Retinal chromophore charge delocalization and confinement explain the extreme photophysics of Neorhodopsin

Abstract

The understanding of how the rhodopsin sequence can be modified to exactly modulate the spectroscopic properties of its retinal chromophore, is a prerequisite for the rational design of more effective optogenetic tools. One key problem is that of establishing the rules to be satisfied for achieving highly fluorescent rhodopsins with a near infrared absorption. In the present paper we use multi-configurational quantum chemistry to construct a computer model of a recently discovered natural rhodopsin, Neorhodopsin, displaying exactly such properties. We show that the model, that successfully replicates the relevant experimental observables, unveils a geometrical and electronic structure of the chromophore featuring a highly diffuse charge distribution along its conjugated chain. The same model reveals that a charge confinement process occurring along the chromophore excited state isomerization coordinate, is the primary cause of the observed fluorescence enhancement.

Automated QM/MM Screening of Rhodopsin Variants with Enhanced Fluorescence

“…Notice that this mechanism is strongly supported by ref that presented an extensive study on Archaerhodopsins carried out using the 2-root state average level of theory (see the Supporting Information Sections S6 and S8). Such study, produces, for the terminal part of the reaction path, results that are consistent with the available experimental data (see refs and ) and with the charge behavior schematically illustrated in Figures and . In this case, we hypothesize that the diabatic states associated with the 1Ag and 1Bu cross one time in the region corresponding to the S 1 energy maxima.…”

“…Mechanism A2 (see Figure D), originally reported in this work, is instead due to the coupling between the reactive S 1 state with the bounded S 0 state and on the destabilization of the CI structure with respect to the FS region (see refs , for a more detailed description of this mechanism). Notice that, in contrast to mechanism A1, this mechanism involves a double bond twisting motion/deformation.…”

Surface hopping modeling of charge and energy transfer in complex environments

“…55 The recent simulations by Palombo and co-authors illustrate the state of the art of such a QM/MM surface hopping approach. 56 In this work, they employed it to explain the fluorescence of the retinal chromophore within neorhodopsin. This group has also developed protocols for automatically generating QM/MM models.…”

“…Although it goes beyond the scope of this Perspective, restricted to atomic and molecular environments, we cannot avoid mentioning that the nonadiabatic dynamics of an excited chromophore can also be affected by confined electromagnetic fields in the so-called polaritonic chemistry. 55,56 Over the last years, polaritonic chemistry has emerged as a gateway for remarkable functionalities but imposing a plethora of theoretical challenges. Polaritons are hybrids between light and matter and occur when the light-matter interaction becomes strong enough.…”

“…60 This strong coupling regime can significantly modify the photochemistry and photophysics of molecular systems, opening novel opportunities to control chemical transformations. 56,58 Once more, surface hopping is up to the challenge. 62 In a recent publication, Fregoni et al present theoretical strategies and challenges in polaritonic chemistry, mainly focusing on situations where molecular electronic transitions are coupled to light modes.…”