again; HC2,H, show corresponding absorption in the UV part of the spectrum. These have been measured previously in the gas phase, for n = 2-5, using a standard absorption approach,]g and also for the ones with n up to 10 in solution.20 6 Carbon anion chains To apply the mass-selected approach to characterize the electronic transitions of the bare carbon chains and their ions, it 800 proved necessary to implement a different ion source. This is a caesium sputter source, which produces copious amounts of 700 carbon anions. Caesium cations are accelerated towards a 600 graphite rod and the resulting carbon anions are extracted.In Fig. 5 is shown the observed mass pattern; species up to C12-500 are produced with sufficient current for the measurement of the absorption spectrum to be possible. 400 Consider Cg-as an example. After the matrix is formed the I,! IIIIIIII I I 4 5 6 7 8 9 10 11 12 13 14 15 16 spectrum included in Fig. 6, with origin near 600 nm, is Number of carbon atoms 0b~erved.l~It is readily confirmed that this spectrum is of an Fig. 3 The wavelength of the origin band of the JC-JC electronic transition of anion by photobleaching experiments, and that it is a member of the polyynes shows an approximate linear dependence on the number of an homologous series, because similar spectra, but red-shifted carbon atoms in the chain by regular increments, are observed for the successively larger 0.2 0.1 0.0350 400 450 5000.3 0.2 0.1 0.0 hl nm hl nm Fig.4 Absorption spectra of the n-JCelectronic transition (3C,--X3C,-symmetry) of the HC2,+ 1Hmolecules in neon matrices. These were grown using a mass-selection of the corresponding cations and subsequent UV irradiation. 1 O-”A csc; I II I 1 20 40 60 80 100 120 140 mlz Fig. 5 Mass spectrum of the carbon anions produced using a caesium sputter source. A particular species is mass-selected and codeposited with excess of neon for the spectral measurement. The neutral chains are observed when the matrix is irradiated during or after deposition with UV light, photodetaching the electrons from the anions.Chemical Society Reviews, 1997 23 Afwu~lJl.JL. oh ' ' ' ' ' ' ' ' 400"450" "800' ' 900 1000 01600 1700 2i2 1 .,...,,dM,J. 10 550 600 8 1100 1200 1300 0 2000 2100vi,l 31,,;4, 81 0 0 700 800 8 1400 1500 2300 2400 A/nm A/nm A/nm Fig. 6 The *H-X2JJ electronic transitions of carbon anions measured in absorption in neon matrices Om2 -c4 0.1 -I Q);0.0 300a 350 400 00,0.02 ClO rl El 0.00 650 700 750 hl nm hl nm Fig. 7 The 3Xu--X3X,-absorption spectra of mass-selected carbon chains C, (n = even) in neon matrices species.ll The nature of the transition is also clear; Cg-is have been able to identify the strong transitions, 3Z,--X3Zg-isoelectronic with HC6H+, and thus it is of 211-X211 symmetry.(n = even)" and lZU+-X1Zg+(n = odd)*1 for the C, chains. The Franck-Condon profile and vibrational pattern of these two The spectrum of a specificneutral carbon chain is obtainedby ions is similar (cf. spectrum of HC6H+ in Fig. 2). Also the codeposition of the corresponding C,-anion with excess of vibrational frequencies of the corresponding modes are compa-neon to grow the matrix at 5 K, with concomitant irradiation rable: HC6H+:212 = 2053, 213 = 1880, 214 = 617; with broad band UV light. The photobleaching can also bec6-:v1 = 2064, v2 = 1817, v3 = 607 cm-l. The 2n-x2n achieved after deposition; in both cases the identified electronic transitions of the even-numbered carbon anions up to C20-have transition of the carbon anion disappears while a new band been observed.system appears. By this means, the 3Zu--X3Z,-band systems for C, n = 4, 6, 8, 10 have been observed as can be seen in Fig. 7. The assignment is based on (1) mass-selection, (2)7 Neutral carbon chains photobleaching behaviour, (3) trend within an homologous The C, chains with n = even have 3C,-ground state symmetry, series (Fig. 8), and (4) in the case of the smaller species, C4 and whereas those with n = odd have a lZg+ closed-shell c6,by comparison with high level a6 initio calculations. It is configuration. The IR spectra of most of the n = 4-13 linear interesting to note, that it has not proved possible to detect the species have been obtained in the gas phase.5 However, their corresponding transitions for species larger than Clo.The electronic transitions have not been identified, though the few initially reported spectral1 of Clo, C12and C14 have turned out articles reporting the absorption spectra of carbon vapour to be the transitions to higher electronic states of their anions; condensed in rare gas matrices have made suggestions on the the Clo system has now been detected and is the one included in assignment of bands to specifically sized carbon species.4.6 The Fig. 7. This may be taken as an indication that the cyclic forms main support for this has come from correlation of intensities of dominate for the neutral species of these sizes, in accord with electronic and IR bands.7 Using the mass-selected approach, we the conclusions drawn from ion mobility measures.21 Pre-24 Chemical Society Reviews, 1997 I I I 0 C2n A C2n+1 700 600 E5 500 400 300 I I I 4 6 Fig.8 Dependence of the origin band wavelength of the JC-JC IZu+--X1Xg+)on the number of carbon atoms 1+c, tx IcS' I I I I I I I I I I I I I I I 7 8 91011 I I I 13 15 Number of carbon atoms electronic transition of the bare carbon chains C, (n = even: TZc,--X3X,-; n = odd: lXu+-XIXg+ transition of C3 should be located near 170 nm. The well-known Comet band system of C3, A1IIU-X1Xg+,lies near 300 nm, and the corresponding transitions of C5 and C7 are also discernible in the matrix near 510 and 542 nm, respectively.22 Om2 cg 8 Monohydrogenated carbon chains 0.0 The electronic spectra of the C2,H chains, with n = 3-8, have also been detected by mass-selection of C2,H- anions, and photodetachment during growth of the matrix." The hot- 0 Oml cathode anion source with diacetylene as input proved expe- a 1 A Cll dient for the C2,H- production.The C2,H chains are isoelectronic with the C2,- and HC2,H' s 0.0ions, and accordingly show the strong 213-X211 transition in a similar wavelength region. Furthermore, the discernible vibra- 5: tional frequencies for such isoelectronic species are similar as is c13 the overall Franck-Condon shape of the band systems. The ' k-0.0 A c15 LL 300 350 400 450 hl nrn Fig. 9 Absorption spectra of the carbon chains, lX,+-XICg+ electronic transition, in neon matrices using mass-selection.The weaker structure above 300 nm in the spectrum of C9 is due to a forbidden transition. sumably, the sensitivity of the mass-selected approach is not yet sufficient to detect the weaker electronic transitions of the cyclic isomers. On the other hand, the lzI,+-XIZg+ transition of the odd- numbered carbon chains could be detected up to n = 15.22 These band systems for the longer species are shown in Fig. 9. A plot of wavelength vs. length of chain dependence is shown in Fig. 8, an extrapolation of which yields a prediction for the hitherto unmeasured longer species. Furthermore, the trend on the high energy size predicts that the yet to be observed corresponding transitions of the chains with odd-number of carbon atoms, C2, + 1H have not yet been obtained.9 Nitrogen containing chains It proved possible to measure and assign the 2II-X2Il electronic transitions of cyanopolyacetylene cations HC,CN' (n = 4-12) and NCC,CN+ (n = 2-10).23 This was carried out using a hot- cathode discharge source for the cation production with cyanoacetylene or dicyanoacetylene as precursor gas. The same pattern as for the carbon chains is manifested for these homologous series. Because the HC,CN+, NC,N+, C, + 2H and HC,+2H+ species are isoelectronic, the series can be directly compared and they indeed show the 211-X211 band systems in a similar region. This can be seen by comparison of the spectra of C12-, C12H, HC12H+, HCIIN' and NCloN+ in Fig. 10; the origin bands lie within a 0.6 eV span.Table 1 shows the wavelengths of the observed origin bands of the electronic transitions of the carbon chains identified hitherto in neon matrices using the mass-selected approach. 10 Gas-phase studies Because it has always been the aim to use the matrix observations as a basis for gas-phase studies of the carbon chains, it is useful to consider the data for the species where this Chemical Society Reviews, 1997 25 Table 1 Wavelength (h/nm) of the origin band of the characteristic n-n transition of carbon chains observed in neon matrices C2, + 1: I&+ cx 1Xg+ c2,-: 2rl tx 2n C2,: 32"- tx 32,-C7 253 c4-457 C4 380 Cg 295 c6-608 c6 511 CI~336 c*-773 C8 640 c13 380 Clop 967 ClO 735 C15 420 C12-1249 C14-1460 C16-1729 C18-2069 (220-2440 HC2,+ 1H: 3Cu- tX 3Cg-C2,H: 211 tX 2l-I HC2,N+: 2ll tX 2ll HCSH 434 CGH 530 HC6N+ 570 HC7H 505 CgH 631 HCsN+ 657 HCgH 582 CloH 722 HC ION+ 747 HCllH 655 C12H 801 HC12N+ 832 HC13H 721 C14H 866 HC15H 781 C16H 924 HC2,+ IN+: 2ntX 211 NC2,N': 211tX 2ll NC2,+ 1 N+: 211 tX 2ll HC5N+ 584 NC4N+ 598 NC7N+ 629 HC7N+ 674 NC6N+ 659 NCgN+ 7 13 HCgN+ 77 1 NCSN+ 74 1 NCI IN+ 795 HCIIN+ 871 NCloN+ 831 HC 13N+ 973 NC12N+ 923 HC2,H': *nucX TIg HC2, + 1H+:TI tX 2lI HC4H+ 509 HC5H+ 499 HC6H+ 605 HC7H+ 600 HCsH+ 7 13 HCgH+ 659 HCloH+ 823 HC1 IH+ 789 HC12H+ 934 HC 13H+ 873 HC14H+ 1047 H&H+ 959 Hc16H+ 1160 7 21-ICX211 0.002.nJ,L,,, 0.000J 1200 1250 dL, , , , , , , 700 750 800 850 900 h/nm Fig. 10 The 2n-X2ll electronic absorption spectra of isoelectronic carbon chains in neon matrices has already proved possible. Also relevant is a comparison of Recently, the 21T-X21T transitions could be detected in the gas- the gas-neon matrix shifts and apparent trends. phase for the three carbon anions C,-n = 4,6,8 using a two- Prior to the study of the electronic spectra of mass-selected colour photodetachment approach.10 The latter experiments carbon chains and their ions in neon matrices, the 21T-X211 could be carried out because the location of the transitions was transitions of cations of three polyacetylenes, HC,H+ n = 4,6, known from the matrix studies." The 2rI-X211 band system of 8, and of three cyanopolyacetylenes, HCsN+,NC,N+ n = 4,6, C6H could for the same reason be observed in a discharge by a were observed in the gas-phase by emission spectro~copy.~~ sensitive laser absorption technique ('cavity ring-down').25 Chemical Society Reviews, 1997 Table 2 Gas-neon matrix shifts of the origin bands of the 2Il tX 2Il electronic transitions of carbon chains.All values in cm-1. Species Gas Neon Shift Ref. 19724 19645 79 16, 17 16670 16535 135 16, 17 14160 14017 143 16, 17 17190 17130 60 23,24 16781 16719 62 23, 24 15260 15173 87 23,24 18996 18854 142 11,25 2 1872 21896 -24 10,ll 16476 16458 18 10, 11 12963 12933 30 10,ll In Table 2 is given a comparison of the gas and matrix frequencies of the origin bands of the electronic transitions of these carbon chains.It can be seen that the shift increases with size of the molecule; in the gas-phase the transitions are found to higher energies (with the exception of C,-). The anions show rather modest shifts, and it appears that cations and neutrals which have about the same lengths show similar displacements: HC6H+ (135 cm-'), C6H (142 cm-l). On the other hand, the isoelectronic cyanopolyacetylene cations show smaller shifts: HC5N+ (60 cm-'), NC4N+ (62 cm-1). 11 Predictions for other carbon chains As is evident from Fig. 10, carbon chains which are isoelec- tronic have the corresponding electronic transitions in a similar spectral region. Therefore this information can be used to predict the absorption characteristics of the yet unstudied species.For example, the HC,+, and CnP1Nf, ions are isoelectronic with the bare carbon chains, and will follow their pattern (Fig. 8). Similarly, the neutral C, -IN, and HC,, chains, will show strong n--JI transitions in the same region as the isoelectronic HC,H+ species, whose 3C,--X3C,-band systems are located in the plots of Fig. 3 and can be extrapolated accordingly. 12 Relevance to the diffuse interstellar bands Carbon chains are among the particularly attractive candidates as carriers of the diffuse interstellar bands (DIBs),26 especially in view of the detection of carbon chains in dark clouds and carbon stars.' Thus it is worthwhile to relate the understanding of their electronic spectra to this problem.In fact, on the basis of the observations made on the absorption spectra of mass- selected species in neon matrices in the initial experiments, the number of coincidences (i.e.within a certain uncertainty taken to be representative of the gas-matrix shift) between the absorption bands and DIBs, indicated that the carbon chains and their monohydro derivatives are good candidates for the carriers .27 One can now consider the species in more detail by combining the spectroscopic results with the astronomical observations as well as physical and chemical restrictions on the molecules. The stellar observations are that nearly two hundred absorption features are attributed to DIBs.~~ These are found in the 400-900 nm region, though a few absorptions below and in the near IR have also been so interpreted.Thus from the observed trends among the carbon chains studied, whereby the strong n-n transition shifts by a particular increment to the red as the number of carbon atoms increases (Figs. 3,8), the length of the chain necessary for the molecule to absorb in the DIB window can be determined from the plots. Analogously, this can be predicted for the hitherto unmeasured, but isoelectronic, or structurally similar chains, also those including nitrogen or oxygen atoms. The series of carbon chains likely to be easily formed in the diffuse clouds are: C,, C,H, HC,H (or their H2C, isomers) and their ions, as well as the related N-and O-containing species.The astrophysical conditions dictate that the species have to be large enough to be stable with respect to photodissociation to starlight penetrating the diffuse clouds, or that efficient syntheses are operative.29 Thus a sufficient size has been considered to be molecules with say > 10-15 atoms.30 If this criterion is applied, then a number of the smaller carbon chains that would absorb in the 400-900 nm spectral window can be eliminated. Examples of this are the bare carbon chains with even number of atoms. As is seen in Fig. 8, C, n = 6, 8, 10 would absorb in the DIB region but are deemed as too small to be photostable. On the other hand the odd-numbered carbon chains, C, n = 15-37 will show their strong n--JItransition in the 400-900 nm gap and are large enough.However, it has been shown both experimentally and theoretically, that carbon species compris- ing more than 20 atoms prefer a ring structure,*l which may be the chemical restriction on the length of the chains to be considered. These arguments lead to a natural restriction on the number of possible species, which is attractive because there appear to be a limited number of stronger DIBs. The chains which would satisfy the above discussed criteria are then the odd carbon chains C2, + 1, and their isoelectronic analogues HC2, + If and C2,Nf, with n > 9 but perhaps terminating in the mid-twenties. Not specifically discussed, but chains which will have similar spectral characteristics and need to be considered are the oxygen-containing ones, C,O, and the cumulene type structures H2C,, H2C,O.As an example, the C,,O species with n = odd have lECg+ground state, whereas those with n = even YZc,-, and will behave spectroscopically like the odd- or even-numbered C, chains, respectively (cJ Fig. 8). It is relevant to note that H2Cn, C,H and C,O type chains have been detected in dark clouds by radioastronomy.31 13 Outlook The observation of the electronic spectra of a number of homologous series of the carbon chains in neon matrices by utilising mass-selection, has given the breakthrough in provid- ing the location of the transitions so that gas-phase studies are a realistic proposition, as well as for astrophysical considerations. The interesting chains still to be characterized by this technique are the species containing oxygen and the cumulenes.In connection with the DIBs assignment, the data define on which type of carbon chains interest should be focused. The next stage is then a concerted effort at obtaining the electronic spectra of the relevant species in the gas-phase. To this end a variety of laser-based approaches are envisaged. In the case of the anions the two-colour laser photodetachment approach has already proven to be successful for the smaller species; lo for the neutrals laser absorption methods, such as used for C6H detecti01-1,~~and resonant photon ionization approaches are likely to succeed because the wavelength region of the electronic transitions is known in neon matrices.14 Acknowledgements The studies in Base1 have only been possible due to the motivation and ability of a number of PhD students and postdoctoral fellows, who are authors in the cited articles. The research has been financed throughout the years by the Swiss National Science Foundation (current project no. 20-41 768.94). 15 References 1 H. W. Kroto, Int. Rev. Phys. Chem., 1981, 1, 309. 2 H. W. Kroto, Int. J. Mass Spectrom. Ion Processes, 1994, 138, 1 and references therein. Chemical Society Reviews, 1997 27 3 D. Fomey, M. Jakobi and J. P. Maier, J. Chem. Phys., 1989, 90, 600. 4 W. Weltner, Jr. and R. J. Van Zee, Chem.Rev., 1989, 89, 1713. 5 T. F. Giesen, A. V. Orden, H. J. Hwang, R. S. Fellers, R. A. Provencal and R. J. Saykally, Science, 1994, 265, 756. 6 W. Kratschmer, N. Sorg and D. R. Huffman, Surf. Sci., 1985, 156, 814. 7 J. Kurtz and D. R. Huffman, J. Chem. Phys., 1990, 92, 30; J. Szczepanski and M. Vala, J. Phys. Chem., 1991, 95, 2792. 8 G. H. Herbig, Annu. Rev. Astrophys., 1995, 33, 19. 9 J. P. Maier and M. Rosslein, J. Chem. Phys., 1988, 88, 4614. 10 Y. Zhao, E. de Beer and D. Neumark, J. Chem. Phys., 1996,105,2575; Y. Zhao, E. de Beer, C. Xu, T. Taylor and D. M. Neumark, J. Chem. Phys., 1996, 105, 4905. 11 P. Freivogel, J. Fulara, M. Jakobi, D. Forney and J. P. Maier, J. Chem. Phys., 1995, 103, 54. 12 M. E. Jacox, J.Phys. Chem. Ref Data, 1988, 17, 269. 13 V. E. Bondybey, T. J. Sears, J. H. English and T. A. Miller, J. Chem. Phys., 1980, 73, 2063. 14 D. Fomey, J. Fulara, P. Freivogel, M. Jakobi, D. Lessen and J. P. Maier, J. Chem. Phys., 1995,103,48. 15 Q. Fan and G. V. Pfeiffer, Chem. Phys. Lett., 1989, 162, 472. 16 P. Freivogel, J. Fulara, D. Lessen, D. Forney and J. P. Maier, Chem. Phys., 1994, 189, 335. 17 M. Allan, E. Kloster-Jensen and J. P. Maier, Chem. Phys., 1976, 7, 11. 18 J. Fulara, P. Freivogel, D. Fomey and J. P. Maier, J. Chem. Phys., 1995, 103, 8805. 19 E. Kloster-Jensen, H.-J. Haink and H. Christen, Helv. Chim. Acta., 1974, 57, 1731. 20 R. Eastmond, T. R. Johnson and D. R. M. Walton, Tetrahedron, 1972, 28, 4601. 21 N.G. Gotts, G. von Helden and M. T. Bowers, Int. J. Mass Spectrom. Ion Processes, 1995, 1491150, 217. 22 D. Fomey, P. Freivogel, M. Grutter and J. P. Maier, J. Chem. Phys., 1996,104,4954. 23 D. Fomey, P. Freivogel, J. Fulara and J. P. Maier, J. Chem Phys., 1995, 102, 1510. 24 J. P. Maier, 0.Marthaler and F. Thommen, Chem. Phys. Lett., 1979,60, 193;G. Bieri, E. Kloster-Jensen, S. Kvisle, J. P. Maier and 0.Marthaler, J. Chem. SOC.Faraday Trans. 2., 1980, 76, 676; E. Kloster-Jensen, J. P. Maier, 0. Marthaler and M. Mohraz, J. Chem. Phys., 1979, 71, 3125. 25 M. Kotterer and J. P. Maier, Chem. Phys. Lett., in the press. 26 A. E. Douglas, Nature, 1977, 269, 130. 27 J. Fulara, D. Lessen, P. Freivogel and J. P. Maier, Nature, 1993, 366, 439; P. Freivogel, J. Fulara and J. P. Maier, Astrophys. J., 1994, 431, L151. 28 P. Jenniskens and F.-X. Desert, Astrophys. Astron. Suppl., 1994, 106, 39. 29 R. P. A. Bettens and E. Herbst, Int. J. Mass Spectrom. Ion Processes, 1995, 1491150, 321. 30 S. Leach, in The Diffuse Interstellar Bands, ed. A. G. G. M. Tielens and T. P. Snow, Kluwer, Dordrecht, 1995, p. 281. 31 P. Thaddeus, C. A. Gottlieb, R. Mollaaghababa and J. M. Vrtilek, J. Chem. SOC.,Faraday Trans., 1993,89,2125. Received, 13th September I996 Accepted, 10th October 1996 28 Chemical Society Reviews, 1997

