摘要:

ISSN 0306-0012 CSRVBR 25(5) 297-370 Chemical Society Reviews Volume 25 Issue 5 Pages 297-370 October 1996 ~~--module4 modules I Specificity and Versatility in Erythromycin Biosynthesis By Rembert Pieper, Camilla Kao, Chaitan Khosla, Guanglin Luo and David E. Cane (pp.297-302) 6-DeoxyerythronolideB synthase is a modular pol yketide synthase consisting of three large, multienzyme proteins with at least 28 distinct active sites that together catalyse the formation of 6-deoxyerythronolide B, the parent macrolide of the medicinally important erythromycin family of broad spectrum antibiotics. The combined use of molecular genetic and enzyme mechanistic tools has provided exciting new insights into the organization and function of these fascinating catalysts and allowed the rational generation of novel ‘unnatural’ natural products.Environmentally Friendly Catalytic Methods By James H. Clark and Duncan J. Macquarrie (pp. 303-310) The use of supported reagents as catalysts in liquid phase organic reactions can provide ‘clean’ alternatives to many traditional and environmentally unacceptable reagents and catalysts. Mesoporous support materials can give the best balance between reactivity and selectivity. Successful applications are diverse and include various acid- catal ysed reactions such as Friedel-Crafts reactions, halogenations and nitrations, selective oxidations and base- catalysed carbon-carbon bond forming reactions. Designing New Lattice Inclusion Hosts By Roger Bishop (pp.31 1-320) The discovery of new lattice inclusion hosts traditionally has been an exciting but entirely serendipitous branch of chemistry.Although crystal lattice arrangements of organic molecules still cannot be predicted by computation, our rapidly-developing understanding of molecular packing, intermolecular attractions, and crystal engineering techniques, is rapidly changing this situation. This article surveys major synthetic approaches currently being employed in the design of new lattice inclusion compounds, and attempts to describe how and why these compounds operate as host-guest systems in terms of their supramolecular chemistry. Potential Energy Surface Crossings in Organic Photochemistry By Fernando Bernard;, Massimo Olivucci and Michael A. Robb (pp.32 1-328) Modern experiments and quantum chemical computations show that low lying potential energy surface crossings (conical and singlet-triplet intersections) are a general feature of photochemically relevant excited states.This review focuses on the computational and experimental investigation of the efficiency of internal conversion at a surface crossing, the competition with fluorescence when an excited state barrier is present, and the relationship between the molecular structure at the intersection and structure of the photoproducts. It is shown that single or successive low-lying intersections provide the bottlenecks controlling the evolution of a photoexcited molecule from the Franck-Condon region to the photoproduct valleys. Glutamate and 2-Methyleneglutarate Mutase: From Microbial Curiosities to Paradigms for Coenzyme B,,-dependent Enzymes By Wolfgang Buckel and Bernard T: Golding (pp.329-338) Glutamate mutase and 2-methyleneglutarate mutase are coenzyme B ,,-dependent enzymes that catalyse carbon- skeleton rearrangements of their substrates.These reactions are initiated by homolysis of the coenzyme’s cobalt-carbon a-bond. This gives cob(I1)alamin and 5’-deoxyadenosyl radical, which abstracts a hydrogen atom from a substrate molecule. The resulting substrate-derived radical rearranges to a product-related radical, possibly by a fragmentation-recombination mechanism involving, for glutamate mutase, an acrylate molecule and glycinyl radical as intermediates. Evidence for this remarkable process derives from spectroscopic investigations (EPR),isotopic labelling and model studies.’Covalent‘ Effects in ’Ionic’ Systems By Paul A. Madden and Mark Wilson (pp.339-350) Many materials which might be thought ‘ionic’, on the basis of the electronegativity difference between the elements involved, exhibit non-ionic (or ‘covalent’) structural features. Electronic structure investigations reveal the key concept that the properties of ions and their interactions are crucially influenced by their local coordination environment and that this gives a many-body character to the interionic forces. Simulations with suitable interaction models show that a wide range of ‘covalent’ behaviour may be accurately recovered within an ionic model. Non-porphyrin Photosensitisers in Biomedicine By Mark Wainwright (pp.351-360) Conventional drugs used in the photodynamic therapy of cancer (PDT) are porphyrins or porphyrin congeners such as chlorins, phthalocyanines etc.Natural and synthetic alternatives to porphyrins are available which exhibit improved photoactivity in terms of singlet oxygen quantum efficiency, increased maximum wavelength and intensity of absorption. In addition, differences in structure and/or electronic charge can lead to intracellular tumour localisation and sites of action such as mitochondria, lysosomes etc., rather than destruction of tumour vasculature. Non-porphyrin antibacterials and antivirals are also under development. Nitrous Acid and Nitrite in the Atmosphere By Gerhard Lammel and J. Neil Cape (pp.361-370) Nitrous acid is a minor trace gas, yet has an important influence on OH concentrations in the troposphere.Gas phase concentrations in both rural and urban air are larger than predicted from laboratory studies of homogeneous or heterogeneous chemistry. A better understanding of the mechanisms which produce nitrous acid in the atmosphere will lead to improved models of nitrogen oxide and OH chemistry, particularly in polluted air. Articles that will appear in forthcoming issues include Scanning Transitionietry Stanislaw L. Randzio Inhibitors of Glycosphingolipid Biosynthesis Thomas Kolter and Konrad Sandhoff The Chemistry of the Semiconductor Industry Sean O’Brien An Odyssey from Stoichiometric Carbotitanation of Alkynes to Zirconium-catalysed Enantioselective Carboalumination of Alkenes Ei-ichi Negishi and Denis Y. Kondakov Photo- and Redox-active [ 21Rotaxanes and I2jCatenanes Andrew C. Benniston Artificial P-Sheets James S. Nowick, Eric M. Smith and Mason Pairish Dynamic Resolutions in Asymmetric Synthesis S. Caddick and K. Jenkins The Role of Short-lived Oxygen Transients and Precursor States in the Mechanisms of Surface Reactions; a Different View of Surface Catalysis M. W. Roberts Shining Light on Catalysis John Evans The Science and Humanism of Linus Pauling (1901-1994) Stephen F. Mason Electronic Spectroscopy of Carbon Chains John P. Maier

ISSN:0306-0012    

DOI:10.1039/CS99625FP017

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Pollution Causes, Effects and Control 3rd Edition Edited by RM Harrison, University of Birmingham, UK The third edition of Pollution has once again been updated and expanded to reflect the changes that have taken place in recent years. In particular, if contains new chapters on marine pollution, soils and contaminated land and the effects of air pollutant exposure on human health. The book’s treatment of its subject is essentially introductory, although some aspects are covered in greater depth. The contributions combine to give a broad over- view, touching on most of the important areas and delving deeper into many of them. More than ever, before, the environment is high on the political agenda, illustrating the need for authoritative scientific information on the subject.Pollution is a must for graduated and undergraduates with an interest in environmental and pollution research. “This book is useful as a textbook and is highly recommended.” Environmental International (reviewing 2nd edition) Softcover xxi + 480pages ISBN 0 85404 534 1 1996 f35.00 Environmental Impact of Chemicals Assessment and Control Edited by M Quint, Dames & Moore, UK D Taylor, Zeneca Environmental Lab, UK R Purchase, Environmental Chemistry Group, RSC, UK Environmental Impact of Chemicals contains a collection of views and theoretical discussions from industrialists, scientists and regulators which outline the latest legislative position and current state of the art on the rapidly changing field of environmental risk assessment.Risk assessment in safety and, to an increasing extent, chemical product registration, has been practised for many years. It is only relatively recently, however, that it has been routinely applied to chemicals released into the environment. This book describes the underlying science of such assessment, the problems associated with it and the difficulties involved in communicating the results to the general public. The book is highly practical and written from an applied perspective, with the majority of contributors being practitioners in the filed. It will prove useful to researchers and professionals in industry as well as to consultancy and governmental bodies. Special Publication No 7 76 Hardcover viii + 242 pages ISBN 0 85404 795 6 1996 f69.50 Simple Guide on Management and Control of Wastes This guide derives from a study carried out by a specialist committee of The Royal Society of Chemistry for the European Commission.As its title suggests, this is a basic guidebook which identifies with major moral, legal and administrative duties associated with the minimisation, control, and ultimate disposal of liquid, semi-solid and solid waste. Simple Guide on Management and Control of Wastes provides a useful reference work for those who need to acquaint themselves with the principles of waste management, identifying each of the major processes, such as incineration, landfill, recycling and ecologically acceptable waste reduction by physical, chemical and biological treatment.Throughout, the text is supported by data in diagrammatical form, together with tables of the EU waste identification criteria. Softcover 75pages ISBN 0 85404 990 8 1996 f9.95 Electrochemical Processes for Clean Technology By K Scott, University of Newcastle Upon Tyne, UK This new book describes the technology and engineer- ing of electrochemical systems that are relevant to clean technology, such as chemical synthesis, effluent treat- ment and recycling. It explains basic scientific and engi- neering principles, and describes relevant cell and reac- tor technology with examples. It emphasises the increas- ing importance of electrochemistry in the synthesis of organic and inorganic compounds for the bulk, fine chemical, pharmaceutical and electronic industries. There is full coverage of effluent treatment and recycling for heavy and precious metals, organic contaminants, inorganic aqueous and gaseous effluents, and includes important coverage of electrochemical membrane-based separations, and electrochemically enhanced processes such as ion exchange and ultrafiltration.Hardcover xiv + 308 pages ISBN 0 85404 506 6 1996 f59.50 Ion Exchange Developments and Applications Edited by JA Greig, Nutra Sweet Kelko Company, UK This book concentrates on the application on this tech- nology in industry. In particular, it covers such topics as environmental and pollution control, water treatment, hydrometallurgy, the nuclear industry, ion exchange fun- damentals and separations, resin development and inor- ganic ion exchangers.New insights contained in this book throw light on many aspects of the science, engi- neering and implementation of ion exchange technology, and the range of industries affected is very broad. Special Publication No 182 Hard cover xvi + 560 pages ISBN 0 85404 726 3 1996 f89.50 Chemical Aspects of Drug Delivery Systems Edited by DR Karsa, Akcos Chemicals, Manchester, UK RA Stephenson, Chemical Consuftant Chemical Aspects of Drug Delivery Systems reflects the modern challenge to devise effective drug delivery and targeting systems, giving particular emphasis to recent innovations in the field. Delivery systems described include carbohydrate derivatives, novel non- ionic surfactant vescicles and various polymers, includ- ing polyacrylates and aqueous shellac solutions, as well as hydrogels. In addition, many of the key issues, such as the understanding of biosystems and targets and the development of materials to provide the deserved carrier and excipient properties for controtled, targeted drug delivery are considered in depth.Hard cover viii + 162 pages ISBN 0 85404 706 9 1996 f49.50 The Chemistry of Paper By JC Roberts, UMlST; UK This book provides an overview of the process of mak- ing paper from a chemical perspective. It deals with both the chemistry of paper as a material and the chemistry of its production, setting out the main principles involved at every stage. It provides a chemical definition of paper in the light of the many uses to which it is put, as well as dealing with the processes involved in the production of paper: the delignification of the wood fibres, the bleach- ing of the cellulose-rich pulp using environmentally- friendly systems, the formation of the pulp into sheets of fibres strengthened by extensive inter-fibre hydrogen bonding, and finally the coating of the sheets in a man- ner appropriate to their end use. Softcover xiv + 182 pages ISBN 0 85404 518 X 1996 f15.95

ISSN:0306-0012    

DOI:10.1039/CS99625BP019

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

The Royal Society of Chemistry Chemical Society Reviews Editorial Board Professor H. W. Kroto FRS (Chairman) (University of Sussex) Professor M. J. Blandamer (University of Leicester) Dr. A. R. Butler (University of St. Andrews) Professor E. C. Constable (University of Basel, Switzerland) Professor T. C. Gallagher (University of Bristol) Professor D. M. P. Mingos FRS (Imperial College London) Consulting Editors Dr. G. G. Balint-Kurti (University of Bristol) Dr. J. M. Brown (University of Oxford) Dr. J. Burgess (University of Leicester) Dr. N. Cape (Institute of Terrestrial Ecology, Lothian) Professor B. T. Golding (University of Newcastle upon Tyne) Professor M. Green (University of Bath) Professor A. Hamnett (University of Newcastle upon Tyne) Dr.T. M. Herrington (University of Reading) Professor R. Hillman (University of Leicester) Professor R. Keese (University of Bern, Switzerland) Dr. T. H. Lilley (University of Sheffield) Dr. H. Maskill (University of Newcastle upon Tyne) Professor A. de Meijere (University of Gottingen, Germany) Professor J. N. Miller (Loughborough University of Technology) Professor S. M. Roberts (University of Liverpool) Professor B. H. Robinson (University of East Anglia) Professor M. R. Smyth (Dublin City University, Republic of Ireland) Professor A. J. Stace (University of Sussex) Chemical Society Reviews aims to foster current progress in the chemical sciences and related disciplines. The journal has the broad appeal necessary to enable scientists to benefit from recent advances made in research outside their immediate interests.In particular, students embarking on a research career should find Chemical Society Reviews a particularly Chemical Society Reviews (ISSN 0306-001 2) is published bimonthly by The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge, UK CB4 4WF. All orders accompanied by payment should be sent directly to The Royal Society of Chemistry, Turpin Distribution Services Ltd., Blackhorse Road, Letchworth, Herts., UK SG6 IHN. N.6. Turpin Distribution Services Ltd., distributors, is wholly owned by The Royal Society of Chemistry. 1996 annual subscription rate: EEA f120.00; Rest of World f123.00; USA $225.00.Customers in Canada will be charged the Rest of World price plus a surcharge to coveP GST. Customers should make payments by cheque in sterling payable on a UK clearing bank or in US dollars payable on a US clearing bank. Second-class postage is paid at Jamaica, NY 1141-9998. Airfreight and mailing in the USA by Publications Editorial Staff Managing Editor Martin Sugden Editorial Production David Bradley; Peter Whittington Editorial Secretary Debbie Halls Editorial Office The Royal Society of Chemistry Thomas Graham House Science Park Milton Road Cam bridge UK CB4 4WF Telephone +44 (0)1223 420066 Facsimile +44 (0) 1223 420247 Electronic Mail (Internet) csrl@rsc.org or sugdenm@rsc.org http://c hem ist ry. rsc.org/rsc/ Advertisement sales Telephone +44 (0)171 287 3091 facsimile +44 (0) 171 494 1134 Typeset by Servis Filmsetting Ltd.Printed in Great Britain by Black Bear Press Ltd. stimulating and instructive springboard to further reading. The Editorial Board encourages an international and interdisciplinary approach to science, which is reflected in the succinct, authoritative articles commissioned. The Board members welcome comments and suggestions; these should be directed to the Managing Editor Expediting Services Inc., 200 Meacham Avenue, Elmont, NY 11003, and at additional mailing offices. US Postmaster: send address changes to Chemical Society Reviews, c/o Publications Expediting Services Inc., 200 Meacham Avenue, Elmont, NY 11003. All despatches outside the UK by Bulk airmail within Europe and Accelerated Surface Post outside Europe. PRINTED IN THE UK. 0 The Royal Society of Chemistry, 1996. All rights reserved. No parts of this publication may be repro- duced, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, recording, or other- wise, without the prior permission of the publishers.

ISSN:0306-0012    

DOI:10.1039/CS99625FX021

出版商:RSC    

年代:1996

数据来源: RSC

ISSN:0306-0012    

DOI:10.1039/CS99625BX023

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Specificity and Versatility in Erythromycin Biosynthesis Rembert Pieper Camilla Kao and Chaitan Khosla" Department of Chemical Engineering Stanford University Stanford CA 94305-5025 USA Guanglin Luo and David E. Cane* Department of Chemistry Brown University Box H Providence RI 02972 USA 1 Introduction More than 40 years ago Woodward and Gerzon suggested that macrolide antibiotics such as erythromycin A (1) might be formed from simple propionate building blocks.'** Since that time not only has this prediction proved to be remarkably perceptive but a wealth of information has been gained concerning the biosynthesis of this medicinally important class of natural products. Incorporation experiments with [ I4C]- [ 13C]- [ 1801-,and [*H]-labelled sub- strates and intermediate analogues have confirmed the propionate origin of erythromycin and related metabolites and established that formation of the parent erythromycin macrolide 6-deoxyery- thronolide B (6-dEB 2) occurs by a processive mechanism in which the oxidation level and stereochemistry of the growing polyketide chain are adjusted immediately after each step of polyketide chain el~ngation."~ Intriguingly although more than 100 individual macrolides made up of various combinations of acetate propionate and butyrate subunits have been identified all of these metabolites can be described by a general stereochemical model illustrated in Figure 1 first proposed by Celmer." Indeed the existence of such striking regularities among a large number of metabolites produced by a wide range of Actinomycete species first suggested the possible modularity of the biosynthetic enzymes responsible for the formation of these polyketide natural products.' The central challenge has therefore been to unravel the mystery that shrouds the molecular genetic and biochemical basis for the intricate programming of the biosynthesis of complex polyketides. 2 Isolation and Characterization of the Genes for a Modular Polyketide Synthase The first direct experimental evidence for the modular hypothesis came from the work of the groups of Peter Leadlay at the University Rembert Pieper was born in 1963 in Osnabruck Germany and graduated from Philipps Universitat Marburg Germany with a degree in pharmacy in 1989. This was followed by a PhD from the Technische Universitat Berlin in I993 on the isolation and char- acterization of enniatin synthetase postdoctoral work (1994-1 996) at Stanford University on the enzymology of polyketide synthases and a current position as research associate at the National institutes of Health Bethesda. Camilla Kao was born in 1970 in Midland MI and graduated in chemical engineering j-om Rice University Houston TX in May 1992. This was followed by graduate school at Stanford University in September 1992 also in chemical engineering and a current position as Lieberman Fellow at Stanford University. Chaitan Khosla (born 1964) is Assistant Professor of Chemical Chaitan Khosla (left) Engineering of Chemistry (by David Cane (right) courtesy) and of Biochemistry 0 It '"'0" ErythromycinA (1) R Celmer Macrolide Model Figure 1 The broad spectrum antibiotic erythromycin A 1 and Celrner's macrolide stereochemical model. of Cambridge and Leonard Katz at the Abbott Laborat~ries.*.~ Working independently these two groups of investigators demon- strated that the structural genes responsible for the formation of 6-dEB consist of three contiguous open reading frames of 10kb each encoding three large (ca. 3000 amino acid) multidomain proteins designated deoxyerythronolide B synthase (DEBS) 1 2 and 3 by Leadlay (Figure 2). Detailed sequence comparisons revealed that each of these proteins consists of eight to ten domains with consid-erable sequence similarity to enzymes responsible for each of the individual steps of fatty acid biosynthesis. Moreover these domains (by courtesy) at Stanford University. He received his PhD in I990 at Caltech. After completing his postdoctoral studies in the lahorn- tory of Professor Sir David Hopwood at the John lnnes Centre in the UK he joined Stanford in 1992. His current research interests focus at the interface of biological chemistry and hiomolecular engineering. Guanglin Luo (horn 1967) graduated from Fudan University in Shanghai with a BSc in 1987. AJter receiving his MSc in organic chemistry in 1990 from the Shanghai Institute of Organic Chemistry Academia Sinica where he obtained the First Grade Award as one of the top four students he entered the PhD pro- gramme in chemistry at Brown University. Upon receiving his PhD in 1996 he was awarded the Potter Prize for the outstanding thesis in chemistry. He is currently a postdoctoral researcher in the laho- ratory of Professor E. J. Corey at Harvard University. David E. Cane (born 1944) is Vernon K. Krieble Professor of Chemistry and Professor of Biochemistry at Brown University. After receiving his PhD in 1971 from Harvard University under Prof. E. J. Corey he carried out postdoctoral research with Professor Duilio Arigoni at the ETH in Zurich. Hejoined the,fucult-y at Brown in 1973. His current research interests are centred on the biosynthesis of natural products with special emphasis on the mechanistic enzymology of isoprenoid und polyketide biosynthesis . 297 CHEMICAL SOCIETY REVIEWS 1996 7f DET ,~ ,D X DEBf module 1 module 3 module 5 module2 module4 module6 7 AT ACP KSAT KR ACP KS AT KR ACP KS AT ACP KS AT DH ER KR A KS AT KR ACP KSAT KR ACP TE I.