The Critical Helping Hand of Water: Theory Shows the Way to Obtain Elusive, Granular Information about Kinetic Asymmetry Driven Systems

Kinetic asymmetry is crucial in chemical systems where the selective synthesis of one product over another, or the accelera-tion of specific reaction(s) is necessary. However, obtaining precise information with current experimental methods about the behavior of such systems as a function of time, substrate concentration and other relevant factors, is not possible. Com-putational chemistry provides a powerful means to address this problem. The current study unveils a two-pronged computa-tional approach: (i) full quantum chemical studies with density functional theory (DFT), followed by (ii) stochastic simula-tions with a validated Gillespie algorithm (GA) (using representative model systems where necessary), to study the behavior of a kinetic asymmetry driven unidirectional molecular motor (1-phenylpyrrole2,2′-dicarboxylic acid) (Na-ture 2022, 604 (7904), 80–85). Our approach allows us to understand what is really taking place in the system, underlining the crucial role played by water molecules in facilitating the rotation of the motor. It is seen that water lubricates the motion by increasing the rotation rate constant of the final step by, remarkably, more than ten orders of magnitude! These insights further serve to explain the efficient rotation of the very recently reported gel-embedded molecular motor (Na-ture 2025, 637 (8046), 594–600), providing an upper limit for the allowed rotation barrier in such systems, and thus also casts light into the functioning of bio-molecular motors. The current work therefore provides a template for carefully and properly studying a wide variety of important, kinetic asymmetry driven systems in the future.