ISSN:0306-0012    

DOI:10.1039/CS9972600021

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

The science and humanism of Linus Pauling (1901-1994) Stephen F. Mason Depurtnzent of’ Chemistry, King’s College London, London, UK WC2R 2LS and Department of History and Philosophy of Science, University qf Cambridge, Cambridge, UK CB2 3RH The versatile and outstanding contributions of Linus Paul- ing to the chemical sciences, including the biomedical consequences of radioactive fallout, were recognised by the award of two Nobel Prizes (1954 and 1963). Pauling’scontributions in historical context are discussed under five headings: X-ray crystallography and theoretical chemistry; the nature of the chemical bond; biological chemistry; global fallout; and molecular medicine. The award of two Nobel Prizes, the first for chemistry at Stockholm in 1954 and the second for peace at Oslo in 1963, measures the eminence of Linus Pauling as a scientist and as a world citiizen.Festschrifts honoured his sixty-fifth, eightieth,* and ninetieth birthday,3 with autobiographical contributions by Pauling himself in two of these, and in the Annual Review of Physicul Chemistry series (1965). Pauling was interviewed many times on his scientific and social concerns, and a selection of his replies and his occasional writings has appeared recently: as well as a collection of tributes to him to the Journal of Chemical Education (No. 1, 1996). Substantial biographies of Pauling are available, one by a philosopher,’ a second co- authored by a sociologist and a psychologist,6 and another, the most comprehensive, balanced, and informed of the three, by a medical writer turned academic administrator.7 The second biography curiously concludes with eight interpretations from expert psychologists of the replies Pauling had given to Rorschach ink-blot tests in the 1960s, when his biochemical view of mental disorders was at odds with standard psycho- analytical thinking.Only one of the experts suspects, what is S. F. Muson ~~rkedon untimalariulsjbr his D.Phi1. (I 94447) with D. LI. Hammi1.k at Oxjord University, where he taught the history c.f science, as well as chemistry (1947-1953). He was then a Research FelloMi with Adrien Albert in the Australian National University’s Department of Medical Chemistry, being built up in the Wellcome Institute, London.In I956 he moved to a lectureship in physical organic chemistr-y at Exeter University and became Reader in chemical spectroscopy. He was Professor of Chemistry at the University oj’Eust Anglia (1964-1 970) and at King’s College London (1970-1 988), working on chirality in its many aspects, summarised in his Molecular Op-tical Activity & the Chiral Dis-criminations (1982). From 1988 he has been Emeritus Professor ,$Chemistry in the University oj London, and Honorary Research Associate in the Department of History and Philosophy of Sci- ence, University of Cambridge. Since completing his Chemical Evolution (I 991), he has been rewriting his History of the Sci- ences (1953). obvious to the layman, that Pauling was joking, making up answers based on Freudian or other psychology.8 Chemistry students of my generation were inspired by Pauling’s Nature of the Chemical Bond (1939), which brought a new ordering to theories of molecular structure and chemical bonding, and answered ‘No!’ to a popular examination question of the time, ‘Is inorganic chemistry a closed and finished subject?’ The book pointed the way ahead to the physical inorganic chemistry of the postwar period, but Pauling ’s interests had moved on by that time to molecular biology, then to the dire consequences of radioactive fallout from nuclear explosions in the biosphere, and finally, to orthomolecular medicine.1 Pauling’s formative years Linus Carl Pauling was the firstborn, in 190 1, of a pharmacist in Portland, Oregon, who died in 191 1 leaving his wife, son, and two daughters with limited means.After high school in Portland, Linus Pauling entered Oregon Agricultural College at Corvallis, precursor of Oregon State University, in 1917, and graduated in chemical engineering in 1922. He worked his way through college, serving as full-time assistant instructor in quantitative analysis 19 19-1 920. The experience may have dissuaded him from accepting a half-time instructor’s post for five years of graduate study for a PhD at Harvard. Instead he moved, in 1922, to a three-year graduate studentship offered by Arthur Amos Noyes (1866-1936), head of the Division of Chemistry and Chemical Engineering in the California Institute of Technology (Caltech) at Pasadena.Noyes had an eye for talent and for promising new fields of research, and it is said that Pauling was Noyes’ greatest discovery. Noyes obtained his PhD with Wilhelm Ostwald (1853-1932) at Leipzig in 1890, then joined the Massachusetts Institute of Technology (MIT) where, as professor of theoretical chemistry 1899-1919, he recruited a number of able younger chemists. These included Gilbert Newton Lewis (I 875-1946), who was at MIT 1908-19 12 before moving to the University of California, Berkeley, as head of the chemistry department. Noyes commuted to Pasadena each winter from 1915 to build up the chemistry division of Throop College of Technology, which changed its name to Caltech shortly after Noyes moved permanently to Pasadena in 19 19.Noyes recognised the importance of X-ray crystal structure analysis from the beginning; and installed X-ray equipment at MIT and Caltech. Roscoe Gilkey Dickinson ( 1894-1 945) was in charge of the powder and single-crystal X-ray apparatus at Caltech in 1922 when Linus Pauling was placed with him by Noyes for research supervision as a graduate student. Dickinson and Pauling published their first paper in 1923, on the structure of the mineral molybdenite, MoS2, establishing a trigonal prismatic coordination of molybdenum by six sulfide ions. Pauling soon achieved scientific standing, as author or coauthor of about a dozen crystal-structure publications over the next three years, and G. N. Lewis offered him a postdoctoral position at Berkeley after his PhD in 1925.Noyes thereupon arranged a Guggenheim fellowship for Pauling’s postdoctoral studies in Europe 1926-1927, centred on the Munich Institute of Arnold Chemical Society Reviews, 1997 29 Fig. 1 Linus Pauling as a young man (courtesy of the Royal Society of Chemistry Library and Information Centre) Sommerfeld (1868-195 l), indicating that a position at Caltech would be available on Pauling’s return.9 In Europe for nineteen months, 1926-1927, Pauling met the principal workers in the field of quantum mechanics as they came to visit Sommerfeld’s Institute at Munich, or on his own visits to Copenhagen and Gottingen for a few weeks, and to Zurich for several months. As a graduate student, Pauling had attended a wide range of advanced courses on mathematics and the physical sciences, and soon assimilated the concepts and procedures of the new quantum mechanics.He said later on that he did not bother overmuch with the deeper philosophical implications of the uncertainty principle and the like. Following the pragmatic tradition of North America, Pauling adopted an operational approach to the new discipline, seeking concrete applications of quantum mechanics to chemical and physical problems. At Bohr’s Institute in Copenhagen Pauling met Samuel Goudsmit (1 902-1978) who, with George Uhlenbeck (190&1988), introduced in 1925 the physical notion of electron spin to account for the two-valued fourth quantum number needed in atomic spectroscopy.The new number had entered empirically into Pauli’s principle (1925), forbidding the same set of four quantum numbers to any two electrons in any given polyelectronic system. Pauling and Goudsmit later collaborated in writing The Structure of Line Spectra (1930). More momentous was Pauling’s visit to Schrodinger’s Institute in Zurich, where he met Fritz London (1900-1954) and Walter Heitler (1904-198 l), who were working on their valence bond (VB) treatment of the bonding in the hydrogen molecule, published in 1927. The two electrons (1) and (2) of the molecule are allocated to the 1s atomic orbital around each nucleus, Ha and Hb, in two ways, [Ha( 1)Hb(2)] and [Hb( 1)Ha(2)], to give two ‘valence structures’.Calculations indicated that, at bonding internuclear separations, the principal source of the molecular binding came from the ‘exchange energy’, arising from the interchange of the two electrons, with opposed spins, between the two ‘valence structures’. About the same time Friedrich Hund (b. 1896) developed the alternative molecular orbital (MO) treatment of the bonding in the hydrogen molecule at Gottingen. On the MO model the paired electrons move in a molecular orbital resulting from the in-phase combination of the 1s atomic orbitals of the two nuclei, [Ha+ Hb]. Subsequent comparisons of the two methods showed that the original MO treatment gave ionic structures of the type [Ha( 1,2)] and [Hb( 1,2)], additional to the neutral valence structures of the first VB treatment, and of equal weight.The two methods became identical, and gave a theoretical bond distance and bond energy closer to the corresponding spec- troscopically measured values, when the weights of the contributions from the ionic structures were reduced in the MO treatment and were added to an equivalent degree in the VB treatment. The conceptual differences between the VB and the MO methods remained, however, in the simplified and approximate methods needed for the treatment of complex polyatomic molecules. These differences occasioned some contention between advocates of the VB and the MO methods until the 1950s, when the growth of chemical spectroscopy brought about the general adoption of the MO procedure, with its more fruitful treatment of excited molecular states.In North America the principal advocate of the MO theory was Robert Sanderson Mulliken (1896-1986), at the University of Chicago from 1928. Mulliken was a close friend of Hund from the rnid-l920s, and regretted that his Nobel Prize (1966) was not shared with Hund.lo During the prewar period, chemists took little note of the MO studies of Hund and Mulliken. The early MO models regarded a molecule as a fixed array of atomic nuclei, each with its own completed inner shells of electrons, while the electrons of the incomplete outer shells of the atoms, the ‘valence electrons’, moved in molecular orbitals spanning the array of atoms as a whole. There were no individual ‘chemical bonds’ in a polyatomic molecule, according to early MO theory, contrary to classical structural theory.Traditionally, chemists constructed molecules, conceptually and in the laboratory, by adding another atom or group, through a well- defined ‘chemical bond’, to a simpler structure. Mulliken opened his Chemical Review of 1931 with the opinion that ‘the concept of valence itself is one which should not be held too sacred’. After devoting a section to the ‘Superfluity of the concept of valence bonds in the “molecular” point of view’, he came to the conclusion that the VB method, ‘when applicable, usually gives, somewhat fortuitously in the author’s opinion, the same results as the present [MO] method. The latter gives, however, a detailed insight into what is going on in the formation of the molecule’.ll During the 1930s few chemists accepted Mulliken’s views of chemical bonding.In contrast, Pauling’s resonance theory, formally based on the VB method, aroused widespread interest, particularly in North America, since it preserved and rationalised much of classical structural theory and the pre-quantum mechanical theories of the role of electrons in chemical bonding, developed mainly by chemists. In 1927 Pauling returned to Caltech as assistant professor in theoretical chemistry, and began a series of investigations on the nature of the chemical bond, alongside his resumed X-ray studies of crystal structures. In 1930 he extended his structural studies to individual molecules in the gas phase, free from complexities of the packing of molecules in crystals, with the new technique of electron-diffraction, developed by Hermann Mark in Ludwigshafen.Pauling visited Mark early in 1930 when he spent some time with William Lawrence Bragg (1890-1971) at Manchester. With Bragg he discussed various crystallographic procedures, including the applications of Pauling’s rules (1928) governing the geometry of the coordina- tion polyhedron of anions around a cation in an ionic crystal, in terms of the radius ratio of the anion and the cation, and their formal charges. These rules were elaborations of rules proposed 1923-1 926 by the geochemist-crystallographer, Victor Moritz Goldschmidt (1888-1947) in Oslo, and they had particular value for the structural analysis of the silicate minerals, which Bragg and Pauling were studying.Pauling recalled in 199 1 that his interest in electronic theories of chemical bonding dated from the time he served as assistant instructor 19 19-1 920. One of the two chemistry seminars that year at the Oregon Agricultural College was given by an agricultural chemist on the frozen fish industry, while Pauling 30 Chemical Society Reviews, 1997 spoke on the shared electron-pair chemical bond. This basic idea had been proposed by G. N. Lewis in 1916 and developed in a series of papers from 1919 by Irving Langmuir (1881-1957), who coined the terms ‘covalance’ and ‘electro- valence’ for the homopolar and the heteropolar sharing.The Coulombic attraction of opposite charges provided a physical basis for the electrovalent (ionic) bond, but the homopolar shared-pair covalent bond had no immediate physical founda- tion, other than the significant correlation with the electron-pair of the lightest noble gas, helium, and the four duplets of the eight electrons in the outer shell of the heavier noble gases, modelling the electron configuration of the central atom in polyatomic systems, such the carbon atom in C&. In Munich and Zurich 1926-1927 Pauling found what he believed to be the physical basis of the homopolar covalent bond in the quantum-mechanical ‘exchange energy’, arising from the interchange of spin-paired electrons between the two ‘valence structures’ in the VB treatment of the hydrogen molecule by Heitler and London.Pauling regarded the electron- pair exchange in a chemical bond as the quantum-mechanical analogue of the classical resonance effect observed in coupled oscillators, terming the bond energy from electron interchange the ‘resonance energy’. He referred the analogy back to the 1926 treatment by Werner Heisenberg (1901-1976) of the separatepara-and ortho-states of the helium atom (spin singlets and triplets, respectively), which resembled a classical case of the resonance splitting between the in-phase and out-of-phase modes of coupled oscillators. Pauling introduced his resonance theory in a 1928 Chemical Review and developed his ideas in a series of seven papers 1931-1933 on The Nature of the Chemical Bond, culminating in his George Fisher Baker Lectures at Cornell University, 1937-1938. The lectures were published, The Nature of the Chemical Bond in 1939, with a second edition in 1940 and a third in 1960.All were dedicated to G. N. Lewis, whom Pauling regarded as the founder of the modem theory of valence. 2 The nature of the chemical bond Classical chemical structural theory provided a number of examples of molecules which could not be represented by a single structure, as in the leading case of benzene, for which August KekulC (1829-1896) had proposed in 1872 an ‘oscilla- tion’ between the two alternative ‘Kekult5 structures’, each with three single and three double carbon-carbon bonds forming a hexagon.This oscillation was required to account for the absence of two isomers of a given 1,2-disubstituted derivative. For Pauling the two KekulC structures were classical analogues of quantum-mechanical ‘valence structures’. The actual ben- zene molecule cannot be regarded as ‘intermediate’ between the hypothetical KekulC structures. The molecule is more stable than either of these structures by a resonance energy of some 36 kcal mol-l (1 cal = 4.184 J). The carbonxarbon bond lengths of benzene are shorter than the mean of standard carbonxarbon single double bond lengths. The resonance energy of benzene, on division by Planck’s constant, gives a resonance frequency on the order of 10’5 Hz, comparable to that derived similarly from the bond energies of simple molecules.Such a frequency refers to electronic motions, being a thousand times greater than that of the nuclear motions implied by KekulC’s proposal of 1872; the nuclear motions involved in tautomerism are slower still.l* Pauling’s disciple, George Wheland, remarked that the benzene molecule is analogous to the real animal, the rhinoceros, described by a medieval traveller as a cross between two mythical beasts, the dragon and the unicorn.13 In 1935 Pauling judged the Heitler-London theory of bonding in the hydrogen molecule as ‘the greatest single contribution to the clarification of the chemist’s conception of valence since G. N. Lewis’s suggestion in 1916 that the chemical bond between two atoms consists of a pair of electrons held jointly by the two atoms’.14 Fritz London was appalled by the compliment, and was irritated by ‘this Pauling’, who had not only taken over and vulgarised the VB theory but had also associated the theory with the physically absurd notions of G.N. Lewis, who postulated a static cubical array of electrons around the atomic nucleus. In 1929 London began a book on Quantum Mechanics and Chemistry, but soon abandoned the project. By 1930 he had moved on to investigate the non-polar inter- molecular forces, the ‘London dispersion forces’, and by 1935 worked out the ‘London equations’ governing superconductiv- ity, with his brother Heinz.15 Heitler moved on to radiation theory, also satisfied, as were Schrodinger and Dirac, that quantum mechanics had now, in principle, solved all problems in chemistry.The first of Pauling’s seven papers on the nature of the chemical bond16 was especially important in reconciling ‘spectroscopic orbitals’ with ‘chemical orbitals’. Quantum mechanics developed symbiotically with atomic and diatomic spectroscopy during the interwar period.17 The atomic orbitals took their designations s-, p-, d- . . . from the sharp, principal, diffuse . . . series of lines observed in atomic spectra. The angular forms of these atomic orbitals, based on the spherical harmonic functions, bore no direct and systematic relation to the stereochemical forms of polyatomic molecules, and the charac- ter of the ‘chemical orbitals’ governing the angles between bonds in polyatomic systems had become problematic by 1930.On a spectroscopic basis, the four valency electrons of the carbon atom formed the atomic ground state with two electrons spin-paired in the spherically symmetric 2s orbital and the remaining two with parallel spin occupying two of the mutually orthogonal 2px, 2p,, and 2p, orbitals. In 193 1, Pauling and the MIT physicist John Slater showed, independently, that the angular functions of the 2s and the three 2p orbitals of the carbon atom, taken with equal weight and mutually exclusive phase relationships give rise to four equivalent hybrid (sp3) atomic orbitals, directed tetrahedrally. Each of these four hybrid chemical orbitals has an equal binding propensity, which is twice that of the 2s-orbital alone, as measured by the fractional overlap with, say, a 1s-orbital of a hydrogen atom at a bonding position.Pauling extended his scheme to trigonal and digonal hybrids for molecules containing the carbon-carbon double- and triple-bond and to octahedral and square-planar hybrids from the 4s-, 4p-, and 3d-orbitals of the transition metals in the first long period for the bonding established in coordination compounds. Chemical Society Reviews, 1997 31 A major element of Pauling’s comprehensive ordering of inorganic bonding lay in this derivation of a quantitative scale of the electronegativities of the chemical elements through the resonance theory. Chemists during the eighteenth century had endeavoured to order the known variety of chemical combina- tions by drawing up hierarchical ‘Tables of Chemical Affini- ties’, based on such observations as the displacement of one acid from its salts by another acid with a greater ‘affinity’ for the base of the salt.l8 After the chemical revolution at the end of the century, attention turned to the avidity with which oxygen combined with other elements, resulting in the ‘Scale of Oxygenicity’ or of universal acidity, evolved from 1809 by Amedeo Avogadro (1776-1856). Jons Jacob Berzelius (1779-1 848), one of the pioneers of electrochemistry, reformu- lated and extended Avogadro’s concept into a ‘universal scale of electronegativity’ of the elements in 1818, based on the observations that oxygen, acids, and oxidised substances accumulated around the positive pole of an electrolytic cell, while metals, bases, and combustible substances passed to the negative pole.Berzelius linked the electronegativity scale to his dualistic electropolar theory of chemical combination, based on the two- fluid theory of electricity. Each atom, Berzelius proposed, carried unequal amounts of the positive and the negative electrical fluid, and the ratio of the amounts registered the electronegativity of the element. Oxygen, the most electronega- tive element then known, carried the largest excess of negative fluid, and potassium at the other end of the scale carried the largest excess of positive fluid. Chemical combination entailed the partial neutralisation of the two electrical fluids, and their union resulted in the liberation of the caloric fluid (heat). The compound formed retained smaller amounts of the two electrical fluids, and so acids, with an excess of negative fluid, combined with bases, carrying an excess of positive fluid, to form salts.The dualistic theory of chemical combination lost ground during the 1840s, primarily because it was unproductive in the new field of organic chemistry. But the concept of electronegativity and chemical affinity lived on, assuming thermochemical forms with the rise of physical chemistry at the end of the nineteenth century.I9 The qualitative electronegativity scale of Berzelius, based largely on his chemical experience and intuition, correlates element by element with the quantitative scale of atomic electronegativities which Pauling derived, from 1932.The electric dipole moment of heteronuclear molecules A-B indicated to Pauling that the bonding involved resonance between covalent and ionic valence structures, the fractional contribution of the ionic structure being gauged by the value of the dipole moment. The bond energy of the heteronuclear molecule A-B turned out to be larger than the arithmetic or geometric mean of the bond energies of the corresponding homonuclear molecules A-A and B-B by an increment A, which represented the additional stabilisation arising from the resonance between the covalent and ionic valence structures. The bond energy increment A(A-B) could be related to the difference between the traditional, but ill-defined, property of the two individual elementary atoms, their electronegativities.The direct relation between A(A-B) and the square of the electronegativity difference [(xA-xB)2] enabled Pauling to evaluate the differences quantitatively, and to draw up a comprehensive table of the atomic electronegativities, ranging from 0.7 for caesium to 4.0 for fluorine. The table of electronegativities gave expectations for the energy and the electric dipole moment of any new type of bond: e.g. 50% ionic character for a difference of 1.7 between the electronegativities of the two atoms. What an atomic electronegativity really respresented was not transparent. Pauling regarded electro- negtivity as a measure of the affinity of a bonded atom for electrons.The resonance theory was extended to conjugated organic molecules in 1933, appearing in the last three of Pauling’s seven Chemical Society Reviews, 1997 papers on the nature of the chemical bond. Thereafter the theory of resonance in organic chemistry was developed mainly by his coworker, George Wheland at Caltech and then at the University of Chicago, who published two books on the subject (1944 and 1955). The application of resonance theory to conjugated organic molecules highlighted the wide latitude in the choice of hypothetical ‘valence structures’ contributing to the ground state of a given molecule. Pauling’s approximation of the VB method gave benzene a theoretical resonance energy of 0.9 J for the two KekulC structures alone, but of 1.1 J with the inclusion of the three Dewar structures, each with an elongated transannular bond between opposite positions.The empirical ‘exchange integral’ J,calibrated from thermochemical data, had a value dependent on the range of resonating structures considered. Pauling formulated rules limiting the choice of ‘valence structures’ to a ‘canonical set’, but the choice remained wide for polycyclic aromatic hydrocarbons. The stage at which to truncate the series of possible ‘valence structures’, judged by chemical intuition, was popularly termed the ‘Pauling point’ by students of chemistry in the 1940s. A molecular orbital theory of conjugated organic molecules with much less latitude had been proposed in 1931 by Erich Huckel (1896-1980), a physicist at Stuttgart, who had been a coworker with Debye at Zurich, deriving the Debye-Huckel theory of strong electrolytes in 1923.Huckel divided the electrons of a conjugated molecule such as benzene into two distinct sets, later termed the a and the x electrons. The molecular plane is defined by the framework of carbon-carbon a-bonds, formed from sp2 orbitals, while the x-electrons move over the framework in MOs nodal in the plane. Huckel showed that cyclic polyenes with [4n + 21 n-electrons, where n is an integer, had a substantial additional stabilisation from the x-electron delocalisation, but not those with [4n] It-electrons. Pauling pointed out that two KekulC-like valence structures could be written for cyclobutadiene and for cyclooctatetraene, which belong to the [4n] series, and resonance between the two structures is expected to stabilise these molecules by a resonance energy comparable to that of benzene in the [4n + 21 series. Richard Willstatter (1872-1942) at Munich had syn- thesised cyclooctatetraene in 1905 and in 1911.He found the substance to be olefinic in its properties, with none of the aromaticity predicted from a theory of partial valencies linking conjugated carbon-carbon double bonds, proposed in 1899 by his colleague Friedrich Thiele (1 865-19 18). Following the same prediction made by Pauling in 1935, groups of organic chemists from 1939 to 1943 at several American universities, Minnesota, hnceton, Northwestern and Purdue, attempted to synthesise cyclooctatetraene, but without success, on the supposition that Willstatter had inadvertently prepared the isomer styrene.Willstatter, by now a refugee in Switzerland from the third Reich, heard of these efforts and commented in this autobio- graphy that the American chemists appeared to be ‘untroubled’ by his reports of the reduction of his cyclooctatetraene to cyclooctane and its oxidation to suberic acid. Willstatter’s synthesis of cyclooctatetraene was finally reproduced in 1947, after an Anglo-American scientific commission in 1945 discovered kilogram quantities of cyclooctatetraene in the IG Farbenindustrie laboratories at Ludwigshafen, prepared by Walter Reppe (1 892-1969) by polymerising acetylene over a nickel(I1) cyanide catalyst.20 Cyclooctatetraene was shown by electron diffraction (1948) to have a tub-shaped structure: the dianion with 10 x-electrons, following the Huckel rule for aromaticity, was later found to be planar.1.46 A+ lid Cyclooctatetraene By the late 1930s Pauling’s interest had shifted to structural problems in biological chemistry, and he made relatively few positive contributions to the new problems of chemical bonding in mainstream chemistry during the postwar period. His book The Nature of the Chemical Bond remained conceptually unchanged between the first two editions (1939, 1940) and the third (1960). The new and intellectually inspiring book of the 1940s became a classical inorganic text of the 1960s.3 Biological chemistry In 1931, Pauling introduced a magnetic criterion of bond type for transition metal coordination compounds, together with hybrid atomic orbitals for stereochemically defined bonding. In the ‘ionic’ complexes of the transition metals all five of the d-orbitals were available for occupation by unpaired d-electrons with parallel spins, whereas in the corresponding ‘covalent’ complexes one or two of the d-orbitals were unavailable, being employed in square-planar or octahedral hybrid formation. Accordingly, for a number of d-electron configurations, measurements of the magnetic moment arising from spin- parallel d-electrons distinguish the ‘ionic’ from the ‘covalent’ complexes of a given transition metal ion.Magnetochemical measurements directed by Pauling at Caltech in 1935 showed that the iron(I1) complex haemoglobin of red blood cells had four parallel-spin electrons per haem unit, corresponding to an ionic complex of ferrous iron (with the d6 configuration). The addition of either carbon monoxide or oxygen produces a covalent complex, with all electrons spin- paired. This is a remarkable result for oxyhaemoglobin, since a molecule of free oxygen carries two unpaired electrons. The electronic structures of both the haem and the oxygen are profoundly reorganised on binding. Thereafter Pauling and his coworkers investigated further types of haemoglobin deriva- tives, and those of related biomolecules, myoglobin, haemocya- nin, and the cytochromes, moving on to the problem of the chain-folding of the globulins and other proteins.Pauling and the biochemist Alfred Mirsky (1900-1974) suggested in 1936 that the relatively weak forces of hydrogen- bonding between polypeptide chains determine the folding of protein chains. Protein solutions are denatured by heat, which breaks the weak hydrogen bonds, or by hydrogen-bonding substances, such as urea or ethanol, which compete for the protein inner-binding sites. For explorations of the secondary structure of proteins, Pauling adopted the strategy of con-structing models of the likely folding in polypeptide chains, since the direct X-ray diffraction analysis of protein crystals in detail presented insuperable technical problems in the 1930s.The known bond-lengths and angles for the amide groups in polypeptides were not adequate for his purpose, and Pauling turned to X-ray structural studies of the small ‘building block’ units of proteins. In 1937 Robert Corey (1897-1971) transferred from the structural unit at the Rockefeller Institute to Caltech, where he took up the X-ray crystal analysis of the structures of amino acids and small peptides. During 1938, Corey reported the first detailed structure of a peptide, the cyclic dimer of glycine, diketopiperazine, and over the following years he and his coworkers determined the structures of glycine, other amino acids, and small peptides. The acccumulated structural data enabled Corey and Pauling to formulate conditions for stable folded conformations of polypeptide chains: planar amide groups, with specific bond lengths and bond angles internally and externally.Pauling returned to model-building and, while he was George Eastman visiting professor at Oxford in 1948, he worked out the a-helix rod-like conformation of polypeptide chains, with 3.7 peptide residues per turn of the helix. Each amide group is hydrogen bonded >C=O-.H-N< to the third residue from it in each direction along the chain. On this return to Pasadena, Pauling worked out the details with Corey, and they devised additional stable polypeptide conformations. Pauling and Corey reported the a-helix conformation in 1950, and the parallel and antiparallel p-pleated sheet conformations of polypeptide chains in the following year.Poly-L-peptidea-helix Poly-L-peptide /I-sheet Chemical Society Reviews, 1997 33 Members of the Medical Research Council (MRC) X-ray crystallography unit in the Cavendish laboratory at Cambridge had expected on good, but limited, X-ray data that a helical protein conformation would contain four peptide residues per turn, and looked for distinguishing evidence. Max Perutz, in 195 1, worked out the X-ray reflections required for the a-helix conformation, and observed them in the diffraction pattern of fibrous proteins and a synthetic L-polypeptide. The introduction of the electronic computer to X-ray diffraction analysis provided direct evidence for the prevalence of the a-helix structure in native globular proteins, first in myoglobin, solved at a near-atomic resolution by John Kendrew at Cambridge in 1960, and then in haemoglobin, four times larger than myoglobin, finally solved by Perutz two years later. The stable P-sheet protein conformation derived by Pauling and Corey was confirmed in 1965 by David Phillips and his associates at the Royal Institution, London, by the X-ray structural analysis of the enzyme, lysozyme, from egg-white.The Royal Institution group reported the X-ray structure of lysozyme complexed with a trisaccharide fragment of its physiological substrate, a hexasaccharide unit of the poly- saccharide chain in a bacterial cell wall. The report supported not only the P-sheet conformation, but also Pauling’s develop- ment of the ‘key and lock’ hypothesis of enzyme-substrate interaction, first proposed by Emil Fischer (1 852-1919) in 1894.J. B. S. Haldane (1892-1964) suggested in 1930 that a degree of misfit between the enzyme and its substrate is needed to drive the chemical reaction forward: ‘Using Fischer’s lock and key simile, the key does not fit the lock perfectly but exercises a certain strain on it’. In 1946 Pauling pointed out that, since enzyme reactions are reversible, there is a comparable steric misfit between the enzyme and the product, so that the complementarity of the stereochemical matching is an optimum for the transition state common to the forward and the reverse reaction, accelerating both processes.21 Pauling developed and applied the concept of complementary structural matching in biomolecular interactions after discus- sions from 1936 with the immunologist Karl Landsteiner (1 868-1943).Landsteiner, a native of Vienna, had characterised the four main blood groups. A, B, AB and 0, in 1909. He emigrated in 1923 to work at the Rockefeller Institute for Medical Research, discovering the blood-cell rhesus factor in 1940. The research on haemoglobin at Caltech interested Landsteiner, who encouraged Pauling to examine antibody- antigen interactions from a structural point of view. Paul Ehrlich (1854-1915), who had worked with Emil Fischer, regarded the specificity of the toxin-antitoxin and the antibody-antigen interaction as further examples of Fischer’s ‘key and lock’ hypothesis.The work of Ehrlich established this hypothesis in immunological theory, in which a principal concern became the mechanism whereby the animal body produces the range of individually specific antibodies to combat the enormous variety of antigens to which the body is prey. In 1940, Pauling proposed that polypeptide chains fold and wind around the exterior of the antigen structure, serving as a template. The product is a close- fitting complementary antibody structure, which neutralises the toxic surface features of the antigen in vivo, and precipitates the antigen-antibody complex in vitro.22 Pauling directed an experimental programme at Caltech on the serologial properties of simple substances throughout the 1940s.Like other template theories of the time, Pauling’s hypothesis failed to account for the transmission of specific antibody formation to daughter cells from the parent cell challenged by a particular antigen.23 The theoretical physicist, Pascual Jordan (1902-1980) at Rostock, proposed in 1940 that the injection of an antigen into an animal body led to the natural selection of proto-antibody molecules of like kind, through the quantum-mechanical resonance force between like molecules, from a varied set of proto-antibody molecules maintained by the animal. The complex formation was autocatalytic and led to the proliferation of antibodies specific for the antigen. Pauling was critical of this 34 Chemical Society Reviews, 1997 view, and of Jordan’s earlier (1938) analogous conjecture that the duplication of the gene and the pairing of chromosomes were dependent upon an attractive quantum resonance force which was especially strong between identical or near-identical molecules.With the biophysicist Max Delbriick (196O-1981), Pauling in 1940, argued that the autocatalysis of gene replication is expected to involve complementary rather than identical structures. During his visit to Britain in 1948, Pauling depicted the gene as two congruent templates with com-plementary structures, each to ‘serve as the mould for the production of a replica of the other part, and the complex of the two complementary parts thus can serve as the mould for the production of duplicates of itself‘ .24 Pauling made no use of his concept of the gene as paired templates with structural complementarity in constructing his model for DNA in 1953; with other protein chemists, he was not yet convinced that DNA alone was the primary genetic substance.The twenty natural amino acids appeared to offer far more diversity by permutation and combination than the four nucleic acid bases. With hindsight, the 1944 work of Oswald Avery (1877-1955) and his associates at the Rockefeller Institute Hospital, showing that the substance transforming the non-virulent pneumococcus to the virulent form was purely DNA, is generally regarded as the first definitive evidence that the genetic material consists of DNA.Avery himself made this claim, against the opposition for several years of protein chemists such as his colleague Alfred Mirsky at the Rock- efeller.25 Pauling ’s model for DNA, three polynucleotide chains coiled helically around an internal core of hydrogen-bonded phosphate groups, was flawed from the outset by the assump- tion that the P-0-H groups (pK, ca. 2) remain undissociated under physiological conditions (pH ca. 7) to provide the hydrogen bonding. It was left to Francis Crick and James Watson in 1953 to combine Pauling’s method of model building and his conjecture that the genetic material consisted of paired complementary structures, with the view that DNA was indeed the genetic substance, to construct the successful double-helix model of DNA with antiparallel complementary strands.One of Pauling’s coworkers at Pasadena, Harvey Itano, working on the electrophoresis of haemoglobins found in 1949 that the haemoglobin from patients suffering from sickle-cell anaemia carries a charge less negative than that of normal haemoglobin. Individuals carrying the sickle-cell trait had haemoglobins of both charge types in comparable quantities. These individuals were the heterozygotes with paired genes, one for normal and the other for sickle-cell haemoglobin, affording some protection against the malaria parasite. Pauling and Itano termed sickle-cell anaemia a ‘molecular disease’, arising from a mutation in the protein moiety of haemoglobin which changed an acidic amino acid of a polypeptide chain to a neutral or basic type.Bulk analysis of the animo acid composition of the two types of haemoglobin protein showed only that any difference was too small to be detected by this method. Similarly, Perutz at Cambridge detected no difference in the X-ray diffraction pattern of the two types of haemoglobin. His colleague in the MRC unit, Vernon Ingram, adopted for the haemoglobins the methods used by the Cambridge biochemist, Frederick Sanger, to determine the amino acid sequences of the two polypeptide chains of insulin, completed in 1955. Ingram in 1956 digested normal and sickle-cell haemoglobin with the enzyme trypsin, which specifically cleaves polypeptide chains on one side of a lysine or an arginine position, to obtain some thirty fragments about ten units in each case.Separation by paper chromatography and electrophoresis showed that the fragments from normal and sickle-cell haemoglobin matched one-to-one in all but one case. Subsequent sequencing of the two non-matching fragments demonstrated that an acidic glutamate residue in the fragment from normal haemoglobin had been replaced by a neutral valine residue in the sickle-cell haemoglobin fragment. The technique of trypsin cleavage of proteins, and the characterisation of the oligopeptides formed, was taken up widely from the late-1950s. Pauling’s group at Pasadena analysed the trypsin oligopeptide pattern of the haemoglobins from a number of animals in 1960, with the view of tracing genetic descent and evolution at the molecular level.In 1962 and 1965 Pauling and Zuckerkandl26 compared the amino acid sequences of haemoglobin proteins available from a variety of species with the fossil record to construct a ‘molecular evolutionary clock’, calibrated to an average of one amino acid mutational change per polypeptide chain every seven million years. Each present-day protein, it was assumed, embodies its own evolutionary history. They correlated changes in homologous polypeptide chains, due to amino acid substitutions, with the dates at which each of the species emerged in the fossil sequence, to obtain three types of evolutionary information: first, the probable amino acid sequence of the ancestral polypeptide from which the chains compared had been derived; second, the approximate epoch at which the divergence had begun; and third, the lines of descent of the changes in the amino acid sequences. Thus the a-and the p-chains of the human haemoglobin tetramer (a$2), show 78 amino acid differences, so that the two chains diverged from a common origin, by gene duplication, some 565 million years ago, around the beginning of the Cambrian period.The common origin, the single chain of a monomeric haemoglobin, has a modern representative in the blood of primitive jawless fishes, such as the lamprey and the hagfish. This monomer lacks the cooperative oxygen uptake and release that evolved with the haemoglobin tetramer. After some initial scepticism, the concept of the molecular evolutionary clock and the method of comparing homologous polypeptide sequences were widely adopted for the construction of genealogical trees of organic descent.As amino acid replacements in a protein are the tertiary product of nucleotide substitutions in DNA, through transcription and translation, more detailed evolutionary information became available from comparisons of homologous nucleotide sequences, after the characterisation of the genetic code during the mid-1960s. The degeneracy of the code indicated that approximately one-third of the primary mutations in coding DNA result in no change of the amino acid residues in the polypeptide coded. Consideration of these synonymous DNA mutations, ‘silent’ at the tertiary protein level, established that biomolecular evolution depends upon the flow of time, the number of elapsed years, rather than the number of successive organic generations.The pioneering innovations of Pauling in the study of biomolecular phylogeny were recognised in 1969 by Kimura,27 who proposed ‘the pauling’ as the term for the standard ‘molecular evolutionary unit’ of amino acid substitutions for each protein site per year. By the 1990s, Pauling had come to be regarded as a principal founder of molecular biology, for the range and impact of his contributions to the subject.28 4 International peace and global fallout Pauling subscribed to a long-established radical tradition, directed to the benefit of human kind at large through the advance of science and its application to social and technical problems.the ‘Luther of medicine’, Paracelsus (1493-1541), strove to transform the wealth-seeking metallurgical alchemy of earlier times into a new iatrochemistry with more humanitarian medical aims, securing a substantial following among the apothecaries and religious nonconformists of the seventeenth century. Iatrochemistry evolved with van Helmont (1579-1 644) into pneumatic chemistry, to which the Unitarian minister, Joseph Priestley (1733-1 804), made spectacular contributions. Priestley’s attempts at social and religous reform met with such crude and irrational reaction, the torching of his manse, laboratory and library in Birmingham, that he felt obliged to emigrate to the newly independent United States of America in 1794. Like Joseph Priestley, Linus Pauling was gifted with a fertile scientific imagination and worked largely by chemical intuition, regarding mathematics as the handmaiden rather than the queen of the sciences.Both adhered to the concepts of their youth long after these ideas ceased to be productive, Priestley to the phlogiston theory, Pauling to his resonance theory of chemical bonding. Both addressed social questions of concern to humanity at large, so attracting charges of disloyalty from some politicians of the time. Pauling chose as an epigraph for this General Chemistry (1957) and his College Chemistry (1964) an excerpt of a latter from Benjamin Franklin to Joseph Priestley, written in 1780, rejoicing in the progress of the natural sciences, with the lament, ‘0that moral Science were in as fair a way of improvement’. Linus Pauling and his wife, Ava Helen Miller (d.1981), a fellow student at Oregon Agricultural College, whom he had taught in 1922 and married in the following year, supported Roosevelt’s New Deal, widely opposed as socialist paternalism in Republican California. After the fall of France early in 1940 they joined the Union Now movement for a federation of the world democracies under US leadership against totalitarianism. In 1941 Pauling fell victim to Bright’s disease, often considered incurable at that time, but he gradually recovered on a low- protein, salt-free diet, allowing his damaged kidneys to heal.Within a year he was back at Caltech, engaged on military research into new forms of rocket propellants, the growth of synthetic quartz for sighting optics, the development of a synthetic blood plasma, and an instrument for measuring oxygen levels in confined spaces, as in aircraft or submarines, based on the paramagnetism of oxygen. Truman in 1948 awarded Pauling the Presidential Medal of Merit, the highest US civilian award, for his war-time projects. In 1946 Pauling joined the Emergency committee of Atomic Scientists, chaired by Albert Einstein (1879-1955), set up to inform the public of the realities and the consequences of the development of nuclear weapons. In his public lectures on atomic weaponry Pauling called for negotiations to solve all Cold War issues peacefully.President Truman introduced the loyalty oath for all federal employees in 1947, to weed out Communists and their associates, and the peace movement was soon labelled ‘The Communist Peace Effort’ by Senator Joe McCarthy and his followers. As President of the American Chemical Society in 1949, Pauling strongly criticised the denial of an academic career to talented young American scientists who were alleged to have present or past Communist associa- tions, including his own former students. The FBI-funded informer, Luis Budenz, required to produce new names, denounced Pauling as a Communist in 1950 and in 1952, and his evidence was dismissed as hearsay gossip only in 1970.Pauling preempted summonses from state and federal un- American activities committees in 1950 by a public declaration, lodged with the President of Caltech, that he was a Rooseveltian Democrat, and was not, nor ever had been a Communist, and that he had no objections to legitimate loyalty oaths, genuinely grounded on national security. Despite Pauling ’s affirmations of loyalty, he was denied a US passport in 1952 when he was invited to speak on his new polypeptide conformations at a Royal Society Discussion on Proteins in London. In response he organised his own protein research conference at Pasadena in 1953, but the British pioneer of protein X-ray crystallography, Dorothy Crowfoot Hodgkin (1910-1994)’ was denied a US visa to attend the conference.Fearing an even greater international protest than that of 1952, the US State Department restored Pauling’s passport for unrestricted travel in late 1954, shortly before the ceremony in Stockholm awarding him a Nobel Prize ‘for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances’. Chemical Society Reviews, 1997 35 McCarthyite hysteria during this period was such that Patrick Blackett (1897-1974), the former coworker of Rutherford and a future President of the Royal Society, was denited entry to the USA following the critical analysis of his book, Military and Political Consequences of Atomic Energy (1 948), which exposed the fallacies of those who ‘thought the unthinkable’, and who advocated preemptive atomic bombing of the Soviet Union.Blackett was then arrested when an intended overflight from Mexico to Canada had to make a refuelling stop in the USA.29 Counter hysteria in the Soviet Union extended to denunciations of all things American, including Pauling’s resonance theory of the chemical bond over the years 1949-1 952.30 The ‘valence structures’ contributing to a given ‘resonance hybrid’ were denounced as ‘idealistic’ and ‘wholly imaginary’, rehearsing the criticisms made in western Europe by a brother of the MO theorist, the chemist Walter Hiickel (1895-1973), and by his English tran~lator.3~ Pauling responded in 1957 at an international biochemistry meeting in Moscow, and again in 1961 at the Moscow celebrations of the 250th anniversary of the birth of the pioneer chemist Lomonosov (1711-1765),32 giving a dozen or so lectures on the achievements of the ‘corrupt’ resonance theory of chemical bonding, on inherited molecular diseases and the underlying molecular mechanisms of Mendelian genetics, a productive science in contrast to unfruitful Lysenkoism, and on the global dangers of radioactive fallout from nuclear weapon testing, emphasising the outstanding need for negiotiated international peace.The criticisms of the ‘Ingold-Paulingites’ soon faded away in the Soviet Union, but they resurfaced briefly in Britain in 1976,33 provoking Pauling’s spirited defence, with a recapitulation of the history of resonance theory in quantum mechanics and in ~hemistry.3~ After the award of his first Nobel Prize, Pauling promoted more actively the campaign to halt the further testing of nuclear weapons, particularly when Japanese radiochemists showed, from the isotopic composition of its exceptionally heavy fallout, that the US Bikini Atoll test of 1954 involved a new fission- fusion-fission device, a hydrogen bomb encased in a shell of uranium-238 (the U-bomb).Pauling subscribed to the manifesto drawn up by Einstein and Bertrand Russell in 1955, calling on the governments of the world to find peaceful means to settle all matters of dispute between them, and contributed to the ensuing Pugwash Conferences. These conferences took their name from the first meeting place, the Pugwash estate in Nova Scotia of the first sponsor, Cyrus Eaton, a Cleveland industrialist.Among those present were the vice-president of the Soviet Academy of Sciences, a former director-general of the World Health Organisation, and three Nobel Laureates. In all controversy, Pauling was an assiduous collector of precise data as a basis for secure conclusions. Much of the data on the local radioactive fallout from the atomic bombs dropped on Hiroshima and Nagasaki in 1945 were in the public domain, but less was known of the radioactive products from atmos- pheric tests of the later H-bomb and U-bomb. In the mid-1950s it emerged that each test produced a substantial pulse of radioactive carbon- 14 from the transmutation of atmospheric nitrogen, as well as dust fallout.The carbon-14, with a halflife of some 5600 years, dispersed globally as carbon dioxide, entering the food chain to produce additional mutations in all plant and animal life. Willard Libby (1908-1980), who was a member of the US Atomic Energy Commission, and received the 1960 Nobel Prize in chemistry for his invention of the carbon-14 dating method, estimated that the carbon- 14 produced in atmospheric nuclear tests was an unimportant hazard compared to the carbon-14 generated by cosmic rays. Pauling used Libby’s own data to show the enormity of the new hazard. Over the period of the next scheduled series of atmospheric nuclear tests, the addi- tional mutations, due