-is HO I HO HOu HO HO 0 2 Figure 2 Model for the modular organization of 6 deoxyerythronolide B synthase (DEBS) and the biosynthesis of 6-deoxyerythronolide B (2) by DEBS 1 + 2 + 3 Each DEBS subunit carries two complete modules and each of the six modules accounts for one cycle of polyketide chain extension and 0-ketore duction as appropriate The active sites are designated as follows acyltransferase (AT) P-ketoacyl ACP transferase (KS). acyl carrier protein (ACP). p-ketoreductase (KR) dehydratase (DH) enoylreductase (ER) and thioesterase (TE) are arranged such that each protein contains two functional units or modules each of which carries all the requisite catalytic activities for one of six cycles of polyketide chain elongation and reductive modification of the resultant P-ketoacyl thioester The significance of this discovery cannot be overstated Not only did the availability of the structural genes for 6-DEB synthase provide an invaluable tool for much of the subsequent experimental work in the polyke- tide synthase area but the model that emerged from these studies reshaped the thinking about the programming of complex polyke- tide synthases and has provided the conceptual framework for the design of many of the most important experiments carried out over the last several years According to the now widely accepted model (Figure Z) the acyl- transferase (AT) domain at the N-terminus of DEBSl initiates the polyketide chain-building process by transferring the propionyl- CoA primer unit via the pantetheinyl residue of the first acyl carrier protein (ACP) domain to the active site cysteine of the ketosyn- thase of module 1 (KSl) The acyltransferase in module 1 (ATl) loads methylmalonyl-CoA onto the thiol terminus of the ACP domain of module 1 KSI then catalyses the first polyketide chain elongation reaction by decarboxylative acylation of the methyl- malonyl residue by the propionyl starter unit resulting in the for- mation of a 2-methyl-3-ketopentanoyl-ACPthioester The latter intermediate is then reduced by the ketoreductase of module 1 (KR l) giving rise to enzyme-bound (2S,3R)-2-methyl-3-hydroxy-pentanoyl-ACP At this point module 1 has finished its task and the diketide product is transferred to the core cysteine of KS2 where- upon it undergoes another round of condensation and reduction resulting in the formation of the corresponding triketide This process is repeated several times with each module being respon- sible for a separate round of polyketide chain elongation and reduc- tion as appropriate of the resulting P-ketoacyl thioester Finally the thioesterase (TE) at the C-terminus of DEBS3 is thought to catalyse release of the finished polyketide chain by lactonization of the product generated by module 6 Following the characterization of the DEBS genes Leadlay and coworkers succeeded in purifying the corresponding three DEBS proteins from the natural erythromycin producer Sac-charopolyspora erythraea The three proteins were as predicted from the DNA sequence of unusually large size -DEBSl (M 370000) DEBS2 (M 380000) and DEBS3 (M 330000) Partial proteolysis studies further established that propionyl-CoA specifi- cally acylates the N-terminal domain of DEBS 1 consistent with the proposed role of this region in loading the propionate starter on the polyketide synthase I1 In a very important set of experiments the Cambridge group also established that (2S)-methylmalonyl-CoA is the exclusive substrate for polyketide chain elongation based on the stereospecific acylation both of intact DEBS proteins and of selected partial proteolytic fragments I2 Unfortunately neither the native protein preparations isolated from Sac erythraea nor recombinant derivatives expressed in Escherichia coli which lacked the requisite pantetheinyl moieties were able to catalyse polyketide chain elon- gation In fact until recently there had been no reports of successful cell-free synthesis of macrolide-type polyketides in spite of more than 30 years of intense efforts by numerous research groups Very recently the Cambridge group have reported the results of experiments which shed light on the subunit organization of the DEBS multienzyme system Gel filtration and ultracentrifugation experiments both indicate that the individual DEBS proteins (as well as entire modules derived therefrom) are associated as homo- dimers These conclusions were reinforced by crosslinking experi- ments in which purified module 5 obtained by partial elastase digestion of DEBS3 was crosslinked with 1,3-dibromopropanone a reagent previously used to crosslink the sulfhydryl residues of the 4'-phosphopantetheine of the ACP domain and the active site cys- teine of the ketosynthase in yeast and animal fatty acid synthases In a control experiment an elastase fragment representing module 6 but lacking its ACP did not undergo dimerization upon addition of 1,3-dibromopropanone These results suggest that the ACP of one module interacts with the KS from its identical partner within each homodimeric unit 3 Genetic Manipulation of DEBS The availability of the cloned DEBS structural genes opened the door to genetic modification of the DEBS proteins themselves In a SPECIFICITY AND VERSATILITY IN ERYTHOMYCIN BIOSY NTHESIS-R PIEPER ET AL pioneering experiment Katz and his coworkers generated a Sac erythraea mutant carrying a large in-frame deletion in the ketore- ductase domain of DEBS module S (KRS) and demonstrated that this mutant produced erythromycin analogues derived from 3 with a keto group at the predicted site C-5' (Figure 3) The latter exper- iment provided not only direct experimental verification of the modular hypothesis suggested by the DEBS gene sequences but established that the downstream domains in module 6 were capable of processing modified polyketide chain-elongation intermediates thereby opening up the exciting possibility of rationally engineer- ing the production of novel polyketide metabolites The Katz group also effected a similar reprogramming of polyketide synthesis by mutation of the presumed NADPH binding motif of the enoyl reductase domain of module 4 (ER4) The resulting mutant strain produced macrolides derived from 4 with the predicted A6 7-anhy-droerythronolide skeleton l4 0 3 4 Figure 3 Novel analogues of 6-dEB produced by DEBS mutants carrying a deletion in KR5 (compound 3) or a mutation in ER4 (compound 4) In 1994 using a specially engineered host-vector system for the expression of recombinant polyketide synthases we succeeded in expressing the complete set of DEBS structural genes in an actino- mycete host species Streptomyces coeficolor,which normally pro- duces neither erythromycin nor any other macrolides Is The resultant strain designated S coeficolor CH999/pCK7 produced substantial quantities (> 40 mg dm ?) of 6-deoxyerythronolide B 2 accompanied by a novel cometabolite 8,8a-deoxyoleandolide 5 (> 10 mg dm ') (Figure 4a) Analysis of the protein constituents of S coeficolor CH999/pCK7 by sodium dodecyl sulfate -polyacryl-amide gel electrophoresis (SDS-PAGE) revealed the presence of three characteristically large proteins DEBS 1 2 and 3 The pro- duction of 6-dEB demonstrates that DEBS I 2 and 3 carry all the necessary biosynthetic activities to support generation of the full- length polyketide and cyclization to the aglycone 2 Furthermore it is evident that ancillary activities required for the essential phos- phopantetheinylation of the ACP domains are present in the host strain and that the recombinant DEBS is fully functional in the het- erologous host That 6-dEB is being formed by the normal biosyn- thetic pathway was confirmed by the incorporation of [ 1-13C~pr~pionate,giving rise to the expected labelling pattern in the 13CNMR spectrum of the resultant sample of 6-dEB In an anal- ogous experiment the starter unit of 8,8a-deoxyoleandolide 5 was labelled by 1 1,2-I3C2jacetate thereby confirming that DEBS can tolerate an acetate starter in place of its normal propionyl-CoA sub- strate and re-emphasizing a potential catalytic flexibility first sug- gested by the molecular genetic experiments of Katz The utilization of acetyl-CoA as a starter is presumably due to the lower intracellular concentration of propionyl-CoA in S coelicofor as compared to the native erythromycin producer Sue er>thraea Together these results have raised intriguing possibilities for the use of PKS systems for the controlled formation of 'unnatural' natural products by rational control of the modular composition of the PKS as well as the structures and relative amounts of the avail- able substrates In further experiments with S coelicolor CH999/pCK7 feeding of (2S,3R)-I 2,3- I 3C I-2-methyl-3-hydroxypentanoyl-N-acetylcys-teamine (NAC) thioester 6 to the engineered organism resulted in the formation of 6-dEB 2 labelled with I 3C at C- 12 and C- 13 as evi- denced by the appearance of the predicted set of enhanced and coupled doublets consistent with the intact incorporation of the diketide chain elongation intermediate'" (Scheme 1) The level of 0 0 - SNAC CH999/pCK7 "'OH I ' 6 O.i\/ 1 "'OH 2 Scheme 1 Incorporation of the intact chain elongation intermediate 6 into 6 dEB 2 by S corlicolor CH999/pCK7 enrichment (1 5-20 atom%) was especially noteworthy. being nearly 100 times more efficient than the levels usually observed for the incorporation of NAC thioesters into microbial polyketide metabolites Whatever the levels of incorporation however it is evident that the DEBS protein can recognize the relevant structural and stereochemical features of the exogenously administered NAC thioester and load the intermediate analogue on to the appropriate ketosynthase domain presumably KS2 from where it will be processed in the normal manner These results as well as the intact incorporation of advanced polyketide chain elongation intermedi- ates into a wide variety of other polyketides strongly suggest that superimposed on the purely organizational level of control over the programming of polyketide biosynthesis intrinsic to the sequential organization of the modular DEBS proteins there is an additional level of substrate molecular recognition exercised by the various catalytic domains In order to explore further the function of the modular DEBS proteins we next constructed a plasmid pCK9 carrying only the genes for the first open reading frame of the DEBS clusteri7 (Figure 4b) When this plasmid was used to transform S c odic olor CH999 protein extracts of the resultant recombinant strain were found to contain a protein shown to be identical with DEBS 1 by a variety of methods Moreover S coelicolor CH999/pCK9 pro- duced 1-3 mg dm ? of a triketide lactone (2R,X,4SSR)-2,4- dimethyl-3,5-dihydroxy-vi-heptanoicacid CZ-lactone 7 the structure of which was unambiguously established by direct spec- troscopic and chromatographic comparison with an authentic sample of 7 prepared by total synthesis Feeding of [I -I 3C]propi-onate resulted in the formation of 7enriched as expected at C-1 C-3 and C-5 These results established for the first time that the DEBSl protein is fully competent to support the first two cycles of polyketide biosynthesis involved in the formation of 6-dEB and does not require association with either DEBS2 or DEBS3 for activity Interestingly 7,which is generated by lactonization of the corresponding acyclic triketide intermediate attached to the ACP of module 2 has previously been reported by Katz to be an abortive chain-elongation product generated by the DEBS con- struct carrying the deletion in KR5 It is apparent that the triketide lactone can be released from DEBSl alone without a requirement for the thioesterase (TE) domain In order to analyse the substrate specificity and function of the thioesterase we next constructed yet another mutant CH999IpCK12 which expresses a PKS DEBS 1 + TE in which the thioesterase. originally at the C-terminus of DEBS3 has now been fused to the C-terminus of DEBSl (Figure 4c) In fact the latter strain not only produced substantially enhanced amounts of the j),triketide lactone 7 (> 20 mg dm but up to 10 mg dm of a cometabolite originating from incorporation of an acetate starter (2R,3S,4S,5R)-2,4-dimethyl-3,5-dihydroxy-vz-hexanoicacid 6-lactone 8 As with the formation of 8,8a-deoxyoIeandolide 5 from an acetate starter the production of 8 most likely reflects some combination of the limited availability of propionyl-CoA in the S coelicolnr host strain as well as the greater abundance of the alter- native substrate acetyl-CoA Meanwhile the Cambridge group had reported analogous results CHEMICAL SOCIETY REVIEWS 1996 OH AT ALP KSAT KR ALP KS AT KR ACP Ks AT ALP K9 AT DH ER KR ACP KS AT KR ACP KS AT KR ALP y 2 5 (40mg dm-3) (10 mg dm-3) ‘1,. b) AT ACP KS AT KR ACP KS AT KR A cox,I 7 (3 mg drns) c) AT ACP KS AT KR ACP KS AT KR ACP I ,a\\I! :.:111)) HOd) 1ATACP KS AT KRACP KS AT KR A+I KSAT ACP KSAT DH ERKR A+F~ ”‘OH 9-(20 mg dmA3) Figure 4 Polyketides produced by engineered S corlrcolor CH999 strains (a) CH999IpCK7 (b) CH999/pCK9 (c) CH999/pCK 12 (d) CH999/pCK 15 on the formation of 7 2o Using genetic recombination techniques in Sac erythrueu they fused the thioesterase domain from DEBS3 to the C-terminus of DEBSl Through a second recombination they also deleted the structural genes for DEBS2 and DEBS3 Each of the resultant mutants produced the expected triketide lactone 7 while neither produced the macrolactone 6-dEB indicating that not only was the thioesterase capable of cyclizing the normal triketide product of DEBSl but that this process completely suppresses transfer of the acyclic triketide intermediate to the downstream enzymes By contrast a mutant carrying an inactive TE fused to the C-terminus of DEBS 1 produced significantly lower levels of trike- tide lactone (<0 I mg dm 3 These results not only confirmed that DEBS 1 is fully competent to support the formation of triketide but that the thioesterase can play an active role in catalysing the release of this substrate In a further series of experiments the Cambridge group also expressed a DEBSl + TE construct in S coelicolor 21 Consistent with our own results with DEBSl + TE in this organism both the triketide lactone 7 and the C,-lactone 8 were produced but the natural tripropionate triketide 7 was found to be the minor con- stituent The reasons for these differences in product ratios is unclear given the more than 30-fold preference of DEBS 1 + TE for a propionyl-CoA over an acetyl-CoA primer (see below) but most likely reflects differences in timing and levels of protein expression as well as the varying sizes of intracellular pools of the two primers and the methylmalonyl extender under the growth conditions used for S coelicolor by the two research groups Our group has constructed yet another deletion mutant of DEBS expressed by S coelicolor CH999/pCK 15,containing the first four DEBS modules present as DEBSl and DEBS2 plus a chimeric fifth module in which the ACP6 TE didomain region has now been fused just downstream of KR5I9 (Figure 4d) Assuming that KS5 and ACP6 could productively interact to catalyse a fifth condensa- tion it was expected that the mutant strain would be able to support five complete rounds of polyketide chain elongation and that the thioesterase/cyclase would catalyse the lactonization of the resul- tant polyketrde Indeed S coelicolor CH999/pCK 15 produced 20 mg dm of a completely new macrolactone (8/?,9S)-8,9-dihydro- 8-methyl-9-hydroxy- 10-deoxymethynolide 9 The structure of 9 which is a novel analogue of 10-deoxymethynolide the aglycone of the macrolide antibiotic methymycin was unambiguously con- firmed by extensive 2-D NMR and mass spectrometric analysis supplemented by specific labelling by a variety of 1 i3C]enriched propionate precursors The latter results established that the TE activity which naturally supports the formation of a 14-membered ring product catalysed exclusive formation of the 12-membered ring lactone by esterification of the acyl thioester with the C-11 hydroxy in preference to the ordinarily kinetically favoured gener- ation of a &lactone by esterificatron with the C-5 hydroxy These results further confirmed the structural and functional independence of individual modules of modular PKSs They also demonstrated the feasibility of constructing hybrid modules viu genetic engineer- ing 4 Cell-free Formation of Polyketides Unlike the related peptide synthetases for which well-developed enzymological methods have been available for the past several decades,22 detailed mechanistic studies on PKSs have been seri- ously hampered by a lack of fully active cell-free systems Indeed until quite recently 6-methylsalicylic acid synthase and its closely related homologue orsellinic acid synthase were the only known examples of microbial PKSs the activities of which (Including chain-elongation activity) had been reconstituted in vitro 23-25 The situation has changed dramatically over the past few years with several reports demonstrating enzymatic synthesis of pol yketrdes using the PKS responsible for the pol yketide component of cyclosporin?6 the tetracenomycin synthase?’ truncated forms of SPECIFICITY AND VERSATILITY IN ERYTHOMYCIN BIOSY NTHESIS-R PIEPER ET AL modular PKSS,~~ 29 and the complete DEBS assembly 28 In at least the last three cases the development of fully active cell-free systems has benefited from the availability of high-level expression systems derived via genetic engineering As described above DEBS 1,2 and 3 are large multifunctional proteins carrying a total of at least 28 distinct active sites The DEBS proteins were present in a cell-free protein preparation from S coelicolor CH999/pCK7 at a level of ca 3-5% total cellular protein 3o In the presence of 1-50 mmol dm-3 sodium phosphate buffer the multi-enzyme assembly was found to catalyse the for- mation of 6-dEB 2 as well as the abortive chain elongation product 7 upon addition of propionyl-CoA (2RS)-methylmaIonyl CoA and NADPHz8 (Scheme 2a) A high phosphate concentration in the protein preparation and reaction buffers was found to be very important for the observed enzymatic activity presumably by enhancing the assembly of the multi-enzyme complex via hydrophobic interactions z8 3o The DEBS-catalysed formation of 6-dEB as well as the formation of the triketide lactone 7 described below is inhibited by both cerulenin and N-ethylmaleimide each a well-known inhibitor of the condensation reactions of fatty acid biosynthesis 28 The apparent k, parameters for the formation of 6-dEB and the triketide lactone 7by DEBS 1,2 and 3 are 0 5 and 0 23 rnin I respectively pointing to the relative inefficiency of chain transfer from DEBSl to DEBS2 in vitro The complete DEBS system has been substantially purified (to > 50% homogeneity) without significant losses in specific activity The individual recom- binant proteins behave as expected as homodimers upon gel filtra- tion Analogous to the above studies with the complete DEBS system similar (and more extensive) investigations have also been carried out on the formation of the triketide lactone 7 by the truncated DEBS1 + TE protein (Figure 2b) Despite the relative simplicity of the system it harbours key molecular recognition features of the overall DEBS system the first two modules generate methyl- branched carbon centres as well as secondary alcohols with both D and L stereochemistry Furthermore this mini-PKS has been shown to be highly active as judged by a k, value (3 4 min I) that is com- parable to the estimated rate constant in VIVO~~and by the fact that products can be synthesized on scales that facilitate structural analysis via NMR spectroscopyzR The apparent K, for methyl- malonyl-CoA in DEBSl + TE catalysed synthesis of the tripropi- onate lactone 7 is 24 pmol dm 30 In contrast the K for propionyl-CoA is not easily measured since the enzyme can readily decarboxylate methylmalonyl-CoA (or methylmalonyl-ACP) to 0 MeMal-CoA NADPH * a) FSCoA DEBSl+2+3 2 b) 8SCoA MeMal-CoA NADPH DEBSI+TE t '4 I+ a0 ' 7 c' SNAC;:I"'0H MeMal-CoA NADPH DEBSI+TE rn 't JY',a0 30 1 generate a propionate primer which is turned over into 7 without any effect on the apparent k, 3o In the presence of (2RS)-methyl- malonyl-CoA and NADPH DEBSl + TE could also convert the exogenously added diketide chain elongation intermediate (2S,3R)-2-methyl-3-hydroxypentanoyl-NACthioester 6 to the triketide lactone 7,as verified by both I4C- and 13C-labelling exper- imentsz8 (Scheme 2c) completely consistent with the previously described experiments with intact cells which had demonstrated the incorporation of 6 into 6-deoxyerythronolide B 2 DEBSl + TE has a remarkably broad specificity towards alter- native primer units In addition to propionyl-CoA both acetyl- and butyryl-CoA can serve as surrogate chain initiators giving rise to the corresponding triketide lactones 8 and 10 respectivelyz931 (Scheme 3) Consistent with these observations DEBSl + TE can be acylated by radiolabelled acetyl- propionyl- and butyryl-CoA with comparable efficiency 31 Preincubation of DEBS 1 + TE with iodoacetamide fails to inhibit acylation by propionyI-CoA,28 while partial proteolysis of the labelled protein indicates exclusive acyla tion of the N-terminal portion of the protein containing the first AT domain Notwithstanding this tolerance for different starter units however DEBS 1 + TE exhibits a 32-fold and an eight-fold kinetic preference towards propionyl primers over acetyl and butyryl primers respectively suggesting the existence of one or more active sites with discriminating molecular recognition features The broad substrate specificity of DEBS towards unnatural sub-strates 1s also illustrated by two other types of experiments First DEBSl + TE can also recognize the unnatural diketide 11 pro-cessing it to the corresponding C triketide lactone (Scheme 3c) Second if NADPH is excluded from the reaction mixture the enzyme can convert propionyl-CoA and methylmalonyl-CoA to the pyran-2-one 12 presumably formed by lactonization of the unre- duced diketoacylthioester product3' (Scheme 4a) Alternatively incubation of DEBSl + TE with methylmalonyl-CoA and the NAC-diketide 6 in the absence of NADPH leads to formation of the ketolactone 1332(Scheme 4b) emphasizing the ability of the DEBS protein to mediate the formation of polyketides in a variety of oxi- dation states 5 Programming and Reprogramming of Modular Polyketide Synthases The example of the erythromycin PKS presents an elegant evolu- tionary solution to the problem of programming a complex sequence of biosynthetic reactions based on the repetitive utilization of a small repertoire of biochemical transformations Two levels of catalytic control are evident in this multi-enzyme assembly First the modular OH /)#,0 MeMal-CoA NADPH a) ACOA + \\" a0 DEBS1+TE 8 y MeMal-CoA NADPH b) DEBS 1+TE NADPH I DEBSl+TE 11 6 6 Scheme 3 Broad substrate specificity of the DEBS enzyme Processing of Scheme 2 Enzyme catalysed formation of (a) 6 dEB catalysed by DEBS 1 anomalous primer substrates (a) acetyl CoA (b) butyryl CoA and (c)11 + 2 + 3 (b) and (c)triketide lactone 7by DEBS1 + TE by DEBS1 + TE CHEMICAL SOCIETY REVIEWS 1996 MeMal-CoA b FXOA DEBS 1-tTE 12 MeMal-CoA L ""IX'""' ,\\" &6'"OH DEBS1+TE ' 13 Scheme 4 Catalysis of polyketide chain elongation by DEBS 1 + TE In the absence of NADPH using a) propionyl-CoA and b) 6 as substrates structure of the proteins provides organizational control at the level of dictating the sequence of reactions to be employed in the overall catalytic cycle Secondly the molecular recognition features of some or all individual domains introduce an additional level of selectivity into the multi-step transformation Importantly neither of these two control mechanisms results in absolute specificity as illustrated vividly by several examples reviewed here Thus the intrinsic toler- ance within modular PKSs towards reprogramming presents an exciting opportunity for the rational design of novel 'unnatural' natural products and for the combinatorial generation of molecular diversity within this medicinally important family of molecules Several diverse and complementary strategies for genetic and/or chemical reprogramming can be envisioned As discussed above a few examples suggest the feasibility of genetically knocking out individual active sites without impairing the remainder of the cat- alytic cycle In an extreme case it may even be possible to delete entire modules as illustrated by experiments in which the terminal thioesterase is fused to various upstream modules Beyond inacti- vation it will be interesting to explore the extent to which individ- ual modules (or domains therein) can be substituted by heterologous modules/domains with unnatural molecular recogni- tion features This has been successfully demonstrated in the cases of the structurally smaller aromatic PKSs as well as the modular peptide synthetases Finally the potential for genetically engineer- ing new catalytic functions into existing PKS pathways also remains to be evaluated In addition to genetic reprogramming the availability of fully active cell-free systems in conjunction with facile mutagenesis tools opens up new possibilities for chemically reprogramming modular PKSs to produce polyketides that might otherwise be inac- cessible viu itz vzvo engineered biosynthesis For example as reviewed above modular PKSs can turn over a variety of unnatural substrates into polyketide products They can also function under non-biological conditions such as in the absence of reducing equiv- alents Given the structural complexity of most natural or engi- neered products of modular PKSs 'one-pot' enzymatic synthetic methodologies could be an attractive complement to established chemical synthesis efforts aimed at elucidating the structure-activ- ity relationships of lead molecules with potential human therapeu- tic veterinary and agrochemical utility Acknowledgments. This work was supported by a grant from the National Institutes of Health (GM22172) to D E C and in part by a grant from the National Institutes of Health (CA 66736-Ol) a National Science Foundation Young Investigator Award and a David and Lucile Packard Fellowship for Science and Engineering Oto C K 6 References 1 R B Woodward Angew Chem 1957,69,50 2 K Gerzon E H Flynn M V Sigal P F Wiley R Monahan and U C Quarck,J Am Chem Soc 1956,78,6398 3 D E Cane H Hasler P B Taylor and T -C Liang Terrahedron 1983 39.3449 4 D E Cane TC Liang P B Taylor C Chang and C C Yang J Am Chem Soc 1986,108,4957 5 D E Cane and C -C Yang,J Am Chem Soc . 1987,109,1255 6 W D Celmer J Am Chem SOC ,1965,87 1801 7 D E Cane. W D Celmer and J W Westley. J Am Chem Sue. 1983 105,3594 8 J Cortes S F Haydwk G A Roberts D J Bevitt and P F Leadlay Nature 1990,348,176 9 S Donadio M J Staver J B McAlpine S J Swanson and L Katz Science 1991,252.675 I0 P Caffrey D J Bevitt J Staunton and P F Leadlay FEBS Lett 1992 304,225 I 1 J F Aparicio P Caffrey A F A Marsden J Staunton and P F Leadlay J Bid Chem 1994,269,8524 12 A F A Marsden P Caffrey,J F Aparicio M S Loughran J Staunton and P F Leadlay Scfence. 1994,263,378 13 J Staunton P Caffrey J F Aparicio G A Roberts S S Bethel1 and P F Leadlay Nuture Struct Biol 1996,3 188 14 S Donadio,J B McAlpine,P J Sheldon,M JacksonandL Katz Proc Nutl Acad SCI USA 1993,90,7119 15 C M Kao L Katz and C Khosla Science 1994,265,509 16 D E Cane,G Luo,C Khosla,C M KaoandL Katz,J Antibiot ,1995 48,647 17 C M Kao G Luo L Katz D E Cane and C Khosla J Am Chem Soc ,1994,116 I1612 18 S Donadio. M J Staver J B McAlpine S J Swanson and L Katz Gene 1992,115,97 19 C M Kao G Luo L Katz D E Cane and C Khosla J Am Chem Soc 1995,117,9105 20 J Cortes,K E H Wiesmann,G A R0berts.M J B Brown,J Staunton and P F Leadlay Science 1995,268 1487 21 M J B Brown J Cortes,A L Cutter P F Leadlay and J Staunton,./ Chem SOC Chem Commun ,1995,1517 22 H Kleinkauf and H von Dohren Eur J Biochem 1990,192,l 23 P Dimroth H Walter and F Lynen Eur J Biochem ,1970,13,98 24 J B Spencer and P M Jordan Biochemi 'fry 1992.31,9 107 25 E R Wo,I Fujii,Y Ebizuka,U Sankawa,A Kawaguchi,S Huang,J M Beale M Shibuya U Mwek and H G Floss. J Am Chem Soc 1989,111,5498 26 M Offenzeller Z Su G Santer H Moser R Traber K Memmert and E Schneider Scherzer J Biol Chem 1993,268,26127 27 B Shen and C R Hutchinson Science 1993,262,1535 28 R Pieper G Luo. D E Cane and C Khosla Nature 1995,378.263 29 K E H Wiesmann. J Cortes M J B Brown A L Cutter. J Staunton and P F Leadlay Chem Biol ,1995,2,583 30 R Pieper S Ebert Khosla D E Cane and C Khosla Biochemistry 1996.35.2054 31 R Pieper G Luo D E Cane and C Khosla J Am Chem Soc ,1995 117. 11373 32 G Luo R Pieper C Khosla and D E Cane Bioorg Med Chem ,1996 4.995

