Honig, Wurshel, and Karplus
92
i\,cconnts CJEChemical R,esearch
Barry Honig Department of Physical Chemistry, T h e Hebrew i h i v e r s i l y , Jerusalem, Israel
Arieh Warshel Department of Chemical Physics, W e i z m a n n l n s t i t u l e of Science, Rvhovot, Ksrael
Martin Karplus" Department
o i Chemist?,
IIarcard L'nicersity, Cambridge. Mcissachuselts, and Lahorntoirr d e Chimie 'i'hhricjiie. LhniuPrsit+ de Pari,s VII, Paris, FrariccJ Receiued J u n e 28, 1974
The past few years have seen a renewed effort by physical chemists to understand the structure and electronic properties of the retina! isomers, Interest in these molecules has been stimulated by their importance in the visual process. The compound Il-cisretinal is the chromophore of the visual pigment, rhodopsin, absorption of light by which appears to be the initial step in a series of processes that finally result in the generation of a nerve impu1se.I The retinal isomers are linear polyene aldehydes. many of whose physical properties are determined primarily by their delocalized a electrons Since molecular quantum mechanics has been very successful in treating a-electron systerns,2--6 the visual pigments provide a rare opportunity for theory to aid in the understanding of a molecule essential to a biological process. Moreover, the retinal isomers have proved to be interesting in their own right, and attempts to fully understand their properties have stimulated theoretical, spectroscopic, and photochemical investigations that bear on a range of This Account is devoted primarily to a discussion of the conformational and spectroscopic properties of the retinal isomers, with emphasis on 11-cis .retinal. However, it must be realized that even a complete characterization of these molecules represents only a first step in the understanding of the visual pigment, in which 11-cis-retinal is covalently bound t o the protein opsin by a protonated Schiff base linkage with a lysine.8 Little is known of the details o f Ihe lipoprotein environment of the chromophore in the pigment. The large spectral shift observed in going Barry Honig is Senior Lecturer in the Department of Physical Chemistry at the Hebrew University, Jerusalem He was born in New York in 1941, and received his B.Sc. degree from the Polyrechnic institute of Brooklyn. He studied at Weizmann Institute of Science for the Ph.D., and then spent 2 years (1968-1970) as postdoctoral ieliow at tiarvard University. He has been a Lecturer in the Department of Biological Sciences at Columbia University. Dr. Wonig's research mainly concerns the properties of visual pigments and the factols that determine protein folding. Arieh Warshel was born in Kibbutz Sdeh Nahum, Israel, in 1940, and studied for his B.Sc degree at the Technion, Haifa He received the Ph.D. degree from Weizmann Institute of Science, where he I S now Senior Scientist. During 1970-1972, he was a postdoctoral fellow at Harvard University. His research interests inciude the spectroscopic and conformational properties of large molecules, dynamical aspects of photoisomerization, and enzymatic reactions. Martin Karplus is Professor of Chernistry at liarvard University and at the University of Paris VI1 tie was born in Vienna. Austria, in 1930. He received his B.A. degree from Harvard University and the Ph.D. from California institute of Technology in 1953. Professor Karplus's tesearch is in theoreticai chemistry
from an isolated chromophore t,o the pigment suggests that there are significant changes in the electronic structure, whose exact origins are s?,ill h i from certain. It is clear, nevertheless, that, recent advances in our understa-n-dingof the ground-. and c x cited-stat,e properties of the retinal isoiirers provide a firmer foundation for the discussion of t,he sper:ho. scopic properties of the visual pigment. This is p ticularly true at the present time when a variety of techniques, such as resonance R.arnan,"-"l cireula.r dichroism,12-21 and picosecond laser22 studies, are being applied to unblea.ched rhodopsin and the vari-. ous intermediates that occur in the visual cycle and when artificial pigments formed from synthetic ana-logs of retinal and opsin are being iised to probe the nature of the c ~ r ~ ~ ~ ~ p h ointkrackion ~ e - p ~~ 2o3 -~~ 2e( j ~ ~ ~ (1) G . Vt'ald, ,Science, 162, 230 (1968). ( 2 ) H . 13. Jafl'e and M ,Orchin, "Theory anti Applimtion (11 I'll
Spectroscopy," Kiley. New Y o r l ~N. ~ Y., i962. ( 3 ) .J. N . Murr?ll. "The Theory of the Jilectronic Spectra oi Orgaiiic ?dolecules." Wiley, New York. K,Y.,1963. ( 4 ) 13. E. Siiiimoiis,Pr'og. Phys. 07:: Chein., 7. I ( 1 9 7 0 ) . ( 5 ) I I . Suzuki. "Electronic Absorption Spectra and Geonietrv oi' Organic. Molecules," Academic Prrns. Kew York, N.Y . , 1967. (6) I,. Salem. "The hlolecular Orbital 'rheory ol' Conjrrqatcd Syntcms." W . A . Benjamin. New York. K.Y., 1966. ( 7 ) B. Horiia and T. Ebrey. Ann. R e u . f i i o p i q a f l i w r q . , 5 , 151 (197.1) (8)D.Rownds, vaticr re (London),21R, 1178 (19C7j. (9) K . Mendeleohn, N a t u r e (London),2-13, 22 ( i 9 ' ( i ) . (10) A . Lewis and J . Spoonhower in "Kc.utmii troscopy in Biophysics and Chemistry," Arademi 1974.
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S e i . l T , SA , , Xi, IT29 (19G6). (13) M. 'I'akezuki and Y. Kito, ,Vatuw (London),2 4 i 9 1197 (196'7). (14) Y.Kito; M . ilzuma, and 1'. Maetlii, Uiochh I l i o p h ) s . A ( , ~ ( Ll:;L,, 362 (1968). in "Handhook of Sensory P l i y s ~ o h inger-i'erlag, Berlin, 197?, 1) 180. and 'r.Yosliizawa, E . L ~E;?? fips , (18) A S . Waggonsr a n d L . Slryer, Riocheinistri,. 10, X Z J O (1971). (19) E. M. ,Johr:ston aiid R. %and., Riocheni. ! h p h ~ h. ' c ~ r . ('o!nmurT., 47, 712 l1972). (20) W . F. Momaerts in "The liejina," 1%. II. Straatsms, R d . U i i i of Calilhrnia Press: Los Angeles. Calif., 1969. pp 225 234. (21) Ivl, J. Rurlie, n. C. Pratt, T. R . Fauikiiw, arid A . Moscwitz. F,'L/I E,ye Res., 17, 557 (1973).
h d a . slid 1'.
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