# Solvent-Driven Modulation of Shuttling Dynamics in an Autonomous Chemically Fueled Information Ratchet

## TL;DR

This paper explores how solvents influence the movement of a molecular machine, revealing how different solvent properties affect its performance.

## Contribution

The study introduces a framework for understanding solvent effects on molecular shuttling dynamics using a combination of advanced simulation techniques.

## Key findings

- Highly polar solvents lead to symmetric macrocycle distribution between binding sites.
- Low-polarity solvents induce conformational collapse favoring single-site occupancy.
- Free-energy barriers remain similar, but transition pathways show solvent-dependent asymmetries.

## Abstract

The performance of artificial molecular machines relies
on the
interplay between molecular design and environmental factors, yet
how solvation shapes their energy landscapes and kinetics remains
poorly understood. Here, we combine well-tempered and infrequent metadynamics
to investigate equilibrium shuttling in a minimal [2]­rotaxane inspired
by Borsley’s fuel-driven molecular motor. By systematically
varying solvent polarity and hydrogen-bonding capacity, we uncover
distinct thermodynamic and kinetic regimes that govern macrocycle
motion. In highly polar, hydrogen-bond-accepting media, the macrocycle
adopts a symmetric distribution between binding sites, with enthalpic
and entropic forces in direct competition. Conversely, in low-polarity,
hydrogen-bond-donating environments, the axle undergoes a conformational
collapse that entropically biases occupancy toward a single station
in the absence of chemical fuel. Despite comparable free-energy barriers
across conditions (9–13 kcal/mol), the transition pathways
exhibit pronounced solvent-dependent asymmetries and energetic ruggedness.
These findings provide a molecular-level framework for understanding
how solvation dictates passive ratchet behavior and offer strategic
insights for designing high-performance molecular machines tailored
to complex media.