The retinal chromophore/chloride ion pair: Structure of the photoisomerization path and interplay of charge transfer and covalent states

Abstract

Ab initio multireference 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-␥-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 S 1 energy barriers along all of the isomerization paths except the one mimicking the 11-cis 3 all-trans isomerization of the rhodopsin chromophore model; and (iii) changes the nature of the S1 3 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.ab initio ͉ counterion ͉ conical intersection ͉ protonated Schiff base R etinal proteins (1-4) include the retina visual pigment rhodopsin (Rh) and the bacterial proton-pump bacteriorhodopsin (bR). The biological activity of these pigments is triggered by the ultrafast light-induced cis-trans isomerization of their chromophores. These correspond to the 11-cis (PSB11) and all-trans (PSBT) stereoisomers of the protonated Schiff base (PSB) of retinal respectively. Recently, we have reported (5-7) the computed photoisomerization path of different models of PSB11 and PSBT in vacuo. It has been shown that, invariably, the excited state branch of the path develops entirely along a charge transfer state (that can be related to the 1B u , i.e., hole pair, state of polyenes) that corresponds to the first singlet excited state (S 1 ) of the system and ends at a peaked conical intersection (CI) where the S 1 and ground (S 0 ) state energy surfaces cross. Because the CI features an Ϸ90°t wisted double bond, its geometrical and electronic structure is consistent with that of a twisted intramolecular charge transfer (TICT) state (5-7). The corresponding S 1 isomerization coordinate, starting at a planar Franck-Condon (FC) point, is bimodal being sequentially dominated by two uncoupled modes. The first corresponds to a stretching mode involving C-C bonds order inversion. The second mode breaks the planar symmetry and is dominated by a one-bond-flip (OBF) (8, 9) twisting of the reacting double bond.In Fig. 1, we report the computed energy profiles and give a pictorial view of the structure of the S 1 energy surface of the PSB11 model 4-cis-␥-methylnona-2,4,6,8-tetraenimin...

Molecular bases for the selection of the chromophore of animal rhodopsins

“…The same three-state model may control the excited state dynamics of unsubstituted and certain substituted PSBAT in solution displaying S 1 picosecond lifetimes (47). The presence of an S 2 /S 1 degeneracy in solvated PSBAT models has been proposed (48) and held responsible for the observed solution dynamics of PSBAT (49). Similar data have been reported for PSB11 (50,51), suggesting that the Rh cavity has important effects on the electronic structure of its chromophore.…”

How a small change in retinal leads to G‐protein activation: Initial events suggested by molecular dynamics calculations

“…Multiple research groups are performing quantum chemical calculations of the initial events in photoisomerization. [35][36][37][38][39][40] We wanted to address the longertime scale (nanosecond towards millisecond) relaxation of the system following the initial light activation. While quantum chemical calculations have advanced significantly in the last few decades, they continue to be limited by the number of heavy atoms in the system and to explore very fast (femtosecond to picosecond) time scales.…”

“…[35][36][37][38][39][40] Our initial model covers that change by forcing the main cis-trans isomerization and then allowing relaxation from that state within the CHARMM potential function. The response to this change is then followed throughout the remainder of the simulation.…”

Tracking the primary photoconversion events in rhodopsins by ultrafast optical spectroscopy

“…few ps) and the low QY (∼20%) observed. In proteins, it has been proved by both experiments 38,39 and computations 25,40,41 that the reaction does not only involve the torsion around the reacting double bond driving the isomerization process (C 11 vC 12 for Rh and C 13 vC 14 for BR), but also other high-frequency normal modes, such as CvC and C-C stretching and hydrogen-out-ofplane (HOOP) motion, especially in the early stages. Therefore…”

“…The overall structure of retinal in photoRh is more similar to that of the reactant than of the final product bathoRh, which is not surprising given the extremely rapid formation of this state, but clearly calls for a multi-dimensional isomerization model, driven by more than one vibrational coordinate. 40,41 FSRS data also enable to understand the role of the tight protein binding pocket in promoting the reaction and maximizing its QY: (i) by pretwisting the retinal backbone, it primes the molecule for rapid excitedstate decay along the HOOP coordinate; (ii) it restricts the possible motion of the excited chromophore through steric interactions with surrounding amino acids; and (iii) it captures the high-energy bathoRh product and efficiently transfers this energy into protein conformational changes that activate signal transduction cascades.…”