ISSN:0306-0012    

DOI:10.1039/CS9962500297

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Environmentally Friendly Catalytic Methods James H. Clark and Duncan J. Macquarrie Department of Chemistry University of York Heslington York UK YO1 5DD 1 Introduction Increasingly demanding environmental legislation public and cor- porate pressure and the resulting drive towards clean technology in the chemical industry with the emphasis on reduction of waste at source will require a level of innovation and new technology that the industry has not seen in many years.I Established chemical processes that are often based on technology developed in the first half of the 20th century may no longer be acceptable in these envi- ronmentally conscious days. ‘Enviro-economics’ will become the driving force behind new products and processes. The cost of clean- ing up chemical processes and plants and adopting the best envi- ronmental option will be high and could even exceed current R&D expenditure within the European Union. This level of expenditure brings with it an unprecedented opportunity for applied research aimed at developing new and more environmentally friendly chem- ical processes and for the introduction of new technology. Catalysts played a major role in establishing the economic strength of the chemical industry in the first half of the 20th century and the clean technology revolution in the industry will provide new opportunities for catalysis and catalytic processes. While the overwhelming majority of chemical processes introduced in the last SO years depend on catalysis the market growth potential for catalysis is still considerable and especially in the fine and special- ity chemicals industries where catalysts are relatively rarely used or where homogeneous catalysts are difficult to separate and require additional processing stages. Some of the major goals of clean technology in the chemical industry are to increase process selectivity to maximise the use of starting materials (aiming for 100% atom efficiency) to replace stoichiometric reagents with cat-alysts and to facilitate easy separation of the final reaction mixture including the efficient recovery (and hopefully reuse) of the cata- lyst. The use of solid mostly inorganic catalysts often based on common porous support materials promises to go a long way towards achieving these goals in many important chemical processes where current technology is very inefficient or leads to unacceptable levels of waste. Their use is also a good example of ‘heterogenisation’ whereby the inorganic reagents or catalysts are segregated from the liquid phase facil itating their separation recovery and reuse. Supported reagents based on inorganic materials have been known for almost 30 years and the development of the subject is apparant from the steady increase in the number of research articles James Clark obtained his BSc and PhD degrees from King5 College London. Following postdoctoral research appointments in Canada and England he joined the academic stafS at York in 1979. He was appointed to the Chair in Industrial and Applied Chemistry at York in 1994. His research interests cover Clean Synthesis Supported Reagents Materials Chemistry and Fluorine Chemistry. He has written or edited four books in these areas and his research has led to awards from the SCI RSC RSA and the EU. He cur- rently holds a Royal Academy of EngineeringlEPSRC Clean Technology Fellowship. the appearance of several books ,2-the first international symposia and the first industrial applications.6 Useful inorganic support mate- rials generally have a large surface area (typically > 100 m2 gg1) and are often porous. They include zeolites although their micro- porosity may make them less amenable to liquid phase processes commonly used in fine and speciality chemicals manufacturing than vapour phase processes (where they are well established) due to poor diffusion rates and pore blockage by larger molecules. Silica gels aluminas and clays are often used as supports and newer meso- porous inorganic supports such as the MCMs7 are likely to become increasingly important in this context. This review will focus on supported reagent type catalysts based on porous inorganic support materials and liquid phase organic reactions in which they are used. 2 Supported Reagents The original principle behind the use of supported reagents was to achieve an increase in the effective surface area and hence activity of potentially useful but insoluble inorganic reagents via their dis- persion over high surface area inert support materials. The majority of supported reagents reported since then have been stoichiomet- ric21.8in their chemistry so that at best only the support material could be recovered and reused. Increasingly the emphasis has been shifted towards truly catalytic materials which can involve dis- persed acid or basic sites or other reagents that are catalytic in their action or have been rendered catalytic by interaction or reaction with the support. Thus Bronsted and Lewis acids can be supported (eg.silica-H,PO clay-ZnCI,) as can bases (e.g.alumina-NaOH alumina-KF) but it is also possible to prepare other catalytic sup- ported reagents (e.g. supported phase-transfer catalysts) and to prepare catalytic forms of species that are normally stoichiometric in their chemistry (e.g.alumina-Crv’).5 The factors likely to be considered in preparing a supported reagent are (i)Choice of support material. (ii) Support pretreatment (including drying to remove loosely bonded water and treatment with aqueous HCI to maximise the cov- erage of surface OH groups). Duncan Macquarrie received his BSc and PhD degrees from the University of Strathclyde Glasgow. In 1985 he moved to the University of York as a Postdoctoral Fellow under the supervision of Prof. James Clark researching into the phase transfer catalvsis of nucleophilic juorination reactions. He then moved to Contract Chemicals where he was a member of the team which developed the range of Envirocat cata-lvsts. After spells in research at Ciba Geigy (Traflord Park) arid R+ D at Lonza (Switzerland) lie returned to York in October 1995 to take up a position as Royal Socie8 UniverJitv Research Fellow where hir current reseurch interests are in novel heterogeneous cutul y.5 ts via chemical surface modijca- tion. He is co-author of a hook on supported reagents und i the author of several paperr and patents. 303 Table 1 Methods of preparing supported reagents Method Comments linpregnation (evuporation) -filling Widely used the pores of a support with a solution Good control over dispersion of the reagent followed by and loading evaporation of the solvent Requires an appropriate solvent Precrpitatronlcoprecipitution-of the Valuable for poorly soluble reagent on to the support reagents Difficult to control AdJorption from solutiori -selective Easy to carry out removal of the reagent from the May be inefficient solution Intiinate solids mixing Simple to carry out Avoids the use of any other chemical Unlikely to be efficient loti e rchatige Simple and effective for materials with exchangeable ions (largely zeolites and clays) Sol-gel techniques -starting from a Does not require a pre formed functionalised silane monomer support Silane monomer must be synthesised Difficult to control material structure Srl~latronof the support Utilises the known structure of a pre formed support Silane monomer must be synthesised Resulting surface groups can be easily lost Chlorinution and denvatisation Efficient surface chlorination of the upp port is quite easy Six1 groups are highly reactive Further reaction may require an organometalI ic (m)Reagent loading (often assumed to be at best at monolayer coverage which enables the amount of reagent to be calculated but physisorbed reagents will not be completely dispersed and the loading of chemisorbed functions is in practice variable there are also examples where unexpected high loadings or low loadings can apparantly be beneficial) (w)Method of preparation (see Table 1) (v) Supported reagent post-treatment (e g calcination to fix the reagent) Generally the aim is to achieve maximum dispersion so as to achieve maximum activity per unit area of support Other factors may also prove to be important such as ensuring that the reagent is fixed to the support and will not be removed under the conditions of any reaction or separation For industrial applications long-term catalyst stability may be more important than initial activity if that early activity is followed by rapid decay The successful application of supported reagent catalysts requires a reasonable understanding of the bulk and surface struc- tures of the material Stability surface area porosity and the dis- persion and nature of the active sites are all important factors that can critically affect the catalytic value of the supported reagent Fortunately there are numerous spectroscopic and non-spectro- SCOPJC techniques available for the study of solids and supported surfaces The application of supported reagents can be hindered or limited by instability due to (I) Thermal decomposition of active sites (most common sup ports are stable up to very high temperatures although a few less CHEMICAL SOCIETY REVIEWS 19% commonly used materials such as some pillared clays may break down at moderate temperatures) (10Reaction of active sites with the atmosphere (solid bases for example can rapid1 y adsorb C0,-forming carbonates) (ill) Removal of active sites in the course of a rewtion (a common problem which causes contamination of the organic mixture and prevents reuse of the catalyst) Thermal analysis techniques (TGA DSC DTA) can be used to study the thermal stability of supported reagents which generally show a low temperature loss of loosely held water (and other solvent molecules) a gradual loss of chemisorbed water at higher temperatures (from surface hydioxyls) and the thermal decompo- sition of catalytic sites Chemisorbed organic functions will nor-mally decompose at ca 300 "C or higher which is adequate for most liquid phase reactions Low temperature thermal events from changes to inorganic reagents are less common but can be impor tant leg the decomposition of supported Fe(NO,) the reaction between CuO and the charcoal support or phase changes in sup-ported ZnCI,] The thermal behaviour of the superficially simple supported fluorides such as the widely used solid base KF-alumina is particularly complex and very important (Figure 1) OH- -F(H20)K+ HEAT OH- -FK+ OH-F(H20)K+ -H20 OH-FK+ Figure 1 Changes in the nature of KF-alumina on heating While dispersion of the reagenuactive sites over the surface of the support material is often only one of several factors affecting the performance of a supported reagent it remains a very important one Generally high surface areas are preferred although the choice of support material ISunlikely to depend on that alone Surface areas of common supports are in the 100-1000m2 g range with the new MCM materials having particularly high values (even to > 1000 m2 g I) Most commonly used support materials are either micro- porous (pore diameters 3-20 A)or mesoporous (20-500 A)with mesoporosity likely to give a reasonable balance between good dif- fusion rates and useful in-pore effects (e g high local concentra- tions of reagent sites to enhance reaction) lo Zeolites are the best known microporous solids although swelling clays also commonly have interlamellar spacings of less than 10 8 Pillared clays and non-aluminosilicate molecular sieves (1 e porous solids with regular structures) have pore diameters in the 10-20 A range Acid treated clays can contain mesopores as a result of the break up and reorganisation of the aluminosilicate structure (dealumination) I I Until recently mesoporous solids were restricted to amorphous materials with broad pore size distribution (silicas and aluminas) In 1992 the first truly mesoporous molecular sieves were reported These 'MCM' materials opened the way to the synthesis of ordered porous solids with high surface areas and tunable pore diameters bridging the zeolites and the common amorphous silicas Little is known about the use of these materials as supports but the potential IS considerable Reactive reagents notably hydroxides and fluorides will corrode the surfaces of common support materials so that the actual surface species present may be more complex than might be expected (see Figure 1 for example) and surface areas can be much reduced Even the simplest methods of supported reagent preparation can give good dispersion of most reagents as witnessed by techniques such as electron microscopy X-ray diffraction and where the reagent is amenable diffuse reflectance Fourier transform infra red (FTIR) spectroscopy ENVIRONMENTALLY FRIENDLY CATALYTIC METHODS-J H CLARK AND D J MACQUARRIE 305 One of the most interesting features of supported reagent chem- istry which has become particularly significant in recent years is that the activity of the composite material (ASR) is not usually a simple sum of the component parts (A +AR) The value of this in catalysis is when A >A +A This increase in activity is a result of a synergistic effect between the reagent and the support The exact nature of this effect when it occurs is variable In extreme cases it can be due to actual reaction between the support and the reagent such as in the case of some sup- ported fluorides In other cases it is more subtle with an increase in the number of available sites and/or the local in-pore concentration of sites (mini reaction vessels) being responsible such as is the case for supported zinc chloride lo The nature of an adsorbed reagent can be investigated by numer- ous techniques Diffuse reflectance FTIR and magic angle spinning (MAS) NMR spectroscopies are especially popular The useful information that can be obtained by such studies incI udes (I) Identification of the surface species (eg to confirm that the original reagent is intact or to identify new species formed via support-reagen t reaction) (II) Information on the strength of the interaction between the support and the reagent ([if) Identification of sites including Lewis and Brgnsted acid sites and determination of their relative strength (eg through the use of spectroscopic titration techniques such as those based on the use of pyridine") (~v)Determination of any changes to the bulk support structure as a result of corrosion of the support by attack of the reagent Through the use of spectroscopic and non-spectroscopic tech- niques it is possible not only to understand the behaviour of sup- ported reagent catalysts but also to help optimise their performance in organic reactions 3 Catalysis using Supported Reagent Solid Acids*~~,~ Solid acids are the most widely studied and commonly used het- erogeneous catalysts They are used in many important large-scale vapour phase manufacturing processes such as catalytic cracking (X and Y zeolites) alkylation (zeolites Si0,-H,PO,) and paraffin iso- merisations (chlorinated Pt-AI,O,) with the scale of larger reac- tions exceeding lo9kg per year All solid acids are characterised by the presence of surface protons or coordinatively unsaturated cationic centres which give Brcbnsted or Lewis acidity The number of acid sites gives the total surface acidity while their structure determines the acid strength Lewis and Brcbnsted acid sites are often present together and may be sufficiently strong to justify the term 'solid superacids' (H <-12) which can enable the catalysis of demanding reactions such as transformations of alkanes Suitable solid acid catalysts for reactions under more moderate conditions than typical petrochemical type reactions and in the liquid phase include those based on clays silicas and zeolites In many cases they are sought as replacements for inexpensive liquid or soluble acids such as H,SO HF and AlCl and relatively low cost solids are required The environmental unacceptability of using large volumes of corrosive acids and of the waste resulting from the work-up of such reactions which usually requires the neutralisa- tion/decomposition of the acid is a strong driving force for devel- oping environmentally friendly processes based on solid acids The range of acid-catalysed liquid phase reactions is enormous and includes Friedel-Crafts reactions halogenations and nitrations with relevance to almost all sectors of the fine speciality and inter- mediates chemical industries Friedel-Crafts reactions probably represent the most important range of 'named' reactions in organic chemistry They include acy- lations benzoylations alkylations and sulfonylations giving an enormous range of useful products including ketones alcohols alkylaromatics and sulfones Many batch processes operating in a very large number of companies use AlCI as the soluble acid cata- lyst The reagent is inexpensive and very reactive being one of the most powerful Lewis acids Unfortunately it is difficult to handle being readily hydrolysed by water (and therefore unstable to the atmosphere) giving health and safety and storage problems The work-up reactions using AICI present further problems with the usual water quench creating an acidic aluminium-rich waste stream The problem is particularly acute with reactions involving products that are capable of acting as Lewis bases such as ketones which complex the AlCl In these cases at least stoichiometric quantities of AlCI are required indeed in the case of sulfone- forming reactions up to three mole equivalents are used to ensure good conversion The quantity of waste generated in these reactions greatly exceeds the amount of product' Other problems with AICI 'catalysed' reactions include lack of selectivity with polyalkylation being a particular problem Alternative homogeneous reagents fare little better Hydrogen fluoride has useful activity but presents its own special hazards due to its extremely corrosive nature Solid acid supported reagents based on inexpensive inorganic solids notably clays and silica show promise as Friedel-Crafts cat- alysts as do some modified zeolites Many clays have been investi- gated including bentonites vermiculites halloysites and kaolinites Ion-exchanged clays can show much improved activity over the raw materials and especially those based on acid treated clays such as the commercial material KIO (which can itself be a useful solid Bronsted acid) The activity of ion-exchanged clays is very depen- dent on the cation so that in the benzylation of benzene using benzyl chloride for example (I) the order is Fellr >Zn" >Cull >ZrIV> PhH +PhCH,CI -PhCHzPh (1) TiiVTaV>All1'>Coil >K10 >NbV The order does not corre- spond to the order of Lewis acidities for homogeneous cations with the low activity for All1' (very active in solution) and the high activ- ity for Zn" (weakly active in solution) being especially noteworthy It is likely that at least part of the activity is due to the polarisation of water molecules by the cations within the highly polarising environ- ment of the interlamellar regions of the clays At best ion exchanged clays can show activities in reaction (1) 20 times greater than the simple acid-treated clay Selectivity to the monoalkylated product was little improved by ion exchange with only 57% isolated diphenylmethane from the fastest reaction and never better than 66% Alcohols and alkenes can also be used as alkylating agents but the rates of reaction are significantly reduced and the orders of activ- ity of the clay are not the same although the Ti1" exchanged clay in particular is active with all of the alkylating agents It is also impor- tant to note that these catalysts are reusable at least to some extent Perhaps the greatest breakthrough in the use of solid acid cata- lysts in Friedel-Crafts reactions came with the discovery that sup- ported (as opposed to ion exchanged) zinc chloride on K 10 was an extremely active and reusable catalyst for benylation reactions such as (1) The activity is several orders of magnitude greater than that of the ion-exchanged materials with the model reaction being com- plete in minutes at room temperature and giving a particularly high yield of diphenylmethane (80%) Like the ion-exchanged materials. the activity of the K10 supported reagents does not correlate with solution phase activities of the reagents so that supported ZnCI and CuCI are especially active while supported AlCl is a poor catalyst 'Clayzic' has been the subject of intense research since its dis covery in 1989 and also forms the basis of an industrial catalyst It is a particularly striking example of a supported reagent that is con siderably more active than its constituent parts and this is in part explained by a structural change to the support Acid treatment of the montmorillonite clay causes a breakdown in the lamellar struc- ture and the creation of mesopores which are occupied by the ZnCI (Figure 2) lo Thermal activation of clayzic results in further struc- tural changes but the catalytic activity of the material does not cor- relate with its surface areal4 -a good example of a supported reagent catalyst where surface area is not the most important factor Spectroscopic titration of the active sites on clayzic reveal the pres- ence of weak Lewis acid sites but little Bronsted acidity (KlO itself shows BrGnsted acid sites only).1° indeed mesoporous silica sup- ported ZnCI which can be as active as clayzic can be a pure solid Lewis acid The remarkable activity of supported ZnC1 cannot be M 00 oo om a0 00 M"+ M"+ b 0. 0. ee .a@ M"+ M"+ c 0. 00 a0 00 "+M M"+ M "+ severe acid ZnCl2 treatment1 Figure 2 Structural representation of the formation of clayzic due to strong acid sites -rather it is likely to be due to a high con- centration of sites within the constrained in-pore environments Clayzic has been used to catal yse various Friedel-Crafts reac-tions including those of aromatic substrates with alkyl halides alde- hydes and alcohols In the commercial manufacture of diphenylmethanes for example product yields of over 75% can be achieved by using this catalyst which is also easily recovered and can be reused Use of homogeneous AICI leads to product yields of less than 50% and the work-up procedure is difficult and destroys the AICI Other applications include the preparation of benzothio- phenes by cyclisations of phenylthioacetals (normal catalysts can cause extensive polymerisation of the thiophenes and the pores in clayzic are believed to favour the desired intramolecular cyclisation at the expense of the polymerisation -Figure 3)," and the olefina- tion of benzaldehyde (involving a previously unknown reaction mechanism -Figure 4) l6 Interestingly when two or more possible substrates are present ClayxicII I Figure 3 Formation of benzothiophenes using clayzic CHEMICAL SOCIETY REVIEWS 1996 *Y EPZ10 MeN02 room temp Figure 4 Olefination of benzaldehyde using clayzic (in its commercial form ' EPZl 0') reaction occurs first with the more polar substrate whatever its normal relative reactivity Thus with a mixture of an alcohol and an alkyl halide the alcohol will always react first although the alkyl halide is more reactive l7The discrimination can be more subtle so that for haloaromatics the order of activity in clayzic-catalysed alkylations is PhBr > PhCI > PhF PhH which parallels the polar- isibility of the substrate although it is the exact opposite of the activ- ities in solution phase reactions These observations are consistent with the presence of highly polar pores in the catalyst and with mol- ecular sieving on the basis of molecular polarity/polarisibil~ty The widespread use of AICI in Friedel-Crafts and other acid- catalysed reactions along with its environmental unacceptability makes it an obvious target for heterogenisation via a supported reagent Early attempts to prepare an active form of supported alu- minium chloride had limited success with promising results in vapour phase processes such as long chain alkane isomerisations and hydrocarbon cracking reactions but poor activity in liquid phase reactions l9 More recently a new form of the supported reagent has been prepared and found to be highly active in some liquid phase Friedel-Crafts reactions 2o Mesoporous silica and acid- treated montmorillonite supported aluminium chloride (prepared by reaction of the support with either AlCI or RAICl in an aromatic solvent) is particularly effective in catalysing the reactions of alkenes with aromatics such as that of oct-l-ene with benzene eqn (2) -remarkably the activity of the solid acid is comparable to PhH + CH,(CH,),CH=CH -Ph(CH,),CH (2)(complete conversion of the alkene within 2 h at room temp and up to 80% selectivity to the monoalkylate) that of homogeneous AICl but its selectivity towards monoalkyla- tion is significantly superior Greater selectivity is also observed in the dodecene-benzene reaction with the desired 2-alkyl isomer (this isomer gives the best emulsibility characteristics in detergency applications) being produced in 47% yield (32% with homogeneous AICI 13-20% with HF) As with clayzic and other supported reagents the o timum pore size is at the low end of the mesoporous range (ca 70 R) Alkyl halides also react quite well with aromatics in the presence of supported aluminium chloride so that dichloromethane for example reacts with benzene to give diphenyl- methane in a yield of 62% dfter 2 5 h at 40 "C A comparison of sup-ported aluminium chloride with supported zinc chloride two of the more promising solid acids for Friedel-Crafts alkylations would suggest that the former is considerably more active (strong BrGnsted and Lewis acid sites are revealed by spectroscopic titra- tion) but the latter is an extremely useful mild Lewis acid catalyst Supported reagents have been used rather less to catalyse aro- matic halogenations althougth zeolites have been proved to give enhanced para-selectivity in for example the chlorination and bromination of alkylaromatics (up to 75% in the chlorination of toluene using elemental chlorine21 and up to 95% in the bromina- tion of toluene using elemental bromine22) Aromatic nitration a particularly wasteful and hazardous indus- trial process has benefited relatively little from the use of supported reagents with very low conversions usually accompanying any good isomer selectivities (eg using zeolites) or good conversion and selectivity requiring inconvenient reaction times at high dilu- tion The combination of the H+ form of zeolite beta and acetyl nitrite as the nitrating agent can however give good selectivities (e8 79% para for toluene) in fast reactions 23 Numerous other typically acid-catal ysed reactions have been ENVIRONMENTALLY FRIENDLY CATALYTIC METHODS -J H CLARK AND D J MACQLJARRIE successfully carried out in the presence of supported reagent-type solid acids where the solids have replaced conventional acids such as mineral acids AICl BF and FeCI among others Some of the more interesting recent examples include the single-pot synthesis of methyl tert-butyl ether from tert-butyl alcohol and methanol using dodecatungstophosphoric acid supported on clay2 and the use of pillared acid-activated clays for Bronsted catalysed processes such as alkene alkylations and alcohol dehydrations 25 It is also worth noting the early successes emerging from studies on the use of MCM type materials as solid acids'" -this area seems likely to develop quickly 4 Oxidation Catalysis using Supported Reagents The partiaJ oxidation of organic substrates provides routes to a wide range of important functionalised molecules including alcohols aldehydes ketones epoxides and carboxyl ic acids Traditional methods of oxidation often involve the use of stoichiometric quan- tities or large excesses of poisonous high oxidation state chromium manganese and osmium reagents Environmental and economic factors make the use of these reagents increasingly unacceptable Oxidation processes based on lower oxidation state transition metals such as Coil Mnii and Cult in acetic acid media are also known and some are catalytic in the metal using molecular oxygen as the consumable oxidant but the conditions are often harsh the reagent mixture is corrosive (bromide is used as a promotor) and the chemistry is rarely selective Environmentally acceptable cat- alytic partial oxidations of inexpensive substrates (including hydro- carbons) that operate under moderate conditions in the liquid phase (most suitable for many of the industrial beneficiaries) with a high degree of selectivity are clearly desirable A large number of supported reagents have been used In the liquid phase partial oxidation of organic substrates The low cost of the support (commonly chromatographic materials such as silica gel) the mesoporosity of many of these supports and the other general advantages of supported reagents (ease of handling use and recovery low toxicity and the avoidance of solvents) make them very attractive in the context of clean synthesis However in oxi-dations supported reagents have generally acted as stoichiometric reagents being effectively dispersed forms of traditional oxidants There are notable exceptions to this which promise much for the future of supported reagent oxidation catalysis These are the new molecular sieves which incorporate active metal centres (notably Ti and V) in their structures and chemically modified support materi- als which have active metal centres on their surfaces While established aluminosilicate zeolites have proved popular in high temperature oxidation processes,' -their value in selective oxidations typically carried out in the liquid phase is less There has however been considerable early success in the use of other mole- cular sieves notably the titanium silicates such as TS-1 which are already being used in commercial units 27 The catalysts are syn- theised from typical sol-gel preparations involving tetraethyl- orthotitanate and tetraethylorthosilicate High Si Ti ratios minimise titanium centres with titanium nearest neighbours and maximise activity The pore diameter of TS-1 is only 5 5 A which is very restrictive in terms of accessible substrates and products but despite this it has been successfully used in the hydroxylation of aromat- ics the epoxidation of alkenes in ammoxidation amine oxidation and the oxidation of alcohols and thioethers In the hydroxylation of toluene for example the selectivity to para-cresol is an impres- sive 8 1% (Figure 5) The most important application for TS- 1 to date IS probably the hydroxylation of phenol giving mixtures of hydroquinone and catechol This represents a very clean option giving excellent conversion to product and very little waste The TS-1 process is not only cleaner than the alternatives (avoiding the use of strong acids or soluble transition metal catalysts) it also out- performs them particularly in terms of conversion (because of the much lower amounts of tars which result from side reactions and overoxidation) Catalytically active Si-0-Ti sites can also be formed via treatment of preformed silica with an active source of Ti such as TiF TS-1 lH20* y3$.Q'OH+ @OH OH 81YO 7% 12% Figure 5 Hydroxylation of toluene catalysed by TS 1 Vanadium silicate molecular sieves are capable of selectively oxidising 4-chlorotoluene to 4-chlorobenzaldehyde using hydrogen peroxide as the source of oxygen in acetonitrile solvent (Figure 6) 2x CH3I Cl vs-2f H*02 373 K i MeCNI CHO CH20H CH3I 1 I CI CI CI 66% 21Yo ao? Figure 6 Oxidation of chlorotoluenecatalysed by a vanadium silicate Vanadium has also been incorporated into the structure of MCM materials to give efficient catalysts for the oxidation of large mole- cules such as cyclodecane with hydrogen peroxide 29 Molecular sieves containing structural chromium can also be active in oxida-tions notably those of amines to nitro compounds using ?err-butyl hydroperoxide as the oxidant 30 While original forms of supported reagents involving high oxi-dation state metal oxidants were stoichiometric e g KMn0,-silica and K,Cr,O,-silica genuinely catalytic materials derived from the reaction of dichromate and permanganate with alumina were reported in 1989 3i The materials are prepared from aqueous solu- tion by careful control of pH and other reaction conditions The con- centrations of metal centres at the support surface are very low and while their identity is unknown a surface structure for the supported chromium species based on chemically bonded CrVi has been sug- gested as part of a proposed mechanistic pathway in catalytic oxi- dations (Figure 7) The supported chromium catalyst is active in alkyl benzene oxidations using only air as the source of oxygen and the neat substrate as the reaction medium -the ideal system from an environmental point of view In a typical oxidation that of ethyl- benzene to acetophenone the only other product is water and the catalyst can be used in very small quantities and is reusable The major drawback with the catalyst and the manganese analogue are their low activities -rates of oxidation of alkylaromatics of only II IMeH'CH Me' 'Ph 1-b0 l-l-O\ /O 02 Ct HO' 'H PhCOMe Figure 7 Possible mechanism for oxidations catalysed by supported chromium (VI) 1-2% h are possible at > 100 "C so that prohibitively long reac tion times are required for good overall substrate conversions Recent reports of oxidation catalysts based on chemically modi- fied support materials that can complex metal ions with useful redox properties including cobalt copper and iron may well represent a way forward in this field Such materials can be more robust than simpler metal-support materials and can show activity very similar to their homogeneous analogues Effective catalysts include cobalt immobilised on silica which has been derivatised with carboxylic acid functions (Figure 8) 32 This will catalyse the epoxidation of H' iH201 Figure 8 Formation of a supported cobalt catalyst based on a chemically modified silica alkenes using air and a sacrificial aldehyde Significant features of the catalysis include the high selectivity normally leading to the epoxide product only (diols commonly formed in homogeneous peracid reactions are not observed) and the ability of the catalyst to retain its metal ion even under harsh conditions 5 Catalysis using Supported Reagent Solid base^^-^ In contrast to the areas of heterogeneous oxidation catalysis and solid acid catalysis the use of solid base catalysis in liquid phase reactions has not seen the same level of major breakthroughs This is partly because the negative environmental impact of chemical processes using conventional acids and metal oxidants has attracted CHEMICAL SOCIETY REVIEWS 1996 more attention than those based on such as NaOH Base catalysis is however widely used both on a laboratory and industrial scale and the handling separation treatment and disposal of basic reagents and basic waste can all be troublesome Several different supports have been used for preparing solid bases with alumina based catalysts being the most widely studied in organic synthesis Most common basic reagents have been sup- ported including alkali metals (eg alumina-Na and silica-K) alkali metal hydroxides (eg alumina-KOH) and metal alkoxides (eg xonotlite-KOBu') Zeolite materials that have been exchanged with alkali metal cations and Cs+ in particular can also act as solid bases being particularly useful for higher temperature vapour phase processes Of these some of the more interesting are the immobilised alkali metals which can be prepared in a variety of ways including treatment of the support with a solution of the metal in liquid ammonia The solids are often brightly coloured which is due to the formation of colour centres of one electron donor char- acter Na + [2+] -Na+ + !+I Na + 0 -Na+ + 0' Na + OH (or 20Hj -ONa + H2(or H,Oj These materials have been referred to as solid superbases (estimated H > 37) and they are capable of promoting reactions of hydrocarbons such as the isomerisation of 5 vinylbicy-~1012 2 1 Ihept-2-ene to 5-ethylidenebicyclo(2 2 1 Ihept-2-ene (used as a comonomer in the production of synthetic rubber) Surprisingly perhaps the most widely studied supported reagent solid base in the context of organic synthesis is not based on a con- ventional base Attempts to support ionic fluorides and hence render them more active for nucleophilic fluorinations have been largely unsuccessful but have led to the discovery of remarkably useful solid bases459 Simple metal fluorides such as KF are known to be weak bases but their dispersion over a support is not enough to explain the often powerful basicity exhibited by KF-alumina for example The surface chemistry is in fact quite complex (see Figure 1) and oxide and hydroxide sites are likely to contribute to the basic properties When at their most active sup- ported fluorides are capable of adorbing large quantities of carbon dioxide from the atmosphere which reduces their activity through the formation of surface carbonates These facts help to explain the diversity of claims in the literature over their activity which has been variously described as weakly basic strongly basic and even superbasic 1 Supported fluorides have been used in a wide range of typically base catalysed reactions (Table 2) as well as several stoichiometric reactions KF-alumina is certainly the most widely studied although important variables such as loading and supported reagent post-treatment remain contentious issues The basic catalyst is espe- cially effective in carbon-carbon bond forming Michael reactions (eg reaction 4) and it is interesting to note that some of these have been translated into continuous flow reactions based on fixed cata lyst beds Table 2 Some of the reactions catalysed by KF-alumina Reaction Example Oxidation of alkylaromatics Ph,CH -PhCO Alkylations PhOH + MeOH -z PhOMe Condensations EtCHO + MeNO? -EtCHOHCH2N0 Rearrangements ArCH,CH =CH -ArCH =CHMe Michael reacti on s AcCH=CH + EtNO -Ac(CH2),CHMeN02 Additions CHCl + m O,NC,H,CHO -m O2NC6H,CH(OH)CCI ENVIRONMENTALLY FRIENDLY CATALYTIC METHODS-J H CLARK AND D J MACQUARRIE 309 6 Other Supported Reagent-catalysed Reactions and Future Trends Numerous other types of supported reagents (including those based on organic polymers which are beyond the scope of this review) have been developed and applied to liquid phase organic reactions These include catalysts for Diels-Alder reactions which enable the reaction to be applied beyond the normal electron rich dienes and electron poor dienophiles and in some cases allow the use of water as the solvent (a particularly important goal in clean synthesis) Perhaps the best solid catalyst for these reactions is Fe3+ -mont-morillonite which can result in a dramatic improvement in reaction rates (e g see Figure 9) Conditions Isolated product yield (9%) Fe7+-K10clay,p-ButC,H,0H (IO%),O”C lh 77 200 “C 20 h no catalyst 30 Figure 9 Diels-Alder reaction catalysed by Fe3+ -montmorillonite Apart form solid acid catal ysed halogenations other supported reagents have been used in halogenation reactions These include supported phase transfer catalysts such as alumina-Bu,PBr which will catalyse the halogen scrambling reactions between halo- alkanes eqn (5) The immobilisation of phase transfer catalyst may CH,CI + C,H,Br -CH,CIBr + CH,Br + C,H,CI (5) intuitively seem surprising but the concept of ‘triphase catalysis’33 has in fact been known for some 20 years The insoluble supported catalyst can act very effectively at the organic-aqueous interface and offers the usual advantages of supported reagents notably easy separation and reuse It is often physically difficult (due to very good solubility in most solvents and limited thermal stability) and rarely economic to recover a soluble phase transfer catalyst These facts have restricted their use and added to the waste generated from chemical processes Chemically fixing a catalytic structure such as an organometallic complex to a support material is a simple illustration of ‘hetero- genisation’ whereby the useful properties exhibited by the catalyst in solution are hopefully maintained in the solid base Apart from applications relevant to acid catalysis and oxidation catalysis out- lined earlier the principle has been successfully applied to other important reactions in the liquid phase such as hydrogenation asymmetric reduction and the deprotection of acetals Very sig- nificantly the direct grafting of an organometallic complex onto the inner walls of a mesoporous silica has recently been used to prepare via removal of the organic ligands by calcination a new form of supported Ti4+ This method is superior to other more conventional forms of grafting as it does not lead to undesired titano-oxospecies The catalyst is active in epoxidations with tert-butyl hydroperoxide as the oxidant 34 Supported reagent type catalysts have already proved their value in many organic reactions as environmentally friendly replace- ments for established reagents and catalysts that through their cor- rosive or toxic nature or difficulty in separation and recovery from reactions lead to unacceptable chemical waste The scope of these catalysts in liquid phase reactions is expanding on many fronts and commercial catalysts and industrial processes based on their use are now a reality 35 While serendipitous discoveries will continue to be made our understanding of the problems associated with clean synthesis and of the nature of solid catalysts will enable an increasingly more logical approach to the subject Much remains to be done including improvements in catalyst activity selectivity and stability particularly in areas such as Friedel-Crafts acylation nitration and base catalysis Process engineering aspects of the subject such as separation techniques and the translation of batch- type processes to continuous processes are also very important issues There are many interesting new developments emerging including the availability of controlled pore materials that may enable the right balance between activity and selectivity in liquid phase reactions to be achieved Chemical surface modification also has much to offer and research into ways of achieving high surface coverage and robust structures is very important if the catalytic potential of these materials is to be fully realised The way is clear for a greener future’ Acknowledgements The authors would like to express their sincere thanks to the many researchers at York and elsewhere who have contributed to the clean synthesis programme at York None of that would have been possible without the generous support of our spon- sors of whom Contract Chemicals the EPSRC Clean Technology Unit and the Royal Society (for a University research fellowship to D J M ) deserve special mention 7 References 1 ‘Chemistry of Waste Minimisation,’ ed J H Clark Chapman and Hall London 1995 2 ‘Preparative Chemistry using Supported Reagents,’ ed P Laszlo Academic San Diego 1987 3 ‘Solid Supports and Catalysts in Organic Synthesis,’ ed K Smith Ellis Horwood Chichester 1992 4 J H Clark A P Kybett and D J Macquarrie ‘Supported Reagents Preparation Analysis and Applications.’ VCH New York 1992 5 J H Clark ‘Catalysis of Organic Reactions using Supported Inorganic Reagents,’ VCH New York 1994 6 TW Bastock and J H Clark in ’Speciality Chemicals,’ ed B Pearson Elsevier London. 1992 7 J S Beck J C Vartuli W J Roth M E Leonowicz C T Kresge K D Schmitt C T W Chu D H Olson. E W Sheppard S B McCullen. J B Higgins and J L Schlenker. J Atn Chem Soc 1992,114 10834 8 A W McKillop and K W Young S\nthesis 1979,401 and 48 I 9 T Ando. S J Brown J H Clark D G Cork. T Hanafusa J Ichira J M Miller and M J Robertson J Chem Soc. Perkiti Truiis 2 1986 1133 10 J H C1ark.S R Cullen,S J Barlow andT W Bastock J Chern Snc Perkin Trans 2.1994 I 1 17 11 J P ButrilleandT J P~nnavaia.Cutaf Todab 1992,14. 141 12 12 P Laszlo and A Mathy Heir Chitn Actu ,1987,70,577 13 J H Clark A P Kybett D J Macquarrie S J Barlow and P Landon J Chem Soc Chem Comrnun . 1989,1353 14 D R Brown Geofogica Carpathica Series Cfavs (Brurisiuvu),1994 1 45 15 P D Clark,A Kirk and J G K Yee.J Org Chem . 1995,60.1936 16 H P van Shaik. R J Vjin and F Bickelhaupt Angeu Chem Int Ed Engf 1994,33 1611 17 A Cornelis. C Dony. P Laszlo and K M Nsunda. Tetruhedrorr Lett 1993,2901 and 2903 18 J H Clark,S R Cullen,S J Barlow andT W Bastock J Chern Soc Perkin Truns 1994,41 1 19 R S Drago S C Petrosius and P B Kaufman J Mol Cut 1994 89 317 20 J H Clark. K Martin A J Teadale and S J Barlow J Chein Six Chern Commun . 1995.2037 21 A P Singh and S B Kumar. Appl Cut A General 1995.126,27 22 K Smith and D Bahzad J Chern Soc Chetn Comtnuti . 1996,467 23 K Smith A Musson and G A DeBoon. J Chein Soc Chem Cornmun 1996.469 24 G D Yadav and N Kirthivasan J Chetn Soc Chem Cornmiin 1995 203 25 R Mokaya and W Jones. J Chetn Sac Chetn Cornrnirn 1994,929 26 J Aguad0.D P Serrano,M D RomeroandJ M Escola J Chrm Soc Chem Commun ,1996,725 27 A W Ramaswarmy. S Sivbasanker and P Ratnasamy. Mic roporoict Mater 1994,2.451 28 T SelvamandA P Singh,J Chern Soc Chem Corntnun 1995,883 29 K M Reddy. I Moudrakovski and A Sayari J Chem Soc Chem Cotntnun 1994. 1059 30 B Jayachandran M Sasldharan A Sudalai and T Ravindranathan J Chetn SOC Chetn Cotntnun 1995. 1523 CHEMICAL SOCIETY REVIEWS 1996 3 1 J. H. Clark A. P. Kybett P. Landon D. J. Macquarrie and K. Martin J. 34 T. Maschmeyer F. Rey G. Sankar and J. M. Thomas Nature 1995,378 Chem. SOC.,Chem. Commun . 1989,1355. 159. 32 A.J. Butterworth J. H. Clark,S. J. Barlow and T. W. Bastock UK Patent 35 Envirocats Contract Catalysts Knowsley Industrial Park Prescot Appl. 1996. Merseyside UK L34 9HY. 33 S. L. Regen J. Am. Chrm. SOC. 1975,97,5956.

