Understanding the Granular Behavior of a Unidirectional Molecular Motor Through Combined DFT-Stochastic Simulation Studies

Developing autonomous, chemically fueled, unidirectional molecular motors is currently a very vibrant area of research. Possibly the most exciting recent advancement in this field was the report of a 360° rotatory chiral catalyst-driven motor using the 1-phenylpyrrole 2, 2′-dicarboxylic acid motor molecule (Leigh and coworkers, direct reference). This molecule was seen to undergo complete rotation in one direction along a C-N bond with the aid of double kinetic gating provided by (i) a chiral fuel-waste reaction and (ii) a chiral catalyst aided hydration reaction. While this is a remarkable development, it is important to note that the final step of the rotation process in this system could not be tracked by experiment, and was hypothesized based on the assumed ease of rotation along the C-N bond at that step. Since the rotor also has the option of reverting back in a reverse rotation step from this point, it is important to investigate carefully all the possibilities of movement of the system and determine the correctness of the complete rotation, as well as the efficacy of such motion, along with a granular understanding the nature and behavior of the system at every step of the process. Such a desirable study is only possible through carefully conducted and validated computational studies. This is the motivation of the current work. We have employed a two-pronged approach, employing (i) full quantum chemical studies with density functional theory (DFT) to elucidate the proper reaction mechanism for every step and obtain information about the thermodynamics and the kinetics of the processes, as well as (ii) exact stochastic simulations with the Gillespie algorithm, with the information obtained. We have first employed this approach on an analogue of the actual motor system (which was also reported by Leigh and co-workers in the same study), and properly validated our computational results with the experimental results obtained for this analogue. Subsequently, we have employed our validated approach to the actual motor system, and obtained interesting results that (i) show that the system indeed does behave like a molecular motor by rotating through 360° in a unidirectional fashion while the fuel exists, but (ii) it does so with poor efficiency, not utilizing all the energy of the fuel-waste reaction to do so. This work, therefore, provides important insights into the nature and behavior of such systems, which can lead to the development of more improved autonomous, unidirectional molecular motors in the near future.