Theoretical and Computational Chemistry

Effect of Stacking Interactions on Charge Transfer States in Photoswitches Interacting with Ion Channels



The activity of ion channels can be reversibly photo-controlled via the binding of molecular photoswitches, often based on an azobenzene scaffold, in their internal cavity. Those azobenzene derivatives mainly interact non-covalently with aromatic residues via stacking interactions. In the present work, the effect of face-to-face and t-shaped stacking interactions on the excited state electronic structure of azobenzene and p-diaminoazobenzene integrated into the NaV1.4 channel is investigated via quantum mechanics/molecular mechanics calculations combined with classical molecular dynamics. The formation of a charge transfer state, characterized by electron transfer from aromatic protein residues to the photoswitches, is observed. This state is strongly red shifted when the interaction takes place in a face-to-face orientation, and electron donating groups are present on the aromatic ring of the aminoacids but not on the photoswitches. The low-energy charge transfer state can interfere with the photoisomerization process after excitation to the bright state and lead to the formation of radical species, which can permanently damage the protein and the surrounding environment


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Supplementary material

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Computational Details
Computational details of the systems setup, molecular dynamics simulations, QM/MM calculations and vacuum calculations.