ISSN:0306-0012    

DOI:10.1039/CS9962500303

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Designing New Lattice Inclusion Hosts Roger Bishop School of Chemistry, The University of New South Wales, Sydney 2052, Australia 1 Introduction Organic inclusion compounds may be classified, in the majority of cases, into two distinct categories. The more widespread group comprises unimolecular compounds where one host molecule interacts with one guest species.’ Familiar examples include host types such as the cyclodextrins, crown ethers, cryptands, carcerands and their related derivatives. The synthesis of new materials of this type has become an extremely active and highly sophisticated branch of chemistry, partly because of their inherent 1: 1 stoichiometry and because molecular modelling often permits reliable prediction.2 On the other hand, there are many other inclusion systems where the arrangement of molecules comprising the host lattice itself results in the observed host-guest properties.* Synthesis of new examples of these multimolecular or lattice inclusion compounds is problematical because lattice packing arrangements (even for simple organic molecules) cannot yet be predicted by computa- tional methods -despite innovative approaches toward this end.7 How, therefore, can new lattice inclusion hosts be discovered? The traditional answer to this question used to be ‘by fortunate acci- dent’: but in this article I shall describe how systematic approaches involving crystal engineering5 can now help us towards overcom- ing these formidable synthetic difficulties.The black comedy Cut’s Cradle by Kurt Vonnegut6 relates how Dr Felix Hoenikker succeeds in synthesising the polymorph ice- nine.In the hands of his dysfunctional offspring, the existence of this close-packed and thermodynamically stable substance leads to an all-too-inevitable outcome -but how was this molecular lattice designed? This strikingly successful fictional example of crystal engineering was inspired by analysis of stacking arrangements of the cannon balls decorating court-house lawns and through model- ling using the permutations of a cat’s cradle -techniques not so far removed, perhaps, from current methodology. The concept of ionic close-packing is widely used to explain the structure of simple lattices such as that of sodium chloride.Similarly, one of the basic tenets of practical organic chemistry is that recrystallisation of a crude reaction product will yield crys- talline material of high purity. Both these everyday illustrations presume that simple ions or molecules will pack together efficiently to yield high density structures, without void spaces which might contain guest species.’ Roger Bishop was educated at George Heriot’s School in Edinburgh, the University of St. Andrews (BSc)and the University of Cumbridge (PhD). In 1974 he took up a Lectureship at the University of New South Wales in Sydney, Australia, where he is currently an Associate Professor in the Department of Organic Chemistry. He has also held visiting research posi- tions at Ohio State and Durham Universities, and was the 1993 Olle‘ Prize winner of the Royal Australian Chemical Institute.His principal research inter- rests lie in the areas of alicyclic and supramolecular chemistry, and in the synthesis and appli- cation of new inclusion systems. In contrast, crystallisation of the extremely simple molecule H,O results in formation of a rather open lattice structure accompanied by the remarkable density decrease from 0.9998 to 0.9168 g cm-3. This is caused, of course, by formation of the highly directional hydrogen-bonding network present in ice. Furthermore, a crystallo- grapher would not be surprised if protein crystals for X-ray struc- tural determination contained associated components such as water molecules, sodium ions, and the crystallisation solvent itself -sometimes in large quantities.Hence, it is also possible that appropriate intermolecular forces combined with ‘awkward’ molecular shapes can lead to difficulties in close-packing, which might be alleviated by guest inclusion. Successful approaches to new lattice inclusion hosts, therefore, must take into account factors such as molecular size, shape and symmetry; and must also seek a fine balance between the intermol- ecular repulsive forces and attractive forces present. In supramole-cular synthesis, specific types of intermolecular non-covalent attraction are akin to the synthons of conventional synthetic chem- istryex We must learn to recognise these motifs, discover their influ-ence on molecular packing, and develop the ability to use such arrangements to our ad~antage.~The subtle interplay of these diverse factors is illustrated here for a selection of synthetic approaches to recently reported lattice inclusion systems.2 Propeller Blades, Wheels and Axles Since the initial report of the triphenylmethane-benzene compound by KekulC in 1872 it has become recognised that inclusion proper- ties are frequently associated with polyaryl systems that can adopt propeller-shaped arrangements. This is because the aryl-aryl inter- actions8 that predominate in such structures tend to result in forma-tion of void spaces suitable for guest entrapment. An interesting example is tris(5-acetyl-3-thienyl)methane1, reported to be a versatile host by bin Din and Meth-Cohn in 1977, but only now receiving proper structural attention.’O In the A-form of its 2:l cyclohexane compound (Fig.1) the near planar acetyl- thienyl groups are the propeller blades, which interact through two distinct offset face-face intermolecular mechanisms. One pair of blades overlaps thienyl.. .thienyl, while the other two pairs overlap carbonyl-*. thienyl. For all three the interplanar separation is about 3.6 A -a characteristic value for this type of interaction. The het- eroaromatic groups of 1function just as effectively as the benzenoid rings traditionally associated with polyaryl propeller-shaped hosts, indicating considerable potential for further host design in this area. Direct connection of two polyaryl groups by a linear spacer leads to the wheel and axle compounds first recognised by Toda and since developed into a major class of inclusion hosts.” Hence, in struc-ture 2, the wheels are tris(m-toly1)phosphine groups and the axle comprises a gold acetylide moiety.In the benzene compound of 2 the guest molecules occupy barrel-shaped cavities created by neigh- bouring m-tolyl rings (Fig. 2). Three m-tolyl groups describe the top, another three the bottom, and six others define the staves, of each barrel.I2 Inclusion properties of both the above categories may be modi- fied (and frequently enhanced) by incorporating hydrogen-bonding groups. Typical structures such as 3 and 4 suffer moderate crowd- ing around their hydroxy groups, which can inhibit intermolecular hydrogen bonding.Consequently, polar guests able to act as bridg- ing links between separate host molecules now tend to be incl~ded.~~ Inclusion systems stabilised by varying proportions of complex- ation and lattice dispersion forces have been termed coordinato- clathrates by Weber, and these often exhibit novel guest selectivity 31 I 3 12 CHEMICAL SOCIETY REVIEWS, 1996 co I CH3 I 2 Figure 1 Crystal packing in l2*(cyclohexane) viewed along a For clarity the tris(5 acetyl 3 thieny1)methane hosts are drawn as molecular frame works, cyclohexane carbons are shown as filled spheres, and all hydrogen atoms are omitted Thienyl thienyl interactions are edge on, and the carbonyl thienyl interactions are inclined, in this view The cyclohexane guests occupy channels along a arising from the balance between these factors l3 For example, the acetylenic alcohol 3 is able to remove ethanol from aqueous solu-tions through formation of the complex 3-(ethanol) Heating of this solid liberates the pure guest, thereby providing an unusual and valuable isolation procedure l4 The crystal structure of 3-(ethanol) (Fig 3) reveals that two mol ecules of each type are hydrogen bonded together through the cyclic Figure 2 Benzene in a barrel For clarity only the P(m tolyl), partial struc ture of compound 2, which IS directly involved in the host-guest con struction, is drawn here Hydrogen atoms are omitted and phosphorus atoms are hatched The six peripheral edge on m tolyl groups define the walls, while the other SIX define the ends, of the barrel shaped cavity present in 2.(benzene) 4 5 6 array (-0-H), which is a well-known supramolecular motif amongst alcohols I5 In this instance, this is the dominant interaction present The parallel aryl groups visible in Fig 3 are actually about 5 5 8, apart and do not interact, but inter-complex stabillsation IS provided through =C-CH3 aryl interactions 3 Inclined Planes and Rigid Spacers Another key strategy is the targeting of molecules the structures of which involve inclined planar sub-structures For example, two planar units may be joined edge-dge to give scissor-shaped mole- cules, or edge-face to give either T-shaped or roof-shaped mole- cules As demonstrated most convincingly by WeberI6 significant numbers of such compounds exhibit inclusion properties These characteristics often persist in the extended structures obtained through addition of further planar sub-structures and/or rigid spacer groups as shown here DESIGNING NEW LATTICE INCLUSION HOSTS -R.BISHOP Figure 3 The unit cell of 3-(ethanol) viewed along a and with the host-guest hydrogen bonded cycles (-0-H), represented by dashed lines. For simplicity all molecules are reproduced as framework drawings and all hydrogens are omitted. The hydrogen bonded units are linked through =C-CH 3.. .aryl interactions. Figure 4 The filled molecular cleft compound 5-(1,3$-trinitrobenzene). Oxygen atoms are lightly stippled, nitrogens are heavily stippled, and hydrogen atoms are omitted.Three planar units joined edge-face-edge as a U-shaped cleft can result in a unimolecular compound, as illustrated in Fig. 4for the combination of 5 and 1,3>-trinitrobenzene. In this structure the sep- aration between the dibenzofuran units and the aromatic guest is about 3.3 A. However, if the depth of the cleft is insufficient, as in the related molecule 6, then multimolecular inclusion compounds result instead. I The inclusion properties of tetraarylporphyrin derivatives have been developed extensively by Strouse and his colleagues. Indeed, these porphyrin sponges arguably now constitute the most compre-hensive family of lattice clathrate hosts.18 The peripheral aryl groups of these hosts are attached in edge-on fashion to the central planar ring and, consequently, these molecules pack as corrugated sheets, which stack to produce parallel guest-containing channels.This is illustrated in Fig. 5 by the host zinc tetraphenylporphyrin 7 as its inclusion compound 7.(naphthacenequinone). Extension of the wheel and axle concept by replacing the central linear spacer by a rigid planar group is typified by the polythiophene derivatives8 and 9 reported by Kobayashi.I9 Both compounds form Figure 5 A typical porphyrin sponge inclusion structure (zinc tetraphenyl- porphyrin 7)-(naphthacenequinone), showing the characteristic guest- filled channel arrangement. Hydrogen atoms are omitted for clarity.7 8 fi hydrogen-bonded complexes with Me,SO, but the stoichiometry and structural type alternate with the number of fused thiophene units in the central planar group. When this is odd then hydrogen- bonded host dimer formation is possible resulting in a compound such as 8;(Me2SO),, but if even then materials like 9.(Me,SO), are produced. The crystal structures of these closely related compounds are compared in Fig. 6. Further implications of this particular design concept are explored later in Sections 5 and 6. 3 14 CHEMICAL SOCIETY REVIEWS, 1996 Figure 6 Variation of inclusion structure with the number of fused thio phene rings in the central planar spacer group Top odd number of units yielding S2 (Me,SO), Bottom even number of units giving 9-(Me,SO), 4 Hydrogen Bonded Lattices Inspired by Hydroquinone Hydroquinone 10 is such a small and highly symmetrical molecule that one would expect it to pack in a trivial lattice arrangement Surprisingly, therefore, its most stable crystal form at room tem- perature (ahydroquinone) has a highly convoluted structure con- taining an amazing 54 molecules per unit cell 2o As for the case of ice, the demands imposed by intermolecular hydrogen bonding and symmetry dominate other contributing factors such as molecular size and shape Hence, hydroquinone 10 exhibits molecular sim plicity but supramolecular complexity Because of these remarkable properties it has played a central role in the development of inclu sion chemistry Packing difficulties can be overcome, in part, by adopting the P-hydroquinone lattice (Fig 7) and by including small guest mole- cules Such materials were first noted by Wohler in 1849 but their exact nature was not proved till nearly a hundred years later through the work of Powell who largely founded the modern era of struc- ture-based inclusion chemistry The P-hydroquinone structure is a superlattice constructed from two identical interpenetrating (but unconnected) simple cubic sublattices Small voids between these sublattices imprison the guest molecules within the superlattice The design of new organic superlattices built up from two or more equivalent interpenetrating sublattices is a fascinating current aspect of crystal engineering and is frequently associated with guest inclusion Readers are directed to the excellent account in this Journal by Zaworotko 22 MacNicol noted the characteristic hydrogen-bonding pattern present in P hydroquinone and realised that it was also present in inclusion compounds formed by Dianin's compound 11 and related 'OH 10 11 ArAr Ar ArI I Ar Ar d * Ar Ar Ar Figure 7 Top Diagrammatic representation of one p hydroquinone sublat tice emphasising the network characteristics of this part structure The solid tapering rods represent hydroquinone molecules 10,and the dashed lines indicate hydrogen bond cycles (-0-H), Bottom left Representation of one hydrogen bonded hexamer motif which is the supramolecular core of the above structure Bottom right Diagrammatic representation of the hexa host principle, showing aryl (Ar) and linking (L) groups, and comparing the interatomic separation (d') with that present (d)in the (-O-H), core of p hydro quinone derivatives In a brilliant piece of thinking he realised that the 'arms' of a hexa-substituted benzene would adopt a closely related geom- etry, which also would be favourable for guest inclusion (Fig 7) Hence, for the first time an entire family of new lattice inclusion hexa hosts such as 12, without a direct molecular relationship to previously known compounds, were successfully designed and syn- thesised 23 This striking outcome represents the first direct applica- tion of what we would now describe as the supramolecular synthesis of new inclusion hosts A more recent strategy by the MacNicol group affords novel inclusion hosts termed Piedfort assemblies24 where the central aro- matic core is doubled in thickness (Fig 8) This is achieved by assembly of two stacked tri-substituted aromatic units, which replace the previous hexa-substituted molecule but retain its three- fold symmetry Hence, for example, 2,4,6-tris[4-(2-phenylpropan-2 yl)phenoxy]-l,3,5 triazine 13 forms the highly crystalline 1 2 adduct with dioxane illustrated in Fig 9 More recently, inspection of the P-hydroquinone superlattice suggested to Ermer25 that the dimensions of [ 60lfullerene closely matched those of a single sublattice unit Furthermore, he reasoned that aryl aryl interactions between the electron-acceptor fullerene and the electron-donor hydroquinone rings should provide consid- erable stabilisation if a host-guest compound were produced On testing this outstanding idea it was indeed found that crystallisation of a mixture of the two components afforded black crystals of com- position lO;(C,,) where the fullerene was embedded within just one P-hydroquinone sublattice as illustrated in Fig 10 5 Other Hydrogen-bonded Network Structures Of course, hydroquinone is by no means the only molecule capable of providing a strong hydrogen bonded host network containing guests Indeed, allusions to interpenetrating lattice structures22 and Dianin's compound 1127have already been made Hydrogen bonding is usually stronger, and often more directional, than the other intermolecular attractions present in a lattice inclusion struc- ture Therefore, the requirement here is for the host to exert a DESIGNING NEW LATTICE INCLUSION HOSTS-R.BISHOP Figure 8 The Piedfort unit of 2,4,6-tris(4-(2-phenylpropan-2-yl)phenoxy1-1,3,5-triazine molecules 13 in its inclusion compound 13.(dioxane),. emphasising its symmetry, the double thickness aromatic core, and the six pendant arms. Non-hydrogen atoms of one molecule of 13 are represented by open spheres, and those of the other by shading. The inter-triazine aryt...aryt separation is ca. 3.5 A. SPh I (332I SPh 12 13 dominant effect on the molecular combination by providing a strong intermolecular network of low density.Three quite different cases of this phenomenon are described here. The steroidal bile acids are an important family of compounds involving a flexible side chain with a terminal carboxylic acid group, attached to a rigid fused-ring steroidal skeleton whose @-face is hydrophobic and a-face hydrophilic owing to the presence of hydroxy substituents. These materials frequently self-associate by means of convergent intermolecular hydrogen bonding, thereby producing head-tail bilayers. Crystal packing results in flexible par- allel hydrophobic channels, which frequently enclose less polar guest molecules .*6 An illustration of how this behaviour can be modified and con- trolled is provided by cholanamide, the amide derivative 14 of the natural product cholic acid.In its inclusion compounds one amide hydrogen atom participates in the host-host hydrogen-bonding 3 15 w Figure 9 Lattice packing in 13.(dioxane), showing four Piedfort units and their associated guest molecules. For clarity, all molecules are shown in framework representation, all hydrogens are omitted, and no distinctions are made between carbon and heteroatoms. Each triazine core is shown as a solid hexagon to emphasise the Piedfort units in this structure. / (I 1 \ \L--A L--d Figure 10 Diagrammatic representation of (hydroquinone),. (CHI) viewed along c. The small solid hexagons represent the aryl rings, and the large dashed hexagons the (-0-H), cycles. network. However, the other hydrogen protrudes from the channel wall and is now available as a molecular hook for polar hydrogen- bond acceptor groups like alcohols and ethers, as shown in Fig. 1 I for 14-(dioxane).26 Our own work has uncovered a remarkable family of inclusion hosts related to the simple diol 15 where the hydroxy groups assem- ble around a threefold screw axis producing a hydrogen-bonded 'spine'. The alicyclic framework functions as a rigid spacer group and results in these diols crystallising as lattices containing large parallel canals (Fig. 12) in which guests are trapped on a size and shape basis.This spine motif is another example of a supramolecular synthon* and CHEMICAL SOCIETY REVIEWS, I996 14 15 16 17 can be transplanted into other alicyclic systems thereby providing a family of hosts termed the helical tubulands.These have exactly the same crystal packing but differ considerably in their canal dimensions and resulting inclusion proper tie^.^^ The cutaway view of 15; (chlorobenzene) shown in Fig. I3 reveals the head-tail guest packing arrangement along one such canal of this helical tubulate compound. The third example illustrating network hydrogen-bonding hosts is Aoyama's phenol 16,2*which combines this property with those of the inclined plane systems discussed in Section 3. In the inclu- sion compound 16.(benzophenone),, the four phenol groups of 16 hydrogen bond to their neighbours creating a rather open layer structure in which the protruding anthracene groups are orthogonal to the phenolic rings.This results in the construction of a series of open cages with two benzophenone guest molecules occupying each cage. Each guest is stabilised by its carbonyl oxygen accept- ing a phenolic hydrogen bond and through aryl. . . aryl interaction with the anthracene groups (Fig. 14). Offset stacking of these layers affords a series of tubes formed by placing the open cages on top of each other. These tubes can be envisioned by imagining an infinite number of Fig. 14 units directly stacked on top of each other in a fully eclipsed manner. Consequently, the benzophenone guests occupy parallel tubes running through the crystal lattice. It is particularly noteworthy that, despite the considerable dif- ferences in molecular structure between the building blocks 15 and 16 and also in the construction of their inclusion networks, both compounds behave rather similarly.Both include guests in parallel tubes, their networks can survive as apohosts on removal of guest species, and their inclusion structures can be regenerated on exposure to guest vapour. These properties are remarkably similar to some of those exhibited by inorganic zeolitic struc- tures. Figure 11 Structure of (cholanamide 14).(dioxane) viewed along the b axis. Oxygens are shown as solid spheres, nitrogen atoms are striped, and hydrogen bonds are indicated by dashed lines. All hydrogen atoms are omitted. Figure 12 Projection in the ab plane of a section through the helical tubu- land lattice of diol 15 showing the parallel canals of triangular cross- section.The helical characteristics of each canal are largely masked in this representation. Oxygen atoms of the helical hydrogen bonded spine motifs are stippled. DESIGNING NEW LATTICE INCLUSION HOSTS-R. BISHOP Figure 13 View of one canal of 15,.(chlorobenzene) with one column of canal wall diol molecules removed to show the guest arrangement. In this instance head-tail packing is adopted through utilisation of a 2.4 8, Ar-H..-CI interaction between neighbouring guests. 6 Selective and Stereoselective Inclusion Properties A particularly important area of inclusion chemistry is the design of hosts capable of highly selective inclusion properties, and the fol- lowing three very different cases illustrate this aspect.The roof- shaped host 17 bears em-bromo substituents which reduce efficient awl-aryl packing and encourage neighbouring molecules to asso-ciate in other ways. This results in 17 being a selective host for small polyhalogenated guests that help create a network of halogen-..halogens interactions, as illustrated in Fig. 15 for 17.(CHCI,). Non-halogenated molecules of comparable size and shape are excluded.29 Chirally pure materials are assuming ever-growing importance in organic chemistry, and hence there is considerable interest in devis-ing chiral host systems capable of controlling stereoselective sepa- rations or reactions. Inclusion hosts are especially valuable for such processes since, subject to mechanical losses, the active agent is fully recoverable.These areas have been pioneered especially by Toda and his colleagues who have developed highly original appli- cations of new chiral hosts.3O An illustration is provided here by (S,S)-(-)-18, which can be used to resolve racemic 2-methylpiperi- dine 19 through two distinct procedures. First, if host and racemic guest are crystallised from toluene then a I: 1 complexof(S,S)-( -)-18and(R)-( -)-19isproduced. Distillation under reduced pressure then affords a 67% yield of (R)-(-)-19in 7 1 '31 ee. In this inclusion structure one hydroxy group of 18 is hydrogen bonded to both the piperidine and a second molecule of 18. In contrast, if the materials are crystallised from methanol solu-tion then the quite different 1: 1 :1 complex of (S,S)-( -)-18, methanol, and (S)-(+)-19 is obtained.This time distillation pro- duces a 67% yield of (S)-(+)-19 in 62% ee. This crystal structure differs in having the methanol acting as a hydrogen-bonded link between the two molecules of 18,and creates an environment suited to the alternative enantiomer of 19. In these, and other similar res- olution experiments, repetition of the procedure generates products of extremely high optical purity. K Figure 14 The hydrogen bonding network present in a molecular sheet of lC(benzophenone), showing incorporation of two guests in the supramolecular cavity. Repeated eclipsed stacking of this unit affords an example of the guest-filled zeolite-like tubes which run parallel through- out this structure.Figure 15 The different intermolecular halogen-halogen attractions (3.46-4.10 A) present in the structure 17-(CHCI,)indicated by heavy dashed lines. These form a network allowing specific trapping of small polyhalogenated guests. Brorno and chioro atoms are shown as large filled spheres, and hydrogens as small filled spheres. c1 18 19 OH 20 21 The structure of host 18 represents further development of the wheel and axle and inclined plane design strategies (see Sections 2 and 3),as does its interesting cousin 20 developed by Weber 31 In this case, use of bulky camphor groups as the wheels allows facile intro- duction of chirality from natural sources without any need for resolu-tion This host includes the aromatic epoxide (S)-(+)-21 as a 1 1 compound, but totally excludes the (-)-enantiomer, on crystallisation from solution Design features readily discernible in this inclusion structure (Fig 16) involve both host-host and host-guest hydrogen- bonding, aryl aryl interactions, and coordinatoclathrate attractions 7 Conclusions The design of new lattice inclusion compounds has now left tradi- tional serendipity far behind Synthetic approaches using analogy with known examples, or based on design elements such as planes and spacers, are well-established and frequently successful With our rapidly advancing understanding of intermolecular attractive forces, opportunities for synthesis are entering an excit-ing new phase Lattice inclusion compounds are an excellent choice for developing applications of these supramolecular synthons, since the formation of poorly packed host lattices must depend on impor-tant factors, which are capable of our recognition and exploitation Such knowledge, backed up by strong chemical intuition, eventu- ally will allow design to order of entirely new lattice inclusion systems Materials capable of specific inclusion behaviour will be especially important targets Acknowledgements I thank Dr Marcia Scudder for data retrieval from the Cambridge Structural Database32 and for generation of the figures illustrating this article Additional artwork was kindly carried out by Martin Dudman We thank the Australian Research Council for financial support of our own research into inclusion chemistry 8 References 1 D D MacNicol, J J McKendrtck and D R Wilson, Chem Soc Rev, l978,7,65 2 'Inclusion Compounds,' ed J L Atwood, J E D Davies and D D MacNicol, Academic Press, London, 1984 Vols 1-3, Oxford CHEMICAL SOCIETY REVIEWS, 1996 Figure 16 The molecular arrangement in 20-[(S)-(+) 211 with hydrogen bonding represented by dashed lines Oxygen atoms are indicated by solid spheres and only hydroxy hydrogens are drawn The stabillsing aryl-aryl interactions between the guest molecules and the planar naphthyl spacer group are clearly apparent University Press, Oxford, 1991 Vols 4-5.'Comprehensive Supramolecular Chemistry,' ed J M Lehn and J L Atwood, J E D Davies. D D MacNicol and F Vogtle, Pergamon Press, Oxford, 1996 Vols 1-11 3 J Maddox, Nature, 1988,335,201, A Gavezzotti,J Am Chem Soc , 1991,113,4622 4 J E D Davies, W Kemula, H M Powell and N 0 Smith, J Inch Phenom , 1983,1,3 5 G R Desiraju, Crystal Engrneerrtig The DeJign of Organic Solids, Materials Science Monographs No 54, Elsevier, Amsterdam, 1989 6 K Vonnegut, Jr , 'Cat's Cradle,' Gollancz, UK,1963 7 A I Kitaigorodskii, 'Molecular Crystals and Molecules,' Academic Press, New York, 1973 8 G R Destraju,Angew Chem , Int Ed Engf , 1995,34,23 1 I 9 M Mascal,Contemp Org Svnrh , 1994,1,31 10 L bin Din and 0 Meth-Cohn,J Chem SOC , Chem Cotnmun , 1977, 741.L Pang and F Brisse, Can J Chem , 1994,72,2318 I1 F Toda and K Akagi, Tetrahedron Lett, 1968, 3695, F Toda, in 'Inclusion Compounds,' ed J L Atwood, J E D Davies and D D MacNicol, Oxford University Press, Oxford, 1991 Vol 4 ch 4,pp 126-187 12 M I Bruce, K R Grundy, M J Liddell, M R Snow and E R T Tiekink,J Organomer Chem , 1988,344, C49 13 E Weber, in 'Inclusion Compounds,' ed J L Atwood, J E D Davies and D D MacNicol, Oxford University Press, Oxford, 1991, Vol 4, ch 5,pp 188-262 4 F Toda, K Tanaka and T C W Mak, Bull Chem Soc Jpn , 1985,58, 2221 5 S C Hawkins,M L Scudder,D C Craig,A D Rae,R B Abdul Raof, R Bishop and I G Dance,J Chem Soc Perkin Trans 2,1990,855 6 E Weber and M Czugler, Top Curr Chem , 1988,149,45 7 M Harmata and C L Barnes, J Am Chern Soc, 1990,112,5655.Tetrahedron Lett . 1990,31, I825 8 M P Byrn,C J Curtis, I Goldberg,Y Hsiou,S I Khan,P A Sawin, S K Tendtck and C E Strouse,J Am Chem Soc , 1991,113,6549 DESIGNING NEW LATTICE INCLUSION HOSTS-R BISHOP 19 Y Mazaki, N Hayashi and K Kobayashi, J Chem Soc Chem Commun ,1992,1381 20 S C Wallwork and H M Powell, J Chem Soc , Perkin Trans 2,1980, 21 H M Powell, in ‘Inclusion Compounds,’ ed J L Atwood, J E D Davies and D D MacNicol ,Academic Press, London, 1984 Vol 1,ch 1,pp 1-28 22 M J Zaworotko, Chem SOC Rev, 1994,23,283 23 D D MacNicol, in ‘Inclusion Compounds,’ ed J L Atwood, J E D Davies and D D MacNicol, Academic Press, London, 1984, Vol 2, ch 5, pp 124-168, D D MacNicol and G A Downing, in ‘Comprehensive Supramolecular Chemistry, Vol 6 Solid State Supramolecular Chemistry Crystal Engineering,’ ed D D MacNicol.F Toda and R Bishop, Pergamon Press,Oxford, 1996,ch 14,pp 421464 24 A S Jessiman, D D MacNicol, P R Mallinson and I Vallance, J Chem Soc ,Chem Commun ,1990,1619 25 0 Ermer, Hefv Chim Actu, 1991,74,1339 26 K Sada, T Kondo. M Miyata, T Tamada and K Miki,J Chem Soc Chem Commun ,1993,753,M Miyata and K Sada, in ‘Comprehensive 3 I9 Supramolecular Chemistry. Vol 6 Solid State Supramolecular Chemistry Crystal Engineering,‘ ed D D MacNicol, F Toda and R Bishop, Pergamon Press, Oxford, 1996, ch 6, pp 147-176 27 A T Ung, D Gizachew, R Bishop, M L Scudder, I G Dance and D D Craig, J Am Chem Soc , 1995.117,8745, R Bishop. D C Craig I G Dance,M L ScudderandA T Ung,Supramol Chem 1993,2. I23 28 K Endo, T Sawaki, M Koyanagi, K Kobayashi, H Masuda and Y Aoyama,J Am Chem Soc , 1995,117,8341 29 C E MarJo,R Bishop,D C Cra1g.A O’Brienand M L Scudder,J Chem SOC, Chem Commun . 1994.251 3 30 F Toda, K Tanaka. I Miyahara, S Akutsu and K Hirotsu. J Chem Soc Chem Commun , 1994, 1795. F Toda. Top Curr Chem . 1988. 149, 21 1 31 P P Korkas. E Weber, M Czugler and G Naray Szabo, J Chem Soc Chem Commun . 1995,2229 32 F H Allen, J E Davies, J J Galloy, 0 Johnson. 0 Kennard, C F Macrae. E M Mitchell. G F Mitchell. J M Smith and D G Watson. J Chem Inf Comp Scr , 1991,31,187