to the carbon- 14 generated, would be responsible for 500,0000 more miscarriages, 55 000 more children born with gross physical and mental defects, and as much leukaemia and bone cancer as had been generated by the fission products of all the previous nuclear tests combined.After his lecture on the global ecological consequences of nuclear weapons tests at Washington University, St Louis, in 1957, Pauling was joined by the biologist, Barry Commoner, and the quantum theorist of atomic spectroscopy, Edward Condon. They set up a petition to all nations from scientists worldwide, calling for an end to the testing of nuclear explosives. Commoner had measured the level of radioactive strontium-90 from fallout in the milk teeth of children across North America, and Condon had been a prominent target of unAmerican activities for many years, being obliged to resign as Director of the National Bureau of Standards in 195 1.35 During 1958, Pauling sent a copy of the petition opposing nuclear weapon testing, with endorsements by 1 1 02 1 scientists from 49 countries, to Dag Hammarskjold, the Secretary General of the United Nations Organisation in New York.The signatories included 2705 American scientists, 40 of them members of the US National Academy of Sciences, 216 members of the Soviet Academy of Sciences, 35 Fellows of the Royal Society of London, and 36 Nobel Laureates. Pauling enlarged on this theme in his 1958 book No More War! with an appeal for the peaceful settlement of political differences by negotiation.Public opinion worldwide led the nuclear powers to schedule test-ban negotiations in Geneva for late 1958. In the meantime 63 nuclear devices, one third of the total since 1945, were tested in the ten months before the talks. A moratorium on nuclear weapon testing was agreed at the end of 1958 by the USA, the UK and the USSR, but not by France. When the French tested their first atomic bomb in the Sahara desert in 1960, Khrushchev announced the end of the voluntary test-ban agreement, and a large Soviet nuclear bomb was tested in 1961 on the island of Novaya Zemlya. The 1961 test was opposed by Andrei Sakharov (1921-1989), the ‘father of the Soviet hydrogen bomb’, who advised Khrushchev that a global agreement could probably be reached to confine tests to deep underground sites, even though an absolute ban internationally on all nuclear weapon tests was unrealistic, as shown by the French action.This would avoid the ecological hazards of radioactive fallout and the addition of further carbon-14 to the atmosphere worldwide.36 Khrushchev was persuaded, and in 1963 the partial test-ban treaty was agreed with President Kennedy and Prime Minister MacMillan banning nuclear weapon testing in the atmosphere, the oceans, and in outer space. On the day that the treaty came into force, the Norwegian Committee responsible for the Nobel Peace Prize awarded the Peace Prize deferred from 1962 to Pauling. Sakharov received the 1975 Peace Prize when his influence upon Soviet policy and his liberal humanism became generally known.By that time Sakharov’s social manifesto Reflections on Progress, Coexistence and Intellectual Freedom (London, 1968) had been translated into English from the samizdat circulating in the Soviet Union, calling for tolerance, openness, and purely peaceful competition between the USA and the USSR. The publication led to Sakharov’s loss of Soviet security clearance and his transfer to the Lebedev Physics Institute in Moscow, where he had devised the magnetic thermonuclear reactor, the tokomak, in 1950. Following the award of a Nobel Peace Prize and his opposition to the war in Afghanistan, Sakharov was exiled to Gorki (Nizhniy Novgorod) 1980-1986, but kept his post at the Lebedev Institute and was often visited by colleagues.Pauling was harassed to a degree after presenting the collectively signed petition opposed to nuclear weapon testing to the United Nations in 1958, and his Nobel Peace Prize in 1963. He was ordered to appear before the Senate Internal Security Subcommittee, which termed him ‘the number one scientific name in virtually every major activity of the Communist peace offensive in this country’. The Committee questioned the authenticity of some of the 11 021 signatures of scientists endorsing the petition, and enquired into the source of 36 Chemical Society Reviews, 1997 the funding employed in their collection, alleged to run to some $100000. The Committee compared their own list of signatures with the originals produced by Pauling.He declared the costs of the collection to be some $250 for the postage stamps of mailings from his home address to scientific colleagues overseas, who obtained an average of 15 signatures each. An extraordinary headline in Life Magazine, ‘A Weird Insult from Norway’, greeted the award of the Nobel Peace Prize to Pauling. The editorial declared that the limited test-ban treaty had nothing whatsoever do do with Pauling’s 1958 petition to the UN from scientists worldwide.37 At Caltech the President, Lee DuBridge, under pressure from the Trustees, asked Pauling in 1958 to resign as Chairman of the Division of Chemistry and Chemical Engineering, a post he had held for twenty-two years.Although Pauling had professorial tenure, his salary was frozen, and the area of his laboratory space was progressively eroded. Even his Nobel Peace Prize in 1963 met with a chilly response at Caltech. President DuBridge decleared ‘there is much difference of opinion about the value of the work Professor Pauling has been doing’ for world peace and averting nuclear war. Pauling thereupon resigned from his chair at Caltech, in his sixty-third year. Pauling also resigned from the American Chemical Society in 1963, when the Board of Directors declined to withdraw (what he considered to be) misrepresentations in Chemical & Engineering News of his campaign for the banning of nuclear-weapon tests. Fig. 2 Linus Pauling in later life (courtesy of the Royal Society of Chemistry Library and Information Centre) 5 Molecular medicine After resigning from Caltech, Pauling accepted a position 1964-1967 at the Santa Barbara Center for the Study of Democratic Institutions.The Center had no laboratories, being devoted to the social sciences, and Pauling turned to theoretical studies of atomic nuclei and to evolutionary and medical issues arising from his earlier work in biological chemistry. He developed a close-pack spheron theory of nuclear properties, but physicists were unimpressed and he soon abandoned this field. Since his interests in biological and medical chemistry required access to laboratory facilities, he moved on to the University of California at San Diego 1967-1969, and then the University of Stanford 1969-1974.A network of supporters organised the funding and maintenance 1974-1994 of his own centre, the Linus Pauling Institute of Science and Medicine, at Palo Alto, California. Pauling’s concerns with medical chemistry dated back to his early studies of haemoglobins. He had close contacts with the biologists at Caltech, particularly the geneticists studying the mutations produced by X-rays in the fruitfly, then in a simpler organism, the pink bread mould Neurospora crassa. George Beadle (1903-1989) and Edward Tatum (1909-1975) traced out the biosynthetic pathways in Neurospora by generating mutants which could no longer produce an intermediate substance in a given metabolic sequence, and so required the addition of that substance for normal growth.Their studies from 1941 created the new field of biochemical genetics, with the slogan ‘one gene-one enzyme’. The work, recognised by the award of the 1958 Nobel Prize for medicine or physiology to Beadle, Tatum and Joshua Lederberg, drew attention to the long-neglected medical studies of Archibald Garrod (1857-1936) at St. Bartholomew’s Hospi- tal, London. Garrod investigated rare inherited diseases running in families, such as the production of black urine (alcaptonuria) and analogous disorders. Garrod in his book, Inborn Errors of Metabolism (1909, 1923) ascribed such diseases to a genetic error of recessive Mendelian character, leading to the loss or malfunction of an enzyme essential for a particular step in normal metabolism.Pauling drew on the new field of biochemical genetics for his characterisation of inherited haemoglobin abnormalities as molecular diseases. He developed the view that the human nutritional needs for the vitamins, due to the genetic loss of stages in common metabolic pathways, were not always met by normal foodstuffs, and often required augmentation. The loss of a capacity to manufacture essential biomolecules, available from foodstuffs, had lightened the overall biosynthetic load, giving the affected organisms an advantage in natural selection. Thus, organisms had developed the biosynthesis of ascorbic acid, vitamin C, as an anti-oxidant when photosynthetic oxygen began to appear in the atmosphere.Some 25 million years ago the common ancestor of the hominids and other primate species lost the liver enzyme converting L-gulonolactone to ascorbic acid, following a genetic mutation. Other mammalian species, except for the guinea pig and a fruit-eating bat, retained vitamin C biosynthesis, as did most of the vertebrate species. The loss of vitamin C biosynthesis had little adverse affect on the early development of humankind, judging from the skeletons of palaeolithic hunter-gatherers, who appear to have been as large and well-built as modern Americans. Following the development of agriculture, and the early urban civil- isations, the human diet was based largely on grains, which produced small and stunted people, judging again by their skeletal remains.From the 16th century on, the long voyages of geographical exploration, and then of overseas trade and colonisation, promoted the deficiency disease of scurvy, alleviated by the addition of citrus fruit juice to the diet. Early 20th century studies of such deficiency diseases resulted in the discovery of the vitamins and their biochemical role in normal human metabolism. Pauling noted that many people in modern urban societies live close to the edge of vitamin deficiency. The National Research Council under the US National Academy of Sciences has a Committee on the Feeding of Laboratory Animals, and a Food and Nutrition Board concerned with human diet. The Committee recommends an optimum daily intake of vitamin C (ascorbic acid) for laboratory primates, between 1.75 grams per day for rhesus monkeys and 3.50 grams per day for squirrel monkeys, scaled to 70 kg body mass.The Nutrition Board, however, recommends a human allowance of only 60 milli- grams per day, corresponding to the minimum human intake of vitamin C required to avoid scurvy. Animals which manu- facture their own ascorbic acid produce an average of ca. 10 g per day, scaled to 70 kg body mass. Pauling deduced that the Chemical Society Reviews, 1997 37 diet of an adult human should contain at least 2.3 to 10 g of vitamin C per day. The human immune system depends for efficient action on the vitamin level available in its several components, and some of these levels are depleted during a viral attack.The common cold virus reduces by one half the vitamin C level in leucocytes, impairing their action as phagocyctes. A regular daily intake of 0.25 to 4 g of the vitamin decreases the chances of catching a cold or influenza and of developing a secondary bacterial infection. Some 16 trails, with placebo-taking controls, showed a decrease in illness of 34% on average, even though the daily dose of vitamin C administered, 0.07 to ca. 1 g, was smaller than the dose Pauling recommended. Pauling found that the habitual colds from which he suffered were reduced in number and severity by taking several grams of vitamin C each day from the rnid-l960s, as described in his book, Vitamin C and the Common Cold (1970), which enjoyed wide popular appeal.By the 1990s substantial support had emerged for a reduction of the severity, if not the frequency, of common colds by vitamin C administration. The medical profession in general dismissed Pauling ’s work, but individual physicians had made similar or related trials and reported their experience to him. In 1971, Pauling heard from Ewan Cameron, surgeon of the Vale of Levan Hospital near Glasgow, who had treated terminal cancer patients with 10 g of vitamin C a day over several years, finding that the treatment extended the survival time and the quality of life of his patients. Cameron held that vitamin C reinforced connective tissues that were weakened in cancer as in scurvy. Collaboration followed, with trials of vitamin C for the treatment of animal cancer at Pauling’s Institute, and the visit of Cameron for a year in 1978, resulting in a joint publication of the book, Cancer and Vitamin C (1979). The US National Cancer Institute (NCI) sponsored trials in the 1970s which reported no benefit to cancer patients from large doses of vitamin C.Pauling pointed out that Cameron’s protocol had not been adopted in these trials. By 1990, the NCI was more sympathetic, and sponsored an international symposium on ‘Vitamin C and Cancer’ with Pauling as a main speaker. The symposium, and a New York Academy of Sciences meeting in 1992, brought to light the general role of vitamin C and vitamin E as antioxidants, quenching the free radicals implicated in the genesis of cancer and other maladies.38 In his last book, How to Live Longer and Feel Better (1986), Pauling summarised the evidence and outlined the potential of his ‘orthomolecular medicine’.His therapy involved the boosting of normal essential metabolites to an optimum level, usually higher during illness than in normal health. These substances are generally limited in supply from foodstuffs or commensal gut flora, and have a wide range of beneficial functions and of tolerance in the body. In contrast conventional medicine involved the administration of physiologically alien natural or synthetic pharmaceutical products, with specific therapeutic effects, undesirable side-effects, and often-limited tolerance. His approach led Pauling to support and popularise medical reports of the value of vitamin treatments of viral and cardiovascular diseases, cancer, some forms of mental retarda- tion or mental disorder, allergies, arthritis and rheumatism, and the moderation of the infirmities of old age.Pauling attracted the support of physicians in the Ortho- molecular Medical Association, which numbered some 500 members by 1986. Albert Szent-Gyorgyi (1 893-1986), who had first isolated ascorbic acid in 1928, receiving the 1937 Nobel Prize in medicine and physiology for his discovery of the biochemical dicarboxylic-acid oxidation cycle, joined the crusade for vitamin C supplementation, as did other bioche- mists. Szent-Gyorgyi wrote in 1970 that the medical profession misled the public by specifying only the ascorbic acid intake required to avoid scurvy, which he called ‘a premortal syndrome’.The optimum vitamin C intake was uncertain, but Szent-Gyorgyi considered it to be much higher than the medical recommendation, and he himself took about a gram a day. Pauling allowed for biochemical individuality, recommending his readers to discover their own optimum daily intake of vitamin C, which he thought probably lay between 6 and 18 g. He specified a daily supplementation of other vitamins and minerals, together with regular exercise and dietary moderation, particularly sucrose and alcohol, to promote a general regimen for longer life and better health. 6 Conclusions Pauling’s remarkable achievements came from his fecundity of imagination, the zealous collection of data to frame his theories, and a crusading spirit to popularise his conclusions.He confessed that many of his new ideas turned out to be non- productive. Examples from his troubled 1960s were his spheron theory of the atomic nucleus (1964-1967), or his theory of general anaesthesia (1961-1965). The latter theory illustrates Pauling’s general approach of coordinating diverse studies of a common subject. From the discovery of the anaesthetic action of xenon, and the X-ray analysis of the clathrate hydrate crystals formed by the noble gases, Pauling surmised that anaesthetic action involved the formation of clathrate crystals in nervous tissue around the anaesthetic agent, thereby reducing the electrical activity of the nerves and the brain.Clearly, he was extraordinarily versatile. He engaged in each of his highly productive enterprises for a decade or so, then left further development to others and took up new projects. His theories of atomic orbital hybridisation, atomic electronegativ- ity, and covalent bonding through electron-resonance between valence structures, had matured by the mid-l930s, and he left further extensions to George Wheland and others. Pauling was one of the pioneers of crystal and molecular structure analysis by X-ray diffraction during the 1920s, and countered the early limitations of the technique by the strategy of model-building to determine the secondary structures of biopolymers from the late 1930s. By the time that the electronic computer allowed direct X-ray crystal structure analysis of complex molecules Pauling had moved on to comparative studies of the amino acid sequences in the polypeptide chains of the haemoglobins, deriving the concept of the ‘molecular evolutionary clock’ (1960-1965). Subsequent comparisons of the nucleotide se- quences in ribosomal RNA he left to other workers.In his later years, Pauling was alert to striking or puzzling discoveries with no ready interpretation. In the 1980s he joined in the speculations on a basis for high-temperature super- conductivity, and for the paradoxical fivefold rotational sym- metry found in the diffraction pattern of quasicrystalline alloys. He had been interested in the structure of intermetallic compounds from 1923 and, in the first of his contributions to the 1991 symposium, celebrating the centenary of Caltech and his ninetieth birthday, Pauling presented the evidence he had gathered over the years for the thesis that these quasicrystals are essentially icosahedral twinnings of cubic crystals with large unit cells.At Caltech the disapproval of trustees and administrative officials of Pauling’s political activities declined after his departure in 1963. Later trustees and officials appreciated that both of Pauling’s Nobel Prizes enhanced the standing of Caltech. After a symposium in 1986 celebrating his eighty-fifth birthday, Caltech honoured him by instituting the Linus Pauling Professorship of Chemistry, together with a lecturehip and lecture hall bearing his name.His efforts to eliminate the global dangers of increased radioactivity in the biosphere from nuclear weapon tests, and his campaign for negotiated world peace, were increasingly appreciated over time, and he came to be regarded as the American scientist comparable to the Russian physicist, Andrei Sakharov, for humanitarian leadership of the scientific community worldwide during the chillier years of the cold war. Historically, Pauling takes a place among the major figures in the development of modem chemistry, recapitulating some of 38 Chemical Society Reviews, 1997 their contributions and social concerns at a new level. The supporters of his orthomolecular medicine reflect the Paracel- sian iatrochemists, who merged with orthodox medicine, as their more successful innovations, such as the treatment of anaemia with iron salts, were generally adopted.Pauling’s opposition to the contamination of the atmosphere with the radioactive products of nuclear weapon tests recalls Joseph Priestley’s dismay, during the early phase of the industrial revolution, with the degradation of our atmosphere, the providential sustainer of the breath of life. Priestley ’s concern led him to introduce his nitric oxide test for ‘the goodness of the air’, then to discover the atmospheric component supporting vitality, oxygen (1774), and the property of green plants in sunlight to restore the oxygen lost from air ‘spoiled’ by respiration or combustion. The influence of Pauling’s resonance theory of chemical bonding from the 1930s to the 1950s was comparable to that of Berzelius’s dualistic theory from the 1820s to the 1840s.Both theories, with the common concept of a universal scale of atomic electronegativities, appealed primarily to inorganic chemists. Theoretical physicists regarded both theories as primitive, relative to the current principles of physics, classical electrostatics in the 1820s and quantum electromagnetism in the 1930s. Each theory first lost ground in the organic field. During the 183Os, such discoveries as the replacement of electroposi- tive hydrogen by electronegative chlorine in acetic acid to give products of a common vinegar-type cast doubts on the theory of dualistic electropolar chemical bonding.Likewise, the con- firmation in the late-1940s that cyclooctatetraene is indeed an olefinic substance, with none of the aromatic properties of benzene, indicated that resonance theory of unsaturated organic molecules was flawed. Pauling worked in so many different fields that he had no single contemporary peer in chemistry. Biochemistry, mole- cular biology, and geochemistry, he held, were all chemical sciences, alongside the mainstream subdivisions, and so too were the nutritional and pharmaceutical aspects of medicine. The range of his major contributions over these sciences mark him out as the greatest chemist of the century.39 7 References 1 Structural Chemistry and Molecular Biology, ed.A. Rich and N. Davidson, Freeman, San Francisco, 1968, pp. 907. 2 The Roots of Molecular Medicine: A tribute to Linus Pauling, ed. R. P. Huemer, Freeman, New York, 1986, pp. 290. 3 The Chemical Bond: Structure and Dynamics, ed. A. Zewail, Academic Press, London, 1992, pp. 313. 4 Linus Pauling in his own words, ed. B. Marinacci, Simon and Schuster, New York, 1995, pp. 320. 5 A. Serafini, Linus Pauling: A man and his science, Paragon House, New York, 1989, pp. 310. 6 T. Goertzel and B. Goertzel, Linus Pauling: A life in science and politics, Harper Collins, New York, 1995, pp. 300. 7 T. Hager, Force of Nature: The Life of Linus Pauling, Simon and Schuster, New York, 1995, pp. 721. 8 Patterns in ink, pp.255-276 in ref. 6. 9 J. W. Servos, Physical Chemistryfrom Ostwald to Pauling: The Making of a Science in America, Princeton University Press, Princeton, NJ, 1990, pp. 275-298. 10 K. J. Laidler, The World of Physical Chemistry, Oxford University Press, 1993, p. 352. 11 R. S. Mulliken, ‘Bonding Power of Electrons and Theory of Valence’, Chem. Rev., 1931,9, 347, 369, 386. 12 L. Pauling, The Nature of the Chemical Bond, Cornell University Press, Ithaca, NY, 1960, 3rd edn., pp. 215-220; 563-570. 13 G. W. Wheland, Resonance in Organic Chemistry, Wiley, New York, 1955, p. 4: the analogy is credited to J. D. Roberts. 14 L. Pauling and E. Bright Wilson, Zntroduction to Quantum Mechanics: with Applications to Chemistry, McGraw Hill, New York, 1935, p.340. 15 K. Gavroglu, Fritz London: A Scientific Biography, Cambridge University Press, 1995. 16 L. Pauling, J.Am. Chem. Soc., 1931,53, 1367; reprintedpp. 851-884 in ref. 1. 17 J. C. D. Brand, Lines of Light: Sources of Dispersive Spectroscopy, 1800-1930, Gordon and Breach, 1995. 18 A. Duncan, Laws and Order in Eighteenth-Century Chemistry, Clarendon Press, Oxford, 1996. 19 W. B. Jensen, ‘Electronegativity from Avogadro to Pauling’, J. Chem. Educ., 1996,73, 11-20. 20 P. J. T. Morris, ‘The technology-science interaction: Walter Reppe and cyclo-octatetraene chemistry’, Brit. J. Hist. Sci., 1992, 25, 145. 21 L. Pauling, ‘Molecular Architecture and Biological Reactions’, Chem. Eng. News, 1946,24, 1375. 22 L. Pauling, ‘A Theory of the Structure and Process of Formation of Antibodies’, J.Am. Chem. Soc., 1940, 62, 2643. 23 A. M. Silverstein, A History of Immunology, Academic Press, New York, 1989, pp. 69-83. 24 L. Pauling, Molecular Architecture and the Processes of Life, 21st Sir Jesse Boot Foundation Lecture, Nottingham, 1948, p. 10. R. Olby, The Path to the Double Helix, Macmillan, London, 1974, p. 120. 25 F. H. Portugal and J. S. Cohen, A Century of DNA: A History of the Discovery of the Structure and Function of the Genetic Substance, MIT Press, Cambridge, Mass., 1977, pp. 137-158. 26 E. Zuckerkandl and L. Pauling, ‘Molecular Disease, Evolution, and Genetic Heterogeneity’, pp. 189-225 in Horizons in Biochemistry: Albert Szent-Gyorgyi Dedicatory Volume, ed M. Kasha and B. Pullman, Academic Press, New York, 1962; ‘Evolutionary Divergence and Convergence in Proteins’, pp. 97-166 in Evolving Genes and Proteins, ed V. Bryson and H. J. Vogel, Academic Press, New York, 1965. 27 M. Kimura, The neutral theory of molecular evolution, Cambridge University Press, 1983, p. 74. 28 Zewail ed., ref. 3: M. F. Perutz, pp. 17-30. F. Crick, pp. 87-98. 29 B. Lovell, ‘Patrick Maynard Stuart Blackett, Baron Blackett of Chelsea, 1897-1973’, Biog. Mem. FRS., 1975,21; 75 ff. 30 I. M. Hunsberger, ‘Theoretical Chemistry in Russia’, J. Chem. Educ., 1954, 31, 504.-31 W. Huckel, Structural Chemistry of Inorganic Compounds, 2 vols, Elsevier, Amsterdam, 1950, transl. L. H. Long, translator’s note, vol. 1, pp. 434-437. 32 Mikhail Vasil’evich Lomonosov on the Corpuscular Theory, translated with an introduction by H. M. Leicester, Harvard University Press, 1970. 33 A. R. Todd and J. W. Cornforth, ‘Robert Robinson, 1886-1975’, Biog. Mem. FRS., 1976,22,415-527, pp. 465-478. 34 L. Pauling, ‘The Theory of Resonance in Chemistry’, Proc. R. SOC. Lond. A, 1977,356,433. 35 J. Wang, ‘Science, Security, and the Cold War: The Case of E. U. Condon’, Isis, 1992, 83, 238. 36 Sakharov Remembered: A Tribute by Friends and Colleagues, eds. S. D. Drell and S. P. Kapitza, Am. Inst. Physics, New York, 1991. 37 The text of the editorial in Life magazine following Pauling’s Peace Prize award, and the comments of the Senate Internal Security Subcommittee on Pauling’s petition, are reproduced by D. A. Daven- port, ‘Letters to F. J. Allen: An Informal Portrait of Linus Pauling’, J. Chem. Educ., 1996, 73, 21. 38 Hagan, ref. 7, pp. 621-623. 39 J. D. Dunitz, ‘Linus Carl Pauling, 29 February 1901-19 August 1994, Elected For. Mem. R. S. 1948’, Biog. Mem. FRS, 1996, 42. Received, 19th September I996 Accepted, 3rd October 1996 Chemical Society Reviews, 1997 39

