Absolute configurational determination of an all‐trans‐retinal dimer isolated from photoreceptor outer segments (original) (raw)
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Solution and biologically relevant conformations of enantiomeric 11-cis-locked cyclopropyl retinals
Journal of The American Chemical Society, 2002
To gain information on the conformation of the 11-cis-retinylidene chromophore bound to bovine opsin, the enantiomeric pair (2a and 2b) of 11-cis-locked bicyclo[5.1.0]octyl retinal (retCPr) 2 was prepared and its conformation was investigated by NMR, geometry optimization, and CD calculations. This compound is also of interest since it contains a unique moiety in which a chiral cyclopropyl group is flanked by triene and enal chromophores, and hence would clarify the little-known chiroptical contribution of a cyclopropyl ring linked to polyene systems. NMR revealed that the seven-membered ring of retCPr adopts a twist chair conformation. The NMR-derived structure constraints were then used for optimizing the geometry of 2 with molecular mechanics and ab initio methods. This revealed that enantiomer 2a with a 11 ,12cyclopropyl group exists as two populations of diastereomers depending on the twist around the 6-s bond; however, the sense of twist around the 12-s is positive in both rotamers. The theoretical Boltzmann-weighted CD obtained with the π-SCF-CI-DV MO method and experimental spectra were consistent, thus suggesting that the conjugative effect of the cyclopropyl moiety is minimal. It was found that only the -cyclopropyl enantiomer 2a, but not the R-enantiomer 2b, binds to opsin. This observation, together with earlier retinal analogues incorporation results, led to the conclusion that the chromophore sinks into the N-terminal of the opsin receptor from the side of the 4-methylene and 15-aldehyde, and that the binding cleft accommodates 11-cis-retinal with a slightly positive twist around C12/C13. A reinterpretation of the previously published negative CD couplet of 11,12-dihydrorhodopsin also leads to a chromophoric C12/C13 twist conformation with the 13-Me in front as in 1b. Such a conformation for the chromophore accounts for both the observed biostereoselectivity of retCPr 2a and the observed negative couplet of 11,12-dihydro-Rh7.
Quantitative aspects of the photochemistry of isomeric retinals and visual pigments
Journal of the American Chemical Society, 1976
The photoisomerization quantum efficiencies of all-trans-, 9-cis-, 1 1-cis-, 13-cis-, and 9-cis, 13-cis-retinal were determined upon direct excitation in polar and nonpolar solvents and biacetyl triplet sensitization in a polar solvent. The four cisretinals had quantum yields of 20% in nonpolar solvents and 4-5% in polar solvents. The biacetyl triplet sensitized quantum yields of the cis isomers were also ca. 20%. while all-trans-retinal underwent no detectable triplet isomerization. High-pressure liquid chromatography was used to analyze the photoproducts. It was found that only two types of carbon double bonds isomerized, the cis bonds and the terminal carbon double bond. Photobleaching of rhodopsin, isorhodopsin, and 9.1 3-isorhodopsin (isorhodopsin 11) gave stereospecifically all-trans-retinal. When rhodopsin was treated with the unique triplet sensitizer, trimethyl-1,2-dioxetane, the protein was denatured and the chromophore isomerized. Based on product studies and quantum yield measurements, it is concluded that in the cis-retinals the photoisomerization occurred from the singlet and triplet states. In visual pigments it is not possible to assign the state from which isomerization occurred.