ISSN:0306-0012    

DOI:10.1039/CS9962500311

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Potential Energy Surface Crossings in Organic Photochemistry Fernando Bernardi and Massimo Olivucci Dipartimento di Chimica "G.Ciamician" dell'Universita di Bologna Via Selmi 2 40 126 Bologna ltaly Michael A. Robb Department of Chemistry King's College London Strand London UK WC2R 2LS 1 Introduction As a result of complementary experimental and theoretical work in the last five years new aspects of the excited state behaviour of organic molecules have emerged. The most general of these is that low-lying intersections (crossings) between the photochemically relevant excited state and the ground state occur with a previously unsuspected frequency. Thus an organic molecule moving on an excited state potential energy surface has a high probability of entering a region of surface crossing during the excited state life- time. Such crossings conical intersections in the case of two singlet (or two triplet) surfaces or singlet-triplet surface intersec- tions provide a very efficient 'funnel' for radiationless deactiva- tion or for chemical transformation of the system (see for example the 'highlight' article by M. Klessinger'). As a consequence many of the 'textbook' models for the treatment of the photophysical and photochemical behaviour have been considerably refined. The purpose of this review is to outline the computational and experi- mental results that support this new view of photochemical reac- tivity. In textbooks the efficiency of internal conversion (IC) and intersystem crossing (ISC) is usually discussed in terms of the interaction between the vibrational energy levels of the ground and excited state potential energy surfaces using the Fermi Golden Rule. The traditional view of photochemical reactions (mainly due to the work of Van der Lugt and Oosteroffz) assumes that the absorption of a photon results in the generation of an excited state species (M"). This intermediate represents the precursor of the photoproducts (P) which are generated ilia decay to the ground state. This decay was predicted to take place at an woided cross- ing of the excited and ground state potential energy surfaces. At such an avoided crossing if the energy gap is larger than few kJ Fernando Bernardi is Professor of Organic Chemistry at the University of Bologna. He received his degree in Industrial Chemistrv at the University of Bologna in 1962 and studied with S.F. Boys in Cambridge (I969- f971). Hi5 research interats spun all aspects of theoretical organic chemistry. mol-I M* will rapidly thermalyse and the decay probability will be determined by the Fermi Golden Rule. Accordingly such processes are supposed to occur on the same timescale (several molecular vibrations) as fluorescence. Modem experimental measurements and new computational techniques are now providing results that challenge such models for understanding organic photochemistry. Issues such as the effi- ciency of IC at a surface crossing the competition with fluores- cence when an excited state barrier is present and the relationship between the molecular structure at the intersection and the struc- ture of the photoproducts provide the intellectual motivation for the experimental and computational investigation of various pho- tochemical reactions. The rate and the energy thresholds control- ling IC can now be experimentally measured by exploiting the advances in laser spectroscopic techniques that have pushed the time resolution of various experimental techniques below the picosecond timescale. Thus very fast IC processes and short excited state lifetimes can now be detected. For example many detailed experiments are available in the photophysics and photo- chemistry of conjugated hydrocarbons in solution or isolated con- ditions. Femtosecond excited state I ifetimes have been observed for simple dienes,< cyclohexadienes? hexatrienes,5 and in both free6 and opsin-bound7 retinal protonated Schiff bases. Experiments on isolated molecules in cold matrices or expanding jets have revealed the presence of 'thermally activated' fast radia- tionless decay channels in hexatrienes? octatetraene~~~'~) and aro- matic compounds (see refs. collected in ref. 1 I). While laser experiments provide information on the structure and energetics of the excited state potential energy surfaces controlling fast decay more traditional photochemistry such as quantum yield measure- ments provide information on the molecular structure of the decay Massimo Olivucci is Ricercatore at the Utziversity of Bolognu where he obtained his PhD in 1989. He u~usa post-doctoral fellow at King's College London I989- 1992. His research interests lie in the theoretical modelling of photochemistry. Michael Rohb is Prc$es.tor of Chemistry at King :s College London. He obtained his PhD from the University of Toronto in 1970 and was awarded the DSc from the University of London in I988. His research interests lie in the development of MC-SCF methods and appli- cations to chetnical reactivitv. Fernando Bernardi Massimo Olivucci Michael Robb 32 1 channel and on the product formation paths The detailed charac- terisation of the stereo- and regio-chemistry of the primary photo- products and transient intermediates their quantum yields and the effect of specifically designed sterically and rotationally hindered reactants on these quantitiesi2 is now possible An alternative view of photochemical reactions that is consistent with recent experiments was suggested more than 30 years ago by the physicist Edward Telleri3 at the 20th Farkas Memorial Symposium He suggested that it was the electronic factors that may play the dominant role in the efficiency of radiationless decay Teller made two general observations (I) In a polyatomic molecule the non-crossing rule which is rigorously valid for diatomics fails and two electronic states even if they have the same symmetry are allowed to cross at a conical intersection (11) Radiationless decay from the upper to the lower intersecting state occurs within a single vibrational period when the system ‘travels’ in the vicinity of such intersection points On the basis of these observations Teller pro- posed that conical intersections may provide a common and very fast decay channel from the lowest excited states of polyatomics In the field of photochemistry Zimmermani4 and Michlt5 were the first to suggest independently that certain photoproducts originate from IC at a conical intersection Zimmermant4 and Michl l5 use the term ‘funnel’ for this feature In this review we will show that in agreement with the sugges- tions of Teller Zimmerman and Michl recent computational” l6 work when taken in conjunctionwith modern experimental studies indicates that the radiationless decay process does not occur via an excited state intermediate in many cases but rather through a conical intersection (1 e an unavoided surface crossing) between excited and ground states Radiationless decay at a conical inter- section implies that (a)the IC process will be 100% efficient (i e the Landau-Zerner17 decay probability will be unity) (b) any observed retardation in the IC or reaction rate (I e the competition with flurorescence) must reflect the presence of some excited state energy barrier which separates M* from the intersection structure and (c)in the case where the decay leads to a chemical reaction the molecular structure at the intersection must be related to the struc- ture of the photoproducts 2 The ’Physical Chemistry‘ of Conical Intersections The precise nature of the molecular mechanism that controls radia- tionless decay in polyatomics is a problem that has intrigued pho- tochemists and photophysicists for several decades An excited state species decays non-radiatively via internal conversion (IC) to a state of the same spin multiplicity and via intersystem crossing (ISC) to a state of different spin multiplicity In textbooks the effi ciency of IC and ISC is usually discussed in terms of the interaction between the vibrational energy levels of the two potential energy surfaces using the Fermi Golden Rule,i8 see eqn (1) where klhfis the rate of transition from initial (1) to final # states,W,and Wfare wavefunctions of initial and final states and pE is the density of states Upon simplification this term reduces approxi mately to eqn (2) where (x,Ixf>are Franck-Condon factors (i e vibrational overlaps) and plSC/lc is an electronic factor The efficiency of IC and ISC is often discussed in terms of Franck-Condon factors and plsc/lcis assumed to play a minor role The Landau-Zener model provides an alternative semi-classical model for radiationless decay As shown by Desouter-Lecomte and Lorquet,17 the probability of radiationless decay is given in eqn (3) where 6 is the Massey parameter given as eqn (4) CHEMICAL SOCIETY REVIEWS 1996 5= Wq) (4)LIsllg(s)l2Tr where q is a vector of nuclear displacement coordinates The term g(q) is the non-adiabatic coupling matrix element defined in eqn (6) while Iq I is the magnitude of the velocity along the reaction path q and AE is the energy gap between the two states IP and W2 Unless AE is less than a few kJ mol I the decay probability is van- ishingly small However as we approach a point where the surfaces actually cross the decay probability becomes unity To understand the relationship between the surface crossing and photochemical reactivity it is useful to draw a parallel between the role of a transition state in thermal reactivity and that of a conical intersection in photochemical reactivity ~~~ Reaction Co-ordinate Reaction Co-ordinate Scheme 1 In a thermal reaction the transition state forms a dynamical bottle- neck through which the reaction must pass on its way from reactants to products (Scheme la) A transition state separates the reactant and product energy wells along the reaction path A conical intersection (Scheme lb) also forms a structural bottleneck that separates the excited state branch of the reaction path from the ground state branch The crucial difference between conical intersections and transition states is that while the transition state must connect the reactant energy well to a single product well via a single reaction path an intersection is a ‘spike’ on the ground state energy surface (see inset in Scheme 1b) and thus connects the excited state reactant to two or inore products on the ground state via several ground state reaction paths The nature of the products generated following decay at a surface crossing will depend on the ground state valleys (reac- tion paths) that can be accessed from that particular structure Theoretical investigations of surface crossings have required new theoretical techniques based upon the ‘mathematical’ description of conical intersections and we now briefly review the central theoret- ical aspects The double cone shape of the two intersecting poten tial energy surfaces can only be seen if the energies are plotted against two special internal geometric coordinates of the molecule (x,and x in Scheme 2) The coordinate x is the gradient difference vector given in eqn 6 while x2 is the gradient of the interstate coupling vector see eqn (7) x = (c;(g)c,) (7) where C and C are the configuration interaction (CI) eigenvectors in a CI problem and H is the CI hamiltonian The vector x2 is POTENTIAL ENERGY SURFACE CROSSINGS IN ORGANIC PHOTOCHEMISTRY -M A ROBB ETAL parallel to the non-adiabatic coupling given in eqn (5) These geo- metric coordinates form the so called ‘branching space’ As we move in this plane away from the apex of the cone the degeneracy is lifted (see Scheme 2a) and ground state valleys must develop on the lower cone In contrast if we move from the apex of the cone along any of the remaining n -2 internal coordinates (where n is the number of degrees of freedom of the molecule) the degeneracy is not lifted This space of n -2 internal coordinates the ‘intersec- tion space’ is a hyperline consisting of an infinite number of conical intersection points (see Scheme 2b) n-2 dimensional intersection-space 2-dimensional state branching-space Scheme 2 Often the chemically relevant conical intersection point is located along a valley on the excited state potential energy surface Figure 1 illustrates a two-dimensional model example Here two potential energy surfaces are connected via a conical intersection This inter- section appears as a single point (CI) since the surfaces are plotted along the branching space (x x2) The intermediate M* is reached by relaxation from the Franck-Condon region (FC) and it is sepa- rated from the intersection point by a transition state (TS) In this case the molecular structure of the intersection and the reaction pathway leading to it can be studied by computing the minimum energy path (MEP) connecting FC to M* and M* to CI using the standard intrinsic reaction coordinate (IRC) method l9 However there are situations where there is no transition state connecting M* to the intersection point or where an excited state intermediate on Figure 1 Model conically intersecting potential energy surfaces plotted along the branching space (x 3,) The arrows indicate the direction of the minimum energy path connecting the FC point to the photoproducts P and P’ M* is the excited state intermediate and TS is a transition state con necting M* to the conical intersection (CI) the upper energy surface does not exist In such situations mech- anistic information must be obtained by locating the lowest lying intersection point along the n -2 intersection space of the mole- cule The practical computation of the molecular structure of a conical intersection energy minimum can be illustrated by making an analogy with the optimization of a transition structure As illus-trated in Scheme la a transition structure is the highest energy point along the path joining reactants to products and the lowest energy point along all the n -1 directions orthogonal to it One can opti- mize such a structure by minimising the energy in n -1 orthogo-nal directions and maximising the energy in the remaining direction corresponding to the reaction path The technique for locating the lowest energy intersection point** exploits the fact that the branching space directions x and x2play a role analogous to the reaction path at the transition state Accordingly the lowest energy point on a conical intersection is obtained by minimising the energy in the n -2 dimensional intersection space (x,x xn),which preserves the degeneracy (see Scheme 2b) The techniques outlined above provide information on the struc- ture and accessibility of the intersection point which controls the locus and efficiency of IC The evolution of ground state photo- products following decay ~’iasuch an IC channel requires a study of the possible ground state relaxation process Observe the shape of the ground state surface in the region of the conical intersection in Figure 1 The double cone in this case is ‘elliptic’ and two sides are steeper than the others This situation is typical of many cases and relaxation valleys develop more quickly in these directions We have recently implemented a method to locate and characterize all the relaxation directions that originate at the lower vertex of the CI cone 2’ The MEP starting along these relaxation directions defines the ground state valleys which determine the possible relaxation processes and the photoproducts This information is structural (i e non-dynamical) and provides insight into the mechanism of photo- product formation from vibrationally ‘cold’ excited state reactants such as those encountered in many experiments where slow excited state motion or/and thermal equilibration is possible (in cool jets in cold matrices and in solution) In many cases such structural or static information is not suffi- cient The excited state may not decay at the minimum of the conical intersection line Alternatively the momentum developed on the excited state branch of the reaction coordinate may be suffi- cient to drive the ground state reactive trajectory along paths that are far from the ground state valleys In such cases a dynamics treatment of the excited state/ground state motion is required For small systems a parametrised potential can be developed and full semi-classical quantum dynamical treatment is possible 22 In our own work:? we have used classical dynamics with a parametrised hybrid quantum-mechanical/force-field (MMVB the molecular mechanics valence bond method) This method employs a ‘direct’ procedure for solving the equations of motion and avoids the tedious and often unfeasible parametrisation of an analytical expression of a multidimensional energy surface The trajectory- surface-hopping algorithm of Tully and Preston (see ref 23 for details) is used to propagate excited state trajectories on to the ground state in the region of a conical intersection 3 Reaction ’Funnels’ in the Photochemistry of T-T* and n-n* States The application of different spectroscopic techniques to low tem- perature samples of ‘isolated’ conjugated molecules has begun to provide very detailed information on the excited state dynamics of these organic systems In Figure 2 we illustrate the results of two different experiments The first experiment (Figure 2a) is due to Kohler and coworkerslO who recorded the fluorescence lifetime of S ,(2A,) all-trans-octa- 1,3,5,7-tetraene (all-trans OT) as a function of the temperature In this experiment the all-tram OT molecules are isolated in a molecular cavity of frozen hexane and do not inter- act with each other From Figure 2(a) one can see that at tempera- tures above 200 K the fluorescence lifetime drops dramatically indicating fast decay of the excited state molecules to the ground 324 CHEMICAL SOCIETY REVIEWS. 1996 100 200 Temperature/ K (a) -n qr50 I?$ -1003CD Radiationless 0CD-50 Y 13 -0 5 I 0 1000 2000 3000 4000 A EnergyAbove the Origin / cm-’ Figure 2 ‘Opening’ of a fast radiationless decay channel in all trans octate traene in (a) matrix isolated conditions (b) in a expanding cool jet state This event was assigned to the opening of a thermally acti- vated efficient radiationless decay channel with a barrier height of ca 1500 cm-(1 1 9 kJ mol-I) The second experiment (Figure 2b) is due to Christensen Yoshihara Petek and coworkers,’ who reported the fluorescence decay rate of S all-trans OT molecules measured in free jet expansion as a function of the excitation energy These authors propose that cis-trans isomerisation is responsible for the radiationless decay channel which opens up at ca 2 I00 cm I (25 kJ mol I) excess energy The data from both experiments can be explained using the model surface shown in Figure la In both experiments the fluorescence lifetime decreases slowly and almost linearly by increasing the S I excess vibrational energy until an energy threshold is reached and a dramatic decrease in excited state lifetime is observed Similar observations have been documented In other conjugated molecules In S benzene there is a ca 3000 cm I (35 9 kJ mol I) threshold for the disappearance of S fluorescence (see ref I I) This observation is assigned to the opening of a very efficient radiation- less decay channel (termed ‘channel 3’) leading to the production of fulvene and benzvalene In S cyclohexadiene which is produced via a fast decay from the spectroscopic S state there must be a small barrier (ca 4 kJ mol I) to decay to S since the photoprod- ucts of the ring-opening reaction are detected a few picoseconds after initial excitation Ab initio CAS-SCF and multi-reference MP2 show that the topology of the first (T-+) excited state energy surface is indeed consistent with the model surface shown in Figure I (except for cyclohexadiene in which there is no transition structure between the excited state energy minimum and the intersection pointlhfl Thus the observed energy thresholds which are well reproduced in theoretical computations correspond to the energy barriers which separate an excited state S intermediate from a S ,/Soconical intersection point The molecular system spends very little time in the neighbour- hood of geometries characterised by conical intersections Thus such geometries are not amenable to direct experimental observa- tion and can only be derived from theoretical computations The optimized conical intersection structures for all-trans OT S benzene and S cyclohexadiene intersections are collected in Figure 3 Comparison of these structures reveals common struc- tural and electronic features Each structure contains a triangular Figure 3 Structures of S ,/So conical intersections in conjugated hydrocar bons showing the -(CH),-kink (framed) (a) all trans octatetraene. (b) benzene (c) cyclohexadiene Interatomic distances are in 8 arrangement of three carbon centres corresponding to a -(CH),-kink of the carbon skeleton in all-trans OTIhh and benzene“ and to a triangular arrangement of the -CH and -CH-CH terminal frag- ments in cyclohexadiene 16(’ The electronic structure in each case corresponds to three weakly interacting electron5 in a triangular arrangement which are loosely coupled to an isolated radical centre (this is delocalised on an ally1 fragment in all-trans OT and benzene and localised in cyclohexadiene) This type of conical intersection structure appears to be a general feature of conjugated systems and has been documented in a series of polyenes and polyene radicals The electronic origin of this feature can be under- stood by comparison with H where any equilateral triangle con- figuration corresponds to a point on the D,/D conical intersection in which the three H electrons have identical pairwise interactions Moving from conjugated hydrocarbons to other classes of organic molecules the electronic structure of the lowest lying inter- section changes We now have detailed results on the Paterno-Buchi reaction,’& a,P-enonesI&’ the oxadi-n-methane and [ 1 ,.?J-acyl sigmatropic rearrangements of /3,y-enones,16p azo-compounds (diazomethanel ’”) and photorearrangement of acyl- cyclopropenes to furans I6x While hydrocarbon photochemistry typically involves a low energy covalent state the photochemistry of bichromophoric (C=O and C=C) compounds is complicated by the competition between triplet 3( r-n-) pathways and singlet ](T-7.r) and triplet ’(n-n-) pathways The novel feature of our results is the discovery of points in the surface where all four states are degenerate This feature rationalises the singlet-triplet photochem- istry in a novel way The new features that arise in bichromophoric (C=O and C=C) compounds can be illustrated with the structure of the So/S conical intersections found in a,p-enones In this case the first singlet POTENTIAL ENERGY SURFACE CROSSINGS IN ORGANIC PHOTOCHEMISTRY -M A ROBB ETAL 325 Figure 4 Low lying intersections in CIS acrolein (a) Sl(n-+)/So conical intersection (b) Tl(r-+)/S0 triplet/singlet crossing excited state is not a v-7F state but an n-+ state where the lone- pair orbital n becomes singly occupied This fact alone results in an electronic and molecular structure which is very different from the -(CH),-kink seen in conjugated hydrocarbons The case of cis-acroleinl6" is instructive (see Figure 4a) The S,/S conical inter- section has a 90" twisted terminal CH and corresponds to a diradical with radical centres on CH and 0 with a central C-C double bond (1 34 A) This structure corresponds to a point of degeneracy between the n-+ and ground state because the radical centres do not interact with each other and with the central .sr-bond Thus in this structure the S state and the l(n-7F) state differ only in a 90" rotation of the position of the singly occupied orbital on the oxygen Since the position of this radical centre is isolated from the CH radical centre the states have the same energy The structure of the S,/Soconical intersection in acrolein ration- alises the observed wavelength dependent photochemistry of a,P-enones Direct irradiation with 310 nm light produces cis-trans double bond isomerisation exclusively In contrast irradiation with 250 nm light produces a mixture of isomerisation and ring-closure products The 310 nm photochemistry comes from the enone TI triplet state Computations on acrolein demonstrate that this state is populated by ISC from the initial S (n-+) excited state molecule to a TI (.sr-+) diradical intermediate the structure of which is shown in Figure 4b The 3( n-+) diradical intermediate is not gen- erated directly but involves decay through successive SJT and a T,/T intersections The T intermediate is located at a T,/S inter- section and is the precursor of the photoproducts which are gener- ated via a slow ISC process The stability and structure of this diradical correlates nicely with the observed phosphore~cence~~ and lack of production of the four-membered ring oxetene upon >300 nm irradiation 25 In fact while the two radical centres are located on two vicinal carbons the carbonyl bond is fully formed Consequently relaxation to the Sostate can only result in a@-enone formation structure via cis-trans motion The production of oxetane requires a very different decay point which is assigned to the Si/So conical intersection described above The fact that 250 nm radiation is required for populating this decay channel is consistent with the fact that this is located at least 40 kJ mol above the initial S struc ture 4 Butadiene Photochemistry Beyond the Woodward-Hoffman rules The cyclisation of butadienes and ring-opening of cyclobutenes are textbook examples of pericyclic reactions The stereochemistry of both thermal and photochemical pericyclic reactions can be pre- dicted on the basis of the Woodward-Hoffman (WH) rules l8 Despite the fact that the success of these rules has been demon- strated in many cases it is not obvious why they work in the case of the photochemistry of polyenes The WH rules predict the stere- ochemistry of the motion on the (HOMO-LUMO singly excited) I B spectroscopic state (see Figure 5a) However the spectroscopic investigation7 of short polyenes shows that after photoexcitation these systems decay to a lower lying doubly excited (2A,) state Thus the photoproducts must originate from this state via IC Why is the 'disrotatory ' stereochemistry predicted for the spectroscopic state of s-CISbutadiene not lost on the 2A state? Further while a rigid disrotatory stereochem is try has been experimental 1y observed for the s-CISbutadiene ring-closure Leigh et a1 26 have demon- strated that the reverse photoreaction the ring-opening of cyclobutene occurs with a low degree of stereospecificity About 20 years ago Van der Lugt and OosterofP proposed that along distinguished disrotatory and conrotatory ring-closure coor- dinates the 2A state has two deep minima The observed disrota- tory stereochemical preference was then explained on the basis of a higher rate of IC at the disrotatory 2A minimum (see arrows in Figure 5a) owing to a substantially smaller excited statelground state energy gap in this point The recent computational re-investi gation of the interplay between the 2A dark state potential energy surface the lB surface and the lA ground state surface of S-CI~ butadiene rationalises its photo-stereochemistry16/fIn Figure 5b we show the energy profiles along the reaction paths computed for the first two excited states of s-cis butadiene Upon relaxation from the FC region the photoexcited molecule undergoes a barrierless relax ation leading ultimately to decay to the 1A I ground state There are two successive intersection points involved in the relaxation process The first intersection occurs between the spectroscopic 1 B state and the dark 2A state and is located in the vicinity of the FC region This IS consistent with spectroscopic studies on isoprene (2 methylbutadiene),3 which indicates that the 1B state is depopulated on a timescale of 10 fs owing to fast internal conversion to the nearby 2A state The second intersection involves a conical inter section between the 2A and the lA state which will be entered after 2A geometric relaxation Thus photoproduct formation occurs after 2A decay following solvent cooling of the initially hot molecule The 1 B path which describes the relaxation from the FC region (see arrows in Figure 5b) involves a disrotatory motion of the ter- minal methylenes in agreement with the prediction of the WH rules However both a disrotatory and a conrotatory reaction path exist on the 2A potential energy surface which ends in the same 2Al/lA crossing region However while the disrotatory path is barrierless the conrotatory path has a barrier (due mainly to steric effects) and it is located 30 kJ mol higher in energy Thus the (energetically preferred) structural evolution of the system along the 2A energy surface will also be disrotatory but for a reason unrelated to the WH theory Simply the conrotatory motion on the 2A surface is hindered by a barrier The original Van der Lugt and Oosteroff model (arrows in Figure 5a) can now be refined Our computations and experimental work indicate the existence of a disrotatory I B,/2A I crossing in butadienes However there are no CHEMICAL SOCIETY REVIEWS 1996 i F=i disrotatory Figure 5 Butadiene photochemistry (a) WH state correlation diagram The arrows represent the Van der Lugt and Oosteroff mechanism (b) Computed MEP from the S (1 B2) FC structure of s cis butadiene to the S (2A,)/S conical intersection Full lines and light lines represent the energy profile along the dis- rotatory and conrotatory MEP respectively The terminal hydrogen atoms in the structures have been highlighted to indicate the stereochemistry true 2A minima and the lowest energy point on the 2A state is a conical intersection Direct irradiation of s-cis butadienes is known to yield a mixture of cis-trans isomerisation and cyclisation photo product^^^ In a 20 K matrix Squillacote et af have measured the ratios of double-bond cis-trans isomerisation s-cis>s-trans isomerisation ring-closure and reactant back-formation The structure of the computed 2A,/IA conical intersection and the energy profiles of the four relaxation paths that begin at the apex of this conical intersection are shown in Figure 6 Neglecting the effect of dynamical factors which may in principle control the efficiency of the different relax- ation processes it is obvious that double-bond cis-trans isomerisa-tion ring-closure and reactant back-formation will be competitive We have not been able to locate a path leading to the cyclopropyl- methylene diradical which is a precursor of bicyclobutane This observation is consistent with the fact that this product has not been seen experimentally Our theoretical prediction which suggests that the photoreactivity of s-cis butadiene involves simultaneous twist- ing motion about the central C-C bond and one of the original double bonds (see Figure Sb) has been experimentally tested by Leigh et af using a series of C-C ring-locked butadienes l2 Their experiments show that the yield for double-bond isomerisation is indeed affected by the size of the ring blocking the C-C s-cis>s-truns rotation The reaction paths illustrated in Figures 5 and 6 also provide an explanation for the lack of stereochemistry observed in cyclobutene (CB) ring-opening reactions 26 (The WH rules predict a disrotatory stereochemistry) The experimental observations can be explained by assuming that the CB ring opens on the 1B2state In this way CB photolysis would yield 1B2 s-cis butadiene which decays to the dark 2A state following the pathway illustrated in Figure Sb The CB final photoproducts must originate via decay at the same 2A I/1A conical intersection and will follow the relaxation paths shown in Figure 6 It is then obvious that since decay at this point involves concurrent butadiene formation and double-bond cis-trans isomerisation the production of a stereospecific (disrota- tory) ring-opening product is impossible Thus the loss of stereo- chemistry IS due to the unuvoiduble concurrent cis-trans isomerisation and butadiene formation 5 Towards a Dynamic View of Photochemical Processes Benzene and Azulene In our preceding discussion of butadiene photochemistry we have shown how excited state and ground state relaxation paths can provide structural (I e non-dynamical) information on the mech- anism of product formation associated with radiationless deactiva- tion A more realistic picture of these processes requires the description of the reaction dynamics obtained from the computation and analysis of non-adiabatic trajectories We now illustrate this point with some results on benzene and azulene The lifetime of the S state of vapour phase benzene drops dra- matically when the vibrational excess energy overcomes a ca 3000 cm-I (35 9 kJ mol I) barrier In contrast recent spectroscopic investigations have demonstrated that the S state of the pseudo- aromatic molecule azulene has a sub-picosecond lifetime arising from a nearly barrierless fast deactivation process Our recent ab initio computations' rationalise these data and have confirmed that in both molecules a S ,/So conical intersection occurs on the S potential energy surface Non-adiabatic dynamics from benzene23 and azuleneI6' S states give new insight into the quantum yield of prefulvene in the case of benzene and suggest that one may observe coherent vibrations on the ground state of azulene In Figure 7 we show that the S poten-tial energy surfaces of benzene and azulene have different shapes in the region of the conical intersections For S benzene there is a sub- stantial barrier separating an excited state intermediate from the conical intersection region In contrast azulene shows a 'sloped' conical intersection which is slightly higher than the intermediate region Our dynamics studies have been carried out with the MMVB technique discussed in ref 23 Comparison of the MMVB energy and molecular structures of benzene and azulene with the corresponding ub initio parameters (see Figure 7) indicates a good qualitative agreement The computed non-adiabatic dynamics are thus expected to be qualitatively correct In the case of benzene our objective was to understand the origin of the very low quantum yield (cu 0 02) for the production of ben- zvalene Figure 7(a) shows that there is an S transition structure with a geometry that is virtually identical to the optimized intersec- tion Thus there will be two possible types of trajectory that pass POTENTIAL ENERGY SURFACE CROSSINGS IN ORGANIC PHOTOCHEMISTRY -M. A. ROBB ETAL. Table 1 Quantum yield of prefulvene as a function of the initial momentum (excess energy) along the reaction path Excess energy Hopped trajectories (%) Prefulvene yield (%) kJ mol-1 12.9 48 0.0 22.5 100 0.0 25.1 100 2.7 27.6 100 3.1 32.6 100 2.0 37.7 100 2.7 41.8 100 11.3 48.5 100 22.3 0 2 4 6 8 MEP(a.u.) Figure 6 Energy profiles along the computed MEP describing the relax- ation from the S,/Soconical intersection point to the s-cis butadiene pho- toproducts. The terminal hydrogen atoms in the structures have been highlighted to indicate the stereochemistry. through the conical intersection region trajectories that follow the reaction path between the S minimum and the prefulvene structure and trajectories that return to the So minimum after a surface hop. The quantum yield corresponds to the ratio of the numbers of tra-jectories leading to the prefulvene as a function of the total. In our simulation the initial conditions were designed to select trajectories approaching the intersection region. There are two variables asso- ciated with the initial conditions (a)the value of the initial kinetic energy (momentum) along the reaction path and (b)the value of the initial vibrational kinetic energy randomly distributed among the normal modes orthogonal to the reaction path. The effect of the initial momentum along the reaction path is shown in Table 1 which lists the percentage of trajectories that A hopped during the simulation and the percentage that terminated in the prefulvene region for a range of excess kinetic energies. The very small computed yield of prefulvene shows a general increase as the kinetic energy rises. The experimental quantum yield at 253 nm is 0.016 which rises slightly to 0.037 at 237 nm. These results are remarkable for two reasons. First we manage to reproduce the characteristic low quantum yield observed experimentally. Secondly we find that the dynamics associated with passage through the conical intersection can be interpreted using simple classical arguments. If the excess energy is directed along the reac- tion coordinate leading to prefulvene the quantum yield increases. If the excess kinetic (vibrational) energy is directed orthogonal to the reaction coordinate the quantum yield decreases (see Table 2). Thus sampling a larger area of the potential surface at higher kinetic energies produces trajectories that are no longer confined to the bottom of the reaction ‘valley’. Rather the initial kinetic energy will be distributed into a variety of vibrations and not just be directed toward the prefulvene region. The anomalous fluorescence of azulene -emission from S rather than S -was first recognised by Beer and Longuet-Higgins forty years ago (see refs. in 16i). Femtosecond laser studies and spectroscopic linewidth measurements have now established that complete internal conversion from S to the ground state takes place in less than a picosecond. Ab initio computations show how such ultra-fast decay can be explained by the So/S conical inter- section represented in Figure 7(b). The molecular dynamics studies suggest that the decay can take place before a single oscillation 1.JI 1.39 [1.49] c 1.49 [1.47] S1 t ,/ benzene Figure 7 Conically intersecting potential energy surfaces in benzene and azulene. (a) Shape of the S and So energy surfaces in benzene. The arrows repre- sent the MEP connecting S benzene to the product well via the conical intersection. (b) S and S,,energy profiles along the S path from the FC structure of azulene. The ab inirio and MM-VB (in square brackets) geometrical parameters and energies are reported in A and kJ mol-I respectively. Table 2 Quantum yield of prefulvene as a function of the initial vibrational kinetic energy (AE,,,) randomly distributed among the normal modes orthogonal to the reaction path The effect is shown for two values of the initial momentum along the reaction path (excess energy) Prefulvene yield (%) Excess energy Excess energy (27 6 kJ mol I) (43 1 kJ mol I) 0 00 12 7 II 3 0 002 121 68 0 003 20 10 5 0 004 23 86 0 005 08 74 0 006 04 70 0 007 04 51 0 008 00 47 E = Hartree units (1 E = 2626 kJ mol I) AEhmit (a u) m 0001 7.5 8.5 9.5 10.5 11.5 12.5 13.5 Time S1-> SO hop occurred / fs Figure 8 Azulene dynamics simulations distribution of hop times with small and large initial vibrational excess energies (AEII,) through the intersection space is completed The results of this sim- ulation are summarised in Figure 8 The average time taken to reach the hopping region is always ca 10 fs and it is the time dispersion that increases with the available kinetic energy at the hop At low kinetic energies (0 001 a u ) nearly all (observe the single peak in Figure 8) of the surface hops occur within the first half vibrational- period of their excited state lifetime (trajectory A in Figure 7b) At higher initial energies there is a much wider spread of crossing times with two clear peaks corresponding to hops earlier and later than those observed at lower energy The second peak therefore corresponds to molecules that decay after having completed the first half of a vibration along the relaxation coordinate (trajectory B in Figure 7b) 6 Concluding Remarks Excited state reactivity is controlled by three factors (a)the pres- ence and magnitude of barriers in the excited state branch of the reaction coordinate (6) the dynamics of IC or ISC as the system returns to the ground state and (c)the nature of ground state reac- tion pathways that are populated following IC or ISC The concept of the ‘photochemical funnel’ introduced by ZimmermanI4 and Michl Is can now be substantiated via both computational and exper- imental investigations Advances in computer and laser technology CHEMICAL SOCIETY REVIEWS 1996 and the introduction of new computational and experimental methodologies are yielding a new mechanistic picture of photo- chemical reactions This picture is based upon the idea that single or successive low-lying intersections provide the bottlenecks con- trolling the evolution of a photoexcited molecule from the FC region to the photoproduct valleys Both theory and experiment now indicate that such intersection mechanisms are a general feature in photochemical reactivity problems Acknowledgements This research has been supported in part by the EPSRC (UK) under grant numbers GR/J25 123 GR/H58070 and GR/K048 1 1 We are also grateful to NATO for a travel grant (CRG 950748) 7 References I See references collected in M Klessinger Angew Chem Int Ed Engl,l995,34,549 2 W TA M Van der Lugt and L J 0osteroff.J Am Chem Soc 1969 91,6042 3 M 0 Trulson and R A Mathies J Phys Chem 1990,94,5741 4 See (a)P J Reid S J Doig S D Wickham and R A Mathies J Am Chem Soc 1993,115,4754and references cited therein (b)S Pullen L A Walker 11 B Donovan and R J Sension Chem Phys Lett ,1995 242,415 5 D R Cyrand C C Hayden,J Chem Phvs 1996,104,771 6 H Kandori Y Katsuta M Ito and H Sasabe J Am Chem Soc ,1995 115,2669 7 Q Wang R W Schoenlein L A Peteanu R A Mathies and C V Shank. Science 1994,266,422 8 H Petek A J Bell R L Christensen and K Yoshiara. SPIE 1992. 1638,345 9 H Petek A J Bell Y S Choi K Yoshiara B A Tounge and R L Christensen J Chem Phvs ,1993,98,3777 10 B E Kohler,Chem Rev 1993,93,41 11 I J Palmer I N Ragazos F Bernardi M Olivucci and M A Robb J Am Chem SOC ,1992,115,673 12 W J Leigh and A Postigo,J Chem SOC Chem Commun ,1993,1836 13 E Teller Isr J Chem ,1969,7,227 14 H E Zimmerman J Am Chem SOC,1966,88,1566 15 J Michl ,J Mol Photochem ,1972,243 16 (a)P Celani S Ottani ,M Olivucci F Bemardi and M A Robb J Am Chem Soc ,1994,116 10141 (b)P Celani M Garavelli S Ottani F Bernardi M A Robb and M Ol~vucci J Am Chem Soc 1995,117 11584 (c) I J Palmer 1 N Ragazos F Bemardi. M Olivucci and M A Robb J Am Chem Soc 1994 116. 2121 (6) M Reguero M Olivucci F Bernardi and M A Robb,J Am Chem SOC,1994,116 2103. and references cited therein (e) S Wilsey M J Bearpark F Bernardi M Olivucci and M A Robb J Am Chem Soc 1996. 118 176 v> see N Yamamoto F Bernardi A Bottom M Olivucci M A Robb and S Wilsey J Am Chem Soc ,1994,116,2064,and references cited therein (8)S Wilsey M J Bearpark. F Bernardi M Olivucci and M A Robb,J Am Chem Soc ,1996,111press (h)P Celani F Bernardi M Olivucci and M A Robb,J Chem Phvs ,1995,102,5733,(1) M J Bearpark F Bernardi S Cliffort M Olivucci M A Robb B R Smith and TVreven J Am Chem SOC 1996,118,169 17 M Desouter Lecomte and J C Lorquet J Chem Phys ,1977,71,4391 18 A Gilbert and J Baggott ‘Essentials of Molecular Photochemistry’ Blackwell Scientific Publications. Oxford 1991 19 M L McKee and M Page in ‘Reviews in Computational Chemistry’ ed K B Lipkowiz and D B Boyd 1993,4,35 20 I N Ragazos M A Robb,F Bernardi and M Olivucci Chem Phys Lett 1992,197,217 M J Bearpark M A Robb and H B Schlegel Chem Phys Lett ,1994,223,269 2I P Celani ,M A Robb M Garavelli F Bernardi and M Olivucci Chem Phys Lett 1995,243.1 22 H Koppel W Domcke and L S Cederbaum Adv Chem Phys ,1984 57,59 23 B R Smith. M J Bearpark M A Robb F Bernardi and M Olivucci Chem Phys Lett ,1995,242,27 24 R S Becker K Inuzuka and J King,./ Chem Phys 1970,52,5164 25 L E Friedrich and G B Schuster,J Am Chem SOC ,1972,94,1193 26 W J Leigh and K Zeng,J Am Chem Soc 1991,113,2l63 27 M Squillacote and T C Sample J Am Chem SOC 1990,112,5546

