SUPRA MOLECULAR CHE MISTRY - SCOPE A N D PERSPECTI VES M OLEC ULES - S UPER M OLEC ULES - MOLECULAR DEVICES Nobel lecture, Dece mber 8, 1987 b y J E A N - M A R I E L E H N Institut Le Bel, Université Louis Pasteur, 4, rue Blaise Pascal, 67000 Stras- bourg and Collège de France, 11 Place Marcelin Berthelot, 75005 Paris. Abstract Supra molecular che mistry is the che mistry of the inter molecular bond, cover- i n g t h e str u ct ur es a n d f u n cti o ns of t h e e ntiti es f or m e d b y ass o ci ati o n of t w o or more che mical species. Molecular recognition in the super molecules for med by receptor-substrate binding rests on the principles of molecular co mple mentar- ity, as found in spherical and tetrahedral recognition, linear recognition b y coreceptors, metalloreceptors, a mphiphilic receptors, anion coordination. Su- pra molecular catalysis by receptors bearing reactive groups effects bond clea- vage reactions as well as synthetic, bond for mation via cocatalysis. Lipophilic receptor molecules act as selective carriers for various substrates and allo w to set up coupled transport processes linked to electron and proton gradients or to light. Whereas endo-receptors bind substrates in molecular cavities by conver- gent interactions, exo-receptors rely on interactions bet ween the surfaces of the receptor and the substrate; thus ne w types of receptors such as the metallonu- cleates may be designed. In co mbination with poly molecular asse mblies, recep- tors, carriers and catalysts may lead to molecular and supra molecular devices, defined as structurally organized and functionally integrated che mical syste ms built on supra molecular architectures. Their recognition, transfer and transfor- mation features are analyzed specifically fro m the point of vie w of molecular devices that would operate via photons, electrons or ions, thus defining fields of molecular photonics, electronics and ionics. Introduction of photosensitive groups yields photoactive receptors for the design of light conversion and charge separation centres. Redox active polyolelinic chains represent molecular wires for electron transfer through me mbranes. Tubular mesophases for med by stacking of suitable macrocyclic receptors may lead to ion channels. Molecular selfasse mbling occurs with acyclic ligands that for m co mplexes of double helical structure. Such develop ments in molecular and supra molecular design and engineering open perspectives to wards the realization of molecular pho- t o ni c, el e ctr o ni c a n d i o ni c d e vi c es, t h at w o ul d p erf or m hi g hl y s el e cti v e r e c o g ni- J.- M. L e h n 4 4 5 tion, reaction and transfer operations for signal and infor mation processing at the molecular level. 1. Fro m Molecular to Supra molecular Che mistry Molecular che mistry, the che mistry of the covalent bond, is concerned with uncovering and mastering the rules that govern the structures, properties and transfor mations of molecular species. Supra molecular che mistry may be defined as “che mistry beyond the mole- cule”, bearing on the organized entities of higher co mplexity that result fro m the association of t wo or more che mical species held together by inter molecular forces. Its develop ment requires the use of all resources of molecular che mistry co mbined with the designed manipulation of non-covalent interactions so as to for m supra molecular entities, super molecules possessing features as well de- lined as those of molecules the mselves. One may say that super molecules are to molecules and the inter molecular bond what molecules are to ato ms and the covalent bond. Basic concepts, ter minology and definitions of supra molecular che mistry were i ntr o d uce d earlier [ 1- 3] and will only be su m marized here. Section 2.3. belo w provides a brief account on the origins and initial develop ments of our work which led to the for mulation of supra molecular che mistry. Molecular associations have been recognized and studied for a long ti me [4] and the ter m “über moleküle”, i.e. super molecules, was introduced already in the mid-1930’s to describe entities of higher organization resulting fro m the association of coordinatively saturated species [5]. The partners of a supra molecular species have been na med molec ular receptor a n d s ubstrate [ 1, 2, 6 5], t h e s u bstr at e b ei n g usually the s maller co mponent whose binding is being sought. This ter minol- ogy conveys the relation to biological receptors and substrates for which P a u l E hrlic h stated that molecules do not act if they are not bound (“ Corpora non a g u nt nisi fi x at a ”). T h e wi d el y e m pl o y e d t er m of liga nd see med less appropriate in vie w of its many unspecific uses for either partner in a co mplex. Molecular interactions for m the basis of the highly specific recognition, reaction, trans- p ort, r e g ul ati o n et c. pr o c ess es t h at o c c ur i n bi ol o g y s u c h as s u bstr at e bi n di n g t o a receptor protein, enzy matic reactions, asse mbling of protein-protein co m- ple xes, i m munological antigen-antibody association, inter molecular reading, translation and transcription of the genetic code, signal induction by neuro- tra ns mitters, cell ular rec o g niti o n, etc. T he desi g n of artificial, a bi otic, rece pt or molecules capable of displaying processes of highest efficiency and selectivity requires the correct manipulation of the energetic and stereoche mical features of the non-covalent, inter molecular forces (electrostatic interactions, hydrogen bonding, Van der Waals forces etc.) within a defined molecular architecture. In doing so, the che mist may find inspiration in the ingenuity of biological events and encourage ment in their de monstration that such high efficiencies, s el e cti viti es a n d r at es c a n i n d e e d b e att ai n e d. H o w e v er c h e mistr y is n ot li mit e d t o s yst e ms si mil ar t o t h os e f o u n d i n bi ol o g y, b ut is fr e e t o i n v e nt n o v el s p e ci es and processes. Bi n di n g of a s u bstrate t o its r e c e pt or yields the super molecule and Sche me 1 . Fro m molecular to supra molecular che mistry: molecules super molecules, molecular and supra molecular devices. involves a molecular recognition process. If, in addition to binding sites, the receptor also bears reactive functions it may effect a che mical transfor mation on the bound substrate, thus behaving as a supra molecular reagent or catalyst. A lipophilic, me mbrane soluble receptor may act as a carrier effecting the translocation of the bound substrate. Thus, molec ular recog nitio n, tra nsfor matio n a n d tra nslocatio n represent the basic functions of supra molecular species. More co mplex functions may result fro m the interplay of several binding subunits in a polytopic coreceptor. In association with organized poly molecular asse mblies and phases (layers, me mbranes, vesicles, liquid crystals, etc.), functional su- per molecules may lead to the develop ment of m olec ul ar de vices. T h e pr es e nt t e xt describes these various aspects of supra molecular che mistry (diagra m matically sho wn in Sche me 1) and sketches so me lines of future develop ment (for earlier g e n e ra l p re s e n ta tio n s s e e [1 -3 , 6 -9 ]). T h e results discussed here, taken mainly fro m our o wn work, have been co mpleted by references to other studies, in order to dra w a broader picture of this rapidly evolving field of research. E mphasis will bear on conceptual fra me work, classes of co mpounds and types of processes. Considering the vast literature that has developed, the topics of vari o us meeti n gs a n d s y m p osia, etc., there is no possibility here to do justice to the nu merous results obtained, all the more to provide an exhaustive account of this field of science. Supra molecular che mistry, the designed che mistry of the inter molecular bond, is rapidly expanding at the frontiers of molecular science with physical and biological pheno mena. 2. Molecular Recognition 2.1. Recog nitio n - I nfor matio n - Co mple me ntarity Molecular recognition has been defined as a process involving both bi ndi ng a n d selectio n of substrate(s) by a given receptor molecule, as well as possibly a s pecific f u nctio n [ 1]. M er e bi n di n g is n ot r e c o g niti o n, alt h o u g h it is oft e n t a k e n J.- M.