Conformational isomerization dynamics in solvent violates both the Stokes-Einstein relation and Kramers' theory

TL;DR

This study uses molecular dynamics simulations to investigate how solvent friction affects molecular isomerization, revealing violations of classical relations and uncovering complex multi-scale friction effects that influence reaction kinetics.

Contribution

It provides the first direct evaluation of frequency-dependent dihedral friction in solvents, showing deviations from the Stokes-Einstein relation and Kramers' theory.

Findings

Friction does not scale linearly with solvent viscosity.

Isomerization occurs faster than Kramers' theory predicts.

Multi-time-scale friction coupling causes non-Markovian speed-up.

Abstract

Molecular isomerization kinetics in liquid solvents are determined by a complex interplay between the friction acting on a rotating dihedral due to interactions with the solvent, internal dissipation effects (also known as internal friction), the viscosity of the solvent, and the free energy profile over which a dihedral rotates. Currently, it is not understood how these quantities are related at the molecular scale. Here, we combine molecular dynamics simulations of isomerizing n-alkane chains and dipeptide molecules in mixed water-glycerol solvents with memory-kernel extraction techniques to directly evaluate the frequency-dependent friction acting on a rotating dihedral. We extract the friction and isomerization times over a range of glycerol concentrations and accurately evaluate the relationships between solvent viscosity, isomerization kinetics, and dihedral friction. We show that the total friction acting on a rotating dihedral does not scale linearly with solvent viscosity, thus violating the Stokes-Einstein relation. Additionally, we demonstrate that the kinetics of isomerization are significantly faster compared to the Kramers prediction in the overdamped limit. We suggest that isomerization kinetics are determined by the multi-time-scale friction coupling between a rotating dihedral and its solvent environment, which results in non-Markovian kinetic speed-up effects.