Journal of the American Chemical Society, 2002
Multiconfigurational second-order perturbation theory computations and reaction path mapping for the retinal protonated Schiff base models all-trans-nona-2,4,6,8-tetraeniminium and 2-cis-nona-2,4,6,8tetraeniminium cation demonstrate that, in isolated conditions, retinal chromophores exhibit at least three competing excited-state double bond isomerization paths. These paths are associated with the photoisomerization of the double bonds in positions 9, 11, and 13, respectively, and are controlled by barriers that favor the position 11. The computations provide a basis for the understanding of the observed excitedstate lifetime in both naturally occurring and synthetic chromophores in solution and, tentatively, in the protein environment. In particular, we provide a rationalization of the excited-state lifetimes observed for a group of locked retinal chromophores which suggests that photoisomerization in bacteriorhodopsin is the result of simultaneous specific "catalysis" (all-trans f 13-cis path) accompanied by specific "inhibition" (all-trans f 11-cis path). The nature of the S 1 f S0 decay channel associated with the three paths has also been investigated at the CASSCF level of theory. It is shown that the energy surfaces in the vicinity of the conical intersection for the photoisomerization about the central double bond of retinal (position 11) and the two corresponding lateral double bonds (positions 9 and 13) are structurally different.
Journal of Photochemistry and Photobiology A: Chemistry, 2007
The effect of substitution on the intrinsic (i.e. in vacuo) photoisomerization ability of retinal chromophore models has been explored using CASPT2//CASSCF minimum energy path computations to map the S 1 photoisomerization paths of two substituted minimal models of the retinal chromophore: the 2-cis-penta-2,4-dieniminium and the all-trans-epta-2,4,6-trieniminium cations, which have been modified using fluorine or methoxyl substituents as representative examples of electron-withdrawing and electron-releasing groups, respectively. A systematic analysis has been performed involving substitutions in all the possible positions along the chain. It is shown that the photochemical reactivity and photoisomerization efficiency of these systems may be tuned or indeed changed, although this effect strongly depends on the position of the substituent. In particular, we have shown that (i) most of the systems preserves qualitatively the reactivity of the parent (i.e. unsubstituted) compound; (ii) substitution at positions C4 or C6 leads to a different relaxed excited state structure of the chromophore and in general to a very flat photoisomerization path (or to a tiny S 1 energy barrier in some cases); (iii) the nature of the TICT state (i.e. the S 1 → S 0 decay funnel) may be turned from a conical intersection into an excited state minimum; (iv) for the C4 methoxy-substituted system the isomerization path as well as the S 1 /S 0 decay funnel involve an unusual torsional angle. Thus, substitution turns out to be a good tool not only to tune the optical properties (i.e. the absorption and emission features) of the chromophore (as we have already shown in a previous work: I. Conti, F. Bernardi, G. Orlandi, M. Garavelli, Mol. Phys. 104 (2006) 915-924), but it may also play a crucial role in tuning and controlling photoisomerization selectivity and efficiency, affecting excited state lifetime and reaction rate. A rationale for these effects is presented, which provides a basis for understanding reactivity properties and the intrinsic photochemical behavior of substituted retinal chromophores.
The molecular structure of a curl-shaped retinal isomer
Journal of Molecular Modeling, 2008
Computational studies of retinal protonated Schiff base (PSB) isomers show that a twisted curl-shaped conformation of the retinyl chain is a new low-lying minimum on the ground-state potential energy surface. The curl-shaped isomer has a twisted structure in the vicinity of the C 11 =C 12 double bond where the 11-cis retinal PSB isomerizes in the rhodopsin photoreaction. The twisted configuration is a trapped structure between the 11cis and all-trans isomers. Rotation around the C 10 -C 11 single bond towards the 11-cis structure is prevented by steric interactions of the two methyl groups on the retinyl chain and by the torsion barrier of the C 10 -C 11 bond in the other direction. Calculations of spectroscopic properties of the 11-cis, all-trans, and curl-shaped isomers provide useful data for future identification of the new retinal PSB isomer. Circular dichroism (CD) spectroscopy might be used to distinguish between the retinal PSB isomers. The potential energy surface for the orientation of the β-ionone ring of the 11-cis retinal PSB reveals three minima depending on the torsion angle of the β-ionone ring. Two of the minima correspond to 6-s-cis configurations and one has the βionone ring in 6-s-trans position. The calculated CD spectra for the two 6-s-cis configurations differ significantly indicating that the sign of the β-ionone ring torsion angle could be determined using CD spectroscopy. Calculations of the CD spectra suggest that a flip of the β-ionone ring might occur during the first 1 ps of the photoreaction. Rhodopsin has a negative torsion angle for the β-ionone ring, whereas the change in the sign of the first peak in the experimental CD spectrum for bathorhodopsin could suggest that it has a positive torsion angle for the β-ionone ring. Calculated nuclear magnetic resonance (NMR) shielding constants and infrared (IR) spectra are also reported for the retinal PSB isomers.