ISSN:0306-0012    

DOI:10.1039/CS9962500321

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Glutamate and 2-Methyleneglutarate Mutase From Microbial Curiosities to Paradigms for Coenzyme B,,-dependent Enzymes Wolfgang Buckel La bo ra to rium fur Mikrobiolog ie Fac h be reic h Bio log ie Ph ilipps- Un ive rsita t D-35032 Marb urg Germany Bernard T. Golding Department of Chemistry Bedson Building The University of Newcastle upon Tyne Newcastle upon Tyne UK NE7 7RU Dedicated to H. A. Barker in his ninetieth year 1 Introduction In the late 1950s H. Albert Barker discovered a light-sensitive yellow-orange cofactor for the carbon-skeleton rearrangement of glutamate to 3-methylaspartate in Clostridium tetanomorphum a strict anaerobic bacterium fermenting glutamate to ammonia CO acetate butyrate and H,.I The enzyme catalysing this process was isolated named glutamate mutase (EC 5.4.99.1),and shown to act specifically on (S)-glutamate which equilibrated with (2S,3S)-3-methylaspartate (Scheme 1).* Barker proved that the cofactor was (S)-glutamate (2S,3S)-3-methylaspartate Scheme 1 Interconversion of (5’)-glutamate with (2S,3S)-3-methylaspartate catalysed by coenzyme B ,,-dependent glutamate mutase related to vitamin B,,,actually pseudo-vitamin BI2,by showing that treatment with an excess of cyanide gave the characteristic reddish purple dicyanocobalamin (see Box concerning cobamide nomen- clature). Subsequently dark-red crystals of the coenzyme form of vitamin B I ,were isolated from Propionibacteriutn sherrnanii and subjected to X-ray analysis which yielded the structure shown in the Box.’ The presence of a cobalt-carbon a-bond in coenzyme B (adenosylcobalamin) was an unexpected feature that would ulti- mately prove to be of crucial importance for the biological action of the coenzyme. A decade later Thressa C. Stadtman identified 2-methyleneglu- tarate mutase (EC 5.4.99.4) in Clostridium barkeri which fer- ments nicotinate via 2-methyleneglutarate to ammonia CO acetate and propionate! During this degradation the enzyme catal- yses the interconversion of 2-methyleneglutarate with (R)-3-methylitaconate (Scheme 2) and requires coenzyme B as ~~~~~~~ ~~ ~ ~ ~ ~ Wovgang Buckel studied chemistry in Munich and then moved to bioclzernistry working under F. LynenlH. Eggerer for his PhD and postdoctoral studies in which chiral acetates were developed with J. W.Cornforth. He spent 1970171 with H. A. Barker at Berkeley which stim- ulated his interests in energy metabolism and radical reac-tions in anaerobic bacteria. He has been professor of microbi- ology at Marburg since 1987 where he also cycles up and down the hills. w -o2,+R40*-02cH& K = 0.07 Me HR 2-meth yleneg lutarate 3-methylitaconate Scheme 2 Interconversion of 2-methyleneglutardte and (R)-.?-methylita- conate catal ysed by coenzyme B ,,-dependent 2-methylenegulatarate mutase cofactor. Hence the reaction catalysed by 2-methyleneglutarate mutase is very similar to that of glutamate mutase. Both enzymes remained as microbial curiosities until cloning and over-expres- sion of their genes in Esclzerichiu coli enabled the production of relatively large amounts of homogeneous ap~-proteins.~-~ Today there are three distinct classes of molecular rearrangements known to be catalysed by an enzyme in partnership with coenzyme B (see Table 1). In these reactions a migrating group X and a hydro- gen atom exchange places on adjacent carbon atoms. The reac- tions differ according to the nature of the migrating group X and the substituent Y (H or OH) at the adjacent carbon from which the hydrogen atom is abstracted. In this review we focus on the mech- anisms of the reactions catalysed by glutamate and 2-methyleneg- lutarate mutase. We aim to stimulate the reader to learn more about the fascinating chemistry of the radicals postulated as intermedi- ates in these arrangements. 2 Mechanism of Action -Initial Conclusions Early studies of coenzyme B ,,-dependent enzymatic reactions demonstrated that the essence of coenzyme function was to be found in the 5’-methylene group of the 5’-deoxyadenosyl residue bound to cobalt. It was shown by isotopic labelling that the migrating hydrogen became attached to this group leading to the supposition that 5 ’-deoxyadenosine is an intermediate. Bernard Golding studied chemistrv at Manchester. where he worked with Rod Rickards (15 u Ph D student. Pos tdoctoral work in the mid-5ixtier with Albert Esclzenmoser on the s wi-thesis of vitamin B led to investigations of the mode cf action of B coerizvmes. He i profes.wr of orguriic chemistry and currentlv head of depart-ment at Newcastle wherr he also has research group study-ing carcinogenesis arid unti-cancer drug design. arid (I bicvcle to evade the city’s trafic. 329 CHEMICAL SOCIETY REVIEWS 1996 the higher stability of the enzyme from the latter organism Box B Nomenclature Glutamate mutase is composed of two components E a dimer (E 1b Me cc:" In this review coenzyme B refers to the substance adenosyl- cobalamin (AdoCbl) in which R = 5'-deoxyadenosyl in the above structure By definition all cobalamins contain 5,6-dimethylbenzimidazole Coenzyme B is also a cobamide (i e any B ,,derivative as shown with a heterocyclic base connected to the lower ribose) In pseudo-vitamin B ,,the base is adenine connected to ribose at N-7 and ligated to cobalt at N-9 In dicyanocobalamin the 5,6-dimethylbenzimidazolehas been displaced by cyano but remains connected to ring D through the ribose-phosphate-propanolamine however the adenosyl has been replaced by a cyano group HO OH Y-' 5'-deoxyadenosyl= H& I NH2 Homolytic cleavage of the Co-C u-bond generates cob( r1)alamin and the 5'-deoxyadenosyl radical which should be reactive enough to abstract a hydrogen atom even from an unactivated position (e g methyl group) of a substrate molecule SH (see Scheme 3) The substrate-derived radical S* rearranges to a product-related radical P- which is quenched by 5'-deoxyadeno- sine with regeneration of the 5'-deoxyadenosyl radical and for- mation of product PH lo The mode of conversion of S-into Pa has been the subject of controversy At one extreme it has been pos- tulated that the rearrangement proceeds via organic radicals with cob(~)alamin as a mere spectator lo At the other extreme the cob(r1)alamin may conduct the rearrangement through organocorrinoid intermediates I I In Sections 3-7 experimental evidence pertaining to the mechanistic questions is presented leading to decisions about the mode of action of glutamate and 2- methyleneglutarate mutase It is concluded that the most likely mechanisms involve fragmentation of S. to the alkene acrylate and a carbon-centred radical (X-,i e 2-glycinyl radical for gluta- mate mutase and 2-acrylylyl radical for 2-methyleneglutarate mutase) which recombine to give P- perhaps with the assistance of cob(I1)alamin In the conclusion to this review the extension of this mechanism to other coenzyme B ,,-dependent reactions (see Table 1 ) is considered Are glutamate and 2-methyleneglutarate mutase paradigms for coenzyme B I ,-dependent enzymes? 3 Enzymology Glutamate mutase was first isolated from C tetunomorphum2 and more recently from the related C cochlearium l2 The enzymes are very similar in their properties the only significant difference being m = 107 600) and S a monomer (a,14700) The genes coding for the polypeptide chains cr and E have been cloned from both organisms in E coli they were designated as mut genes in C tetanomorph~m~-~and as glm genes in C cochleurium In both organisms the genes are clustered in the same order mutS-mutL-mutE-bma6 and glmS-glmL-glmE-bma? respectively The S-and E-genes code for the corresponding glutamate mutase components whereas the L-genes possibly code for proteins that act as molecu- lar chaperones but are not required for functional expression of the E- and S-genes in E coli The fourth gene of both clusters bma codes for the consecutive enzyme in the glutamate fermentation pathway P-methylaspartase 1(2S,3S)-3-methylaspartateammonia lyase EC 4 3 1 21 I? The deduced amino acid sequences of MutE and GlmE show 90% identity to each other but no significant simi- larity to any other known protein In contrast MutS and GlmS which are only 82% identical to each other share significant amino acid sequence similarities to domains of the cobalamin-dependent enzymes 2-methyleneglutarate mutase (see below) methyl- malonyl-CoA mutases from several microorganisms and mammals including humans (EC 5 4 99 2) as well as methionine synthase from E coli (MetH EC 2 1 1 13) The separate overexpression of the glnzE-and glmS-genes in E coli followed by simple two-step purifications led to homogenous components E and S containing not a trace of a cobamide Addition of an excess of coenzyme B to a mixture of both components immediately led to an active enzyme Activity was not only observed with mixtures of the components from the same organism but also with MutE + GlmS and GlmE + MutS which were active in the presence of the coenzyme (U Leutbecher and W Buckel unpublished) Upon gel filtration the active enzyme composed of GlmE and S eluted as a complex ~p,,which contained 1 0 coen- zyme Hence the coenzyme glues both components together This is not the case however with MutE and S which even in the pres- ence of the coenzyme separate on a gel filtration column Interestingly GlmS is able to bind the coenzyme alone albeit in sub-stoichiometric amounts (0 5 molhnol) whereas GlmE contains no trace of coenzyme after incubation with an excess of adenosyl- cobalamin followed by gel filtration The binding of the coenzyme to GlmS alone is consistent with the amino acid sequence similari- ties of MutS and GlmS with the cobalamin binding domains of other enzymes (n b the binding of the coenzyme to MutS is probably too weak to be observable by gel filtration) It should be mentioned that all these binding experiments were performed with the commer- cially available adenosylcobalamin (coenzyme B rather than with the natural coenzyme which in the case of C tetanomorphum was identified as the corresponding derivative of pseudo-vitamin B I Before the recombinant rnutases became available it was erroneously assumed by all workers in this field that the coenzyme binds to component E rather than to S Now it is obvious that the former purifications of component E from the original clostridia gave a mixture of the colourless apoprotein as well as an inactive E,U complex containing aquocobamide and cob(rr)amide most probably derivatives of pseudo-vitamin B Only GlmE was recently obtained from its native organism C cochlearium as a homogeneous highly active (specific activity 11 s I) colourless apoprotein devoid of any GlmS l4 2-Methyleneglutarate mutase was purified from C barkeri in the dark (n b the Co-C bond of adenosylcobalamin is sensitive towards light) as an apparent homotetramer (a4,267 000) containing up to two adenosylcobalamin and 0 1-0 2 cob(1i)alamin l6 In contrast to glutamate mutase the enzyme required no additional adenosyl- cobalamin for activity owing to its content of this coenzyme Upon treatment with 8 mol dm urea followed by dialysis against buffer the enzyme was completely inactivated but had lost only about half of the cobalamins Addition of adenosylcobalamin restored the activity almost completely Hence the enzyme contains at least four different cobalamin species which are distinguished by their content of 5'-deoxyadenine and by their binding to the enzyme It can be concluded that only those coenzyme B 12 molecules that are reversibly attached to the enzyme yield activity GLUTAMATE AND 2-METHYLENEGLUTARATE MUTASE-W BUCKEL AND B TGOLDlNG 33 1 Table 1 Coenzyme B,,-dependent enzymes (a b and Y are variable substituents; X IS the migrating group -OH NHT or a carbon- centred group) 7 v a-c-c-b a-c-C-bI I I I YH YH n.b. For class I1 enzymes the species on the right-hand side of the above equilibrium loses HX with the formation of bCH,CYa With ribonucleotide reductase the product is the species on the rhs of the equilibrium with X =H Substituent a b X Y Ref Class I carbon skeleton mutuses 1 Glutamate mutase EC 5 4 99 1 2 2 Methyleneglutarate mutase EC 5 4 994 4 Isobutyryl-CoA mutase EC 5 499 3 Methylmalonyl-CoA mutase EC 5 4 992 coy co C02 Me H H H H 2-Glycinyl 2-Acry late Formyl-CoA Formyl-CoA H H H H 2,9,2 1 8,1520 32 39 Class I1 elirninases 5 Propanediol dehydratase EC 4 2 1 28 H H ,CH CF OH OH 42 6 Glycerol dehydratase EC 4 2 130 H CH,OH OH OH 42 7 Ethanolamine ammonia-lyase EC 4 3 1 7 H H CH NH OH 43 8 Ri bonucleottde-triphosphatereductase c 4‘of c 1’of OH OH 28 ECI 1742 ri bonucleotide ri bonucleotide Class 111 aminornutuses 9 P-Lysine-5,6-aminomutase EC 5 4 3 3 4-(3-Aminobutyrate) H N H H 44 10 D-Ornithine-45 aminomutase EC 5 4 3 4 3-~-Alanine H NH H 44 4-( D-2-Ami nobutyrate) coenzyme Q2 cob(ii)alamin (Ado-Cl+ =5’-deoxyadenosyl) H H radical P H Ad0Ado4 H Ado4 H H H H Scheme 3 Pathway for coenzyme B ,,-dependent enzymic reactions illustrated with 2-rnethyleneglutarate as substrate SH and (R)-3-rnethylitaconate as product PH Part (a)shows conversion of SH to the substrate derived radical S. part (b) shows conversion of S-into the product-related radical P- and hence product PH (Ado-CH =5‘-deoxyadenosyl) CHEMICAL SOCIETY REVIEWS 1996 The gene rngrrz encoding the single polypeptide a of which 2- methyleneglutarate mutase is composed has been cloned sequenced and overexpressed in E cofi By comparison with other cobalamin-dependent enzymes the C-terminus (cu 100 amino acids) of the deduced amino acid sequence was identified as the coenzyme-binding domain (see above) In a manner analogous to the genes coding for glutamate mutase,rngm is followed by the gene mil coding for the consecutive enzyme in the pathway of nicotinate fermentation 3-methylitaconate A-isomerase (EC 5 3 3 6) Like p-methylaspartase this enzyme eliminates the methine hydrogen from its substrate The homogenous overproduced apo-2-methyl- eneglutarate mutase contained no trace of a cobalamin consistent with the inability of E colr to synthesise these compounds But on addition of adenosylcobalamin holo-2-methyleneglutarate mutase was immediately obtained with a specific activity twice as high as that of the enzyme purified from C hurkeri (B Beatrix 0 Zelder F Kroll and W Buckel unpublished) Furthermore the reconsti- tuted enzyme also contained no cob(1r)alamin (see above) which was erroneously suggested to be required for activity Is The apo- enzyme was shown to bind one coenzyme B,* per two polypeptides suggesting a similar structure to glutamate mutase from C cochleanurn since the size of the a-polypeptide (66 800) equals about that of E + r~ (68 500) Hence in 2-methyleneglutarate mutase the part of the enzyme containing the active site corre- sponding to subunit E of glutamate mutase apparently is fused together with the coenzyme-binding domain 4 Cryptic Substrate Stereochemistry The diastereotopic methylene protons at C-4 of glutamate and the enantiotopic methylene protons at C-4 of 2-methyleneglutarate are expected to be distinguished by the respective enzymes Isotopic labelling has revealed that H,y,is removed from glutamate,I7 whilst HRe is removed from 2-methyleneglutarate Considering the absolute configurations of the substrate and product molecules it was deduced that both enzymes cause an inversion of configuration Ado% at C-4 during the sequence of hydrogen abstraction and group migration The stereochemical data described are summarised in Scheme 4 To determine the stereochemistry of formation of the methyl groups of (2S,3S)-3-methylaspartate and (/?)-3-methylitaconate from their respective precursors all three hydrogen isotopes have been applied (R)-2-Oxo[ 3-2H I ,3-3H lglutarate was prepared by heating 2-oxoglutarate in D,O and incubating the resulting 2-0x013- 2H,jglutarate with isocitrate dehydrogenase in tritiated water After conversion into (2S,3S>-13-,H I ,3-3H)glutamate the labelled amino acid was fermented with C tetunornorphurn to give labelled butyrate from which chiral acetate was obtained applying two con- secutive Schmidt degradations The acetate contained cu 90% of the original tritium but was racemic (2S,3S)-[3-2H .3- 3HjGlutamate prepared by introducing the hydrogen isotopes in the reverse order also gave racemic acetate l9 This result supports the postulated intermediacy (see Section 2) of a methylene radical cor- responding in structure to 3-methylaspartate (cf Scheme 5) However the experiment should be repeated with purified gluta- mate mutase to exclude the possibility that the racemisation is caused by another enzyme in the multistep fermentation pathway A similar approach to that described for glutamate was used with 2- methyleneglutarate and again there was an apparent racemisation (G Hartrampf P Sanchez J W Cornforth and W Buckel unpub- lished results) In an approach intended to probe for the intermediacy of a cyclo- propylcarbinyl radical in the 2-methyleneglutarate mutase reaction (E)-2-(rnethylet~e-~HI )methyleneglutarate was synthesised and shown to equilibrate with its (a-isomer on exposure to the enzyme 2o The significance of this result is discussed in Section 8 5 Kinetic Properties Both glutamate and 2-methyleneglutarate mutase are highly spe- cific for their respective substrates Despite a wide ranging search no other substrates have been discovered * l5 23 The reason for this H AdoA ,,H H AdoAH Scheme 4 Stereochemistry of the 2 methyleneglutarate reaction (a)and glutamate mutase reaction (6) (a)HKUIS abstracted from C 4 of 2 methyleneglu tarate the abstracted H mixes with the 5’ methylene hydrogens of adenosylcobalamin the acrylate residue migrates to this C-4 with inversion of config uration (b)HStis abstracted from C 4 of (S) glutamate the abstracted H mixes with the 5’ methylene hydrogens of adenosylcobalamin the glycinyl residue migrates to this C 4 with inversion of configuration GLUTAMATE AND 2-METHYLENEGLUTARATE MUTASE-W BUCKEL AND B TGOLDING li Scheme 5 Equilibration of 2 methyleneglutarate and (R)3 methylitaconate and their corresponding radicals either rva a cyclopropylcarbinyl radical (path (I) or by fragmentation to acrylate and the 2 acrylate radical (path 6) unusual specificity could lie in the unique mechanism whereby three carbon centres are implicated in the molecular rearrange- ment Not even fluoro- or methyl-substitution of glutamate permits sub- strate behaviour although some such derivatives are inhibitory (see Table 2) l6 21-23 Of the diastereoisomeric 4-fluoroglutamates only the (2S,4S)-isomer is inhibitory presumably because the fluoro substituent replaces the hydrogen that is normally abstracted the (2S,4R)-isomer does not interact with the enzyme rac-2-Methylglutarate does not inhibit glutamate mutase whereas 2- methyleneglutarate is an active inhibitor presumably by occupying the glutamate binding site in a manner that cannot be matched by either enantiomer of 2-methylglutarate The inhibition of glutamate mutase by 2-methyleneglutarate was taken as an additional argu- ment for the intermediacy of an imino derivative in the glutamate mutase reaction I2 However the recent discovery (see Section 8) that glutamate mutase is inhibited synergistically by acrylate and glycine2l may explain this result if the key structural feature of 2- methyleneglutarate is the presence of an acrylate moiety that occu- pies the acrylate binding site Both enantiomers of 3-methylitaconate are inactive with glutamate mutase It was origi- nally reportedI that (S)-3-methylitaconate inhibits glutamate mutase but this is now known to be due to inhibition of the auxil- iary enzyme j3-methylaspartase a component of an assay system for glutamate mutase Using (S)-12,3,3,4,4-2H,]glutamate as a substrate? a kinetic isotope effect V,lV = 7 was observed whereas K = 2 4 mmol dm remained similar to that observed with the unlabelled amino acid (1 5 mmol dm 7 By applying regiospecifically labelled glu- tamates it was shown that only a hydrogen at C-4 most likely H$ which is abstracted by the 5'-deoxyadenosyl radical contributes much to the rate-limiting step 23 The isotope effect of the transfer of a tritium from the coenzyme to the substrate i Y from 5'-deoxyadenosine to the product-related radical was estimated as 13 5-18 from which a deuterium isotope effect of 6-7 4 was cal- culated In this experiment It was shown that the hydrogen was removed from the coenzyme at a rate comparable to that of its appearance in the product 3-methylaspartate This important obser- vation excludes the intermediacy of a protein-based radical in the catalytic turnover with the coenzyme acting merely as a radical ini-tiator 24 Already 25 years ago Kung and Stadtman reported a series of inhibitors for 2-methyleneglutarate mutase,2* among which ita- conate proved to be the most effective Ih An intriguing result of the earlier work was the purported inhibitory action of tram-1-methyl-cyclopropane- 1,2-dicarboxylate with the corresponding c u-isomer being less active these compounds were regarded as analogues of a presumed intermediate Using a continuous optical assay with homogenous 3-methylitaconate A-isomerase as an auxiliary enzyme it was recently shown that none of the four stereoisomers Table 2 Substrates and inhibitors of glutamate and 2-methyleneglutarate mutase rlJ' Enzyme Compound Effect Km or K,lmmol dm Ref Glutamate mutase (S) Glutamate (2R,3RS) 3 Fluoroglutamate (2S,4S) 4-F1uoroglutamate 2 Methyleneglutarate Glycine + acrylate (2S,3S) 3 Methylaspartate Substrate Competitive inhibition Competitive inhibition Competitive inhibition Inhi bition Substrate 15 06 0 07 04 CYI 5 each 05 12 12 12 12 12 21 2 Methyleneglutarate mutase 2 Methyleneglutarate (R)-3Methylitaconate Itaconate Mesaconate (methylfumarate) Succinate Acrylate Substrate Substrate Com peti tive inhi bi tion Competitive inhibition Competitive inhibition Inhibition 37 < 07 >1 >I ca 1 -10 (see text) 16 16 22 22 21 Glutamate mutase was not inhibited by (R) glutamate (R) or (S) 3 methylitaconate 4 mmol drn '(2s4R) 4 fluoroglutamate 2 methyl 3 methyl z1 4 methyl 23 N methylglutamate (10 mmol dm each) 20 mmol dm glycine 20 mmol dm acrylate 10 mmol drn '(S) aspartate ' 2 Methyleneglutarate mutase was not inhibited by 10 mmol dm (S) glutamate 15 mmol dm (RS)2 methylglutarate 20 mmol dm of all four stereoisomers of I methylcyclopropane 1 2 dicarboxylate Not determined 334 of 1-methylcyclopropane- 1,2-dicarboxylate was able to inhibit sig- nificantly 2-methyleneglutarate mutase The very recent discov- ery of the inhibitory power of the simple compound acrylate leads to an entirely new mechanistic proposal which will be discussed below The plot of the reciprocal initial velocity as a function of the acrylate concentration (Dixon plot) fitted better to a quadratic equa- tion than to a linear one This agrees well with the requirement that two acrylate molecules mimic intermediates in the 2-methylene- glutarate mutase reaction A remarkable feature of coenzyme B I ,-dependent enzymes is their apparent ability to handle safely free radicals which would be highly reactive if detached from the protein 25 The enzymes are not perfect however because they are slowly destroyed in the presence of substrate a process which is accelerated by exposure to air9 Prolonged anaerobic incubation in the dark ( I5 h 37 "C) yields the 'inactive complexes' of glutamate and 2 methyleneglutarate mutase in which the enzyme-bound coenzyme Biz has been con- verted into aquocobalamin and cob(~~)alamin (Section 6) The pres- ence of these inactive complexes in the native clostridia shows that this also happens in vivu I4-l6 It would be of interest to see whether these complexes are repaired degraded or simply washed out by the growing bacteria Remarkably the sensitivity of the coenzyme in 2-methyleneglutarate mutase towards light decreases during catalysis This experiment shows that the Co-C bond of the coenzyme the final target of light with h < 600 nm has already been cleaved during substrate turnover 6 Electron Paramagnetic Resonance Studies Electron paramagnetic resonance spectroscopy (EPR) has proved to be a powerful tool for gaining insights into the structure and func- tion of glutamate and 2-methyleneglutarate mutase According to the mechanism described in Section 2 EPR signals of cob(r1)alamin (gr,ca 2 3) and of an organic radical (g 2 00) should be observable during catalysis The first EPR spectra of the three carbon-skeleton rearranging mutases which were published in 1992,14 Is 27 clearly showed however only one 'catalytic' signal around g ca 2 1 This was generated by addition of the corresponding substrate to the EPR-silent mixture of enzyme and coenzyme Owing to the lack of sufficient amounts of enzymes and to the presence of inactive cob(1r)alaminin some preparations (see Section 3) the signals were of low resolution and therefore difficult to interpret The subsequent introduction of molecular biology into coenzyme B research led to the availability of large amounts of enzymes yielding intense EPR spectra with excellent resolution Thus addition of gluta mate to a mixture of component E with a twofold molar excess of component S (1 0-20 mg proteidsample) and a tenfold molar excess of coenzyme B I ,gave the expected signal in the g ca 2 1 region with an eightfold hyperfine splitting of the g line centred at 1 985 Comparison of this 'catalytic' spectrum with that of cob(~~)alaminrevealed similarities and differences The signal of cob(1I)alamin with g ca 2 3 was shifted to g ca 2 1 whereas the coupling constant (A = 106S G) of the eightfold hyperfine splitting of the g line was reduced to 50 G The characteristic threefold superhyperline splittings of each of the eight g lines due to coupling with the I4N nucleus of the axial base (I = 1) were not resolved The spectrum of the catalytic species was interpreted in terms of a tight coupling of the unpaired electron of cob(1I)alamin with that of a carbon-centred radical Recently the spectrum has been almost perfectly simulated by using parameters similar to those applied for the interaction of a thiyl radical with cob(i~)alamin in ribonucleo- side triphosphate reductase from LactobacilluJ leichmanni 28 The simulation of the spectrum of glutamate mutase revealed that Co" and an organic radical are coupled together by an isotropic exchange coupling which is at least 10 GHz This means that the electrons are interacting either directly via orbital overlap or indi- rectly via a super-exchanget mechanism In addition the electrons are interacting via a zero field splitting term of about 300 MHz A rough estimate of the distance between the two species gives -6 A (G Gerfen personal communication) The very similar and highly resolved spectrum obtained with 2-methyleneglutarate rnutase,' t Medinted hq orbital.. ofnnim acid re\tdue< or the w lvent CHEMICAL SOCIETY REVIEWS 1996 can be explained in the same way Interestingly the inhibitors of glutamate mutase (2S,4S)-fl uorogl utamate and 2-methylenegl u-tarate induced spectra similar but not identical to those induced by glutamate Double integration yielded spin concentrations up to ]SO% as compared to the concentration of component E These high values support the idea of a biradical being responsible for the EPR spectrum In contrast (S)-glutamate induced a spectrum with only 50% spin concentration Freeze-stopped experiments showed that glutamate induced the full EPR spectrum within less than 25 ms whereas (2S,4S)-fluoroglutamate required more than 5 s 12 Interestingly the combination of glycine plus acrylate but not the single compounds induced an EPR spectrum with glutamate mutase showing the characteristic signal at g ca 2 1 This is con- sistent with the synergistic inhibition of the enzyme by both sub- stances 21 Likewise addition of acrylate to 2-methyleneglutarate mutase afforded an EPR spectrum similar to that obtained with 2- methyleneglutarate2I or the competitive inhibitor itaconate l6 In summary the EPR spectra suggest that during catalysis the sub- strate-derived radical closely interacts with Co" Although a direct coordination of the radical by ColI should result in radical pairing and give rise to an EPR-inactive species acrylate itself could coor- dinate to Co" with the 2-glycinyl or 2-acrylate radical located nearby (see Figure 1) The nature of the axial base coordinated to the cobalt of co- enzyme B was also revealed by EPR spectroscopy p-Cresolylcobamide in the Co" state does not show the characteristic threefold superhyperline splitting of the g lines due to the absence of an axial nitrogen base (base off) Upon binding to a methyl- transferase however this splitting occurs indicating coordination to a i4N-containing ligand The latter was identified as histidine by incorporation of (imidazole-isN)histidineinto the protein Now a twofold splitting was observed due the spin 1 = 1/2 of the I5N nucleus 29 X-Ray crystallography of the coenzyme B binding domain of the methionine synthase (MetH) from E cofi directly showed the coordination of the conserved histidine residue (see section 3) to the cobalt atom 30 Mixing of unlabelled component E and glutamate with the completely isN-labelled component S yielded an EPR spectrum of the catalytic species with sharper g lines By using a histidine-requiring mutant of E cofi a I5N-labelled component S was prepared in which only the histidines remained unlabelled Its EPR spectrum could not be distinguished from that of the completely unlabelled component S indicating the coordination of a histidine to the cobalt Upon formation of cob(r1)alamin by prolonged incubation of the completely labelled component S with unlabelled component E and glutamate the typical twofold superhyperfine splitting of the g lines was observed demonstrating that a histidine also coordinates to the inactive species 31 The conserved histidine residue 359 of 2-meth- yleneglutarate mutase which was identified by sequence alignment with methionine synthase? * 30 was converted into a glutamine residue by site-directed mutagenesis The resulting mutant was completely inactive since it was not able to bind coenzyme B Furthermore wild type 2-methyleneglutarate mutase is also active when combined with adenosyl-p-cresolylcobamide,demonstrating the low importance of the axial base of the coenzyme for biological activity (E Stupperich F Kroll and W Buckel unpublished) H adoTH H &7 Figure 1 Postulated intermediate state in the glutamate mutase reaction showing an acrylate cob(ii)alamm complex GLUTAMATE AND 2-METHYLENEGLUTARATE MUTASE-W BUCKEL AND B TGOLDING (la-3a) matching in structure the species proposed as intermedi- ates in the 2-methyleneglutarate reaction (see Scheme 6),gave pn- manly di-tert-butyl 2-methyleneglutarate presumably via the corresponding free radicals The bromides were also reacted with glutamate glutamate dehydrogenm NADH + NH4+1 '"C cobaloxime(I) which gave the alkylcobaloxime lb from bromides la and 3a and the alkylcobaloxime 2b from bromide 2a Alkylcobaloxime 2b did not readily rearrange into alkyl-cobaloxime lb It was therefore proposed that this lack of reactiv- ity of organocobalt species 2b compared to the corresponding free H T D radicals supports the mechanism of Scheme 6 path a (see also loenzymes'2' Scheme 3 and Section 8) Murakami and his coworkers have described attempts to model glutamate mutase by preparing an organocorrinoid bearing an alkyl group derived from 3-methylaspartate and photolysing this mater- ial in a micellar matrix to give glutamate in low yield 35 This is the only model system to achieve the conversion of 3-methylaspartate into glutamate but further studies are needed to elucidate the reac tion pathway 8 Mechanism of Action -Decision For 2-methyleneglutarate mutase model studies (see Section 7) supported a mechanism in which the substrate-derived and product- related radicals are interconverted via an intermediate cyclopropyl- carbinyl radical (see Scheme 6 path a) A similar mechanism was however impossible for glutamate mutase because of the lack of suitable .rr-bond with which the radical centres in S. and P. could interact The proposal7 that such a n-bond could be generated by formation of an imine from the amino group of glutamate and a car- bony1 function within the protein cannot be sustained (see Section 3) Furthermore a mechanism whereby the 2-glycinyl moiety migrates via a bridged transition state can also be excluded because of the predicted high energy of such a species M However the dis- covery of synergistic inhibition of glutamate mutase by glycine and acrylate gave the first experimental support for a fragmen-tation-recombination mechanism for this enzyme (Scheme 7a) already proposed many years ago 36 37 The similarities between 2 methyleneglutarate and glutamate mutase with respect to the reac- tions catalysed enzymes cofactor and EPR data point to a commonality of mechanism We have therefore proposed frag- mentation-recombination mechanisms for both of these enzymes in which acrylate is a common intermediate 21 Such a mechanism for 2-methyleneglutarate mutase arose during our studies of the four isomers of 1 -methylcyclopropane- 1,2-dicarboxyIates as potential inhibitors of 2-methyleneglutarate mutase The surprising failure of any of these compounds to inhibit 2-methyleneglutarate mutase and especially the inactivity of the (R,/?)-isomer led us to re-evalu- ate the long-held mechanistic hypothesis of Scheme 6 path a The startling discovery that 2-methyleneglutarate mutase is inhibited by acrylate,2' with a square dependence on acrylate concentration sup- ports the mechanism of Scheme 6 path b for this enzyme (see also Scheme 76) The stereochemical features of the glutamate and 2-methylene- glutarate mutase reactions (see Section 4) are fully explicable by the mechanisms of Scheme 6 path 6 and Scheme 7 The stereo chemistry of the initial hydrogen abstraction will be governed by the precise positioning of the adenosyl radical with respect to the protein-bound substrate The fact that H is removed from gluta- mate whilst HReis removed from 2-methyleneglutarate is not sur- prising even though the active sites of the enzymes may be similar Thus a 120" rotation about the C(3)-C(4) bond causes a lateral movement of the carboxylate of only ca 2 8 and serves to present either H or HRU to the adenosyl radical Small differences in TD butyrate (2s 3S)-J-methylaspartate (2S)glutamate 2 x Schmidt dagradatmnI T 4 steps V 2-methykneglutarate mutaseHi&'" c-coenzymeBl2D T(3R)-3-methylitaconate 2-mthylenaglutarate Scheme 6 Syntheses of (2S,3S) [3 2H,3 3H]glutamate and (3s)2 methyl enel 3 'H.3 ?Hjglutarate their conversion to chiral methyl labelled (2S,3s)3 methylaspartate and (3R) 3 methylitaconate respectively and the degradation to chiral acetates The conversion of glutamate to butyrate was performed with growing cells of C tetunomorphurn Recently the coordination of a histidine nitrogen to cobalt within the enzymes catalysing carbon-skeleton rearrangements has been confirmed by the crystal structure of methylmalonyl-CoA mutase from P shermanii revealing an extraordinary long Co-N distance of 2 53 A The observed 0 32 A difference from the corresponding Co-dimethylbenzimidazole bond length in free adenosylcobalamin (2 21 A)is thought to facilitate homolysis of the Co-C bond 32 It would be of interest to measure the Co-N distance in methionine synthase which catalyses heterolytic cleavage of the Co-methyl bond 7 Model Studies Possible mechanisms for the equilibration of 2-methyleneglu- tarate with 3-methylitaconate catalysed by 2-methyleneglutarate mutase are shown in Scheme 6 33 The key intermediate in path a is a cyclopropylcarbinyl radical which by cleavage of its C( 1)-C(2) bond connects with the substrate-derived radical whilst cleavage of the C( 1)-C(3) bond leads to the product-related radical (cf Scheme 3) There is ample precedent for these processes in non-enzymatic chemistry Thus conversion of the cyclopropylcarbinyl radical to the but-3-enyl radical is one of the fastest unimolecular reactions known (k = los s I at 298 K) whilst the reverse reaction is also relatively fast (k = lo3s I at 298 K) Many examples of these types of interconversion have been descnbed in which the butenyl or cyclopropylcarbinyl system bears alkyl aryl and/or ester substituents 34 It has been shown33 that treatment with triphenyltin hydnde of each of the bromides H.. Co+Bu tB?73 "pX t Bu@C la X=Br 2a X=Br 3a X=Br 1b X = Co(dmgHhpy 2b X = Co(dmgHkpy 3b X = Co(dmgHkpy CHEMICAL SOCIETY REVIEWS 19% 11 li H.. H 11 H a b Scheme 7 Proposed reaction pathways for coenzyme B ,,-dependent reactions CoA mutasej (from ref. 21). protein structure especially with respect to the positions of car- boxylate-binding functions could suffice to bring about this alter- ation. Fragmentation of the substrate-derived radical requires a specific conformation in which its C(2)-C(3) bond is nearly parallel to the p orbital at the radical centre (see Scheme 7). This leads to acrylate and a 2-glycinyl radical from glutamate and acrylate and the 2- acrylate radical from 2-methyleneglutarate. Addition of the 2- glycinyl radical to the Re face at C-2 of acrylate leads to a product-related radical of correct stereochemistry [i.e. that corre- sponding to (2S,3S)-3-methylaspartate1. Provided that addition of the 2-acrylate radical occurs to the Si face of acrylate a product- related radical of correct stereochemistry is also generated [ i.e. that corresponding to (R)-3-methylitaconate 1. Both processes lead to the observed inversion of configuration at the centre from which hydro- gen is abstracted and to which a group migrates. Throughout the processes described the migrating group remains in contact with a particular face of the acrylate molecule. The observed equilibration of (E)-(methylene-2H,)2-methyleneglutarate with its (2)-isomer catalysed by 2-methyleneglutarate mutaseZ0 (see Section 4 and Scheme 6) can be explained by noting the linearity of the 2-acrylate radical and postulating a time dependent rotation of this radical either about the C( I)-C(2) bond or the C( I)-C(Z)-C(3) axis that is slower than substrate turnover (see Scheme 6 path h).This result however is also consistent with the intermediacy of a cyclopropyl-carbinyl radical (Scheme 6 path a).The fragmentation-recombi- nation route discussed for the Class I enzymes glutamate and 2-methyleneglutarate mutase (see Table 1) can be immediately ;*2-H$co H CoAS 0 H H CoAS-( 0 C I (a)glutamate mutase; (b)2-methyleneglutarate mutase; (c) methylmalonyl-applied to methylmalonyl-CoA mutase (Scheme 7c) with acrylate and the 2-formyl-CoA radical as intermediates. In support of this proposal recent studies in Karlsruhe have shown that methyl- malonyl-CoA mutase is synergistically inhibited by acrylate and formyl-CoA (A. Abend and J. Rktey personal communication). The mechanism shown in Scheme 7ccontains a stereochemical subtlety. In contrast to the glutamate and 2-methyleneglutarate reactions which both proceed with inversion at C-4 of substrate the transfor- mation of methylmalonyl-CoA to succinyl-CoA takes place with retention of configuration at the corresponding carbon centre. This observation can be explained if the acrylate exists in two confor- mations (see Scheme 7c) which interconvert by rotation about their C( l)-C(2)-bond. This enables 'the error in the cryptic stereochem- istry of methylmalonyl-CoA mutase'17.38 to be understood. In addi-tion to the expected migration of H at C-3 of succinyl CoA to the methyl group of methylmalonyl-CoA the 'exchangeable hydrogen' at C-2 of methylmalonyl-CoA migrated to C-3 of succinyl-CoA. To elucidate this result a 1,2-hydrogen shift in the intermediate suc- cinyl-CoA radical was invoked but it can be better explained if there is an occasional removal of H,! from C-3 leading directly to the correct acrylate conformation for further elaboration to (R)-methylmalonyl-CoA.2' Recently it has been shown that isobutyryl- CoA muta~e,3~ to which the fragmentation mechanism may also be applied proceeds with retention of c~nfiguration.~~ The stereo- chemical 'error' made by this enzyme which has to handle propene according to the fragmentation-recombination mechanism is even more pronounced than that observed with methylmalonyl-CoA mutase. GLUTAMATE AND 2-METHY LENEGLUTARATE MUTASE- W BUCKEL AND B TGOLDING 9 Concluding Comments Remarkably the coenzyme B ,,-dependent eliminases and amino- mutases (Table 1 ) have coenzyme B ,,-independent counterparts which catalyse essentially identical reactions The existence of several coenzyme B ,,-independent ribonucleotide reductases is well established ** In addition a coenzyme B ,,-independent but iron- containing diol dehydratase has been reported The iron-sulfur dependent lysine-2,3-aminomutase also uses the 5’-deoxyadenosinyl radical but this reagent is derived from S-adeno- sylmethionine (SAM the “poor man’s coenzyme B,,”) 41 On the other hand no coenzyme B ,,-independent counterpart to the carbon- skeleton mutases (Class I ,Table 1) has been discovered yet This may due to the fact that only the Class I enzymes require Corifor coordi- nation of the acrylate in order to enable the addition of the radical fragment to the a-carbon of this intermediate,leading to the branched products Hence in these enzymes Coilmight act not as a mere spec- tator but as a conductor of the catalysis In contrast the Class I1 and 111 enzymes apparently require coenzyme B ,,only as a generator of 5 ’-deoxyadenosyl radicals The intermediacy of such a hypothetical Coil-acrylate 7r-complex (Figure 1) in the catalysis of the carbon- skeleton mutases causing the enhancement of the reactivity of the a-carbon of acrylate remains however to be established Soon after his discovery of glutamate mutase H A Barker wrote ‘the precise role of the coenzyme in the interconversion of gluta- mate and P-methylaspartate is not yet known’ I Nearly 40 years later one may begin to understand Acknowledgements This work was supported by grants from the Engineering and Physical Sciences Research Council Commission of European Communities Deutsche Forschungsgemeinschaft and Fonds der Chemischen Industrie The authors wish to thank their coworkers Birgitta Beatrix Harald Bothe Gerd Broker Chris Edwards. Friedrich Kroll and Oskar Zelder for their enthusiasm in performing the latest experiments leading to new insights into the mechanism of action of coenzyme B 10 References I H A Barker. H Weissbach and R D Smyth Proc Narf Acad Sci USA 1958,44.1093 2 R L Switzer In ‘B,2’. ed D Dolphin Wiley New York 1982 vol 2. p 289 3 P G Lehnert and D C Hodgkin. Nature. 1961,192.937 4 H F Kung,S Cederbaum.L Tsai andT C Stadtman,Proc Narl Acad Sci USA 1970.65,978 5 E N G Marsh and D E Holloway FEBS Letr 1992,310 167 6 D E Holloway and E N G Marsh J Biol Chem . 1994,269,20425 7 M Brecht J Kellermann and A Pluckthun. FEBS Lett 1993,319,84 8 B Beatrix 0 Zelder D Linder and W Buckel Eur J Biochem 1994 221,101 9 0 Zelder B Beatrix U Leutbecher and W Buckel Eur J Biochem 1994,266,577 10 B T Golding Chem Br .1990,26,950,and references therein 11 E I Ochiai in ‘Metal Ions in Biological Systems’ ed H Sigel and A Sigel Marcel Dekker New York 1994,vol 30 p 255 12 U Leutbecher R Bocher D Linder and W Buckel Eur J Biochem 1 992,205,759 13 H A Barker R D Smyth R M Wilson and H Weissbach J Biol Chem 1959,234,320 14 U Leutbecher S P J Albracht and W Buckel. FEBS Lett 1992.307 144 15 C Michel S P J Albracht and W Buckel Eur J Biochem ,1992,205 767 16 0 Zelder and W Buckel Biol Chem Hoppe Seyler 1993,374,85 17 J Retey and J A Robinson ‘Stereospecificity in Organic Chemistry and Enzymology’ Verlag Chemie Wernheim 1982,and references therein 18 G Hartrampf and W Buckel Eur J Biochem 1986,156,301 19 G Hartrampf and W Buckel FEBS Lett 1984,171,73 20 C Edwards B TGolding F Kroll B Beatrix. G Broker and W Buckel J Am Chem Soc 1996,118,4192 21 B Beatrix 0 Zelder F Kroll. G Orlygssoti B TGolding and W Buckel Angew Chetn Int Ed Engl 1995,34,2398.and references therein 22 H F Kung and T C Stadtman,J Bid Chem 1971,246,3378 23 B Hartzoulakis and D Gani Proc Ind Acad Sci (Chem Sci 1 1994 106,1165 24 E N G Marsh Biochemistrv 1995,34,7542 25 J Retey,Angew Chem 1990,102,373 26 C Michel and W Buckel FEBS Left 1991,281,108 27 Y Zhao,P Suchand J Retey,Angew Chem 1992,104,212 28 S Lrcht G J Gerfen and J Stubbe Science 1996,271,477,and refer ences therein 29 E Stupperich H J Eisinger and S P J Albracht Eur J Biochem 1990,193,105 30 C L Drennan S Huang J T Drummond R G Mathews and M L Ludwid Science 1994,266 1669 31 0 Zelder B Beatrix F Kroll and W Buckel FEBS Lett 1995,369 252 32 F Mancia. N H Keep A Nakagawa. P F Leadlay S McSweeney. B Rasmussen P Bosecke,O Diat and P R Evans.Structure 1996.4.339 and references therein 33 S Ashwell A G Davies B TGolding R Hay Motherwell and S Mwesigye Kibende J Chem Soc Chem Commun 1989,1483 34 D C Nonhebel Chem Soc Rev 1993,22,347 35 Y Murakami Y Hisaeda X M Song and T Ohno J Chem Soc Perkin Trans 2 1992,1527 36 B T Golding and L Radom J Am Chem SOC 1976,98,6331 37 B T Golding in ‘B,?’ ed D Dolphin Wiley. New York 1982,vol I p 543 38 W E Hull,M Michenfelderand J Retey,Eur J Biochem ,1988,173,191 39 B S Moore R Eisenberg C Weber A Bridges D Nanz and J A Rob1nson.J Am Chem Soc 1995.117 11285 40 M G N Hartmanrs in ‘Metal Ions in Biology’ ed H Sigel and A Sigel Marcel Dekker New York 1994. vol 30. ch 7 p 201 41 P A Frey. FASEB J . 1993.7,662 42 T TorayaandS Fukui,in ‘Blz’,ed D Dolphin,Wrley,New York 1982 vol 2,p 233 43 B M Barbior in ‘B,2’ ed D Dolphin Wiley New York 1982,vol 2 p 263 44 J J Baker and T C Stadtman in ‘BIZ’ ed D Dolphin Wrley New York. 1982.~012,p 203