ISSN:0306-0012    

DOI:10.1039/CS9972600029

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Structure of water under subcritical and supercritical conditions studied by solution X-ray diffraction Hitoshi Ohtaki," Tamas Radnaib and Toshio Yamaguchic a Department of Chemistry, Faculty of Science and Engineering, Ritsumeikan University, 1-1-I Noji-Higashi, Kusatsu 525-77, Japan; E-mail: ohtaki@bkc.ritsumei.ac.jp Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest, P.O. Box 17, H-1525 Hungary; E-mail: radnait@cric.chemres.hu Department of Chemistry, Faculty of Science, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka 814-80, Japan; E-mail: yamaguch@sunspl .sc.fukuoka-u.ac.jp Structures of water and aqueous electrolyte solutions under sub- and super-critical conditions studied mainly by X-ray diffraction and also by neutron diffraction are reviewed and the experimental results are compared with those reported by using computer simulations.Some Raman spectroscopic data are included for discussing the existence of hydrogenbonds in water at high temperature and high pressures (HTHPs). The authors propose a classification of supercritical water into three categories: (a) low density water, (b) medium density water, and (c)high density water, because density is a very important thermodynamic quantity to describe properties of sub- and super-critical water. From changes in the water-water intermolecular distance and the coordination number of water with temperature and Hitoshi Ohtaki graduated from Nagoya University in 1955 and obtained MSc and DrSc degrees in I957 and 1961, respectively, from Nagoya University.He became a research associate of the Tokyo Institute of Technology in 1959. He studied complex equilibria under the supervision of Prof. L. G. SilMn, Stockholm, Sweden, as a postdoctoral research fellow from I961 to 1964. He was appointed Lecturer of Nagoya University in 1965 and promoted to Associate Professor in 1967. In I970 he moved back to Tokyo Institute of Technology as an Associate Professor, and then became a Full Professor in 1973. As Professor of the Institute for Molecular Science of the Okazaki National Research Institutes from 1988, he was the Director of the Coordination Chemistry Laboratories. On retirement in I993 he became Professor Emeritus of Tokyo Institute of Technology and the Graduate University for Advanced Studies.He was appointed as Professor of Ritsumeikan University in I993 and the Director of the Institute of Science and Engineering of Ritsumeikan University in 1994. He has published pressure, and especially with density at HTHP, the authors conclude that the compact tetrahedral-like water structure is decomposed and long-distance water-water interactions increase with temperature and pressure, and they propose a model for water: under supercritical conditions water consists of small clusters, much smaller aggregates such as oligomers, and even monomeric gas-like water molecules. 1 Introduction The structural chemistry of water has not yet been fully established even under normal conditions despite a long history of investigation after the pioneering work on solution X-ray diffraction in 1930-193 1 and the first model of water's structure by Bernal and Fowler' in 1933 on the basis of X-ray diffraction more than 200 research papers and reviews, and several books.Tamcis Radnai finished his university course in the Eotvos Lorcind University, Budapest, in I973 with a degree equivalent to an MSc. He received the Doctor University degree (corresponding to a PhD) from the Eotvos Lorand University in I977 and the academic title 'Candidate for Chemical Science', a post-PhD degree, in 1991. He served as a research associate with the Ministry of Education, Science and Culture of Japan from I987 to I989 and was invited to the Institute for Molecular Science as a Guest Foreign Associate Professor in 1991.He has worked as a member of several international research groups in Italy and Germany. He is a senior fellow of the department of solution chemistry in the Central Research Institute for Chemistry of the Hungarian Academy of Sciences. His main interest includes structural studies of electrolyte solutions by using diffraction methods, as well as computer simulations. He has published more than 60 research papers. Toshio Yamaguchi graduated from Nagoya Institute of Tech-nology in 1973, and received his PhD degree from Tokyo Institute of Technology in 1978. After terms as a postdoctoral fellow at Gothenburg Univer- sity, Sweden, from 1979 to I982 and a research associate at Tokyo Institute of Technology from 1982 to 1986, he was appointed Associate Professor of Fukuoka University in 1986, and then promoted to a Full Professor in 1994.He has pub- lished more than 100 research papers. Chemical Society Reviews, 1997 41 experiments, not to speak of the study of water's structure at high temperatures and high pressures. A large amount of thermodynamic data for HTHP and supercritical water has been accumulated in recent years. However, the structures of even simple molecular liquids without extended hydrogen-bonded networks have not been well elucidated under non-ambient conditions. Water, of course, always attracts the interest of many scientists, but due to experimental difficulties, microscopic structural investigations of water at HTHPs and under supercritical conditions have been rare until recently.Spectroscopic investigations have been performed to discuss the structure of subcritical and super- critical water on the basis of changes in vibrational and rotational energies of water molecules.2-6 However, results obtained on the structure are still limited to discussing hydrogen bonding in supercritical water. The application of computer simulation techniques such as Monte Car10 and molecular dynamics simulations has contributed to a better understanding of water's structure at the molecular level under ambient conditions and at HTHP. Several attempts have been made to study water in the subcritical and supercritical regions by using computer simula- tion techniques,7-14 but it is obvious that the reliability of the simulations can only be confirmed when the simulation data are compared with experiments.Recent technical developments for X-ray and neutron diffraction methods allow us to study the structure of water at HTHPs and even under supercritical conditions. Interest in the use of supercritical water has increased rapidly in recent years, because of the ability of supercritical water to decompose some organic waste. Geo- chemistry related to subterranean water and hydrothermal synthetic chemistry require a knowledge of HTHP solution chemistry. However, only a limited number of X-ray's-18 and neutronlg-21 diffraction studies at HTHP have so far been carried out.Nevertheless, we believe that it is worth reviewing recent results on the structure of HTHP water. The properties of supercritical water are often summarized as follows: (1) the relative permittivity (E) and viscosity (q) of water steeply decrease around the critical point, (2) the density of supercritical water at the critical point is about 113 of that of ambient water, (3) the solubility of ionic and polar substances sharply decreases in supercritical water, (4)on the other hand, the solubility of non-polar substances sharply increases in supercritical water, (5) ionic hydration markedly decreases in supercritical water. Some properties like (1) and (2) can be explained in terms of hydrogen-bond breaking of the bulk water at HTHP.However, items (3)-(5) may not always be representative of the characteristic properties of supercritical water near the critical point where the density of water is so small that it is ca. 1/3 of that of normal water. In such low-density water, the solubility of ionic and polar substances may be decreased due to the lack of water molecules to be hydrated. On the other hand, since the density of supercritical water near the critical point is so low that intermolecular water-water interactions are weakened, hydro- phobic non-polar substances can be mixed with the gas-like low density water better than with condensed water in which strong water-water hydrogen-bonding interactions exist. However, it is obvious that supercritical water can have a wide density range and at very high pressure and high temperature, far above the critical point, supercritical water can have a density of 0.8-1.0 g cm-3 (as ambient water has) and we have an extremely limited amount of knowledge of the structure of supercritical water over such a wide range of densities.The aim of the present article is to review recent results reported by using X-ray and neutron diffraction methods, IR and Raman spectroscopies and computer simulations for the structure and properties of supercritical water over a relatively wide range of density. Unfortunately, not many reports have appeared of NMR spectra, probably due to experimental difficulties. 2 Solution X-ray diffraction on sub-and super-critical water X-Ray diffraction studies of liquids and solutions at HTHP have lagged behind those under ambient conditions, because of various technical difficulties: weak scattering from the small sample volume of an HTHP cell, elimination of strong Bragg reflections from the crystalline cell, a narrow measurable range due to geometrical constraints of the cell, etc.Great progress in X-ray diffraction at HTHP has been made, however, when intense X-rays became available in synchrotron radiation facilities world-wide. The most frequently used method there is the energy-dispersive diffraction with a multi-anvil cell made of boron nitride or a diamond anvil cell, with which pressures of 10 GPa, and temperatures of 1000 "C are available, and the maximum scattering variable given by eqn.(1) s = 4 d-1 sin 8 (1) (A the wavelength and 20 the scattering angle) of 0.10 pm-1 has been attained. These sample environments are appropriate for liquids containing heavy metals, but not useful for liquids of light elements like water, since the X-ray scattering intensity from a small volume of sample is too weak to analyse with a good confidence level. In some laboratories, the energy-dispersive X-ray diffraction experiments for sub- and super-critical water were successfully made in a beryllium cell using a table-top type X-ray diffractometer equipped with a rotatory anode, at 500 "C and a pressure of 700 MPa being possible.15.16 However, the energy- dispersive method has the inherent disadvantage of complica- tion in data correction, which can be much simplified in the angle-dispersive mode, and only a limited scattering range is measurable at one time, although it does have the advantage of time saving by using a solid state detector (SSD).In order to overcome the above problems, a solution X-ray diffraction method for the angle-dispersive mode has recently been developed on a laboratory scale by using a two-dimensional imaging-plate (IP) detector.22 Figs. l(a) and (b)show two types of X-ray diffractometers with an SSD22 and an IP detector,23 respectively, which have been used for X-ray scattering measurements of water at HTHPs. In both cases a similar HTHP sample environment [Fig. l(c)] was employed with a spindle-shaped beryllium cell; the part through which the X-ray beam passed had a cylindrical form with a 6 mm outer diameter and a 1.2-2.0 mm inner diameter filled with water.A Mo-Ka X-ray beam (A 71.07 pm) was employed. The diffraction ranges of 1" c 0 c 120" by the SSD detector and 0" c 8 c 144" by the IP detector were covered in each measurement. The high pressure unit was guaranteed by the makers up to 1 GPa. The pressure resistance of the cell was checked and calibrated up to 800 MPa with an uncertainty of 0.05 MPa. The high-temperature and high- pressure sample assembly was mounted in a vertica123 or horizontaP24 manner on a high pressure support unit placed at the centre of the X-ray goniometers. The structure function sH(s) was derived from the observed intensities I(s) and is usually defined by eqn.(2). Ws) = [Icorr(s> -P(s)l/P(s>bp(-bs2) (2) wherefls) is the scattering factor for one water molecule, bis an arbitrary damping factor, and Zcorr(s)is the corrected and normalized intensity function. The pair correlation function g(r) was derived from the structure function sH(s) by the Fourier transform according to eqn. (3). [sin(sr)/ srlh (3)g(r)= 1+ (1 / 2n2p,) s2 ~(s)I where po is the average number density of the molecules, and equal to 3.34 x 10-8 pm-3 at ambient temperature and pressure. The pair correlation function represents the possibility of the existence of atom pairs with definite separations, and 42 Chemical Society Reviews, 1997 high pressure tube Joutsi,de pressure unit Fig.1 High temperature-high pressure X-ray diffiactometers. (a)A horizontal type diffractometer with an SSD detector. (b)A vertical type diffractometer with an imaging plate detector. A: diffractometer,B: beryllium cell, C: cell holder, D: slit, E: collimator, F: shield,G: imaging plate, H: imaging plate reader. (c) High temperature-high pressure cell and the holder. Quoted in refs. 23 and 24. Chemical Society Reviews, 1997 43 g(r) = 1 means that all atoms are distributed randomly so that no atom-atom pair correlation exists. Structural parameters were obtained by a least-squares fitting procedure to minimize the difference X2 between experimen- tally obtained structure function sH(s) and that from the model SHm(S) [eqns.(4) and (5)]: ~2 = Cls~(s)-s~,(s)l2 = min (4) S exp (-Ps2/2) (5)Hm (s) = pa[sin (r~)/r~] The sum in eqn. (4) was extended over each discrete svalue in the measured range. The adjustable parameters of the model function were the distance between nearest neighbouring molecules r, coordination number N, and the parameter characteristic of the width of the main peak (temperature factor) 1. Uncertainties in the values of r, N and 1 are usually 1-2 pm, 0.1-0.2, and k 1-5 pm, depending on the accuracy of measurements, the shape of the peaks, etc. An alternative definition for the coordination number may be given by computing the integral in eqn. (6): N = 4 dp0I:g(r)dr where the upper limit of the integral is extended to the first minimum rmin of the g(r) functions.There are various definitions for the upper limit of the integration, r, in the estimation of N. Diffraction researchers usually adopt the Gaussian distribution of atom pairs, and thus, the r value is the value of the upper tail of the Gaussian distribution (definition 1). On the other hand, simulation researchers usually take the r value as the point where the g(r)function passes g(r) = 1 after the first maximum (definition 2). Some researchers define the integral limit at the value where the g(r) function reaches the first minimum (definition 3), but this definition is not clear when the g(r) function has a very shallow minimum. Of course, depending on the definitions the value of N changes.This definition of the coordination number in terms of the population of atoms until the r value at g(r) = 1 after the first maximum of g(r) (definition 3) is favourable when we compare the coordination number obtained by the diffraction method and that by computer simulations. The coordination number eval- uated by using definition 3 is sometimes called Nmin. 3 Water structure at sub-and super-critical states Thermodynamic data for water at the critical point are given as follows: the critical temperature T,, 647.29 K (tc = 374.14 "C); the critical pressure pc, 22.064 MPa; the critical density pc, 0.322778 g cm-3.25 It should be noted that the critical density is approximately one third of the density of normal water, and thus, when we discuss the water structure at HTHP near the critical point, we should pay careful attention to the density of water samples.In the present paper, we divide water into three categories: (a)low density water; p < pc, (6)medium density water; pcSp < 1 g cm-3, and (c)high density water, 1 g cm-3 d p (Fig. 2). Discussion concerning the low density water will not be included in the present paper. In the high density region of water, in 1985 Gaballa and Neilsonl7 performed the first angle-dispersive X-ray measure- ments on light and heavy water at room temperature over a pressure range from 0.1 to 600 MPa; the densities change from 0.997 g CM-3 at 0.1 MPa to 1.149 g cm-3 at 500 MPa for light water and from 1.104g cm-3 at 0.1 MPa to 1.301 g cm-3 at 600 MPa for heavy water.They observed that with increasing pressure the first neighbour 0-0 peak at 290 pm in the radial distribution functions shifts to the shorter distance side and is enhanced, while the broad peaks at 440 and 700 pm ascribed to the second and third neighbour 0-0 interactions, respectively, shift to the shorter distance side and are decreased for both 44 Chemical Society Reviews, 1997 Pressurep / MPa 22 60 10 150 250 500 lo00 I I I I I I @ I I b I 8-1 0 0.5 1.0 Density p / g ~rn-~ Solid Fig. 2Phase diagram of water around the critical point. A conventional classification of the high, medium, and low density regions is shown in the diagram. Quoted in ref. 32. isotopic forms of water.These findings suggest the weakening of tetrahedral ordering in water as a result of compression, however, it should be noted that the peaks at 290,440 and 650 pm are still clearly observed even at 600 MPa, suggesting that the tetrahedral ice-like structure remains at the high pressures. They analysed the first peak at 290 pm by a least-squares fitting procedure using a single Gaussian and found that the peak position shifts from 289 pm at 0.1 MPa to 284 pm at 500-600 MPa for both light and heavy water. The rate of contraction of the 0-0 separation was estimated to be ca. 100 pm GPa-1 (0.1 %, kbar-I). The nearest neighbour 0-0 coordination number was found to increase from 4.4 at 0.1 MPa to ca. 4.9 at high pressure. More recently, Gorbaty and his coworkers18 published the results of energy-dispersive X-ray measurements of normal water at room temperature over a pressure range from 0.1 to 770 MPa.The pressure dependent features in the radial distribution functions obtained with this technique are broadly consistent with those obtained with the angle-dispersive technique by Gaballa and Neilson, but there are appreciable differences in the radial distribution functions obtained by the two different methods; a distinct shoulder appeared at ca. 320 pm, which has not been observed in the angle-dispersive data, and at ca. 600 MPa the 430 pm peak due to the second 0-0 interactions, clearly seen in the Gaballa-Neilson data, is almost invisible. They employed a least-squares fitting procedure with three Gaussians to resolve the first peak at 290 pm, a shoulder at ca.320 pm, and the background at the longer distance. The first- neighbour 0-0 distance thus obtained showed a peculiar behaviour with pressure; when the pressure was raised from 0.1 to 200 MPa, the 0-0 distance decreased from 282 to 279 pm, but then gradually increases up to 282 at ca. 400 MPa and was almost constant at higher pressures. This result is not consistent with that obtained by Gaballa and Neilson. Since the paper does not show detailed numerical results of the radial distribution functions, we cannot discuss their results in more detail. However, it is difficult to understand such a peculiar change in the 0-0 distance, which may be caused by the peak separation procedure as was noted in the paper.The above inconsistencies in the structure of the high-density water at HTHPs between the two different methods have been discussed by Radnai and Ohtaki,23 who have recently made angle-dispersive X-ray scattering experiments using SSD [Fig. l(a)] on water in the medium-density to high-density region (d = 0.896-1.072 g cm-3) over temperature and pressure ranges of 295-473 K and 0.1-200 MPa, respectively. The radial distribution curves obtained in this work are shown in Fig. 3. The structural parameters finally obtained are summarized in Table 1. The structural data at the different temperatures under vapour pressure agree well with the literature values measured at 298 K and 0.1 MPa (r = 287 pm and N = 3.33 and I-= 285 pm and N = 3.53), at 373 K under vapour pressure (r = 291 pm and N = 3.33), and 473 K under vapour pressure (r = 297 pm and N = 3.03).The structural parameters obtained under normal conditions are also in good agreement with the values obtained in previous X-ray diffraction measurements under similar experimental conditions.15-18.26 As can be seen in Fig. 3, the broad peaks centred at 450 and 600 pm diminish with the increase in temperature, but they did not significantly change Table 1 Structural parameters of water at 295-485 K and 0.1-200 MPa (quoted in ref. 23) 295 (22) 0.I 0.998 286 343 3.4 295 (22) 100 1.038 283 332 3.7 295 (22) 200 1.072 282 326 4.0 373 (100) V.p.1 0.958 292 355 2.5 373 (100) 10 0.963 290 343 2.5 373 (100) 50 0.980 288 358 2.0 0.864 297 368 2.7473 (200) V.P.' 473 (200) 10 0.872 296 358 2.2 " ' " ' ~ ' " ' " ~ ' ' " 0 600 800 t I 0 200 400 600 800 rlpm 473 (200) 50 0.896 2 84d 375 2.2d Densities are quoted from the literature. rmln denotes the r-value at the first minimum after the first main peak in the radial distribution curve.V.p. indicates that the water is equilibrted with the vapour pressure under the given conditions. d Corrected values of those in ref. 23, unpublished data. with pressure. The results indicate that temperature mainly affects both medium- and long-range ordering in the hydrogen- bonding network of water investigated, as has been discussed by many authors.The variation of the first peak at 285 pm with temperature and pressure gives us information about the effect of temperature and pressure on the hydrogen bonding in water. This topic will be discussed below. In the medium-density range of water and supercri tical water, lo00 Gorbaty and Demianets published the first results of energy- dispersive X-ray diffraction of water over a temperature range of 298-773 K at a constant pressure of 100 MPa, with densities 1.1-0.7 g cm-3.15.16 The second peak at 450 pm in the radial distribution function, which provides strong evidence for tetrahedral ordering in water, diminishes gradually and is not observed at the subcritical temperature of 623 K. These findings show that the ice-like short-range order does not exist above this temperature.Furthermore, the peaks at 450 and 700 pm merge into one peak at ca. 600 pm. The position of the first peak changes linearly from 280 pm at 298 K to 304 pm at 773 K. They pointed out that the value of 304 pm at 773 K is shorter than the nearest-neighbour distance of 3 11 pm in liquid neon at the same reduced temperat~re,~' indicating the presence of hydrogen bonds even at the highest temperature. They resolved the first peak into three Gaussians, i.e.the peaks at ca. 290 and 330 pm and the background. On the basis of the X-ray data together with IR spectral data, they calculated a parameter x = alrJ(alrl+ azr:!), as an estimation of the fraction of hydrogen bonds in water,?' where rl and r2are 290 and 330 pm, respectively, and the a1and a2 are their peak areas.The x value changed linearly from 0.55 at room temperature to 0.2 at 773 K and was expressed by the empirical equation x = (-8.68 10-4)T + 0.85I with the absolute temperature T. According to this equation, it would be expected that the hydrogen bonds persist to ca. 30% at the critical temperature. Recently, Yamaguchi and his gro~p2~ reported a result on the water structure at HTHPs including a supercritical region over temperature and pressure ranges of 300-649 K and 0.1-98.1 MPa, respectively, using an HTHP X-ray diffractometer combined with an IP detector22 [Fig. l(h)]. They examined the water structure at constant densities from 1-0.7 g ~m-~ with varying both temperatures and pressures. The measurement has the advantage in investigating the structure change in water with temperature and pressure without significant modification of the nearest-neighbour 0-0 dis-tances by density variation.The radial distribution function is defined as eqn. (7). loo0 Fig. 3 Pair correlation functions g(r) of water at various temperatures and -4nr2p, = (2r / n) sr CIS (7)pressures. Dashed lines represent data obtained by Narten and Levy.26 ~(r) Quoted in Ref. 23. Chemical Society Reviews, 1997 45 where i(s) = K Io&) -and XY Here, po denotes the average scattering (electron) density of water, and M(s) = ~(0)/#’2(s)]exp(-O.Ols2).K is a constant to convert the scattering intensities lobs(s)to the absolute electron unit, nj the number of atoms j in a unit volume, x and y the atom pair of x and y,f,(s)the scattering factor of atomj at s, Afl(s) and Afi”(s) the real and imaginary parts of the anomalous dispersion term, @(s) the degree of incoherent scattering intensities Ijinco(s) reached the counter by atomj at s, ng the frequency factor or the coordination number of atom x around atom y, rxythe distance between atoms n and y, bg the temperature factor of the atom pair x and y, which relates to the mean square amplitude < P > through the relation bg = < Zxy2 >/2.ng, rg, and bxyare the values to be determined. The radial distribution curves obtained by the X-ray diffraction method by using an IP detector at various temperatures and pressures24 are shown in Fig.4. As is seen in Fig. 4, the peaks at 450 and 670 pm are not observed at 416 K when the pressure of 52.9 MPa is applied, 0 0 Ea0 \ n QOrn k go 0 r/ pm Fig. 4 The radial distribution curves of high temperature and high pressure water. The radial distribution curve of the normal water is given to show the reproducibility of the measurement and is shown as the reference. Quoted in ref. 24. 