Direct Measurement of the Isomerization Barrier of the Isolated Retinal Chromophore
Angewandte Chemie (International ed. in English), 2015
Isomerizations of the retinal chromophore were investigated using the IMS-IMS technique. Four different structural features of the chromophore were observed, isolated, excited collisionally, and the resulting isomer and fragment distributions were measured. By establishing the threshold activation voltages for isomerization for each of the reaction pathways, and by measuring the threshold activation voltage for fragmentation, the relative energies of the isomers as well as the energy barriers for isomerization were determined. The energy barrier for a single cis-trans isomerization is (0.64±0.05) eV, which is significantly lower than that observed for the reaction within opsin proteins.
Light activation of the isomerization and deprotonation of the protonated Schiff base retinal
Journal of Molecular Modeling
We perform an ab initio analysis of the photoisomerization of the protonated Schiff base of retinal (PSB-retinal) from 11-cis to 11-trans rotating the C10-C11=C12-C13 dihedral angle from 0° (cis) to -180° (trans). We find that the retinal molecule shows the lowest rotational barrier (0.22 eV) when its charge state is zero as compared to the barrier for the protonated molecule which is ∼0.89 eV. We conclude that rotation most likely takes place in the excited state of the deprotonated retinal. The addition of a proton creates a much larger barrier implying a switching behavior of retinal that might be useful for several applications in molecular electronics. All conformations of the retinal compound absorb in the green region with small shifts following the dihedral angle rotation; however, the Schiff base of retinal (SB-retinal) at trans-conformation absorbs in the violet region. The rotation of the dihedral angle around the C11=C12 π-bond affects the absorption energy of the retinal and the binding energy of the SB-retinal with the proton at the N-Schiff; the binding energy is slightly lower at the trans-SB-retinal than at other conformations of the retinal. Figure a, Rhodopsin protein in cone and rod cells is able to recognize colors. b, Rhodopsin photoreceptor, a transmembrane protein, has a retinal chromophore joined covalently to Lys 296 through a protonated Schiff base linkage (cis-PSB-retinal). In dark conditions, retinal is in cis-conformation. c, Structure of PSB-retinal where the dihedral angle rotates along the orange C11=C12 bond to calculate the potential energy surface of the ground state (S0) and excited state (S1). d, Potential energy surface at ground state (S0) and excited state (S1) for ethene
2005
Ab initio multi-reference second-order perturbation theory computations are used to explore the photochemical behavior of two ion pairs constituted by a chloride counterion interacting with either a rhodopsin or bacteriorhodopsin chromophore model (i.e., the 4-cis-gamma-methylnona-2,4,6,8-tetraeniminium and all-trans-nona-2,4,6,8-tetraeniminium cations, respectively). Significant counterion effects on the structure of the photoisomerization paths are unveiled by comparison with the paths of the same chromophores in vacuo. Indeed, we demonstrate that the counterion (i) modulates the relative stability of the S0, S1, and S2 energy surfaces leading to an S1 isomerization energy profile where the S1 and S2 states are substantially degenerate; (ii) leads to the emergence of significant S1 energy barriers along all of the isomerization paths except the one mimicking the 11-cis --> all-trans isomerization of the rhodopsin chromophore model; and (iii) changes the nature of the S1 --> S0 decay funnel that becomes a stable excited state minimum when the isomerizing double bond is located at the center of the chromophore moiety. We show that these (apparently very different) counterion effects can be rationalized on the basis of a simple qualitative electrostatic model, which also provides a crude basis for understanding the behavior of retinal protonated Schiff bases in solution.