ISSN:0306-0012    

DOI:10.1039/CS9962500329

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

’Covalent’ Effects in ’Ionic‘ Systems Paul A. Madden and Mark Wilson Physical and Theoretical Chemistry Laboratory Oxford University South Parks Road Oxford UK 0x1 3QZ 1 Introduction How wide is the range of applicability of an ionic model of con- densed phase structure energetics and dynamics? The question is posed for practical reasons as well as for its intrinsic interest. For our purposes a system which is ‘ionic’ is one whose properties are reproduced by an interaction model based upon discrete closed- shell ions with integer charges. These ions are not simply charged hard-spheres; they may undergo polarization (induction) and dis- persion interactions and may even undergo changes of size and shape (‘compression’ and ‘deformation’) due to interactions with their neighbours. What is excluded is charge transfer and chemical bond formation involving the sharing of pairs of electrons between atoms. It is well-known that the domain of applicability of the sim- plest ionic model as embodied in Born-Mayer type pair potentials -essentially a model of charged hard-spheres -is severely restricted even the structure of a material like MgCl is not explained despite the large electronegativity difference between the elements involved. Our purpose here is to explore the properties of an extended ionic model which allows for the changes in an ion’s properties which are caused by changes in its environment and hence incorporate a many body character in the interactions. Among such effects are polarization compression and deformation. We will show how they may account for many departures from the predictions of the simple ionic model which are conventionally attributed to ‘covalency’. The reason that the question is a practical one is that such an ionic interaction model has two important characteristics. Firstly it may be used as the basis of tractable computer simulation methods which permit the study of large systems for long times. Such studies are often necessary for an understanding of material properties and many materials of technical interest lie in the domain where ‘cova- lent’ effects are prevalent. The MgCI example is the support for the Ziegler-Natta catalyst used in polypropylene synthesis and its crystal surface properties are therefore of interest. More fundamen- tally because it is based upon the properties of individual ions the ionic model is (or should be) transferable -it may be used on dif- ferent phases of the same material on mixtures and furthermore the interaction model for one material should be recognisably related to that of a chemically similar one by a change in ion size or similar property. A transferable model may be tested on one phase and used on another tested in the bulk and used for a surface etc. Because of the relationship between materials the origin of Paul Madden is a Professor of Chemistry at Oxford University and a Fellow of Queen’s College. He was born in Bradford and obtained his BSc and DPhil at the University of Sussex the latter supervised by Prof. J. N. Murrell. After a period of eight years at Cambridge. and two at the Royal Signals and Radar Establishment (Malvern) he took up his present position in 1984. He was the recipient of the Tilden Medal of the Royal Society of Chemistry in 1993. structural trends may be understood and a first guess at an interac- tion model for one material may be constructed from an established model for another. Born-Haber cycles may be constructed to analyse energetics. The long-standing difficulty with examining the applicability of the ionic model (including the many-body effects) is that the indi-vidual ion properties which determine the interionic interactions in condensed phases cannot be determined from experimental data at least not without further assumptions. However it is now possible to perform electronic structure calculations to determine the prop- erties of single ions within their condensed phase environment. This breaks the impasse and allows an ionic model to be parameterised unequivocally. Recently it has been shown how interaction models which allow for an accurate representation of the many-body effects uncovered by such calculations may be constructed and used in tractable computer simulation schemes.I The basic physics included in these models is the same as in a (breathing) shell model the difference being that the shell model3 makes use of a particular mechanical representation of the many-body effects in order to allow the model’s parameters to be determined empirically (effectively an alternative way of breaking the impasse). However in so doing it enormously reduces the flexibility available to accu- rately reproduce the many-body effects a limitation which becomes clear when comparing with the results of electronic structure calcu- lations of ionic properties (such as induced dipoles).’ We begin with an account of the origin of the many-body effects of the way in which they may be characterised in electronic struc- ture calculations and of their representation in the simulation context. We will then illustrate their role in accounting for various phenomena attributed to ‘covalency’. In this we will focus on crystal structure and energetics since this application provides the most readily appreciated sense of progress but note that the simu- lation methods are also applicable to melts and dynamics. 2 Environmental effects and the resulting many-body potentials To understand the interactions it is not sufficient to think of the con- densed phase as a collection of well-defined gas-phase species. A van der Waals material such as a rare gas or molecular solid can be quite accurately modelled this way but in ionic materials the ions themselves are profoundly influenced by their enviroment . The Mark Wilson was born in Derby. He obtained his BA from Keble College Oxford and his DPhil (supervised by Paul Madden) in 1994. He was then awarded an Alexander von Humboldt Fellowship which he took up at the Max-Planck Institute in Stuttgart. At the time of publira-tion of this article he becomes a Royal Society Research Fellow in the Physical and Theoretical Chemistry Laboratory at Oxford. 339 oxide ion for example is unstable in the gas-phase but commonly occurs in condensed matter Because of this the interaction of one ion with another cannot be expressed without reference to the envi- ronment in which each ion is found Consequently interaction potentials must be expected to have an explicit many-body charac- ter -unlike the van der Waals case where pair potentials (which may implicitly include the average effects of many-body interac tions) are the norm To gain more insight into the environmental effects we consider the potential V(r),experienced by an electron in an i0n4-6 due to both electrostatic interactions with the charges of the other ions in the crystal and to its exclusion from the region occupied by the elec- tron density of neighbouring ions As illustrated in Figure 1 in a perfect cubic crystal this environmental potential contains a spher- ical part Vo(r),plus an angularly dependent potential which varies rapidly with the orientation of the electronic position r When expressed as a spherical harmonic expansion this angular part involves terms of angular momentum 1 = 4 or higher see eqn (2 1) V(r) = V&) V/(d y/ (2 1)+/Z4; Since the ground electronic state of a closed shell ion is an S state the angular potential will only be significant to the extent that it can mix in excited states of G symmetry For many ions (especially s-p valence ions) such states are likely to be very far in energy from the ground state so that only the spherical potential plays any role -the electron density of such ions is unable to adjust to the angularly dependent part of the potential and the electron density of the ion remains spherical The spherical potential V tends to compress their electron density relative to that of the free ion as illustrated in Figure 1 It leads to a marked reduction of the polarizability inter and is responsible for the stability of the oxide ion in con-densed matter for cations. the effect is much smaller 2.1 Ion compression in perfect crystals As the crystal is compressed there will be an increase in the overlap between the charge densities of nearest neighbour anions and cations as illustrated in Figure 2 This will lead to an increase in the energy of the system which we will call U0,,because closed shells c---.)R Figure 1 Origin of the spherical confining potential V,,,which acts on the electrons around an anion in a cubic crystal the electrons in sp valent ions are unable to respond to the rapid angular variation in the potential illus trated by the dashed contour in the upper panel In the lower panel a cross section through the spherical potential V, is shown the dashed line shows the coulombic (Madelung) contribution associated with the point ionic charges This is enhanced by the exclusion from the region occupied by the electron density of the other ions V compresses the free anion charge density (lightly shaded) to the in crystal charge density (heavily shaded) CHEMICAL SOCIETY REVIEWS 1996 may not overlap due to the Pauli exclusion principle If we take electron densities to decay exponentially and the total overlap energy to be the sum of the overlap energies associated with each cation-anion pair then referring to Figure 2 the energy would depend on the total hatched areas associated with the overlapping charge clouds We would therefore have something like eqn (2 2) u<,,= 11 A expl (TIJ q q4p + PJ)l (2 2) 1 /(-I) z e a pair potential of Born-Mayer form to describe the interionic repulsion Here rrJis the separation between i andj u,is a charac- teristic radius for the charge density of ion I and p describes how it falls off with increasing distance from the nucleus To justify this pair potential we have regarded the ions as fixed entities as the crystal is compressed so that the extent of overlap increases as in Figure 2(6) In general what should be anticipated is that as the crystal is compressed the walls of the spherical confining potential will move in and each ion will adjust by shrinking its charge density as illuctrated in Figure 2(c) where the area of overlap is reduced below what would be found with fixed charge densities Hence parameters like p and u,,which reflect the size and shape of the charge density should themselves be regarded as depending on the separation between the ions a,-a,([rNj),etc (where ([rNl)is R' Figure 2 Illustration of the ion compression effect Panel (a)shows the anion charge density (dense shading) in the crystal at lattice spacing R. as confined by V The electron densities of the first cation shell are shown lightly shaded and the region of cation-anion overlap is hatched After shrinking the crystal (to lattice spacing R') the hatched area increases (b) (corresponding to increased repulsion) but the amount of overlap is much reduced las in (c)l if the compression of the anion charge density by the modified confining potential is accounted for The change in shape of the anion charge density gives rise to the self energy ‘COVALENT’ EFFECTS IN ‘IONIC’ SYSTEMS-P A MADDEN AND M WILSON 34 1 intended to imply a dependence on the positions of N other ions in the sample) and the overlap potential acquires a many-body char- acter eqn (2 3) u v = A expI (“ u,IrNl fl,[rNl)h?[rNl+ p,IrNI)I (2 3) This shrinkage of the ions under the influence of the confining potential itself costs energy which might be called a ‘self energy’ or ‘rearrangement energy’ -the energy required to place each ion in the confining potential associated with a particular lattice para meter -and the total energy associated with compressing the crystal written as eqn (2 4) This observation provides a well-defined and practical route for examining the interactions appropriate to ions in the cubic crystal The electronic wavefunctions of an anion and cation confined by the spherical potentials V appropriate to the crystal of interest at a particular lattice constant R is calculated The difference between the energy of this confined ion and the free one gives the self-energy appropriate to lattice constant R The interaction between pairs of these entities is then calculated without further wavefunction relaxation In this way a pair overlap induced-repul- sion potential appropriate to R is obtained Such calculations have been carried out by Pyper5 and his results for Uovand Uselffor an oxide ion in MgO are shown in Figure 3 Results for the MgO in the six-coordinate rocksalt (B l) the eight-coordinate caesium chlo ride (B2) and four-coordinate blende (B3) structures as a function of the lattice parameter R are shown For the oxide ion the self- energy goes to a plateau at large R this is because the free oxide ion is unstable with respect to 0-plus a free electron so that for the oxide ion we must consider the process of placing an 0 ion and an electron in the confining potential rather than simply a free ion The plateau therefore reflects the electron affinity of 0 Note that the self energy is a large component of the total repulsive potential which resists the compression of the crystal Why should we worry about separating the total repulsive energy in this way’ After all the total repulsive energy for say the B1 phase could still be fitted to a sum of pair potentials by dividing the total repulsive energy involving cations and anions U, + Uself amongst the six nearest-neighbour pairs The problem is that this representation would not transfer to ionic environments other than the perfect rocksalt structure Figure 3 shows that U and Usel+.have difSerent dependencies on conrdinatioiz number so that a pair poten- Rlau 101 30 I . 40 . . 50 * . 60 I020 h 1015 08 C 010; (5 06 005 3 ZI 3 000 04 02 00 30 40 50 60 Rlau Figure 3 Ah initlo data for the self energy of an oxide ion (upper family of curves) and for the overlap energy (lower) as a function of the lattice parameter R In four (B3 crosses) six (BI plusses) and eight coordinate (B2,circles) structures for MgO as calculated by Pyper The inset shows the pair potentials calculated from this data for each structure note that these exhibit a coordination number dependence The solid lines in the main figure show the values calculated from the CIM potential which was fit to the B1 data tial calculated with the BI data would be different from that required to fit the B2 or B3 results Hence this pair potential would not be transferable between the different phases of MgO Pair potentials appropriate to each phase obtained from the correspond- ing values of U + Uself,are shown in the inset to Figure 3 and clearly differ However a compressible ion model (CIM) which allows for the dependence of the u values on the coordinates of other ions can be fitted to the data for the rocksalt structure It accu rately predicts the ab initio data for U and Uselfin the other struc- tures? as shown by the solid lines in Figure 3 This model can be used in tractable simulations in place of the pair potential For details the reader should refer to ref 7 The same physical effect of ion compression has traditionally been accounted for in breathing shell models ,2 but these are normally parameterised empirically For halide ions Uselfis found to make a smaller contribution to the total Urepthan is the case for oxidess (reflecting the greater sen sitivity of the oxide ion to environmental effects) Hence for halides we can anticipate that pair potentials will have a wider domain of applicability than is the case for oxides which is consistent with the finding that crystal-parameterised Born-Mayer pair potentials were found to give a good representation of the interactions in alkali halide melts inter alia 2.2 Less symmetrical environments The perfect crystal provides a good reference point for the discus- sion of environmental effects -an ion in a melt is much more like the in-crystal ion than a gas phase one Nevertheless to adequately model melts and surfaces a consideration of environmental effects in much less symmetrical environments than the crystal is required A convenient starting point is to consider how the perfect crystal picture illustrated in Figure 1 is modified when some of the neigh bouring ions are shifted off their lattice sites The spherical har monic expansion of the environmental potential will now in general contain angular momentum 1 = 1,2 components as well as having a modified spherical term As long as the argument -that high angular momentum electronic states are very remote and hence unimportant -remains valid it will be sufficient to consider the effect of the altered l = 0 1 and 2 potentials The l = 0 amounts to a change in the spherical confining potential we discussed above and may result in a change in ion size The 1 = 1 and 2 terms cause deformations of the ionic electron density of dipolar and quadru polar symmetry respectively These may have two consequences Firstly the central ion will acquire a non-zero electric dipole and quadrupole moment which will alter its energy through coulombic interactionswith the charges and multipoles of other ions this is the polarization energy lo Secondly the ion may become non spherical (‘deformed’) as perceived through the short range overlap interac tions with its near neighbours 2 2 I Polarization efsects Polarization effects can be characterized by examining directly using electronic structure methods the induced multipoles on ions in distorted crystals There are some technical problems associated with assigning the displaced charge to a particular ion but these may be overcome II If an ion in the crystal at a relatively large distance (say greater than next-nearest neighbour separation) from the central ion is dis placed off its lattice site its effect on the potential felt by the elec trons in the central ion is simply that of the electric field (1 = 1 ) and field-gradient(1 = 2) at that site There will be induced dipoles and quadrupoles given by the usual multipole expansion,I0 eqn (2 5) where the superscript ‘as’ means that these moments are appropri ate when the sources of the fields are asymptotically far away from ion i Here (Y and C are the dipole and quadrupole polarizabilities and B is the dipoledipole-quadrupole hyperpolarizability the components of a,C and B are specified by a single number for a spherical ion lo These polarizabilities are those appropriate to the ion in its crystalline environment and as already remarked may be much smaller than the free-ion values6 due to the confinement effects Ea and Em are components of the field and field gradient respecti vel y If a near-neighbouring ion is displaced there is an additional effect Figure 4 shows what happens to the confining potential around an anion familiar from Figure I when one of the first shell of cations is displaced outwards Besides the field and field gradi- ent (related to the gradient and curvature of the potential at the origin) a dent appears in the confining potential Whilst the field and field gradient tend to push the electrons in one direction (away from the displaced cation) this 'dent-in-the-wall'll allows them more freedom to move into the space vacated by the cation Hence there is a short-range contribution to the induced dipole pf" which opposes the 'asymptotic' dipole caused by the electric fields This has been studied in electronic structure calculations The effect is substantial The dipole induced by displacing first neighbour cations is reduced below that expected from the asymptotic term alone by ca SO% For induced quadrupoles the effect is even larger the limited evidence available suggests that the short-range term is as large as the asymptotic one so that the net quadrupole on the anion can be very small or even opposite in sign to the asymptotic quadrupole In principle the experimental manifestation of these two effects could be studied in the far-infrared spectra of disordered ionic systems So far as we know this has not been done quantitatively However analogous effects contribute to the polarizability fluctua- tions responsible for light scattering and good agreement has been demonstrated between calculatedI2 and experimental spectra I Normally we think of the anion as the polarizable entity in ionic systems however in some cases cation polarization can also become important For cation polarization the relative sign of the short-range and asymptotic moments is the same -the short-range effect therefore enhances the dipoles and quadrupoles above the values which would be expected from the coulombically induced moments If we consider Figure 4 but reverse the signs of the charges on the ions so as to make the central ion a cation we can see why As a neighbouring anion is Figure 4 Origin of the 'asymptotic' and 'short range' contributions to the dipole induced in an anion in a crystal which has been distorted by an outward displacement of one of the first shell cations A cross section of the confining potential is shown for the undistorted crystal (dashed) and after the distortion where the 'floor' of the potential well has acquired a gradient (the electnc field) and the wall of the confining potential has been pushed outwards These have opposite effects on the electron density Note the arrows represent the direction of the electron displacement and therefore strictly are antiparallel to the associated dipoles CHEMICAL SOCIETY REVIEWS 1996 displaced outwards the electric field generated will tend to dis- place the cation electrons towards the displaced anion which is also the direction favoured by the displacement of the cation charge cloud Again this consideration is true of the higher order multipoles It makes the role of cation polarization much more substantial than would be suggested by a simple consideration of the relative size of the cation and anion polarizabilities 2 2 2 Deformation of ionic shape The development of the multipoles in the less symmetrical struc- tures is a signal that the ion's charge cloud has been distorted from a spherical shape The polarization energy results from the classical coulombic interaction of the mu1 tipoles with the charges and multi- poles of other ions The deformation of the spherical charge density will also have another manifestation since it will affect its overlap with the charge densities of the neighbouring ions and hence it will charge the short-range repulsive interaction with them This effect is contained within the shell model of the interionic interactions The shell is the centre of repulsive interactions and it may be displaced from the ion's centre of mass (and the site of its formal charge) by repulsive interaction -hence the ion may become anisotropic A potential difficulty with this approach is that this same displacement is closely tied in the shell model to the short-range effect on the induced electric dipole which was discussed above A1though these phenomena are clearly linked we believe on the basis of a limited set of ab inirio results that the connection imposed by the shell model is overly restrictive and that to accurately represent them the short-range induced dipole and the consequence of the non-spherical deformation on the short-range repulsion should be treated as separate phenom- ena This may be done by generalising the treatment of compressible ions indicated in section 2 1 Compression was treated by allowing the ionic radius to depend on the relative position of a number of other ions To allow for a deformation of dipole symmetry a vector property of each ion &[rN]is introduced which again depends upon the positions of the other ions in the sample as illustrated in Figure 5 The overlap energy is now given by eqn (2 6)14 -A expI (rVaflrNlglpl S1lrNl)l(p,lrNl(JI,v =c\' + p,l~l>I (2 6) I J('1) The overlap energy between a particular pair of ions now depends notjust on the distance between them but also on the angle between the inter-ion vector and the internal vector &ofeach of the ions and hence on the configuration of the other ions around I If an ion] is positioned such that rJis parallel to & i e corresponding to the dis- placed cation in Figure 5 its repulsive interaction with i is calcu- lated as if the latter's charge density has expanded (enhanced a') &[rN]is also associated with a charge in the self-energy of an ion Figure 5 Representation of the ion 'deformation effect' in the distorted crystal considered in Figure 4,the electron density ceases to be symmet rically disposed about the anion centre -as indicated by the displaced contours in the figure This affects the repulsive interaction between the anion and its first neighbour cations The vector 6 indicates the direction of the deformation and appears in the modified expression for the repul sive interactions eqn (2 6) ‘COVALENT’ EFFECTS IN ‘IONIC’ SYSTEMS-P A MADDEN AND M WILSON A further refinement would be to include a quadrupolar set of inter-the separation between the more highly charged cations These nal degrees of freedom to allow for the flattening or squashing of crystal structures are illustrated in Figure 6 an ion This deformable ion effect may be studied in the same ab initio calculations on distorted crystals used to study the induced multi- poles Whilst the induced multipoles are obtained directly from the charge distribution of the distorted crystals the ion deformation effect is studied via the energies of these distortions -less the energy which is accounted for by polarization effects 23 Representation of the many-body effects The effects described above give a many-body character to the int-erionic interactions This arises because the expressions for the interaction energy of a particular pair of ions now contain variables elrN],pllrN],&[rN]etc ,which themselves depend on the coordi- nates of other particles If we were to express the interaction energy solely in terms of the ionic positions we would find that it involved very complicated expressions containing the coordinates of differ- ent ions simultaneously The key to representing the many-body effects in computer simulations is to treat the extra variables,@[rN] pi[F],&IrNl ,as dynamical coordinates of the system wholly analogous to the positions of the ions and update them along with the ionic coordinates as the ions move In terms of the particle posi- tions and the additional degrees of freedom the interaction energies become a relatively simple function involving the positions and additional degrees of freedom of only pairs of ions For details of how this is done in practice we refer to refs 1 and 7 As described above we can use electronic structure calculations on compressed and distorted crystals to examine how the ion radius etc vary with the ionic environment We can use these calculations to determine suitable functions which allow these properties to be evaluated for an arbitrary ionic configuration These functions then become the input to the simulation procedure The hope is that these functions determined from the crystal calculations will be suffi- ciently robust as to allow the properties to be calculated in the more general environments which will be encountered in the melt at a crystalline defect etc 3 Manifestations of the many-body effects Many-body effects such as those introduced above may affect all aspects of the observable behaviour of ionic systems and influence the properties of melts as well as crystals In order to keep things finite we will focus primarily on the role of these effects in stabi-lizing particular crystal structures As we have stressed the input for the potential models is derived from calculations done on crys- talline environments so that the first step of validating a potential must be to demonstrate that it reproduces and explains observed crystalline behaviour Surveys of the structures of binary materials show that in almost all cases the local structures of the crystal and melt are closely related I5 I6 The backcloth to the rationalization of crystal structures is pro- vided by the simple ionic model effectively a model of charged hard-spheres as embodied in pair potentials of Born-Mayer form For such a model the most stable crystal structure can be under- stood by considering how spheres of appropriate charge and radius may pack together to maximize unlike ion coulombic interactions and minimize like interactions l7 These considerations lead to the prediction of a number of typical ‘ionic’ crystal structures In systems of stoichiometry MX these are the eight-coordinate caesium chloride (B2) six-coordinate rocksalt (B1) and four-coor- dinate blende (B3) or wurtzite (B4)structures which are formed in systems of successively lower cation/anion radius ratio The rock- salt (B1) structure for example may be viewed as a close-packed cubic lattice of one species with the other occupying the octahedral holes this arrangement equalises the nearest-neighbour cation-cation and anion-anion separations r++ = r -and hence minimizes the charge-charge interaction For MX systems the cor- responding sequence is fluorite (eight-coordinate cations) rutile (six-) and ideal crystabolite (four-) Again these crystal structures involve ions symmetrically disposed in such a way as to maximise Crystobalite Rutile Fluorite Layered Figure 6 Illustrations of crystal structures frequently adopted by MX systems the small dark spheres are the cations and the larger pale spheres the anions The fluorite rutile and ideal p crystabolite structures are ‘ionic’ whereas the Cdl IS typical of the layered crystal structures which involve next neighbour anions and a short cation-cation separation CHEMICAL SOCIETY REVIEWS 1996 OBSERVED Figure 7 Structure maps as calculated for alkaline earth halides on the basis of a simple Born-Mayer pair potential (upper) and as observed. Note the agreement in the bottom left corner (large cations/small anions) and the prevalence of layered crystals in the small cation-large anion limit. Departures from the simple ionic model may be recognised qual- itatively in the adoption of crystal structures which do not fit into this pattern. In MX systems SnO has a layered structure with nearest neighbour ions of like charge along certain directions. In ZnO the ions are tetrahedrally coordinated whereas the radius ratio would suggest a rocksalt structure. Such departures are much more common in MX or MX systems. This is related to the excess of both octahedral and tetrahedral holes in the close-packed anion structures over the number of cations available to fill them in this stoichiometry -the cations have a much wider range of choice as to how they will organise themselves in the anion lattice than in MX. ‘Non-ionic’ structures where the cation occupancy does not min- imise the cation-cation interactions are prevalent. For example in MX stoichiometry many systems with small cations crystallize in layered CdI or CdCI structures17 which contain such non-ionic features as nearest neighbour anions see Figure 6. In the following sections we will show how by allowing for envi- ronmental effects on the ionic properties these (and other) anom- alies may be rationalized. 3.1 The role of polarization effects 3.I .I Lqered crystals in MX systems Figure 7 shows that the crystal structures of the alkaline earth halides depart quite markedly from the simple ionic model despite the large electronegativity differences between the elements involved. Figure 7 contrasts the structure map of stable crystal structures predicted by the simple ionic model which depends pri- marily on the radius ratio with those actually observed for these systems. It shows that whilst the structures adopted by the large cation -small anion systems are as predicted there is a large portion of the structure map where ‘non-ionic’ layered crystals are formed whilst the simple ionic model predicts the crystabolite structure. For reference the various structures are illustrated in Figure 6. Note that the ‘ionic’ structures maximize the distance between the highly charged cations and interpose an anion in between a pair of cations whereas the layered CdI structure contains nearest-neighbour ions of like charge short cation-cation separations (i.e. r_-= Y++ despite the higher cation charge). For the halide ion electronic structure calculations reveal that the -2700.0’ 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 0 /A Figure 8 The three lower lines show energies calculated for the various MClzcrystal structures from a simple pair potential supplemented with an account of anion polarization showing agreement with the experimental structural trend 7 (a -fluorite; b -rutile; c -layered). In the absence of the polarization term the fluorite and rutile energies are barely shifted whilst the energy of the layered structure is significantly increased (d). ion compressibility effects are quite small (compared to oxides for example); i.e. that the total repulsive energy is dominated by the overlap term. The alkaline earth cations are not very polarizable (compared to the chloride ion) and very similar in the gas and con- densed phase. Consequently to a first approximation we might restrict the consideration of environmental effects to the polariza- tion of the halide ion and use a simple pair potential for the remain- ing interactions. If we consider a given column of the structure map i.e.a series of systems with the same anion and impose a very trans- ferable ionic picture on the nature of the interactions then we would anticipate that the only potential parameter that should vary from one system to another is the cation radius.’