46 Chemical Society Reviews, 1997 T=649 K,p= 80.4 MPa, p = 0.7 g an-3 I T=469 K,p = 47.8 MPa, p = 0.9 g an-3 I 200 300 400 rlpm Fig. 5 Examples of the peak analysis of radial distribution functions D(r)/ 4nr2po. The experimental values are given by solid lines and the calculated ones by dots.I and I1 indicate the H-bonded and the non-H-bonded nearest neighbour water molecules. Quoted in Ref. 24. showing the loss of the tetrahedral ice-like ordering of water. A typical trend of the radial distribution functions with increasing pressure and temperature is that the first peak gradually broadens and shifts to the longer distance and the second peak at 450 pm and the third one at 670 pm merge into one peak at ca. 600 pm. These features are in qualitative agreement with the energy-dispersive data of Gorbaty, et al. At a supercritical temperature of 649 K with a medium density (p ca. 0.7 g ~m-~), the feature of radial distribution function is very similar to that for liquid mercury at low density (ca.10 g cm-3), suggesting that the overall structure of the medium density supercritical water resembles that of simple liquids except for hydrogen bonding with the nearest neighbours. The first peak of the radial distribution curves was resolved into two peaks I and I1 (Fig. 5), as carried out by Gorbaty, et al. The former had a peak position of 287-292 pm and was ascribed to the 0-0 distance of contacted water molecules. The position of the latter peak appeared at ca. 340-348 pm and it may be attributable to non-bonding water-water distances in water. The 0-0 distances Y found from the position of the peaks I and 11, the coordination numbers N calculated from the peak area, and the half-width of half-height of the peaks 0are given in Table 2 and are also plotted in Fig.6. The sum of the two N values, N = NI + NII, is also shown in Fig. 6. The intermolecular 0-0 distances for peaks I and I1 do not change significantly over the temperature range investigated as expected from the constant density measurement. On the contrary, with increasing tem- perature NIdecreases from 3.1 at 300 K to 1.6 at a supercritical temperature of 649 K, whereas NII increases from 1.3 to 2.3; the sum, N, remains practically constant at ca. 4, although a slight decrease in N may be seen with a decrease in the density. These results show that the hydrogen bonds are gradually broken and/ or distorted with increasing temperature, but the degree of the hydrogen bond formation still remains ca. 40% above the critical point.Another interesting finding is that the values of (3 for peaks I and I1 are almost constant at S604 K but increase when the temperature approaches the critical point. This finding indicates that the nearest-neighbour 0-0 bonds fluctuate largely around the critical temperature. If we assume that the liquid phase homogeneously expands and is compressed by the change of temperature and pressure, the distance between the adjacent water molecules should be proportional to p--113, eqn. (10): r = k ro p-113 (10) where ro denotes the 0-0 distance in the reference state, water under an ambient condition in this case. k is a proportionality constant and should be unity if we assume a homogeneous variation of the volume of water with temperature and pressure.The r values in Table 122 and the rI values in Table 223 are plotted against p-113 in Fig. 7. We can see from Fig. 7 that the 0-0 distance changes almost linearly with p-113 over a limited range of the density change from 0.95-1.04 g cm-3, but in the lower (20.92 g cm-3) density region, the change in the 0-0 distance deviates from the straight line given by eqn. (lo), although the deviation of the 0-0 distance in the higher (1.072 g cm-3) density region is unclear. It is obvious that in the lower density region, the 0-0 distance cannot be elongated to produce the given densities. A plot of the coordination number, N, vs. density, p, is given in Fig. 8. The coordination number increases monotonically with increasing density, and we do not see a particular irregularity in the variation of N with p.Thus, we can conclude that over the temperature and pressure ranges examined, expansion and compression of water by changing temperature and pressure have a more direct effect in changing the coordination number than the 0-0 distance. From the observa- tions in the changes in the 0-0 distance, coordination number, and the temperature factors with density at HTHPs, we can draw the following conclusions: (1) Most hydrogen-bonding in water is weakened and/or decomposed at elevated temperatures and pressures, but some water molecules associate to form a condensed phase with short 0-0 distances under sub- and super-critical conditions.(2) Since the coordination number decreases with a decrease in density and the 0-0 distance does not change in proportion to the change in p--1/3, the condensed water phase cannot expand homogeneously over the whole space, and thus, under supercritical conditions water molecules may form clusters containing a relatively small number of water molecules with a limited 0-0 separation of 280-295 pm. Table 2 Structural parameters of medium density water. Quoted in ref. 24 Peak I T/K (PC) pMPa p/g ~m-~rdpm NI 300 (27) 0.1 1.o 287 3.1 416 (143) 52.9 0.95 291 2.8 441 (168) 98.1 0.95 290 2.8 469 (196) 47.8 0.9 287 2.5 498 (225) 98.1 0.9 290 2.4 523 (250) 5.0 0.8 287 2.1 557 (284) 51.6 0.8 289 2.1 592 (319) 98.1 0.8 287 2.1 610 (337) 36.5 0.7 293 1.8 637 (364) 67.7 0.7 293 1.7 649 (376) 80.4 0.7 292 1.6 (3) The clusters may be spread over the whole space of supercritical water, and there may be smaller aggregates than clusters with a small number of water molecules--oligomers to monomer-to construct a very diffuse phase of water.(4)Since the coordination number decreases rather quickly with density, the size of the clusters may not be so large, because water molecules at the surface of the clusters, which should have a smaller coordination number than those in the core, should contribute significantly to the decrease in N with P. (5)Water molecules in the core of the clusters and aggregates are surrounded by a relatively small number of water molecules at HTHPs due to decomposition of hydrogen bonds, while the number of non-hydrogen-bonded water molecules increases with increasing pressure or density due to compression of the volume of water with pressure.(6) Therefore, it is most likely that water at HTHPs consists of a mixture of clusters containing a relatively small number of water molecules and much smaller aggregates such as oligom- ers and even monomers of water molecules. 4 Comparison of the views derived from the X-ray diffraction measurements and other studies Pair correlation functions of sub- and super-critical water obtained by various experiments and computer simulations are summarized in Fig. 9. Since they have different weights for different atom pairs, the shape of the curves are, of course, not the same, but we can see a qualitative picture of the structure of water under such conditions from the peak shapes and peak positions.More detailed discussion should be done by analysing the curves using eqn. (9) for the results of X-ray diffraction measurements and their equivalents for other studies. Neutron diffraction measurements have been made on three different types of isotopically enriched water under subcritical (423 and 573 K, 10-280 MPa, 0.72-1.0 g ~m-~)and supercritical (673 K, 80 MPa, 0.66 g cm-3) conditions, from which three partial pair correlation functions, goH(r), gHH(r), and goo(r) have been determined.21 Although the contribution of 0-0 pairs to the total intensities is small (ca.lo%), the pair correlation function goo(r)obtained at 673 K is compared with those obtained from other techniques [see Fig. 9(e)]. gND(r) (the superscript ND denotes the data obtained from a neutron diffraction study) and shows a large shoulder at ca. 230 pm, which has not been found in the X-ray diffraction study24 [Fig. 901. The peak at ca. 280 pm is sharper in the gND(r) function than in gXD(r) (XD means X-ray diffra~tion).~~ A broad peak at ca. 500-700 pm appears in both curves, although the former shows it more clearly than the latter. Results from computer simulations for supercritical water give good suggestions for interpretation of diffraction data. Many attempts have been carried out for the structure of supercritical water using various types of pair potentials such as TIP4P,10,11 SPC,12,28 SPCE,l3 and SPCG.29 The pair correla- Peak I1 01/pm rdpm NII %/Pm 0.28 341 1.3 0.37 0.27 341 1.8 0.34 0.27 340 1.9 0.32 0.26 342 2.4 0.36 0.27 342 2.4 0.36 0.26 339 2.2 0.34 0.25 344 2.1 0.35 0.30 343 2.4 0.34 0.31 348 1.9 0.42 0.33 343 2.0 0.42 0.35 342 2.3 0.44 Chemical Society Reviews, 1997 47 1.0Density p/g ~rn-~ 0.95 0.9 0.8 0.7 H HhH 300 400 500 600 700 TIK i 0 i 250 300 400 500 600 700 TIK 200 300 400 500 600 700 TIK Fig.6 The results of peak analysis of the radial distribution functions shown in Fig. 4.(a)Coordination numbers of peaks I and I1 and their sum, (b)their interatomic distances, and (c) their full-width at half height against the temperature. Quoted in ref. 24. tion functions, g(r), obtained with these simulations and diffraction methods are also summarized in Fig. 9. The shape of the curves is similar in all cases, except for gND(r) [Fig. 9(e)], and the first peak at ca. 280 pm in all gCS(r) (CS denotes the function calculated from computer simulation) is sharper than that in gXD(r). Since the density of supercritical water examined by the SPCE model13 (0.33 g cm-3) is much lower than that used for the neutron21 (0.66 g cm-3) and (0.7-0.9 g cm-3) diffraction experiments, a direct comparison between gCS(r) and gND(r) or gXD(r)may be difficult.Results obtained by using the TIP4P model [Figs. 9(a) and (b)]should be similar to those obtained by diffraction methods, because the densities of the examined water are rather similar. However, a remarkable difference is seen in gND(r) from the other g(r) values for the shoulder at ca. 230 pm and a deep valley appearing at ca. 420 pm. A further, careful investigation may be needed for neutron diffraction experi-ments, since the valley appearing in the gXD(r) curves under subcritical conditions [Fig. 9(g)] becomes shallow as tem-48 Chemical Society Reviews, 1997 300 -1 -295295 1 8 290 I L% 0 \ OO 0 4 285 0 280 275,' ' I ' I' I ' ' ' ' I 0.980.98 1.001.00 1.021.02 1.041.04 1.061.06 1.081.08 1.101.10 1.121.12 p-1/3 / g -113 cm Fig.7 Variation of the 0-0 distance (r)in water as a function of p-'13. The solid line represents the change in r calculated by assuming a homogeneous expansion of water with p. The line given by r = k r0p-1/3 at k = 1. 4.0 1 3.5 1 2 2.5,,i 0.7 0.8 0.9 1 .o 1.1 PI g cm-3 Fig. 8 The variation of the coordination number N with density p perature and pressure increase and no marked valley appears in gXD(r)and gCS(r) of supercritical water; the deep valley in gND(r)may be a spurious one, as the shoulder at ca. 230 pm in gND(r)-SPC (p = 7.586 10-30 C m, where p denotes the dipole moment of a water molecule) and SPCE (p = 7.843 10-30 C m) water molecules have dipole moments larger by 23 and 27%, respectively, than that of an isolated water molecule (p = 6.187 X C m).The dipole moment of the SPCG water molecule is the same as that of an isolated water molecule. Therefore, we can expect that hydrogen-bonding interactions and dipole-dipole electrostatic interactions are weaker in the SPCG water than in SPC and SPCE waters. In fact, the goH(r)curve obtained by using the SPCE model has larger peaks at ca. 180 and 320 pm, the former should correspond to the distance between a hydrogen atom of the central water molecule and the oxygen molecule in the adjacent water molecule and the latter indicates the 0.-H separation between the central water molecule and the hydrogen atom in the adjacent water molecule.28 However, the neutron diffraction experiment21 did not show the peak at ca.180 pm (Fig. 10). Probably more careful neutron diffraction experiments should be repeated. On the other hand, more sophisticated pair potentials for supercritical water should be developed toward recent attempts to take into account the effect of polarizability of water and the many-body effect. Diffraction experiments can provide the distribution of distances between atoms. However, the distance does not directly tell us whether they are bonding or not. Such I I I I I I I I I l.51 II T=725 K, p = not given, p = 0.75 g t (spc) n 1 T=673 K, p = 80.0 MPa, p = 0.66 g 01 1 1 T=649 K, p = 80.4 MPa, p = 0.7 g ~m-~ 1 7-A 1 T0l 0 200 400 600 800 1,000 rlpm Fig.9 Comparison of pair correlation functions g(r)of various HTHP water samples examined by different methods. Superscripts MC and MD represent Monte Carlo and molecular dynamics simulations, respectively. ND and XD mean neutron and X-ray diffraction measurements, re-spectively. (a):ref. 10, (b):ref. 14, (c): ref. 12, (4:ref. 13, (e):ref. 21, v>: ref. 24, (g): ref. 23. Data in (g) were obtained under subcritical conditions. Quoted in ref. 3 1 except for (g). information may be given by the value by comparing it with other experimental values which are known as the bond lengths. On the other hand, the frequency measurements by IR and Raman spectroscopies are more sensitive for the bonding nature, but usually they do not give us the value of the distance between atoms.Thus, both methods should be applied com- plementarily. The NMR method is especially useful for obtaining dynamic information of water molecules. However, application of high temperature and high pressure to the NMR cell is not easy and extremely limited attempts have been made by NMR specialists. IR and Raman spectroscopic investigations for supercritical water were carried out much earlier than diffraction experi- ments and computer simulation. Franck and Rothz studied the 0-D stretching frequency of HDO containing 8.5 mol% D20 in H20 at 303-673 K and 5400 MPa (Fig. 11). A sharp band at 2719 cm-l in HDO water having a density of 0.0165 r/pm Fig. 10 Comparison among the partial pair correlation function gOH(r) obtained by computer simulations (dashed line: ref.29) and a neutron diffraction experiment (solid line: ref. 21) for water at T = 673 K and p = 0.66 g cm-3, Dots represent gOH(r)of water under the normal conditions. Quoted in ref. 33. g cm-3 was not observed in water with a higher density than 0.095 g (3111-3. On the other hand, a broad band at 2650 cm-l increased and shifted towards the lower wavenumber side with density, and in water with the density of 0.9 g (3111-3 the band was observed as a big broad band centred at 2600 cm-I. A more intense v0-D band was observed at 2520 cm-1 in water with the density of 1.0 g cm-3 at 303 K. The authors explained that a sharp band found at 2719 cm-1 in water with the density of 0.0165 g cm-3 at 673 K should correspond to the YO-D band without hydrogen bonding, while the broad and intense 2520 cm-1 band observed in the water should indicate that water molecules are hydrogen bonded.Kohl, Lindner and Franck6 employed Raman spectroscopy to a study of water with almost constant density of 0.8-1.0 g ~m-~. According to their results the broad 0-D stretching band in HDO water appeared at ca. 2510 cm-1 at room temperature, which shifted towards the high frequency side and was sharpened with increased temperature. Under supercritical conditions at 673 K (the density of water was 0.04 g ~m-~) the band became very sharp and the band at 25 10cm-completely disappeared. The shape of the sharp band is close to that in the gas phase.From these results we may say that hydrogen- bonding interactions among water molecules still exist in supercritical water with a density greater than 0.1-0.2 g cm-3. Giguere30 measured the 0-H stretching band in water at high temperature and amorphous ice by Raman spectroscopy, and discussed two different 0-H bonds, one having the normal 0-H hydrogen-bonding distance of 185 pm and the other having 230 pm which resulted from a bifurcated O-H--O hydrogen bond. He explained that the former bond was formed predominantly at low temperatures and the contribution of the latter increased with increased temperature. The 0-0 distance may be kept practically unchanged with the change in temperature. His interpretation means that the tetrahedral ice-like water structure is practically unchanged, while the central water molecule rotates along the axis of one O-H..-O hydrogen bond in the tetrahedrally coordinated water structure with temperature.However, it is difficult to say that hydrogen bonds are still formed in the bifurcated form, because the 0-H-0 angle in the bonded water molecules should be bent by more than 50". Since the H...O distance at ca. 330 pm can still be detected in the neutron diffraction study21 and computer simulations,28 the interaction may be better attributed to the weak interaction between the hydrogen atom of the central water molecule and a second neighbour water molecule which approaches the central water molecule to ca. 330 pm. Chemical Society Reviews, 1997 49 A11 T=673K T=298K, p = 10 gc~n-~-T=373K,p=lOgcm-T= 473 K, p = 10 g T = 573 K, P’ T = 673 K, p =O .--I I I 1 I I 1 I 2200 2400 2600 2800 Rainan shift / cm-I Fig.11Isotropic Raman spectra for the Y(D 0)stretching mode in 9 7 mol% HDO in HzO at vanous temperatures and densities Quoted in ref 6 5 Concluding Remarks Supercntical water has attracted scientists’ interest in recent years due to its peculiar physicochemical properties and industrial uses. However, structural information on supercntical water is limited. The lack of structural information prevents the development of physicochemical studies of supercntical water because we do not have sufficient information for inter- molecular interactions. We have reviewed recent investigations on the structure of sub- and super-critical water, and concluded, on the basis of structural data so far obtained, that water at HTHPs consists of a mixture of clusters and the dispersed phase contains low aggregates including monomenc water molecules.We predict extensive development of this field in the near future. Investigations of ionic solvation and complex formation reactions in supercntical water have begun in some laborato- nes.32 33 Knowledge of hydration of ions and polar substances in supercntical water is important to understand ion-water and polar molecule-water interactions which relate to solubility phenomena and decomposition of the substances. The drastic change in the acid-base properties of water is also related to chemical relations of water with polar and non-polar molecules. Studies on the formation and decomposition reactions of organic substances in supercritical water may open another potentially useful field of chemistry.The expected development of chemistry in the 21st century will certainly necessitate a microscopic level exploration of supercntical water. 6 References 1 J D Bernal and R H Fowler, J Chem Phys, 1933,1,515 2 E U Franck and K Roth, Discuss Faraday SOC,1967,43, 108 3 C I Ratcliffe and D E Insh, J Phys Chem , 1982,864897 4 N C Holms, W J Nelhs, W B Graham and G E Walrafen, Phys Rev Lett, 1985,55, 2433 5 G E Walrafen, M S Hokmadadi, W -H Yang and G J Piermanni, J Phys Chem ,1988,92,4540 6 W Kohl, H A Lindner and E U Franck, Ber Bunsenges Phys Chem , 1991,95, 1586 50 Chemical Society Reviews, 1997 7 R W Impey, M L Klein and I R McDonald, J Chem Phys ,1981,74, 647 8 A G Kalmichev, Int J Thermophys ,1986, 7, 887 9 Y Kataoka, J Chem Phys ,1987,87,589 10 R D Mountain, J Chem Phys ,1989,90, 1866 11 A G Kalmichev, 2 Naturforsch Tell A, 1991, 46, 433, 1992, 47, 992 12 P T Cummings, H D Cochran, J M Simonson, R E Mesmer and S Karabomi, J Chem Phys ,1991,94,5606 13 Y Guissani and B Guillot, J Chem Phys , 1993, 98, 8221 14 A G Kalinichev and J D Bass, Chem Phys Lett, 1994,231, 301 15 Yu E Gorbaty and Yu N Demianets, 2 Strukt Khim, 1983, 24, 66 16 Yu E Gorbaty and Yu N Demianets, 2 Strukt Khim , 1983, 24, 74 17 G A Gaballa and G W Neilson, Mol Phys ,1983, 50, 97 18 A V Okhulkov, Yu N Demianets and Yu E Gorbaty, J Chem Phys , 1994,100, 1578 19 T Yamaguchi, Y Tamura, H Ohtaki, S Ikeda and M Misawa, KENS Report, 1986, 6, 125 20 K Ichikawa, Y Kameda, T Yamaguchi, H Waluta and M Misawa, Mol Phys, 1991, 73,79 21 P Postonno, R H Tromp, M -A Ricci, A K Soper and G W Neilson, Nature, 1993, 366, 668, R H Tromp, P Postonno, G W Neilson, M A Ricci, and A K Soper, J Chem Phys, 1994, 101, 6210, P Postonno, M A Ricci and A K Soper, J Chem Phys, 1994, 101, 4123 22 M lhara, T Yamaguchi, H Waluta and S Matsumoto, Advances in X-ray Analysis (in Japanese), 1994, 25,49 23 T Radnai and H Ohtaki, Mol Phys , 1996,87, 103 24 K Yamanaka, T Yamaguchi and H Wakita, J Chem Phys ,1994,101, 9830 25 MPWS Release on the Skeleton Tables I985 for the Thermodynamic Properties of Ordinary Water Substance, 1994, IAPWS Release on the Values of Temperature, Pressure, and Density of Ordinary and Heavy Water Substances at their Respective Critical Points, 1992 26 A H Narten, M D Danford andH A Levy, ORNL-3997, 1966,Disc Faraday Soc, 1967, 43, 97, A H Narten, ORNL-4578, 1970, A H Narten and H A Levy, J Chem Phys , 1971,55, 2263 27 Yu E Gorbaty and A G Kalinichev, J Chem Phys, 1995, 99, 5336 28 J J Pablo, J M Prausniz, H J Strauch and P T Cummings, J Chem Phys ,1990,93,7355 29 A A Chialvo and P T Cummings, J Chem Phys, 1994, 101, 466 30 P.A. Giguere, J. Raman Spectrosc., 1984, 15, 354; J. Chem. Phys., 33 T. Yamaguchi, M. Yamagami, H. Ohzono, H. Wakita and K. Yamanata, 1987,87,4835. Chem. Phys. Lett., 1996, 252, 317. 31 K. Yamanaka, H. Ozono, T. Yamaguchi and H. Wakita, Progress in X-ray Analysis (inJapanese), 1995, 26, 125. 32 E. U. Franck, The Physics and Chemistry of Aqueous Ionic Solutions, ed. M.-C. Bellissent-Funel and G. W. Neilson, Reidel, Dordrecht, Received, 2nd July 1996 p. 337, 1987. Accepted, I 7th October I996 Chemical Society Reviews, 1997 51

