ChemInform Abstract: An Artificial Visual Pigment with Restricted C9‐C11 Motion Forms Normal Photolysis Intermediates.

Abstract

The artificial 11‐cis‐retinal (I) (synthesis already published) forms a pigment when incubated with bovine opsin.

Methyl Substituents at the 11 or 12 Position of Retinal Profoundly and Differentially Affect Photochemistry and Signalling Activity of Rhodopsin

“…[6][7][8][9][10]28 It is suggested that the mechanism underlying the efficient isomerization of the retinylidene group in the excited state of rhodopsin involves the expansion of the C = C double bonds and simultaneous displacement of the hydrogen atoms in the C-11H = C-12H motif from a cis to a trans position with respect to each other. For native rhodopsin, the main displacement would be a rotation at the site of the C-12H element in the chromophore, 6,9,10 which agrees with the observation that the locked 11,19-ethano rhodopsin analog shows normal photointermediate kinetics, 44 and with the recently published crystal structure of Batho. 11 It has been suggested that a prerequisite for an efficient isomerization is a steep and coherent path over the excited state surface, and that the speed and efficiency are correlated closely.…”

“…Although a quantum yield has not been determined, this might at least explain the rather normal early photointermediate kinetics observed for 11,19-ethanorhodopsin. 44 In conclusion, our study completes a series of studies investigating the effect on photoactivation of rhodopsin of a single addition or removal of a methyl group at positions in the central, photoactive segment, C-9-C-14, of the chromophore. First of all, the important conclusion can be drawn that all available data, including those obtained upon methylation of C12, do concur with an outof-plane movement of the = C12 substituent as the primary mechanism of the photoisomerization process.…”

“…11 This will modify the energy surface of the isomerization path. Connecting the C-9 and C-11 methyl groups, as in 11,19-ethano retinal, 44,45 releases a major element of this crowding perturbation yielding a ground-state and an excited-state structure that is closer to the native system. In addition, the unfavorable effect of energy dissipation by molecular motion of this segment is expected to be significantly less for the 11,19-ethano pigment than for 11-methyl rhodopsin.…”

“…In fact, the formation rate of the early photointermediates of the 11,19-ethano pigment is very similar to that of rhodopsin. 44 It is concluded that the 11-methyl analog of 11-Z retinal does not optimally fit into the binding site. Steric hindrance is expected with residues of the E2 loop and of helix II.…”

“…A structurally more restricted analog, 11-Z 11,19-ethano retinal, was reported to generate the corresponding analog pigment efficiently. 44,45 The ethano bridge renders this ligand sterically less demanding, since it restricts the mobility of the C-9-C-11 segment and eliminates the repulsive interaction between the 9-methyl and 11-methyl groups. In fact, the formation rate of the early photointermediates of the 11,19-ethano pigment is very similar to that of rhodopsin.…”