Solvent-Dependent Conformational States of a [2]Rotaxane-Based Molecular Machine: A Molecular Dynamics Perspective

Motion is an essential and fundamental feature of any living organism. The evolved organisms have developed sophisticated and perfect machineries and highly delicate mechanisms to carry out directional and coordinated movements which eventually lead to motion at the macroscopic length scale. By mimicking these natural machineries, attempts to design and synthesize similar molecular motors are made in relevance to their applications in drug delivery, data storage, and molecular sensing. It is highly desirable to establish the rules for controlling the conformational states of molecular motors by tuning some of the external variables which can be used for the design strategies. We contribute to this subject by looking into the solvent influence on the conformational states of a synthetic molecular rotor, namely, diketopyrrolopyrrole (DPP) based [2]rotaxane, using the force-field molecular dynamics approach. We study this system in three different solvents, and we report a strong solvent dependence in the population of three different translational isomers. In chloroform solvent we report the dominant population of the 2-P isomer which is in excellent agreement with experimental results based on H NMR spectra (Org. Lett. 2013, 15, 1274). However, there is a striking difference seen in the population of translational isomers in DMSO solvent, and we attribute these features to negligence of solvent hydrogen bonding induced upfield and downfield effects in the interpretation of experimental proton NMR spectra. In addition, we also report a solvent-polarity-induced fully unstretched to folded conformational transition in the [2]rotaxane system. On the basis of the molecular mechanics Poisson-Boltzmann (and generalized Born) surface area approach, we identify the driving force for the formation of the supramolecular guest-host [2]rotaxane system. Finally, we calculate the relative binding free energies for the macrocycle at different binding sites of the DPP skeleton using the molecular dynamics simulations performed for the macrocycle-rotaxane system in water solvent which suggests the increased stability of the 2-O isomer in polar solvent.