ISSN:0306-0012    

DOI:10.1039/CS9972600041

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

4) S(1Sulfur-nitrogen chains: rational and irrational behaviour* "3 *I Jeremy M. Rawson and John J. Longridge Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK CB2 IEW * Dedicated to Arthur Banister, on the occasion of his retirement; an inspiring teacher to all who have been fortunate enough to work for him. Poly(su1fur nitride), [SN],, was the first example of a polymeric metal, and the discovery of its superconducting properties in 1973 fuelled a generation of research into the areas of sulfur-nitrogen chemistry and molecular con-ductors. The synthesis, structure and properties of [SN],now form part of many undergraduate courses and it is an often cited textbook example. Now, in the 1990s, small fragments of [SN], may prove useful as molecular wires in the development of nanoscale technology.Although the preparations of many thiazyl chains can be carried out in a rational high-yielding manner, it is the diverse reaction chemistry, which often involves unexpected changes in the chain size, which provides one of the most rewarding and stimulating aspects of this area. 1 Introduction Poly(su1fur nitride), [SN], is a one-dimensional polymer in which sulfur and nitrogen atoms form an alternating chain (Fig. 1). Its physical properties are it is a conducting material at room temperature and becomes super- conducting below liquid helium temperature. Its one-dimen- sional structure leads to a large degree of anisotropy. Conse- quently, its conductivity is greatest along the chain, where n-orbitals on sulfur and nitrogen overlap to form a conduction band.In addition to its conducting properties, the high electronegativity of [SN],r, even greater than that of gold, produces several further unusual physical properties. The high electronegativity of poly(su1fur nitride) leads to several en- hancements in device efficiency; for example [SN], can act as an efficient barrier electrode in ZnS junctions,2a increasing the quantum efficiency of the blue-emission by a factor of 100over gold; and it can also be used to increase the efficiency of GaAs solar cells (conventionally Au-GaAs) by as much as 35%.*h In addition [SN], is remarkably inert; it does not react with water or acidic solutions, but slowly decomposes in alkaline solutions.Because of the high electronegativity of [SN],, metal ions interact more strongly with a poly(su1fur nitride) surface than with other metal electrodes.2c In some instances this can lead to enhancement of catalytic properties, e.g. [SN], surfaces pre- treated with metal ions have been used as catalysts and can improve the rates of conversion2c of acetylene to ethylene by factors of up to 107. Despite such appealing properties, industrial exploitation3 of [SN], in modern devices has been hampered by synthetic problems; the classical route to [SN], involves the 'cracking' of red S4N4 over silver wool to give colourless crystals of S2N2 which slowly polymerise over a period of weeks to form golden [SN], (Fig.1). The slowness of the polymerisation, coupled with the explosive nature4 of both the S4N4 starting material and intermediate S2N2 molecule, has prompted researchers to investigate other synthetic5 strategies to [SN],. In addition, other processing techniques6 have been sought so that [SN], can be prepared in thin films on a variety of substrates, such as OTEs (optically transparent electrodes), plastics and other metal surfaces. In particular, vacuum sublimation6" of powdered [SN], and electroreduction6h of [S5N5]+ salts have proved valuable routes to the formation of [SN], films. S4N4 S2N2 polymerise// [SNIX Fig. 1 Synthesis and structure of [SN], Jeremy Rawson obtained both his BSc and PhD degrees from the University of Durham.He was a post-doctoral fellow with Dr Arthur Banister (University of Durham, 1990-1 992) and Dr. Richard Winpenny (University of Edinburgh, 1993-1 994) before returning to Durham to take up a temporary lectureship. He moved to Cambridge in 1995 where he is now a University Lecturer and Fellow of Magdalene College. His current research interests include the magnetic properties of main-group x radicals and polynuclear metal complexes bridged by sulfur-nitrogen rings and chains. John Longridge graduated from the University of Durham in 1995, and is presently a graduate student at the University of Cam- bridge. Chemical Society Reviews, 1997 53 The physical properties of [SN], have led to a great resurgence of interest in group 15/16 chemistry in recent years.In particular the inclusion of carbon-based fragments into the thiazyl backbone would allow the properties of [SN], to be modified by changing the electronic properties of the chain substituents. This has led not only to the preparation of C/N/ S-based polymers7 but also to the development of C/N/S-based heterocyclic rings,8 and sulfur-nitrogen chains (i.e. small fragments of conducting [SN],). These small fragments of conducting [SN], could find novel applications in the field of nanoscale technology, particularly molecular wires .9 Nanoscale devices function on a molecular rather than macroscopic level and one of the key features required for many nanoscale devices to operate effectively is the molecular wire; a functional group which will conduct electrons between different parts of a molecule, allowing the different components to interact in an effective manner.The molecular wires presently used typically possess delocalised n systems and are frequently small fragments of conducting polymers such as acetylene oligomers or fused aromatics. Fig. 2 illustrates how a molecule of this type can respond to light (so-called photo-induced electron transfer) and is exemplified by a Ru(bipy)3 deriva- tive. Phot o-recept or Photo-emitter "r .R;(blPY h Fig. 2 Schematic representation of a photosensitive molecular device The conductivity of pure [SN], is ca. 1 X 103S cm-1 at room temperature (cf.polyacetylene 1 X 10-7 and 1 X 10-2 S cm-1 for cis and trans forms respectively'o) and we might therefore expect that the efficiency of molecular devices with thiazyl linkages might be superior to those of the corresponding acetylene-bridged molecules.This review article aims to describe the chemistry of some of these sulfur-nitrogen chains; the types of sulfur-nitrogen chain we might expect to form; their relative stabilities; their physical properties; their structures and reactivity. In particular, although some references and comparison will be made to short thiazyl chains, containing two or three heteroatoms, this review will highlight the chemistry of the longer-chain compounds (ix., containing at least two thiazyl, -S=N-, units). 2 Types of thiazyl chain and electron counting Thiazyl chains can be split conveniently into three categories dependent on composition; sulfur-rich, nitrogen-rich and even- chain compounds.These are highlighted in Table 1. We can Table 1 Sulfur-nitrogen chain compounds as a function of chain length, with known derivatives highlighted Chain length S-rich N-rich Even-chain 3 RSNSR+ RNSNR 4 RS2NZR 5 RS3N2R RN3 S2R+/- 6 RS3N3R+/- 7 RS4N3R+ RN4S3R 8 RS4N4R 9 RSSN~R RNSS4R+/- 10 RS5N5R+/- 11 RS6NSR+ RN6S5R utilise the same electron-counting rules11 used for sulfur- nitrogen rings to n-electron count these compounds. In these systems, each S donates two electrons to the n system and each N is a one-electron donor. Unlike the sulfur-nitrogen rings where [4n + 2]n Huckel configurations are preferred,? the chain-like structures only favour even numbers of n electrons (Table 2), i.e.a full, or 'closed-shell', electronic configuration. Because N provides only one electron, virtually all thiazyl chains reported to date (highlighted in bold in Table 1) contain an even number of N atoms and are neutral. There are a small number of chains with odd numbers of N atoms, but these are charged so as to retain a full n-shell, e.g. RSNSR+ (R = C1, Br) and RS4N3R+. Indeed cationic chains should be particularly stabilised via the lowering of the filled molecular orbitals induced by the positive charge on the system, and in addition, the ionic contribution to the lattice energy should also assist their stabilisation in the solid state.Intuitively the observation of both ArS4N3Ar+ and XSNSX+ cations indicates that sulfur-rich compounds will have a tendency to form cationic systems, and this can readily be understood by the number of electrons filling antibonding molecular orbitals; For an acetylene chain, (CH),, each C provides one p-orbital for the formation of n molecular orbitals + A number of sulfur-nitrogen systems are also known which are formally 4nn anti-aromatic molecules, but these do not have planar n-delocalised structures analogous to the thiazyl chains and Huckel [4n + 2]n aromatics. Instead they take up cage structures,g e.g. S4N4, S5N6, S4N5+and S6N5+. Table 2 A comparison of sulfur-nitrogen ring compounds and sulfur-nitrogen chain compounds and their respective n electron counts n-electron count 6 8 10 12 14 Ring N-SI I S-N other examples: chain ~3~2~+ R-S \ IN-R R,SI IS/R kS/NN-S S3N3-, S4N42+ER;; :I+ N, ,N, HN R-q p-S, IN--R N-S N-S R-S\ N-S pS SOR I I kS/N other examples RN4SSR 54 Chemical Society Reviews, 1997 and donates one electron to this n manifold. The result is a set of bonding and antibonding n orbitals of which only the bonding orbitals are filled.In comparison, in thiazyl oligomers, each S donates two electrons and each N one electron for n-bonding and some of the formally antibonding orbitals will also be occupied to accommodate the additional electrons, provided by S. Consequently, if the thiazyl chain contains an odd number of electrons, removal of the unpaired electron from its antibonding orbital not only strengthens the n-bonding character, but also lowers the energy of the bonding orbitals through the introduction of the positive charge.In general the removal of an electron to form a cationic system is preferred over the addition of an electron to generate an anionic system since the latter requires the addition of a further electron into an antibonding orbital. This observation also explains the pro- pensity for sulfur-nitrogen rings to form cationic rather than anionic systems, although anionic rings, such as the lox Hiickel S3N3- are known. Compounds with the same chain lengths will also have similar sets of molecular orbitals, and it is perhaps not too surprising to find that the isoelectronic RS4N3R+ and RN&R chains take up similar geometries (see section 5).3 Synthesis of sulfur-nitrogen chains 3.1 Historical background Prior to the 1970s, sulfur-nitrogen chemistry was plagued by structural mis-assignments and the diverse nature of many reactions which typically yielded multiple and sometimes unexpected products. 12 With the development of modern analytical methods (particularly X-ray crystallography and more recently multinuclear NMR) and theoretical studies, the area of sulfur-nitrogen chemistry has been revolutionised and many unusual mechanistic processes have been rationalised. As a consequence, controlled syntheses of many sulfur-nitrogen compounds can now be achieved.In this section we aim to outline early developments in the area of sulfur-nitrogen chains and illustrate more rational synthetic methodologies. 3.2 Initial syntheses of thiazyl chains The first reported syntheses of sulfur-nitrogen chains appeared in the mid-1960s and early 1970s, and de~cribed'3.1~ the preparation of RS3N2R (trithiadiazenes) and the shorter chains, RNSNR (known as sulfur diimides). The chemistry of sulfur diimides is particularly extensive and beyond the scope of this review, except as reagents for tlie synthesis of other sulfur- nitrogen chains. As with many other areas of sulfur-nitrogen chemistry, early syntheses of S/N chains involved the ubiqui- tous S4N4 molecule;13 the reaction of S4N4 with aromatic Grignard reagents or diazomethanes yielded RS3N2R in low yield.The more traditional 'boil-and-bake' approach (involving the condensation of HCl between S-Cl and N-H bonds, and concurrently forming S-N bonds) was also utilised with some success.14 3.3 Rational syntheses For many years the standard synthetic route to inorganic rings and chains has involved condensation reactions, typically with loss of HCl.12J4 Such reactions occur at elevated temperatures, so as to remove the HCl from the reaction mixture. Recently, condensation reactions, particularly involving the loss of Me3SiC1, Me3SiOSiMe3 or metal halides,8 have been used successfully in the synthesis of inorganic rings and chains. These condensation reactions occur smoothly at low tem-peratures and lead to clean products in high yield.This technique has been extensively ernpl~yed'~ in the syntheses of sulfur-nitrogen chains; one of the most common reagents being bis(trimethylsily1)sulfur diimide, Me3SiNSNSiMe3. The syn- thesis of this reagent itself (see Scheme 1) provides a useful example of the use of both LiCl and MesSiOSiMe3 as thermodynamic sinks, the sulfur diimide being formed in excellent yields under mild conditions. l5 ArN4S3Ar t sc12 ArSClArNSNSiMe3-ArS2N2Ar t ArNSO Li[N(SiMe3)2] 1soc12 ArSCl ArSClMe3SiNSNSiMe3--+ ArS2N2SiMe3-ArS3N2Ar J. sc12 ArSCl ArSClMe3SiN4S3SiMe3-ArS4N4SiMe3-ArSSNSAr Scheme 1Rational syntheses of some sulfur-nitrogen chains The stoichiometric condensation of Me3SiNSNSiMe3 with ArSCl in 1 : 1 or 1 :2 mole ratios gives the anticipated ArS2N2SiMe3 and ArS3N2Ar chainsl6 (although an excess of ArSCl yields the ArS4N3Ar+ cationic chain!). The syntheses of other sulfur-nitrogen chains can be designed in an analogous manner17 and are illustrated in Scheme 1.SCl2 plays a particularly important role in the syntheses of longer-chain thiazyl oligomers; coupling of two small thiazyl chains containing the trimethylsilyl functional group provides a convenient route to long-chain molecules. It should be noted that for some long chain compounds, the choice of aryl substituent plays a key role in determining the stability and this is discussed further in section 5.2. Using these simple condensation reactions, chain lengths up to ArS5N4Ar have been prepared.4 Structures of sulfur-nitrogen chains 4.1 Structure of [SN], Despite several structure determinations,' the precise structure of [SN], is still open to some debate. The structure determina- tions have been persistently hampered by crystal defects which arise during the polymerisation of S2N2. Although the way in which the atoms are linked together in the alternating cis-trans configuration is not disputed, the bond lengths are not precise. The X-ray diffraction study tends to indicate an alternating set of long and short bonds [ 1.593(5) and 1.628(7) A], intermediate between S-N (ca. 1.69 A) and S=N (ca. 1.54 A) bonds,l6 although the errors on these bond lengths are so large that they are the same (within three esds).The nature of these bonds, intermediate between S-N and S=N, is consistent with the extensive x delocalisation required for conduction. The 'cis- trans' alternating polymeric chain facilitates a set of secondary S--N interactions between atoms in the same chain, composed of electrostatic S*+-N*-interactions, coupled with pn-px interactions. The bond angles at N and S are about 120" and 106O, respectively. Each [SN], chain deviates only slightly (0.17 A) from planarity, and there is a series of weak interactions between chains. 4.2 Thiazyl chains The structural features described in section 4.1 for [SN], are also observed in many of the sulfur-nitrogen chains, which can be considered as small fragments of [SN],.The structures17918 of 02NC6H&N2C6&0Me, PhN4S3Ph and 02NC6H4S4N4SiMe3 chains are shown in Fig. 3. In each of these cases the chains take up similar conformations to [SN], with an alternating 'cis- trans' configuration. In comparison to [SN],, these oligomers definitely exhibit alternating long and short S-N bonds, consistent with a more localised structure of the form [-S-N=S=N-] , although these too are intermediate between S-N and S=N bond lengths. Secondary interactions between non-bonded atoms within the chains are still significant. However, the 'cis-trans' conformation observed in [SN], is not exclusive, and other conformations are observed16319 in which a Chemical Society Reviews, 1997 55 Fig.3 Molecular structures of 02NC6H4S2N2C6H40Me,PhN4S3Ph and 02NC6H4S4N4SiMe3 ‘cis’configuration is replaced by a ‘trans’ arrangement. This ‘defect’ to the [SN],-type structure can arise either at an N atom [such as N(2) in C1C6H4S3N2C6H4Cl] or at an s atom [e.g. s(3) in the cation MeC6H4S4N3C6H4Me+] (Fig. 4). The energy required to introduce such a ‘defect’ primarily arises through the breaking of one of the transannular interactions and theoretical calculations20 have estimated this to be of the order of 25-30 kJ mol-1. This small energy contribution can be overcome by molecular packing forces, or particularly in the case of the cationic ArS4N3Ar+ salts, through significant ionic lattice contributions. This is highlighted by two different conformations to the RN4S3R chain, depending on substituent; for the PhN4S3Ph derivative17 the ‘ideal’ [SN], type configura- tion is observed (Fig. 3), whereas for ButN&But a ‘defect’ is found21 at N(3) (Fig.4). The longest known thiazyl chain to be crystallographically characterised,22 MeC6H4S5N4C6H4Me is also shown in Fig. 4 and shows a ‘defect’ at N(4); this structure can be envisaged as a pair of ArS2N2 and Ar fragments on an S3N2 chain (which has a characteristic ‘open-ring’ structure). The thiazyl chain compounds exhibit similar bond lengths to [SN], although there is considerable variation in the bond angles depending on the length of the sulfur-nitrogen chain and the terminal groups; bond angles are typically in the region 102-124” and 118-129” at S and N respectively.Without exception, diaryl-substituted thiazyl chains are approximately planar, facilitating the x-delocalisation along both the thiazyl chain and over the aryl substituents. However, other substitu- ents can produce a more pronounced deviation from planarity, and for example, u-O~NC~H~S~N~S~M~~ sits17 on the curve of a circle with an appproximate radius of 50 A. Intermolecular interactions are very important in stabilising the metallic state of [SN],. In [SN],, the secondary interactions between S atoms in neighbouring chains is 3.48 A.l Strong secondary interactions between heteroatoms are also prevalent in many of the thiazyl chain structures, e.g. in 02NC6H&N2- C6H40Me the interplane distance between molecules is only 3.42 A.l8 However, in many instances, particularly when a chain is terminated with a bulky substituent such as SiMe3, then many of these secondary contacts are often appreciably longer,17 although still less than the sum of the van der Waal’s radii [3.63 (Sa-N) to 4.06 A (S-S)], e.g.S-.S in 02NC6H4S4N4- SiMe3 at 3.73 A. In addition the presence of a positive charge on the thiazyl chain leads to electrostatic repulsion between cations and the closest approaches are close to the sum of the van der Waal’s radii, e. [02NC6H4S&C6H4N02] [AsF6] has close contacts at 3.64 % for S.-N and S.-S contacts in the region 3.9 to 4.0 A.23 5 Correlation of sulfur-nitrogen chain lengths and their physical properties 5.1 Jc-Delocalisation Each sulfur and nitrogen atom in the thiazyl chain contributes one p-orbital towards the formation of a set of x molecular orbitals.The energies of the 3t molecular orbitals for two thiazyl chains, HS3N2H and HSSN4H, are shown in Fig. 5. As the chain- length increases, the number of p-orbitals also increases and the energy gap between x-orbitals becomes smaller, consistent with simple band theory.10 The distribution of the energies of these x molecular orbitals is an important feature of such thiazyl chains, and plays an important role in determining some of their physical properties, particularly their optical properties, both in solution and in the solid state. 56 Chemical Society Reviews, 1997 ArS4N4SiMe3 [AT = o-N02C& or 2,4-(N02)&H3] with SC12 does not lead to the 17-heteroatom chain, ArSgNxAr, but Energy rather to the isolation17 of the decomposition products, ArS5N4Ar. The disproportionation of these thiazyl chains is r-9 -described in section 6.4.For short chain oligomers there appear II-to be no such problems with disproportionation. -10 _-11 st --12 --13 + -1 4 1--15 stI--% st 1-Fig. 5 The energies of the n-molecular orbitals of HSsN4H and HS3N2H 5.2 Optical properties and delocalisation As the chain length increases, the energies between different n-molecular orbitals decreases and the energy, hv, to excite electrons between different n-orbitals becomes smaller. This leads to the ob~ervation~~.’~ of a ‘red-shift’ as the chain-length becomes longer and is indicative of a ‘tight’ n-manifold and more extended n-delocalisation.Electron-withdrawing substi- tuents on the thiazyl chains can also lead to a slightly increased red-shift,’b as can the introduction of a positive charge which produces a lowering of the orbital energies.16 The UV-VIS absorption maxima for a series of thiazyl chains are given in Table 3, and illustrate the effect of chain length, electron- withdrawing substituents and charge on the absorption maxima. In general short sulfur-nitrogen chains (less than six hetero- atoms) tend to be brightly coloured; yellow or orange whereas the longer chains (greater than six heteroatoms) tend to produce very intense deep-coloured solutions; typically deep green, royal blue or purple.In the solid state, a similar set of colours is observed; short thiazyl chains tend to be brightly coloured, whereas the longer chains tend to have a metallic lustre, similar to that observed for ‘golden’ [SN], or ‘silver’ polyacetylene, [CHI,. 5.3 Stability The stability of thiazyl oligomers, particularly long-chain (n > 7) derivatives, is particularly dependent on the terminal functional groups. Zibarev and coworkers have noted17 that electron-withdrawing substituents on aromatic terminal groups are particularly good at stabilising longer chain lengths. For example, reaction of Me3SiN4S3SiMe3 with ArSCl (Ar = Ph, o-N02C6H4) in a 1 :2 mol ratio yielded ArS5N4Ar when Ar = o-NO~C~H~.However, when Ar = Ph, the only recovered products were PhS3NlPh and S4N4.The stability of very long thiazyl chains is questionable and, for example, reaction of 6 Reactivity In comparison to the development of synthetic routes to thiazyl chains, their chemistries are poorly understood. Indeed those reactions which have been carried out appear diverse and, like other areas of sulfur-nitrogen chemistry, somewhat unexpected at first glance. A series of reported reactions are described below which initially seem both unusual and varied. However, a common theme appears in many of them and this is discussed in more detail in section 6.5. 6.1 Scrambling of terminal groups and preparation of ArS2N2Ar’ In the presence of a catalytic quantity (5-25 mol%) of alkali metal (Na, K) mixtures of RNSNR and R’NSNR’ undergo rapid scrambling’x of the terminal groups to yield mixtures of starting materials and the mixed product, RNSNR’.The position of the equilibrium is dependent on the nature of the R groups. If they are similar (e.g.Ph and MeC6H4 or MeOC6H4) then there is an approximately statistical distribution of products whereas for dissimilar groups the equilibrium favours the cross-product. An extension of this reaction is the reaction of PhNSNPh with PhS3NZPh in the presence of alkali metal to yield PhS2N2Ph. In this reaction, the radical anion RNSNR--, formed by reduction of the neutral thiazyl chain with alkali metal, possesses 5n electrons and three n molecular orbitals.Oakley and coworkers proposed that two of these molecules could associate in solution to form a dimer’g (dimerisation processes are well known in other areas of sulfur-nitrogen chemistryx) in which the two molecules are weakly associated via overlap of the two singly occupied molecular orbitals, with the S-.S bridge contributing the greatest extent. This dimeric intermediate can then rearrange to form the mixed thiazyl chain (Scheme 2). 6.2 Reduction of ArS4N3Ar+ Wolmershauser and coworkers recently investigated22 the redox behaviour of the ArS4N3Ar+ cation and observed that reduction led to the unstable ArS4N3Ar- radical which dispro- portionated to ArSSN4Ar and ArS3N2Ar. The disproportiona- tion reaction was postulated to proceed through a four-centred S2N2 ring intermediate; this reaction can be considered to occur in a similar manner to that described in section 6.1 for the scrambling of terminal groups in short-chain thiazyl com-pounds. An analysis of the frontier molecular orbitals23u indicates that one electron reduction of the ArS,N,Ar+ cation yields a neutral radical with the unpaired electron occupying a n-type orbital of the same symmetry to that of the sulfur diimides discussed in section 6.1.6.3 Hydrolysis of [ArS4N3Ar]CI and chain lengthening reactions with (NSC1)3 In 1977 Street and coworkers reported16 the first synthesis of an [ArS4N3Ar]+ chain as its chloride salt, and noted that it slowly Table 3 UV-VIS absorption maxima (nm) for a series of thiazyl chain complexes Thiazyl chain ArNSNSiMe3 ArNSNAr ArS3N2Ar ArN4S3Ar ArS4N3Ar+ ArS4N4SiMe3 ArSsN4Ar ~~~~ Ar = O,~-(NO~)~C~H~4 13 476 538 587 CJ-NO~C~H~ 409 476 521 585 P-NO2ChH4 394 458 580 p-ClC6H4 383 449 565 p-MeC6H4 355 448 530 582 ChH5 332 415 450 522 Chemical Society Reviews, 1997 57 Rt RI+ 2e-RI RNSNR + R'NSNR' "I R R' 2 RNSNR Scheme 2 Skeletal scrambling in sulfur diimides decomposed on the open bench to give the shorter, ArS3N2Ar chain. Although a hydrolysis mechanism evidently takes place, the reaction can be conveniently thought of as loss of thiazyl chloride, NSC1, from the starting material.Recently, work has shown that the reverse reaction, i.e. reaction of NSCl with ArS3N2Ar, occurs under ambient conditions and in high yield.23h The mechanism is proposed to involve a four-centred intermediate which facilitates a n-orbital interaction between S and N (Scheme 3).This use of thiazyl chloride as a chain-building reagent has previously been exploited in the synthesis of shorter chains. For example, reaction of NSCl with SC12 and AgAsF6 leads to insertion24 of an SN unit into the S-C1 bond, and condensation of NSCl with ArSNHSAr provides a convenient route14 to ArS3N2Ar via loss of HC1. 6.4 Disproportionation of long chain sulfur-nitrogen compounds In section 5.3, the instability of long-chain thiazyls was described. Two types of reaction appear to occur: either a competing reaction may take place during the formation of the thiazyl chain or the resultant chain itself can decompose, usually accompanied by the loss of S4N4.6.4.1 Competing reactions Condensation of PhNSNSiMe3 with SC12 did not yield the expected product, PhN&Ph, but instead yielded the benzodi- thiadiazine25 (Scheme 4). This reaction is proposed to occur via an intramolecular loss of HC1 (with the abstracted ortho- hydrogen) from the intermediate PhNSNSCl accompanied by ring closure at the ortho-position. 6.4.2 Decomposition reactions To date, there have been no systematic studies of the decomposition of thiazyl chains. However there are several 58 Chemical Society Reviews, 1997 possible mechanisms (Scheme 5); the first mechanism, postu- latedl7 by Zibarev and coworkers, involves either trimethylsilyl or aryl group migration (A), with concomitant extrusion of thiazyl units, as S2N2, from the thiazyl chain; alternatively, the reaction can be considered to involve the breaking and reformation of S-N bonds and a similar loss of S2N2 (B).The ease with which thiazyl chains can undergo rearrangement processes, in comparison to the strength of the C-S bond, indicates that the latter mechanism would appear more favourable. 6.5 On the prevalence of four-centred S2N2 intermediates Although these few reactions constitute the greater part of the known reactivity of long-chain thiazyl compounds, a key mechanistic feature proposed by three different groups (and described in sections 6.1 to 6.3) is the four-centred cyclic S2N2 intermediate formed by the association of two S/N-containing molecules.In organic chemistry the four-centred intermediate, typically formed by a [2 + 21 cycloaddition of two alkene functional groups, is formally symmetry forbidden and tends to occur, for example, upon photolysis or at elevated temperatures where access to excited states alters the orbital symmetry.26 In Ar Ar \ &\ / /& S/s \N c1-0-y "-4 N, ,N, / \ ,N-sS S S 1ci Scheme 3 Mechanism for the reaction of ArS3N2Ar with NSCl SCI2 N, SiMe, -Me3SiC1 Ic1 closure -HC1 Scheme 4 Formation of benzodithiadiazine from PhSNSNSiMes ‘S I I .S N’”\ I7 Q \ I/N=S N‘ A N=S ‘S’ \ B \ asI I I N‘ ’N‘S’ Scheme 5 Proposed chain-shortening mechanisms, for the conversion of ArS5N4Ar to ArS3N2Ar: (A) via aryl group migration; (B) via SzN2extrusion comparison, such four-centred intermediates are favoured in sulfur-nitrogen chemistry since each thiazyl group possesses 3n electrons (2 from S and 1 from N) and the resulting [3 + 3]n interaction yields a favourable 6n electronic interaction.This occurs because the frontier orbitals occupied by thiazyl compounds are different to those occupied by C-based com- pounds. For example, cyclobutadiene possesses 4n electrons, leading to two partially occupied frontier orbitals whereas cyclic-&N2 possesses 6n electrons and the two partially occupied orbitals of butadiene become completely occupied in S2N2.The reactions described in sections 6.1 and 6.2 both involve a radical mechanism involving association via a SOMO-SOMO interaction. The mechanism in 6.3, although involving a four- centred intermediate does not proceed in the same manner but occurs through a HOMO-LUMO interaction in which a pair of electrons from an antibonding ArS3N2Ar n orbital are donated into the LUMO of NSC1; the orbital interaction in this case would therefore appear to be identical but in sections 6.1 and 6.2 the interaction is SOMO-SOMO whereas in 6.3 it is a HOMO-LUMO interaction. 6.6 Other reactions In comparison to sulfur diimides whose chemistries have been examined extensively, the chemistries of the longer S/N chains, as outlined above, have been poorly studied.For example, the sulfur diimides possess a diverse coordination chemistry, but little coordination chemistry of the longer thiazyl chains has been reported. Woollins and coworkers reported27 that reaction of ArS NSNSiMe3 with PtC12 (dppe) gives (ArSNSN)2Pt (dppe) (dppe = 1,2-bisdiphenylphosphinoethane)whereas reaction of ArS3N2Ar with Pt(PPh3), led to reduction of the thiazyl chain and formation28 of (ArS),Pt(PPh,),. The decomposition of thiazyl chains on metal centres is not unexpected and Vrieze and coworkers have shown that simple sulfur diimides undergo unusual rearrangements when coordinated to metals.29 7. Sulfur-nitrogen chains as molecular wires: making the contact 7.1 Thiazyl chains as molecular wires Theoretical calculations show that the majority of frontier orbitals of aryl-substituted S/N chains (irrespective of chain- length) are of n-character, and the majority of these also exhibit some degree of n-delocalisation onto the aryl substituents.Such delocalisation onto the terminal groups is important if these materials are to function as molecular wires; if the aryl groups were nodal in this respect (i.e. did not contribute to the n-framework) then they would insulate the sulfur-nitrogen chain from its surroundings. Instead, this extended n-delocal- isation means that such aryl-substituted thiazyl chains can form an effective means of communication between the two terminal Chemical Society Reviews, 1997 59 groups. The extent to which the x-orbitals are delocalised over the whole molecule and the energy gap between bonding and antibonding orbitals enables us to assess the effectiveness of the intramolecular interactions.‘7 We have already seen (section 5.2) that the longer thiazyl chains produce a more delocalised n-framework with relatively small energy gaps between n-orbitals. If the aryl substituent is provided with metal-binding sites then the sulfur-nitrogen chains can be utilised to facilitate communication between the metal ions. 7.2 Making contacts In order for such thiazyl chains to act as molecular wires betwen metal ions, not only must the x-orbitals extend over both the S/N chain and its substituents, but the substituents must be capable of binding metal centres and also be of the correct symmetry to interact strongly with the metal orbitals.In order for the metals to be able to communicate effectively through the thiazyl linkage, the metal orbitals must interact with the n-cloud. This can be achieved by binding the metals in the plane, facilitating dn-pn orbital interaction, e.g. in pyridine or bipyridine complexes, or via an out-of-plane interaction commonly observed for sandwich and half-sandwich com-plexes such as ferrocenes, in which the d and p- orbitals on the metal interact directly with the x-framework of the sulfur- nitrogen chain (Fig. 6). Fig. 6 Two possible modes of communication between aromatic sub- stituents and metal centres; (a)in-plane interactions and (b)out-of-plane interactions The key to success in this field remains the preparation of thiazyl chains with suitable substituents for binding active metal sites. To date, only a very few short acyclic sulfur-nitrogen chains have been prepared containing metal-binding sites, e.g.the sulfur diimide containing just one coordinating group (perfluoropyridyl) PhNSNC5F4N has been reported,17 but its complexation chemistry has not been explored. Nevertheless, the synthetic methodologies required to prepare such deriva- tives are established and promise to provide some novel properties. 8 Future prospects There are many aspects of the chemistry of thiazyl oligomers which remain unexplored. In section 2 we indicated that the compounds prepared to date constitute just a few examples of a potentially large class of heterocyclic chains. The syntheses of ionic chains are yet to be fully exploited, and we anticipate that the lowering of the energies of the n-molecular orbitals (associated with the presence of a positive charge) will produce 60 Chemical Society Reviews, 1997 a series of new stable chains.In addition we have seen that the reactions of thiazyl chains are sometimes unexpected (section 6) and diverse products can appear from seemingly simple reactions. Further work is required to fully establish these reaction mechanisms and subsequently these can be utilised to assist in the design of new molecules. The coordination chemistry of these chains has scarcely been touched and should provide a wealth of valuable information which can be utilised in the design of molecular devices incorporating sulfur-nitrogen chains as the molecular wire.Oakley and coworkers 18 have already proposed that thiazyl chains with combinations of electron-withdrawing and -donat- ing substituents may prove to be active for non-linear optical applications. Futhermore, it seems apparent that these chains can also fulfil a number of other criteria which provide them with properties desirable for a range of other applications; difunctional materials such as that illustrated in Fig. 7(a)have a rod-like nature and may be suitable for development as liquid crystalline materials; the compound illustrated in Fig. 7(b),in its coordinated form, would facilitate communication between multiple metal ions; and the molecule shown in Fig.7(c) illustrates one of a family of novel macrocyclic systems in which thiazyl chains link the coordinating bipyridyl functional groups. The incorporation of other heteroatoms, such as R-P, into the backbone of the chain will allow the electronic properties of the S *NbN I I I I N, 0N ‘S’ ((.1 Fig. 7 Structures of some molecules ontaining thiazyl linkages chain to be modified by fine-tuning the R-group on the chain The potential of these thiazyl-substituted derivatives has yet to be explored but opens-up fascinating new areas of chemistry coupled with the opportunity to develop new molecular materials with unusual properties. Added zn proof: Herberhold and coworkers have recently reported the synthesis of a bis(ferrocene) derivative in which a sulfur diimide (NSN) functional group bridges between the two metallocene units.30 9 References 1 M M Labes, P Love and L F Nichols, Chem Re\ , 1979, 79, 1 2 (a)A E Thomas, J Woods and Z V Hauptman J Phys D 1983,16, 1123.(h)M J Cohen and J S Harris,Appl Phys Lett, 1978,33,812, (c) Handbook of Conducting Polyrners ed T A Shotheim, Marcel Decker, New York, 1986, vol 1 and refs therein 3 J Emsley, NeK Scientist, 1990, March 17, p 33 4 A J Banister, Inorg Synth , 1977, 17, 197 5 F A Kennett, G K MacLean, J Passmore and M N S Rao J Chem Soc Dalton Ti ans , 1982, 85 1 6 (a) A J Banister, Z V Hauptman, J Passmore, C -M Wong and P S White J Chem SOL Dalton Tians, 1986,2371, (b)A J Banister, Z V Hauptman, J M RawsonandS T Wait, J Muter Chem.1996, 6, I 161 and refs therein 7 J C W Chien and M Y Zhou, J Polym Sci A, 1986, 24, 2947 8 R T Oakley, frog Inorg Chem , 1988,36, 299 9 ((I) M D Ward, Chem Soc Re1 , 1995, 24, 121, (h) B E Bowler, A L Raphael and H B Gray, Piog Inor q Chem , 1990,38, 259 10 L Smart and E Moore, Solid State Chemistry An Introduction, Chapman and Hall, 1992 11 A J Banister, Phosphorus and Sulfur, 1978, 5, 147 12 (a)J D Woollins, Non Metal Rings Cages and Clusters Wiley, 1988, (h)The Chemistry of Inor ganic Ring Systems ed R Steudel, Elsevier, 1992, (c) The Chemistip of Inorganic Homo- and Hetero cycles, ed I Haiduc and D B Sowerby, Academic, 1987, vols I and I1 13 (a)A J Banister and J R House J Inoig Nucl Cheni , 1971,33,4057, (h) E Fluck, Z Anorg Allg Chem, 1961, 312, 195 14 (a)A Golloch and M Kuss, Z Naturforsc h TeilB, 1972,27, 1280, (h) A Golloch and M Kuss Z Naturforsch Teil B 1974, 29, 320 15 (a)Inor qanic Reactions and Methods, ed A P Hagen, vol 17,pp 172-180, VCH, 1990,(h)G Kresze and W Wucherpfennig, AngeM Cheni Int Ed Engl , 1967,6, 149, (c) C P Warrens and J D Woollins, Inoig Syizth , 1989, 25, 43 16 (a)J Kuyper and G B Street, J Am Chem Soc 1977, 99,7848, (h) J J Mayerle, J Kuyper and G B Street, Inoiq Chem 1978, 17, 2610 17 (a) A V Zibarev, S N Konchenko, M A Fedotov and G G Furin, J Gen Chem USSR 1988,58,404,(h)AV Zibarev,Y V Gatilavand G G Furin, J Gen Chem USSR 1990, 60, 2428, (L) A V Zibarev, A 0 Miller, M M Shakirov and G G Furin, J Gen Chem USSR 1991,61, 864, (d)A V Zibarev, Y G Gatilav and I Y Bagryanskaya, Polyhedron 1992,11, 2787 18 K Bestari, R T Oakley and A W Cordes, Can J Cheni , 1991, 69, 94 19 F P Olsen and J C Barrick, Inoig Chem , 1973, 12, 1353 20 (a)R Gleiter and R Bartetzko, Z Natuifoi sth Ted B,198 1,36,492, (h) R M Bannister and H S Rzepa, J Chem Soc Dalton Tranr , 1989, 1609 21 W Isenberg, R Mews and G M Sheldrick, Z Anorg Allg Chem, 1985,525, 54 22 G Wolmershauser and P R Mann, Z Naurforsth Tell B, 1991, 46, 3 15 23 (a) C M Aherne, A J Banister, I Lavender, S E Lawrence and J M Rawson, Polyhedron, 1996, 15, 1877, (h) J A K Howard, I Lavender, J M Rawson and E A Swain, Main Group Chem , 1996, 1,317 24 B Ayres, A J Banister, P D Coates, M I Hansford, J M Rawson, C E F Rickard, M B Hursthouse, K M A Malik and M Motevalli, J Chem Soc Dalton Trans, 1992, 3097 25 A W Cordes, M HOJO,H Koenig, M C Noble, R T Oakley and W T Pennington Inorg Cheni , 1986, 25, 1137 26 R B Woodward and R Hoffman, The ConserLation oj Oihital Symmeti y Weinheim/Bergstr , Verlag Chemie, 1970 27 R Jones, D J Williams, P T Wood and J D Woollins, Polyhedron, 1988, 8,91 28 J M Rawson, unpublished results 29 R Meij, D J Stufkins, K Vrieze, A M F Brouwers, J D Schagen, J J Zwinselman, A R Ourbeck and C H Stam, J Oi qanornet Chem , 1979, 170, 337 and refs therein 30 M Herberhold, B Distler, H Maisel, W Milius, B Wrackmeyer and P Zanello, Z Anorq Allg Chem , 1996, 622, 1515 Received, 23rd September 1996 Accepted, 13th November 1996 Chemical Society Reviews, 1997 61