* Figure 8 shows the energy minima cal~ulated’~ for the different chloride crystal struc- tures with a family of interaction models consisting of Born-Mayer pair potentials with formal ionic charges supplemented with a description of the halide dipole polarization which uses an ab initio calculated value for the chloride ion polarizability in the condensed phase and a description of the short-range dipole also derived from ab initio calculations. In this family the only parameter which varies from one system to another is the cation radius; the anion parameters are conserved from one substance to another and the parameters describing the cations are linked in a well defined and chemically meaningful way. Further calculations show (Figure 8) that the polarization effects have lowered the energy of the layered crystal structures relative to what would be expected from the pair potential alone by a huge amount -ca. 500 kJ mol-I for MgCI -whereas they cause little change in the energies of the ‘ionic’ fluorite rutile and crystabolite structures. Figure 6 shows why this has occurred. In the layered crystals the planes of highly polarizable anions are unsymmetrically sandwiched between a plane of cations and anions and are thus strongly polarized in such a way that the negative ends of their induced dipoles are dragged down into the layer of cations. This negative charge ‘screens’ the repulsion between the positive cations and therefore reduces the unfavourable coulombic energy which results from placing them in such close proximity in the layered crystal. In the ideal ionic structures by contrast the anions sit in sites of such high symmetry that no dipoles are introduced and the energies calculated with the polarizable model are very close to those obtained with the simple pair potential. Molecular dynamics simulations with the polarizable model confirm that the CdI struc- ture is indeed the globally stable structure for MgCI,.” We therefore see a general pattern emerging:- the simple ionic model favours highly symmetric structures whereas polarization favours pushing highly polarizable ions into unsymmetrical sites. Another manifestation of this occurs in the structures of MX melts. A snapshot of the structure in a ZnCI melt,2O simulated with a potential model of the same type as discussed above is shown in ‘COVALENT’ EFFECTS IN ‘IONIC’ SYSTEMS-P A MADDEN AND M WILSON A Figure 9 Snapshot of the ionic positions in a simulation of a ZnC1 melt with a polarizable ion model Cations are small and dark and the anions are larger and more lightly shaded Note the predominant tetrahedral coordination and the corner sharing of tetrahedra involving a bent Zn-C1-Zn bridge The extent of the network is limited by the fact that ‘bands’ to C1 ions not inside the region visualised are omitted Figure 9 It can be seen that the local structure consists of a tetrahe- dral arrangement of C1- ions around each Zn2+ this is an ion size effect contained within the pair potential and is a property of the structures obtained when the polarization effects are included or omitted The polarization effects influence the way these tetrahedral units are linked Whereas the pair potential predicts linear Zn-CI-Zn bridges on average the polarizable model gives a bent ‘bond’ with a bond angle of ca 110” Figure 10 shows that polar- ization is the driving force for the occurrence of this non-trivial bond angle a phenomenon often attributed to ‘covalency’ If the bond were linear the CI would be symmetrically located between two cations and no induced dipole could result If on the other hand the C1 is displaced off the line of centres of the cations a dipole is induced which serves to screen the cation repulsion and lowers the total energy A more open structure containing voids results so that the price paid for the polarization energy is an increase in the ID Coulomb or Madelung energy Numerous observable effects in MX melts may be explained through this phenomenon in particu-lar the relationship between like and unlike radial distribution func- tions,2O and the ‘pre-peak’ which is a characteristic feature of network-forming liquids The specific consequences of the polarization effects depend on a subtle interplay between them the straightforward coulombic interactions between the ionic charges and excluded volume effects as determined by the ion size ratio The polarization effects become more important for highly polarizable ions and when the cation radius is significantly smaller than the anionic one For large cations the simple ionic structures with an anion interposed between the cations emerge as most stable At intermediate size this bridge becomes bent as illustrated above resulting in corner linked polyhedra For very small cations and polarizable anions the bending is such as to give edge-linked polyhedra in which the induced dipoles on two anions screen the cation-cation repulsion as indicated in Figure 10 For example BeCl forms several crystal structures based on chains of edge-linked tetrahedra and edge- sharing octahedra and tetrahedra become the dominant local struc tures in MX melts Both of these phenomena are reproduced with potentials of the type described above 3 I 2 Polarization in silica isomorphs Amongst systems of stoichiometry‘ MX silica (SiO,) is known to exhibit a particularly exotic range of crystalline isomorphs l7 Whilst there are good reasons to expect that the simple model of a pair potential plus polarization will not suffice for oxides (see below) it is of interest to see how polarization phenomena con tribute in these structures by pushing ahead with the simple model described in the previous section At atmospheric pressure all silica polymorphs are based on corner-linked SiO tetrahedra With increasing pressure there is a transition to a six-coordinate cation rutile-like phase (stishovite) and a possible higher pressure transi tion to a fluorite-based or a-PbO structure which may have geo- physical significance We will discuss results obtained with a Born-Mayer potential with full formal charges as parameterised by Woodcock Angel1 and Cheeseman (WAC) and supplemented by an account of anion polarization using the oxide polarizability obtained from the experimental refractive index and the short-range dipole function used in MCI work but scaled by the ratio of sums of ionic radii The limitations of this model will become apparent when we consider the relationship between the energies of struc- tures with different coordination numbers Figure 11 shows the energyholume curves for the important polymorphs calculated using the WAC pair potential2’ (a)without and (b)with induced dipoles on the anions In the absence of polar- ization the lowest energy structures are the ideal-P-crystobalite and tridymite These follow near identical curves (only the ideal-P-crys- tobalite is shown) as they differ only in the packing of the oxide sub- lattice ideal-P-crystobalite as illustrated in Figures 6 and 12 has an fcc oxide lattice whereas the tridymite is hexagonally packed These structures have linear Si-0-Si triplets As discussed above in the absence of polarization effects the driving force for the linear Figure 10 Illustration of the induced dipole as a driving force for bond bending and how wlth decreasing cation size (increasing polarization effects) this eventually favours a polyhedral edge sharing motif 100 20.0 30.0 40.0 50.0 60.0 70.0 80.0 VIA^ -11300.0 -11500 0 -11700 0--z -119000 A25 -12100.0 -1 2300 0 -1 2500.0 -12700 0 10.0 200 300 40.0 500 60.0 700 800 VIA^ Figure 11 Energy vs volume curves for various isomorphs of SiO calcu lated (a)with the simple pair potentialz7 and (6)with the additional effect of anion polarization Note the stabilization of the experimentally observed P-crystabolite and quartz structures relative to ideal crystabo lite and stishovite which occurs because of polarization effects bond is the repulsive cation-cation coulombic interaction which is minimized by interposing an anion between adjacent cations The structures predicted by the pair potential do not agree with experi- ment ideal crystabolite and tridymite are less stable than the form of crystabolite which is illustrated in Figure 12 and less than the a and p forms of quartz In all these structures the Si-0-Si bond is bent The pair potential also overestimates the stability of the denser six-coordinate stishovite structure From Figure 12 it can be seen that stishovite is predicted to be stable with respect to both quartz and the experimentally observed form of crystabolite The inclusion of the polarization effects [Figure 1 l(b)J radically improves this picture Polarization stabilizes the bent Si-0-Si triplets found in the real-crystobalite structures in the same manner as found in the MX systems described above The high symmetries of the oxide sites in the ideal crystabolite tridymite and stishovite structures preclude such polarization effects The result of allowing for polarization is that the real-crystabolite energy minimum is con- siderably reduced and now lies significantly below that of the ideal structure and also that of stishovite The same induction stabilization is seen in the a-quartz structure resulting in the interesting pattern illustrated in Figure 12 Looking down on a plane of SiO tetrahedra as in Figure 12 (corresponding to the crystallographic ab plane) we see alternating up/down spirals of clockwise and anticlockwise induced dipoles which are linked to the piezoelectric properties of quartz The transition pressure from the a-quartz to stishovite rises to around 50 GPa when polarization effects are included This is a direct result of the greater polarization energy in the four-coordinate structures w'th respect to the 'Ix *lthough there Is Some uncer-tainty as to the actual Owing to the metastab''-ItY ofthe four-coordlnate Structure the quoted (5 GPa22)Is well below our calculated value though the quoted reduction In molar volume on going from quartz to stishovite of 38% is in good CHEMICAL SOCIETY REVIEWS 19% accord with the calculations Thus although the inclusion of polar- ization effects has qualitatively improved the description of the silica systems it is clear that more is required than adding polariza- tion effects to a pair potential in order to quantitatively account for the phase behaviour Latz and Gordon23 have argued that the effects of the different environments in these isomorphs on the actual size and shape of the oxide ion must be accounted for to recover the phase transitions accurately we will discuss such effects in the next section 3.2 The role of compressible-ion effects So far we have simply examined the consequences of adding polarization to a heuristic pair potential It is unclear whether such shortcomings as the poor quantitative description of the phase behaviour of silica are due to an inadequacy of the description of Ideal crystobalite p-Crystobalite J-a-Quartz Figure 12 Illustration of the polarization effects in the SiO isomorphs A projection of a single plane of SiO tetrahedra in each structure is shown the Si ions are small dark circles and the 0 ions are larger and grey The ideal crystabolite (shown in '3D' in Figure 6) is compared with P crys tabolite and a-quartz where the Si-0-Si bond is bent The negative ends of induced dipoles on the oxide ions are indicated by small open circles ‘COVALENT’ EFFECTS IN ‘IONIC’ SYSTEMS-P A MADDEN AND M WILSON the short-range interactions between the ions contained in the pair potential or due to a more general limitation of the underlying ionic model To proceed further it is clearly necessary to examine the short-range interactions at an ab initio level As discussed in section 2 1 such an examination in cubic crystals reveals the phe- nomenon of ion compression We therefore now consider the char- acteristic effects of generalising the description of short-range repulsion from that afforded by a pair potential to allow for the many-body effects which arise from the environmental effects on the ion size To demonstrate the role of spherical compression we expand on the MgO example discussed earlier Figure 13 shows the energy/volume curves for the B 1 B2 and B3 crystal structures of MgO calculated using (a)the compressible-ion model (CIM) dis- cussed above and (b)a pair potential fit to the same rocksalt (B 1) data used to parameterise the CIM potential The CIM has been shown to predict both the four- and eight-coordinate ab initio data also shown in Figure 3 wlthout further modtjcatton -it is transfer- able whereas the pair potential is not (inset to Figure 3) Two fea- tures are evident Firstly the value of the Bl -B2 pressure transition is greatly reduced in the CIM (the transition pressure between the two phases is obtained from the gradient of the line which is a common tangent to the corresponding energy vs volume curves) Secondly and perhaps more strikingly the predicted ground state for the pair potential is the four-coordinate B3 struc-ture rather than the experimentally observed Bl (rocksalt) The CIM predicts the correct ground state and gives excellent values for its lattice energy lattice constant and bulk modulus A similar story holds for CaO for which the B 1 -B2 transition pressure is known experimentally and found to be predicted accurately by the CIM potential Thus allowing for the coordination number dependence of the ion compression effects leads to a transferable potential which appears to favour high coordination structures relative to the pre- dictions of a pair potential This appears to be a general observation -2600 0I 1 -2700.0k r ‘5 -2800.0 E 5 -2900.0 -3000.0 -3100 O1 I 10 0 20.0 300 40 0 -3100 0’ I 10.0 20.0 300 40 0 VIP Figure 13 Energy vs volume curves for MgO calculated (a)with the rock salt pair potential (from the inset to Figure 3) and (6)from the CIM poten tial which represents Uouand Use,,separately Key plusses -B2 crosses -B1 circles B3 Note that in (a)the B3 structure (erroneously) emerges as of lowest energy whilst the CIM stabilizes the higher coordination structures for example a single pair potential with sensible ionic radii cannot reproduce the seven-coordinate ground state of ZrO instead pre- ferring a lower six-coordinate option The use of a CIM corrects this by stabilizing the higher coordinate structure 24 This effect could also help to stabilize the stishovite structure relative to quartz in SiO and thus improve the predicted transition pressure as dis- cussed in the last section How important are the compressibility effects for other anions? The oxide ion being unstable in the gas-phase is particularly sus- ceptible to environmental effects Ab initio data are available for CsCl and for CaF28 and indicate that Uselfis a smaller component of the total repulsive energy than in the oxides Nevertheless Pyper8 has shown that a full account of the coordination number depen dence of Uovand Uselfis necessary to obtain the correct ground-state (B2) structure for CsCl When the same ab initio data are used to fit a pair potential this potential overestimates the stability of the lower coordination number BI structure For the fluoride ion in CaF it does seem that a pair potential representation of the repul- sive interactions is sufficient 2s The transition energies from the ground-state fluorite structure to a denser a-PbC1 structure pre- dicted by CIM and pair potential fit to the same ab initio data differ by only 8 kJ mol I in a total lattice energy of cu 2500 kJ mol I and both are in good agreement with experiment The ab initio pair potential (plus polarization) gives a good account of numerous other properties of CaF including its superionicity In the Introduction we stressed that one of the touchstones for assessing the validity of an ionic model should be the transferabil- ity of the potential Not only should the potential work in different phases of the same material but similar potentials in which the parameters change in a chemically reasonable way should describe other chemically related materials The CIM potentials for MgO and CaO are evaluated from specialised electronic struc- ture calculations which focus on the properties of single ions within an idealised representation of the crystalline environment Nevertheless the ab initio potentials which describe the short- range repulsion between an Mg2+ and O2 ion look very similar to those which describe the Ca2+ -02 interaction if they are scaled to allow for the different radii of the Mg2+ and Ca2’ ions Furthermore these potentials may be ‘transmuted’26 into poten- tials for other oxides of stoichiometry MO simply by replacing the values of well-defined ionic radii in the expression for U The self-energy Uselfis a property of the oxide ion and should not be changed from one oxide to another It has been shown that these potentials successfully account for the lowest energy crystal struc- tures energies and lattice parameters of the other alkaline earth oxides and accurately predict the transition pressures to higher density structures Figure 14a shows the energyholume curves for the smallest cation system studied Be0 The observed ground state is now the wurtzite (B4) structure in line with experiment The energy difference between the B4 and B3 structures is entirely consistent with the slight preference for the B4 indicated by the Madelung constant Figure 14(b) shows the same curves for SrO Here the tangent to the B1 and B2 curves predicts a transition pressure of 27 GPa which may be compared to an experimental value of 36 GPa Although the CIM potentials are more complex than pair poten- tials they appear to contain an essential aspect to describe phase transitions in oxides but are nonetheless transmutable in a chemi- cally meaningful manner between materials with different cations 33 Ion deformation In order to illustrate the role of aspherical deformation of ions insofar as these affect the repulsive interactions we depart from a consideration of crystal structures and consider the lattice vibra- tional frequencies in MgO How well does the CIM potential which provides an excellent description of the perfect crystal and its phase transitions do in predicting the lattice vibrations? As illustrated in Figure 15 the answer is ‘very badly’’ We know that since the lattice vibrations involve the movement of ions off their lattice sites polarization effects must be added to the straight CIM potential and that this will lower the energy of the lattice distortions and hence CHEMICAL SOCIETY REVIEWS 1996 -3100. -3500.01 -3700.0I I 5.0 10.0 15.0 20.0 25.0 VIA^ -2300.0 I I20.0 40.0 60.0 80.0 VIA^ Figure 14 Energy vs. volume curves for (a)BeO (6) SrO calculated by scaling the CIM potentials for MgO and CaO to allow for the change in cation radius.33 Key plusses -B2; crosses -B 1 circles -B3 triangles -B4 (wurtzite). For Be0 the wurtzite structure is now (correctly) predicted to be the lowest energy. The B 1 -B2 phase transition in SrO is predicted to occur at a pressure of 27 GPa -in reasonable agreement with experi- ment. reduce the vibrational frequencies. However the calculated phonon frequencies even when the CIM is supplemented with a description of the oxide ion dipole polarization (i.e.with variable ion radius and dipole) are very poor as shown in Figure 15(a).Figure 15(b)I4 shows the additional effect of allowing for a deformation of the ion shape of dipolar symmetry 1i.e.by introducing the variable 51 as suggested in eqn. (2.6)).Even when the self-energy associated with the deformation is introduced on an ad hoc basis as was done in these calculations the shape of the phonon dispersion curves is brought into much better agreement with the experimental ones although the absolute frequencies of the optic modes is still too high. A better parametrization of this term and the inclusion of quadrupolar effects is required to obtain the MgO phonons accu- rately.I4 4 More complex crystals In illustrating the characteristic consequences of each of the many- body effects in the last section we have tried to provide examples which draw attention to the role of an individual effect. In the halides compressibility effects are small and the effects of polar- ization are clearly seen; in the cubic phases of the alkaline earth oxides there is no polarization and the compressibility effects are exemplified. We have seen that each of the effects has a character- istic influence on which crystal structure is adopted -polarization favours unsymmetrical sites for highly polarizable ions neglecting compression leads to an underestimate of the stability of high coor- dination number structures. In general the observed structure will be a consequence of competition between opposing tendencies. In this section we consider some more complex examples than those discussed above in which the observed structure reflects this com- petition. w-L 2oomom0.0 0.0 0.2 0.4 0.6 0.8 1 .o 800.0 1 0.0 0.2 0.4 0.6 0.8 1 .o to 0951 Figure 15 Experimental phonon dispersion curves for Mg034 along the k = (Ook) direction are compared with phonon frequencies calculated (a) with the compressible ion potential plus polarization and (6) with the additional deformation effect. The type of phonon mode is indicated by the linestyle in both cases (long-dash -LO short-dash -TO dots -TA solid -LA) and the calculated points are indicated by the lines with circles. 4.1 A1,0 -higher-order multipoles The competition between the different effects becomes marked when considering the more complex M20 stoichiometry since almost all possible crystal structures for such systems give site sym- metries which are capable of sustaining induced multipoles. Attempts to model Al20 with shell models which allow for dipole polarization cannot account for the higher stability of the observed corundum structure over the less dense bixbyite phase unless unrea- sonably large values for the dispersion interaction between pairs of aluminium ions are included.28 This artificially stabilizes the close approach of a pair of A13+ions a characteristic feature of the corun- dum structure. In both the bixbyite and corundum structures the oxide ions are fourfold coordinated but whereas the coordination is almost tetrahedral in bixbyite in corundum the tetrahedra are twisted towards a planar D geometry. Although neither of these site symmetries can support a significant induced dipole moment in the corundum structure there is an appreciable field gradient at the oxide site which can induce a quadrupole. This suggestion is corroborated by findings from nuclear quadrupole resonance studies29 of the magnitude of the field gradients at '80 and Al nuclei which had been used to estimate the magnitudes of induced quadrupoles on the 02-ions and which are consistent with a value for the quadrupole polarizability Cof 02-of 5-7 a.u.30 Apart from supporting different polarization effects the oxide sites in corun-dum and bixbyite will lead to different degrees of compression of the oxide ions. Simulations of A120331have been carried out with a CIM poten-tial derived from the MgO by a small change in the cation radius ‘COVALENT’ EFFECTS IN ‘IONIC’ SYSTEMS-P A MADDEN AND M WILSON and including dipole and quadrupole polarization [using the asymp- totic model of eqn (2 5)j A C value of 6 a u predicts the corundum structure to be stable with respect to bixbyite with an energy differ- ence between the structures consistent with results fi-om ab initio calculations as well as good structural parameters The dipole polar- ization plays a very minor role because of the relatively high sym- metries of the oxide site in both lattices This is not quite the end of this story however In MgO the ab initio O2 quadrupole polarizability has a value of 26 a u ?2 and its value in A120 would be expected to be similar (in-crystal oxide polarizabil ities are found to depend largely on the cation-anion separation which are very similar in MgO and A1,0,) Such a large polarizability would give a much larger value for the energy differ- ence between corundum and bixbyite and would lead to nuclear field gradients considerably larger than those observed in NQR We would interpret this as a good example of the influence of the short range contribution to the induced multipoles as discussed in section 2 2 1 The effect of these terms is to substantially reduce the induced quadrupoles on anions from the values predicted with the asymp- totic model The influence of the short-range terms is mimicked in the calculations by introducing a much reduced value for the quadrupole polarizability 4.2 SnO (and PbO) -cation polarization As described above a family of CIM potentials can be obtained for the alkaline earth oxides which differ substantially only in the value of a cation radius and which quantitatively account for the phase transitions observed in this series between the ‘ionic’ B2 (CsCl-eight-coordinate) B 1 (rocksalt-six-coordinate) and B3/B4 (blende/wurtzite-four-coordinate)crystal structures We might therefore expect to be able to predict the structures of other oxides of stoichiometry MO simply from the cation radius Amongst the exceptions to the general pattern of ‘ionic’ structures in MO systems is SnO which together with PbO crystallizes into the litharge structure shown in Figure 16 l7 In the ideal structure (sketched the true structure involves a slight distortion) the anions occupy tetrahedral holes in a cubic cation lattice whereas radius considerations would suggest a rocksalt structure as formed by SrO (qyrI2+1 12 8 compared with asr2+ 1 18 A18) in which the = = larger octahedral holes are occupied More strikingly the pattern in which the tetrahedral holes are occupied is different from the four- coordinate cubic blende structure In the latter the occupancy is strictly charge-ordered and r = r++ In the SnO structure since alternate planes of holes are occupied (see Figure 16) r = r++/d2 and nearest-neighbour cations occur an arrangement which clearly does not minimise the charge4harge interactions Further evidence regarding the difference between SnO (and PbO) and the alkaline earth oxides comes from the lattice formation ener gies,Is which are more negative than those of the alkaline earth oxides with similar cation radii The analogy between the SnO structure and the layered crystals formed by MCI systems seems clear There are however two important differences Firstly the greater number of anions in the MX stoichiometry and the greater cation charge lend themselves to the anion-dipole stabilization mechanism -the excess of octahedral holes over cations means that asymmetric structures can arise even for intermediate size cations Only symmetric structures which do not allow dipole induction can arise from occupying octahedral holes in an fcc lattice at MO stoichiometry because of the equal number of ions and holes Secondly previous examples of such dipolar stabilization have been confined to systems in which it is the anion that sits in the asymmetric environment whereas in SnO it is the cation Simple electronic structure arguments suggest that the dipole polarizability of the Sn2+ cation could also be very large Its ground-state configuration is 5s2 which means that there are low energy dipole-allowed transitions (5s + 5p) which could make a very large contribution to the polarizability Ah initio results confirm this,?? with the value of a = 15 a u very similar to that expected for the anion in this system and much larger than the Sr2+ polarizability (5 a u ) Calculations show that polarization energies associated with such a large cation polarizability are sufficient to Figure 16 The SnO crystal structure illustrating the unsymmetrical occu pation of the unit cell by oxide ions Cations are the small dark spheres and oxide ions the larger pale ones overcome the charge ordering tendency and to drive the O2 ions into the tetrahedral holes in the cubic Sn2+ lattice despite the large cation/anion radius ratio in such a way as to generate the layered structure which allows the cation polarization 43 ZnO -the preference for a tetrahedral site From the perspective of the alkaline earth oxide CIM another ‘anomaly’ may be recognised Zn2+ has a slightly larger crystal radius (0 74 Al8) than the Mg2+ ion (0 68 A) and yet the lowest energy isomorph of ZnO is the four-coordinate B4 (wurtzite) struc- ture,I7whilst MgO is rocksalt In the alkaline earth oxides only the tiny Be2+(0 45 Ai8)falls in the four-coordinated B4 domain This preference of the Zn2+ ion for a tetrahedral site relative to Mg2+ is general -seen in the crystal structure of the chlorides for example The application of pressure to ZnO does result in a phase transition to the higher coordinate B 1 between 9 O4I and 9 5 GPa 74 Thus the energy of the B 1 phase is relatively close to that of the B4 in ZnO whilst the former has a smaller molar volume Dipole (and quadrupole) polarisation effects which we have con- sidered previously cannot contribute to the energetics of these structures because the site symmetry is too high to permit such mul- tipoles to be induced Mahan has noted the potential significance of octupole-induction at tetrahedral sites 35 The octupole polarizabil- ity which would control the magnitude of this effect might be large for a post-transition metal ion like Zn2+ because of the possibility of octupole-allowed d + p transitions This is confirmed by elec tronic structure calculations which show that the octupole polariz ability CR of Zn2+ (ca 29 a u ) is ca 50 times greater than Mg2+ suggesting that cation octupole polarization could be responsible for the different coordination preferences of the two ions However the same calculations show that CR for the O2 ion in these systems should be about 161 a u -so that if the octupole polarization were simply that driven by the field gradient from the ionic charges (1 e the asymptotic model of section 2 2) the octupole polarization of the anion would swamp that of the cation so that any discrimination between Zn2+ and Mg2+ from this mechanism would be lost Furthermore were the oxide ion octupole polariza tion energy obtained with the asymptotic model to be included in the energetic considerations for the alkaline earth oxides a B3/B4 ground-state structure would be predicted for MgO as well’ The item missing from these consideration is the short-range contribu tion to the polarization As discussed in section 2 2 I for anions this dramatically reduces higher-order polarization effects such as oxide octupole induction but for cations it enhances it Detailed considerations show that the crystal structure of ZnO can be ratio- nalised on the octupole induction mechanism 26 This finding is a significant one in trying to evaluate the limits of validity of the ‘extended’ ionic model at least in a practical sense The starting point of this model as expounded in section 2 2 IS that ions are basically spherical in high symmetry crystal structures and that only distortions of low multipolar order need to be included to account for the changes in their properties as they sample the envi- ronments typically encountered in the condensed phase The ZnO finding however points to the fact that higher order distortions of post-transition metal cations need to be incorporated even to account for the lowest energy crystal structure -the Zn2+ ion is intrinsically aspherical in a condensed phase This certainly poses a challenge for a computationally tractable implementation of the ‘extended’ ionic model 5 Conclusion In the article we have described an approach to the representation of interionic interactions in which formal ionic charges are used and in which the many-body effects have been broken down into dis- tinct physical effects which may be separately characterized in electronic structure calculations and separatefv represented in tractable computer simulation models We have shown that each of these effects can exert a distinctive influence on condensed phase structures and account for phenomena which have conventionally been regarded as non-ionic (or ‘covalent’) The potentials have been shown to be transferable not only between different phases of a given material but ‘transmutable’ between chemically related systems by substituting parameters with a physically transparent significance We believe that the work has shown that an ionic model where the ions carry formal charges has a wider domain of applicability than has sometimes been supposed This has opened the way for more wide-ranging simulation work with well-founded potentials We have tended to use the expression ‘covalent’ in a somewhat pejorative sense as a catch-all term to ‘explain’ anything not pre- dicted by the simplest ionic picture Enderby and Barnesi6 describe covalency as ‘interactions which change the charge dis- tribution of the valence electrons relative to some conceptual extreme represented in our case by the ionic model’ this seems to sanction the catch-all useage As chemists we would prefer a less catholic use of the term and to retain it for the description of interactions arising from chemical bond formation involving the sharing of pairs of electrons between atoms If we then attempt to find more specific explanations of the most spectacular ‘covalent’ anomalies (layered crystals bent ‘bonds’ etc ) it would seem that many can be attnbuted quantitatively to zunzc polarization -covalency in the chemical sense is not involved Detailed con- siderations of the relative energies of different structures necessi- tate an allowance for the fact that an ion’s size and shape may change in different environments but this may still be encom- passed within a fully ionic picture of closed shell species carry- ing formal charges The invocation of each of these aspects of the ‘extended’ ionic model in a particular material is driven by a con- sideration of the electronic structure of the ions involved Thus the concept of ions as sphencal rests on the remoteness of elec- tronic states of high angular momentum the oxide ion is particu- larly compressible compared to halides due to its instability in the gas-phase cation polarization becomes especially important CHEMICAL SOCIETY REVIEWS 1996 when low-energy dipole-allowed transitions are possible as in Sn2+ Quite how far this picture can be carried beyond the examples we have given at a quantitative level remains to be seen Acknowledgements We are grateful to several colleagues for their work and discussions on the topics we have covered in particular we thank John Harding Nick Pyper Adrian Rowley Nick Wilson and Malcolm Walters We also thank Emily Carter for her com- ments on the manuscript and John Freeman for help with the figures References 1 M Wilson and P A Madden J Phys Condens Matter 1993,5,2687 J Phys Chem 1996,100,1227 2 U Schroder Sol Stat Commun ,1966,4,347 3 B G Dick and A W Overhauser Phys Rev 1958.112,90 4 G D Mahan and K R Subbaswamy ‘Local Density Theory of Polarizability’ Plenum London 1990 5 N C Pyper Adv Sol Stat Chem ,1991,2,223 6 P W Fowler and P A Madden Phvs Rev B 1984,29,1035 7 M Wilson,P A Madden,N C Pyperand J H Harding,J Chem Phys 19% 104,8068 8 N C Pyper J Phys Condens Matter 1995,7,9127 9 L V Woodcock and K Singer Trans Faraday SOC ,1971,67,12 10 A D Buckingham Adv Chem Phys 1967,12,107 11 P W Fowler and P A Madden Phys Rev B 1985,31,5443 12 P A Madden,J Chem Phys 1991,94,918 13 G N Papatheodorou and V Dracopoulos Chem Phys Lert ,1995,241 345 14 A Rowley and P A Madden to be published 15 M Rovere and M P Tosi Repts Prog Phys 1986,49,1001 16 J E Enderby and A C Barnes Repts Prog Phys 1990,53p 85 17 U Muller ‘Inorganic Structural Chemistry’ Wiley Chichester 1993.A F Wells ‘Structural Inorganic Chemistry’ fifth edn Clarendon Oxford 1984 R W G Wyckoff ‘Crystal Structures’ Interscience New York 1%5 18 R D Shannon Acta Crystalfogr Sect A 1976,32,751,J G Stark and H G Wallace ‘Chemistry Data Book’ 2nd edn John Murray 1984 19 M Wilson and P A Madden J Phvs Condens Matter 1994,6. 159 20 M Wilson and P A Madden. J Phvs Condens Matter 1993,5,6833 21 M Wilson and P A Madden Phys Rev Lett 1994,72,3033 22 R A Robie B S Hemingway and J R Fisher Geol Surv Bull 1979 21,1452 23 D J Lacks and R G Gordon J Geophys Res ,1993,98,22147 24 M Wilson U Schonberger and M W Finnis Phys Rev B submitted 25 N T Wilson and P A Madden J Chem Phys ,submitted for publica tion 26 M Wilson and P A Madden Mol Phys ,to be published 97L I G Peckham Proc Phys Soc 1%7,90,657 28 J P Gale,C R A Catlow and W C Mackrodt Modelling Simul Mater Sci Eng ,1992,1,73 29 E Brun E Hundt and H Niebuhr Helv Phys Acta ,1968,41,417 30 S Hafner and M Raymond J Chem Phys ,1968,49,3570 31 M Wilson Y M Huang M Exner and M W Finnis in preparation 32 H M Kelly and P W Fowler. Mol Phys ,1993,80,135 33 M Wilson P A Madden. S A Peebles and P W Fowler Mol Phvs . 1996,88 I 143 34 J C Jamieson Phys Earth Planet Inter 1970,3,201,C H Bates W B White and R Roy Science 1962,137,993 35 G D Mahan. Sol State lonics 1980,1,29,Sol State Commun ,1980 33,797

ISSN:0306-0012    

DOI:10.1039/CS9962500339

出版商:RSC    

年代:1996

数据来源: RSC