ISSN:0306-0012    

DOI:10.1039/CS9972600053

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Towards a general triple helix mediated DNA recognition scheme France This review describes new perspectives offered by the synthesis of non-natural nucleosides to overcome current limitations and extend the triplex-mediated DNA recogni- tion scheme to any sequence. Alternate strand purinebinding, direct pyrimidine recognition, and binding to the whole base-pair are described. The review highlights struc- tural requirements to the design of modified nucleosides, as well as perturbing events such as tautomeric ambiguity and intercalation for the extended heterocyclic bases. 1 Introduction Nucleic acids triple helices were first described in 1957 by Felsenfeld and Rich,' just a few years after Watson and Crick discovered the double-helical nature of DNA.The present interest in triplexes follows the discovery in 1987 by the groups of Hklitne and Dervan that short oligonucleotides can bind in a sequence specific manner to a duplex target in DNA under suitable conditions.2.3 Since binding occurs in the major groove, triplex-forming oligonucleotides (TFOs) have the potential to interfere with regulatory proteins which bind to the same site, hence controlling gene expression. This exciting perspective has stimulated extensive work on triple helical complexes during the past decade (reviewed in refs. 4 and 5). Much effort has been devoted to increasing the stability of triplexes under physiological conditions, as well as overcoming the major drawback of this approach, i.e. the requirement for oligopurine tracts on the target DNA.This limitation arises from the recognition mechanism which involves the purine's two remaining 'Hoogsteen' hydrogen-bonding sites in the major groove of the DNA duplex (Fig. 1); pyrimidines having only one hydrogen-bonding site vacant cannot be efficiently bound. J. P. Behr and S. 0.Doronina This review will mainly focus on new perspectives offered by the synthesis of non-natural nucleosides to overcome current limitations and extend the triplex-mediated DNA recognition scheme to any sequence. Other recent advances to stabilizing triple helices in a sequence-independent manner, such as conjugation of poly- amines or triplex helix-specific intercalating agents, or the widely explored ribose-phosphate backbone modifications5 [peptide nucleic acid (PNA), oligonucleotide N3'-P5' phos-phoramidates and deoxyribonucleic guanidine (DNG)] will not be discussed here.Essentially two families of DNA triple helices have been characterized that differ in their third-strand sequence compo- sition and relative orientation (Fig. 2). In the pyrimidine- *purine-pyrimidine (Py *Pu-Py) family a homopyrimidine (Py) third strand is bound (*) parallel to the purine strand of target duplex (Pu-Py) in the major groove of DNA through iso-morphous T*A-T and G+*G-C base triplets. Within the T*A-T triplex plane a thymine of the TFO interacts with a Watson- Crick A-T base pair by making two Hoogsteen hydrogen bonds with adenine. The requirement of a protonated cytidine for guanosine recognition results in pH-dependent binding with optimal stability much below physiological pH (5.6-6.0).In the purine*purine-pyrimidine (Pu*Pu-Py) family, a purine-rich third strand is bound antiparallel to the purine strand of the target duplex. DNA recognition in this motif involves guanosine binding by reverse-Hoogsteen hydrogen bonding to guanosine of the G-C base pair (G*G-C base triplet), and either adenosine or thymidine binding to adenosine of the A-T base pair (A*A-T or T*A-T). Base triplets within this family are not isomorphous, i.e. location and orientation of the third-strand deoxyribose (dR) is sequence dependent. This leads to helix ~~ Svetlana 0. Doronina was born in Tomsk, Russia. After receiving her Master's degree in Chemistryfi-om Novosibirsk State University in 1985, she became a Junior Researcher in the laboratory of Organic Synthesis at the Novosibirsk Institute of Bioorganic Chemistry.In 1992 she came to France and since 1993 she started her PhD studies dealing with the DNA recognition by modified oligonucleotides under supervision of Dr J. P. Behr at the University Louis Pasteur of Strasbourg. Jean-Paul Behr is Research director at the Centre National de la Recherche Scientifique. He was born in 1947 and graduated from the Chemical Engineering School in Stras- bourg. He joined Jean-Marie Lehn in 1969 for PhD work in physical organic chemistry. After a postdoctoral stay in ShefSield to study molecular motion in biological membranes, he rejoined J.M. Lehn to contribute to the development of artificial receptors, catalysts and carriers. In I989 he moved to the Faculty of Pharmacy to head the Lahoratoire de Chimie Ge'ne'tique. His major interests are now in the development of DNA-binding molecules relevant to bio- technology and gene therapy. Chemical Society Reviews, 1997 63 Major Groove JD A Minor Groove Major Groove n Minor Groove Fig. 1 Watson-Crick hydrogen bond formation (dotted lines) between complementary nucleic bases leaves several H-bonding sites [donor (D) or acceptor (A)] vacant in the major groove of the resulting duplex. Purines (adenine and guanine) have distinct bidentate 'Hoogsteen' sites vacant whereas pyrimidines (cytosine and thymine) have only a single remaining binding site in the major groove.distortion for mixed sequences especially in the case of G*G- C/T*A-T sequences. These triplexes are not pH-dependent but are destabilized by physiological monovalent cation concen- trations. As shown above, DNA recognition by triple helix formation relies on hydrogen bonding interaction within the base triplets. However, the design of new binding motifs should take into account that third-strand binding depends on many factors besides the stability of isolated planar triplets. Indeed, stacking, van der Waals and dipolar interactions between the neighbour- ing heterocyclic bases are widely involved in helix stability. Structural isomorphism of base triplets too is an important concern to avoid ribose-phosphate backbone distortion: triplets are isomorphous if their N-dR bonds are superimposable (e.g.C+*G-C and T*A-T in Fig. 2) and we shall see later that non- isomorphism leads to considerable triplex destabilization for random purine sequences. Cationic heterocycles may be favourable in isolated sites due to their strong H-bonding capacity and to attractive electrostatic interactions in a poly- anionic context. Yet in contiguous sequences electrostatic repulsion between adjacent charges may result in overall destabilization as found when targeting G-stretches with protonated cytidines. Chimeric nucleosides are therefore de- signed to be mostly neutral. Sequence-selective recognition not only means affinity for the target nucleic base, but also discrimination against the three other ones (which is much more stringent).With respect to the latter criterion, tautomerism of heterocyclic bases must seri- ously be considered. Whereas natural bases are a 99.99% in the Watson-Crick tautomeric form shown in Fig, 1, providing both replication fidelity and some possibility of evolution, most polyaza-heterocycles have several tautomeric structures, which may hydrogen bond to more than just one natural base. Ideally, the development of base-modified nucleoside analogues with unambiguous tautomerism would clarify this problem. 2 Current limitations of homopurine triplexes 2.1 Py*Pu-Py triplexes Protonation of cytidine is required in order to establish two hydrogen bonds with guanosine (Fig.2). The pK, of isolated cytidine is 4.3. However, even though its apparent pK, increases when incorporated in oligonucleotides due to the polyanionic environment, optimum C+*G-C triplet stability still requires acidic conditions. This rather limits the potential use of such oligomers in vivo, where intracellular pH is highly regulated at ca. 7.3. The first (and up to now one of the best) solution to provide Py*Pu-Py triplex stability at physiological pH was replacement of cytidine by 5-methylcytidine6 (m5C). This modification enhanced considerably the stability of triple helices at neutral pH and may serve as a reference for G-C base pair recognition for newly designed structures.The influence of cytidine methylation on triplex stability does not appear to result from the 0.2 units pK, increase, but is mainly of entropic origin.7 Recently numerous synthetic nucleosides have been developed that display the hydrogen bonding pattern of protonated cytidine, as we shall see now. 2.1.I Pyrimidine-like analogues of cytidine Pyrimidine-like pseudoisocytidine8 (isOC), pyrazine base9 (pyDDA), 5-methyl-6-oxocytidine10 (m50xC) lead to B*G-C triplets (B = isOC, pyDDA, m5~"C) isomorphous to the canonical T*A-T triplet [Fig. 3(A)]. These heterocycles already have a hydrogen atom at the N3 position which allows them to bind to guanine in a pH-independent fashion. Triplexes containing these modified bases are more stable at neutral pH than cytidine-containing triplexes but generally do not achieve the stability of 5-methylcytidine-containing triple helices.Thus, triple to double helix transition temperatures (T,) of triplexes containing m50xC are still significantly lower at neutral pH than those observed for the corresponding m5C+-containing tri- plexes. This likely reflects the fact that cations are better H-bond donors that show further stabilization on a polyanionic target. To our knowledge, there are no data about the binding specificity of is0C and pyDDA. m50xC has been shown to be very selective, as the only target base pair (besides G-C) that led to detectable triple helix formation was C-G, but with significantly less stability. Both m5oXC and i~oC can adopt several tautomeric structures.X-ray crystallography as well as duplex-DNA melting tem- perature studies suggest that the N3-H tautomer is preferred for m50"C. Indeed m5°xC-containing duplexes are less stable than their natural counterparts. This could be due to steric clash between N3-H of rn50"C and N1-H of G which prevents Wat son-Crick base pairing. isoC has tautomeric structures in which the hydrogen atom can be bound to either N1 or N3 [Fig. 3(B)]. is°C-containing duplexes also show decreased stability, presumably because of steric clash [Fig. 3(C)]. These data lead to the supposition that the tautomeric ambiguity of these nucleoside analogues should not hamper their selectivity of binding. m50xC and isoC seem also to be promising candidates for targeting of G-C stretches.As mentioned previously, such sequences are particularly difficult targets in the Py*Pu-Py motif because of ionic repulsion between adjacent protonated residues when C+ or mT+-containing TFOs are used. Such unfavourable interactions should not be present in adjacent neutral m50xC or is0C nucleotides. Indeed, a triple helix containing the (isoC), sequence was shown to melt at least 22 "C higher at pH 7.5 than the corresponding (m5C+), triplex. Contiguous m5W did not lead to stable triplexes. Undesirable 64 Chemical Society Reviews, 1997 steric effects brought about by the 06 carbonyl atom or poor base stacking could be at the origin of the decreased stability. To illustrate the impact of non-natural base tautomerism on specific nucleic base recognition the example of the pyrido[2,3- dpyrimidine nucleosidel (F) is edifying.This heterocycle can exist in two tautomeric forms F1 and F2 [Fig. 4(A)], which can either bind to guanine or adenine in the Watson-Crick sense to form an antiparallel double helix, Fl-G (3 H-bonds) being considerably more stable than F2-A (2 H-bonds) [Fig. 4(B)]. In Py*Pu-Py triple helixes Fl may bind to G-C or C-G base pairs through a single H-bond, or F2 to A-T through two H-bonds [Fig. 4(C)]. Binding experiments have demonstrated that F recognizes the A-T base pair when incorporated into TFOs, with an affinity similar to that of the canonical T*A-T triplet. This example shows that when tautomers are of comparable stabilities, complementary strand binding selects the tautomers giving the most stable among possible structures, i.e.F1-G (3 H-bonds) and F2*A-T (2 H-bonds). 2.I .2 Purine-like cytidine analogues Some purine-like non-natural nucleotides (shown in Fig. 5) have been described for replacement of protonated cytidine: 3-methyl-5-amino-1H-pyrazolo[4,3-d]pyrimidine-7-one12 (PI), N6-methyl-8-oxoadenosine l3 (8oxA) or N7-guanosine14 (7G). From affinity cleaving analysis, the stability of base triplets containing N7-guanosine decreases in the order 7G*G- C >> 7G*C-G >>7G*A-T = 7G*T-A with affinities compara- ble to those of m5C. Nearly the same results were obtained for the pyrazole analogue PI. Its chemical isomer P2 [deoxyribose is linked to pyrazole N2 for P2 and N1 and PI, see Fig.5(C)], did not show reasonable affinity to any Watson-Crick base pair; this is probably due to energetically unfavourable distortion of the third-strand backbone added to the fact that the methyl group of P2 disfavours the anti conformation. The known tendency of 8-substituted adenosine analogues to be predominantly in the syn conformation led to the use of 8-oxoadenosine as a C+ substitute [Fig. 5(B)]. T, for a given triplex containing 8oXA*G-C was 22 "C at pH 7.0 and 8.0, whereas the corresponding transition in the control triplex (containing canonical C+*G-C) decreased from 28 "C at pH 7.0 to 17 "C at pH 8.0. goxA is also able to form goXA*C-G and goxA*U-A triads, the latter one being stabilized by a hydrogen bond between the N6 exocyclic amino group of 8-oxoadenosine and the O4 of uridine.However, these mismatched triplets are significantly less stable than goxA*G-C. The common drawback of these compounds is the lack of structural isomorphism between B*G-C (B = PI, 7G, goxA) and T*A-T triplets, which prevents complex formation for P2. Although NMR analysisl5 does not reveal any major backbone distortion for PI and 7G, the three orders of magnitude decrease in the affinity of 7G or P1-containing oligonucleotides for targeting an alternated (GA), vs. a contiguous G6 site16 Pv"Pu-Pv Triplexes Pu*Pu-Pv Triplexes Fig. 2 The two families of homopurine-targeted triple helices. In X*Pu-Py, '-' and '*' represent Watson-Crick and Hoogsteen hydrogen bonds, respectively.Half-arrows indicate the relative deoxyribose-phosphate (dR) backbone orientation. Chemical Society Reviews, 1997 65 A dk dk dk C+ isoc PYDDA rnSoXc B dR dk N3-Htautomer N'-H tautomer (a) G -(N3-H) (b) G -(N'-H) Fig. 3 Pyrimidine-like cytidine mimics. ISOC, pyDDA and m5oxC display the hydrogen bonding pattern of protonated cytidine (A). Possible N3-H and N1-H tautomeric forms of pseudoisocytidine (,,oC) (B). N3-H (a) and N1-H (b) tautomers of lS0C in Watson-Crick type I~~C-G base pair (C). confirms the energy penalty for nonisomorphism of adjacent triplets. 2.2 Pu*Pu-Py triplex The obvious advantage of Pu*Pu-Py triplexes is their pH independence: no protonation is required for the G*G-C, A*A- T (or T*A-T) base triplets, which are stabilized by two reverse- Hoogsteen-type hydrogen bonds between bases of the third strand and the purine strand of the Watson-Crick duplex (Fig.2). T*A-T triplets are generally preferred to A*A-T base triplets because the latter, although well characterized for homopolymers, have stabilities critically dependent on the length of the homoA tract and on the presence of divalent cations. Reverse-Hoogsteen T*A-T triplets are able to bind within a G*G-C triple helical structure, but triplexes are far from isomorphism (Fig. 6); A*A-T and G*G-C triplets are not isomorphous either, but more so than T*A-T/G*G-C. The net result is that the stability of Pu*Pu-Py-type triple helices is usually determined by the content of G-residues.2.2.I Inhibition by monovalent cations The development of G-rich TFOs as potential antigene drugs is hampered by the observation that triple helix formation is inhibited by monovalent cations, and especially by potassium which is the predominant intracellular cation. Inhibition is due to the involvement of the TFO into another process. At physiological K+ levels, guanosine-rich oligonucleotides self- associate by stacking of K+/guanine quartets [Fig. 7(A)] which are stabilized by a combination of mutual bidentate H-bonding and coordination of the four 06 atoms of guanosine to K+ located at the centre of the quadruplex. A number of such structures have been identified, including intra- and inter- molecular associations between oligonucleotides.To overcome 66 Chemical Society Reviews, 1997 this problem, guanosine has been replaced by nucleoside analogues that introduce a steric hindrance or disrupt the H-bonding network of the G-tetrad. The larger van der Waals radius and decreased electronegativity of sulfur of 6-thioguan- osine17 (S6-dG), relative to oxygen, was expected to decrease the tetrad stability, but should not directly affect H-bonding of G*G-C triplets (Fig. 2). Experiments showed that S6-dG- containing triple helices were no longer sensitive to potassium, but were also less stable. Complete substitution of S6-dC for G in some model TFOs reduced binding affinity by more than 100-fold.Replacement of guanosine N7 H-bond acceptor by a C-H group (7-deazaguanosinel 8, 7dzaG) or an N-H group (9-deaza- guanosinelg 9dzaG) were supposed to disrupt the H-bonding network of the G-tetrad [Fig. 7(B)], while retaining the hydrogen bond donors and acceptors pattern for formation of dzaG*G-C triplets. Surprisingly, attempts to overcome the binding inhibition in KC1 by substitution of G by 7dzaG or 9dzaG failed. A a 0 dR 0 dR 0 B 0 H F1-G F2-A C H H (a) Fl*G-C (b)Fl*C-G (C) FP*A-T Fig. 4 The tautomers (A) of pyrido[2,3-d]pyrimidine nucleoside (F) bind either single or double stranded DNA. (B) Single-strand binding through FIG and F2-A Watson-Crick type base pairs. (C) Triple helix stabiliza- tion with F1 (a, b) and F2 (c).P1 (ant,) 'G (anti) B dR /CH3 HP1'G-C PS'G-C H Fig. 5 Structures of purine-like cytidine mimics. (A) In contrast to the anti glycosidic bond conformation of most purine nucleosides, *O~Ahas predominantly the syn conformation. Nonisomorphous hydrogen bonding schemes of 7G*G-C and *oxA*G-C (B), and of P1 *G-C and P2*G-C (C) triplets within a Py*Pu-Py triplex. G*G-C A*A-T \J t I , Fig. 6 Non-isomorphism of natural base triplets within a Pu*Pu-Py triple helix. (0)indicates the ribose C1'atom of the third strand. 2.2.2 Towards isomorphous base triplets As mentioned above, another problem within this triplex family is the non-isomorphism of base triplets, especially for the T*A- T/G*G-C triplexes. This results in deformation of the deoxy- ribose-phosphodiester backbone at the transition from a bicyclic purine to a monocyclic pyrimidine, thus decreasing the stability of triple helices.TFOs containing only purines could have a better chance to be isomorphic. 7-Deazaxantosine18 (dzaX) and 2-amin0purine2~ (amp) have been used instead of T (or A) for A-T base pair recognition (Fig. 8). dzaX seems to be very promising: in comparative studies under physiological K+ concentration, the TFO containing G and dzaX showed a greater than 100-fold increase of affinity for the target sequence as compared to the G/T TFO. amP*A-T triplets are isomorphous with G*G-C triplexes in the Hoogsteen orientation [Fig. S(C)] which is different from the typical Pu*Pu-Py reverse-Hoogsteen family [Figs.2,8(B)]. The synthesis of modified TFOs containing amp has been described but no binding experiments have been reported so far. 3 Towards a general triple helix-mediated DNA recognition scheme As discussed previously, triple helix formation is strictly limited to homopurine targets, as a consequence of DNA recognition Fig. 7 (A) G-rich oligonucleotides form G-tetrads in the presence of potassium cations. (B) Putative disruption of the tetrad H-bonding network for 9dzaG. <KAN,HI I dR H dzaX amP ,dR dR H G'G-C dzaX' A-T C ""IK H-N H G'G-C Hoogsteen hydrogen bonds amP'A-T Fig. 8 7-Deazaxantosine (dzaX) and 2-aminopurine (amp) (A) could form isomorphous base triplets with A-T in a G*G-C context, by reverse-Hoogsteen bonding for dzaX (B), or Hoogsteen bonding for amp (C) Chemical Society Reviews, 1997 67 via Hoogsteen-type hydrogen bonds.As further stages towards a general sequence recognition scheme, two types of sequences have been tackled: alternated oligopurine-oligopyrimidine tracts and quasi-homopurine sequences with a single pyrimidine base. 3.1 'Switched' triple helices When the DNA target is made of adjacent oligopurine- oligopyrimidine domains, a continuous oligopurine tract still runs along the helix yet switches strand at each domain junction. Short canonical triple helices of low stability could be formed with each homopurine sequence. However, if all short TFOs are linked via appropriate spacer groups, triplex formation is very much enhanced due to cooperative binding. This approach is called alternate-strand triple helix formation, or 'switched' triple helix.Indeed, short TFOs when joined together form a single third-strand oligomer that zigzags along the major groove, switching from one oligopurine strand to the next one on the other strand. Combining the two canonical triple helix families with opposite strand polarities (Fig. 2) leads to many examples of 'switched' triple helices.21 Non-natural a-ano-meric oligonucleotides,which generally bind in the reverse orientation as compared to p-oligonucleotides, are also attrac- tive blocks to enrich the set of 'switched' TFOS.~~ An alternate-strand recognition scheme exclusively using Py*Pu-Py triplexes is illustrated in Fig.9(A). The alternated purine (R)-pyrimidine (Y) target DNA sequence is R7Y7R7. The third strand is made of three short pyrimidine (Y) TFOs. On both ends, TFOs run in the same direction along the major groove, whereas the central one must have the opposite polarity to stay parallel to its R7 target which is located on the opposite DNA strand. The design of alternate third strands is a complex task requiring linkers adapted to each type of junction crossing the major groove. Molecular modelling is widely used to find optimally rigid linker groups with reduced entropy of binding. Several linkers have been described, such as hexaethylene glycol, propane- 1,3-diol and xylose derivatives.Recently, a direct base-to-base linkage has been described,21 that allows shorter linkers to be used for different types of junctions. Binding tests with a C3'-C3'U-linked oligonucleotide [Fig. 9(B)] as TFO (Py*Pu-Py motif) have shown triple helix formation, but the junction remains to be optimized to increase the complex stability. An as yet unanswered question is the effective participation of the bases close to the junctions in the stability and selectivity of the binding process. A ~~~~~~~~-5'-YYYYYYY 5 YYYYYYY ' 5'-NNNNNRRRRRRR YYYYY RRRRRRRNNN 3'-NNNNNYYYYYYY RRRRRRR YYYYYYYNNN0000000 3'-YYYYYYY-B 5'-YYYYYYYYYYY-dk-3' 3'-dk-YYYYYYYYYYY-5' Fig. 9 (A) Alternate strand recognition in a Py*Pu-Py context.(B) Structure of a short strand-switching pentamethylene C3'-3'U-linker. 68 Chemical Society Reviews, 1997 3.2 Direct pyrimidine base recognition Several solutions have been described to bypass interruption of the target purine stretch by a single pyrimidine. Non-specific stabilization by incorporation of an intercalator at an internal site of the TFO is a simple and efficient solution.23 Alter- natively, pyrazole-, imidazole-, 1,2,4-triazole- and tetrazole- substituted nucleotides have been used in front of a pyrimidine base in an otherwise Pu*Pu-Py triple helix.24 Azole incorpora- tion enhanced TFO binding when compared to that of a natural base. These five-membered heterocycles were not designed for recognition of any particular base but rather to maintain some stacking interaction with neighbouring bases.Furthermore their rather small size reduces steric hindrance, especially when facing T which has a protruding methyl group. The pyrazole derivative seemed to be of particular interest: despite showing only weak preference for T-A over G-C, it discriminated strongly against A-T and C-G base pairs. A fatal limitation to specific recognition of pyrimidine bases in Watson-Crick base pairs is that they possess only a single remaining hydrogen bond-forming site in the major groove (Fig. l), that results in an intrinsically lower stability. Furthermore, thymine binding is obscured by its bulky methyl group. Considerable efforts to solve these problems have been undertaken, yet only limited success achieved.Several non-canonical natural base triplets of intermediate stability, such as G*T-A in a Py*Pu-Py context and T*C-G (Pu*Pu-Py) were discovered following a systematic study.25 Both base triplets involve a single hydrogen bond between the third-strand base (G or T) and the target pyrimidine inversion (T or C) (Fig. 10). GT-A T'C-G Fig. 10 Non-canonical G*T-A and T*C-G base triplets in a Py*Pu-Py and a Pu*Pu-Py context, respectively. In contrast to the canonical purine recognition scheme, only a single hydrogen bond can be drawn between third strand and target bases. Some nucleoside analogues like nebularine26 (N) recognize C-G in a Pu*Pu-Py triple helix. Once again a single hydrogen bond is established, and the N*C-G interaction is weaker than G*G-C, A*A-T or T*A-T. Moreover, nebularine has compara- ble affinities for C and A since it provides a hydrogen bonding ~~~~~ acceptor site to the exocyclic amino group (Fig. 11).Thus solutions found so far have limited destabilization rather than improving pyrimidine recognition. 3.3 Other-strand recognition As stated above, proper pyrimidine recognition with energies comparable to that of purines requires more than one hydrogen bond. Since this is simply not feasible with pyrimidines, an attractive solution would be to bind the facing purine of the opposite strand instead. Along these lines, formycin A (forA) was suggested to form two hydrogen bonds with the guanosine of the other strand at C-G inversions in a Pu*PuaPy triplex,27 as shown in Fig.12(A). To do so however, a 3-5 A translation as well as a rotation around the ribose-phosphate backbone are required, which would result in severe backbone distortion. Incorporation of three forA*C-G instead of G*C-G resulted in a ten-fold increase in binding affinity,27 but this may also coincidentally be due to reduced steric hindrance of formycin relative to guanine. \ H N*T-A N*C-G dR N*A-T Fig. 11 Putative interactions between nebularine (N) and the four Watson- Crick base pairs in an antiparallel Pu*Pu-Py triple helix. Nebularine provides a hydrogen bonding acceptor site to the exocyclic amino groups of C and A. Indeed, when comparing forA*C-G and G*C-G triplets within the Pu*Pu-Py backbone geometry [Figs.12(B) and (C)], formycin escapes the G(N1-H and N2-H)/C(N4-H) clash and may even take advantage of an attractive forA(N1)/C(N4-H) interaction. The future success of this approach will rely on the possibility of crossing the DNA duplex major groove with more extended structures and without backbone distortion. 3.4 Base-pair recognition The most promising way to reconcile affinity and selectivity is to use extended heterocyclic systems that can simultaneously Utilize all major groove hydrogen-bonding sites of a Watson- Crick base-pair for molecular recognition. The first example of A dR such a strategy was the use of 4-(3-benzamidophenyl)imi-dazole28 (D3) expected to hydrogen bond simultaneously C(N4- H) and G(06) of C-G in a Py*Pu-Py triple helix (Fig.13).Other base pairs were supposed to lead to steric clashes with adenine, cytosine and the methyl group of thymine (Fig. 13). Un- fortunately, experimentation showed the following order of stabilities: D3”T-A = D3*C-G > D3*A-T > D3”G-C. The rationale to this was found later, when it was shown that D3 interacts by sequence-specific intercalation, rather than by hydrogen bonding29 When N4-(3-acetamidopropy1)cytidine (adPC) was incorpor- ated in front of C-G inversions, a considerable stabilizing effect was observed relative to third strands with N4-butylcytidine or N4-(3-carboxypropyl)cytidine whose side chains lack hydrogen bond donating groups. The length of the flexible acet-amidopropyl arm of aapC is sufficient to span the duplex major groove and allows the terminal amide to form an additional hydrogen bond with O6 of guanine in the target C-G base pair.To improve binding, a more rigid 6-amino-2-pyridinyl sub- \ H DB*C-G D3*T-A H/ D3*G-C DB*A-T Fig. 13 Best hydrogen bonding fit between the synthetic base analogue D3 and the four base pairs in a Py*Pu-Py triple helix C dR H ‘“A*C-G (“other strand” geometry) ‘“A’C-G (Pu*Pu-Py geometry) G*C-G(Pu*Pu-Py geometry) Fig. 12 (A) For cytosine recognition, forAcould hydrogen bond to the guanine of the opposite DNA strand at the expense of a ca. 5 8,translation (arrow) through the major groove. The dotted line structure indicates the position of guanine in a G*G-C triplex. forA(B)and G (C)facing the same C-G inversion.Chemical Society Reviews, 1997 69 stituent was introduced at the N4 position of cytidine (apyC), thus providing two hydrogen bonding sites for interaction with C-G and three for A-T30 [Fig. 14(A)]. Both triads involve an unusual imino tautomeric form of apyC [Fig. 14(B)] which is supported by 1H NMR and UV spectroscopy of apW. A dR dR amino imino Fig. 14 (A) Possible hydrogen bonding schemes of the irnino tautomer of apyC with C-G and A-T base pairs in a Pu*Pu-Py triple helix. (B) The amino/irnino tautomeric equilibrium of apyC / As shown in Fig. 14(A), the pyridine ring spans the major groove so as to place the 6-amino group of apyC within hydrogen bonding distance of guanine 06 or thymine 04.This interaction is vital and removal of the amino group results in a much decreased affinity or even in no triplex formation at all. Additional stabilization could come from stacking of the pyridine ring with neighbouring bases.Experimentally, stability of the apyC*G-C base triplet was found to be comparable to that of the canonical C+*G-C; unfortunately A-T, and to a lesser extent T-A and G-C base pairs, also recognized. Here again, design [Fig. 14(A)] and experimental facts did not coincide. The apyC-containing oligonucleotide showed two distinct inter-convertible binding modes: hydrogen bonding, as expected, and intercalation as already established for 4-(3-benzamido-pheny1)imidazole (D3, see above).Recently two novel structures for cytidine-guanosine recog- nition have been designed (Fig. 15) and tested in chloroform. Benzaminoimidazole-glycyl31 (BIG) and 2-methyl-8-(N'-butyl- ureido)naphth[ 1,2-d]irnida~ole3~ (UNI) were shown by NMR to bind to a C-G base pair by hydrogen bonding to both bases. Such experiments provide preliminary evidence about com- \ \ H H BIG%-G UNI*C-G Fig. 15 Extended BIG and UNI nucleic base analogues for specific C-G base pair recognition / Fig. 16 A third-strand oligonucleotide centered in the major groove would be able to switch from one DNA strand to the other through the @/a anomerism. 70 Chemical Society Reviews, 1997 plementarity with a given base pair. However they do not take into account base stacking interactions nor isomorphism which are also essential features for triple helix stability. 4 Conclusion A great deal of intellectual effort and organic synthesis has been invested in molecular recognition of double stranded DNA, with the aim of developing antiviral drugs and controlling endogeneous gene expression. Indeed, drugs based on the antigene strategy would have many advantages over those based on the antisense (anti-messenger RNA) strategy.Yet, up to now, the antigene strategy has essentially benefitted from pharmaco- logical advances obtained with antisense oligonucleotides, such as nuclease resistance and intracellular delivery33 due to their common generic structures. Increasing the stability of triple helices in physiological media is just one of the problems related to gene targeting (the adverse corollary being the slow kinetics of triplex formation34).In this review we deliberately focused on ways of extending triplex formation to non-homopurine sequences, as although polyPu-polyPy stretches are not uncommon in the mammalian genome, the conse-quences of making random sequences amenable to targeting are obvious. This remains a challenge for organic chemists.35 The challenge has been taken up as illustrated by the numerous examples described in this review. They highlight, besides unpredictable synthetic difficulties, predictable require- ments for modifying nucleotides, in the area of complementar- ity, triplex isomorphism and base stacking.They also illustrate effects such as intercalation as opposed to hydrogen bonding for extended molecules, and tautomeric ambiguity of heterocyclic bases. Undoubtedly, integration of this knowledge will help chemists to play a pivotal role in the success of drug development based on sequence-selective DNA recognition. Added in proof: Besides this review, our real contribution to a general triple helix mediated DNA recognition scheme has been rather small. Our approach was based on the natural complementarity of primary amides with adenine and of guanidine with guanine. The major difficulty of pyrimidine recognition was circumvented by targeting the opposite purine bases with the same molecular groups, but of the unnatural a-anomer nucleoside.Thus molecular recognition of the four nucleic bases (A, T, G, C) is achieved with only two unnatural bases (X, Z),degeneracy being removed by the anomeric (a, p) pluralism. For this to be possible, and for the four base triplets to be isomorphous, several geometrical constraints apply which severely limit the number of chemically reasonable structures (Fig. 16). Organic chemistry along these lines is in pro- gress.36 5 References 1 G Felsenfeld, D. Davies and A Rich, J Am Chem Soc, 1957, 79, 2023 2 H. E Moser and P. B. Dervan, Science, 1987, 238, 645. 3 T. Le Doan, L. Perrouault, D. Praseuth, N. Habhoub, J. L. Decout, N. T Thuong, J Lhomme and C HClkne, NucZeiL Acids Res ,1987,15, 7749 4 Y.-K Cheng and B.M. Pettitt, Prog Biophys Mol Brol , 1992, 58, 225. 5 J.3. Sun, T. Garestier and C HClkne, Curr Opin Struct Bid , 1996,6, 327 6 J. S. Lee, M. L. Woodsworth, L. J P Latimer and A. R. Morgan, Nucleic Acids Res , 1984, 12, 6603 7 L E. Xodo, G. Manzini, F Quadrifoglio, G. A. van der Marel and J H. van Boom, Nuclerc Acids Res , 1991, 19, 5625 8 A. Ono, P 0. P. Ts’o and L -S Kan, J Am Chem Soc , 1991, 113, 4032. 9 U. von Krosigk and S. A. Benner, J Am Chem Soc, 1995, 117, 5361 10 G. Xiang, R Bogacki and L. W McLaughlin, Nucleic Acids Res , 1996, 24, 1963. 11 A. B. Staubli and P. B. Dervan, Nucleic Acids Res , 1994, 22, 2637 12 J S. Koh and P. B. Dervan, J Am Chem Soc, 1992,114, 1470 13 P S. Miller, P Bhan, C. D Cushman and T L Trapane, Bioc hemistry, 1992,31, 6788 14 J.Hunziker, E. S. Priestley, H. Brunar and P B Dervan, J Am Chem Soc, 1995, 117, 3233 15 1 Radhakrishnan and D. J. Patel, Biochemistry, 1993, 32, 11 228 16 E S Priestley and P B. Dervan, J Am Chem Soc , 1995, 117,4761. 17 T. S. Rao, R. H Durland, D. M Seth, M. A. Myrick, V Bodepudi and G. R Revankar, Biochemistry, 1995, 34, 765 18 J F Milligan, S H. Krawczyk, S Wadwani and M D Matteucci, Nucleic Acids Res , 1993, 21, 327 19 T. S. Rao, A F. Lewis, R. S. Durland and G. R. Revankar, Tetrahedion Lett, 1993, 34, 6709. 20 V Roig, R Kurfurst and N T Thuong, Tetrahedron Lett, 1993, 34, 1601 21 B -W Zhou, C. Marchand, U. Asseline, N T Thuong, J.-S Sun, T. Garestier and C. Helene, Bioconj Chem , 1995, 6, 516 22 S €3 Noonberg, J.-C.Franqois, D. Praseuth, A.-L Guieysse-Peugeot, J. Lacoste, T Garestier and C. Helene, Nucleic Acids Res , 1995, 23, 4042. 23 B -W Zhou, E. Puga, J -S. Sun, T. Garestier and C HClkne, J Am Chem Soc, 1995, 117, 10425. 24 R H Durland, T. S. Rao, V Bodepudi, D. M Seth, K Jayaraman and G. R Revankar, Nucleic Acids Res , 1995, 23, 647. 25 W A Greenberg and P B. Dervan, J Am Cheni Soc , 1995, 117, 5016. 26 H U. Stilz and P B Dervan, Biochemistry, 1993, 32, 2177 27 T. S Rao, M E. Hogan and G. R. Revankar, Nucleosrdes Nucleotides, 1994, 13,95. 28 L. C. Griffin, L. L. Kiessling, P. A. Beal, P. Gillespie and P B. Dervan, J Am Chem Soc , 1992, 114,7976 29 K M. Koshlap, P Gillespie, P. B. Dervan and J. Feigon, J Am Chem Soc, 1993, 115,7908 30 C.-Y Huang, G. Bi and P. S. Miller, Nucleic Acids Res, 1996, 24, 2606 31 S. Sasaki, S. Nakmashima, F. Nagatsugi, Y. Tanaka, M. Hisatome and M. Maeda, Tetrahedron Lett, 1995, 36, 9521. 32 S C. Zimmerman and P. Schmitt, J Am Chem SOL, 1995, 117, 10769 33 0 Boussif, F. Lezoualc’h, M A. Zanta, M. D. Mergny, D Scherman, B. Demeneix and J. P. Behr, Proc Nut1 Acad Scz USA, 1995, 92, 7297 34 S Baillet and J. P Behr, Tetrahedron Lett, 1995, 36, 8981 35 N. Schmid and J. P. Behr, Tetrahedron Lett, 1995, 36, 1447 36 S 0 Doronina, S Blanalt-Feidt and J P. Behr, to be published. Received, 25th October I996 Accepted, 22nd November I996 Chemical Society Reviews, 1997 71

ISSN:0306-0012    

DOI:10.1039/CS9972600063

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

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ISSN:0306-0012    

DOI:10.1039/CS997260000v

出版商:RSC    

年代:1997

数据来源: RSC