A Collective Variable for the Control of Solvation in Cage Compounds

Host-guest complexation has captivated the curiosity of researchers across disciplines, sparking both experimental and computational studies. Yet, the most common guest, the solvent, is often neglected. In this work we propose a collective variable (CV) to control the occupation of any given supramolecular structure in molecular dynamics simulations. The solvent accessible volume of the cage structures is approximated by a tetrahedral tessellation and is thereby able to adapt in shape and size during the simulation for flexible systems. With a symmetric and smooth function, we can determine a continuous loading by switching the solvent molecules from outside to inside. By applying a harmonic bias, the number of solvent molecules within the cavity can be systematically controlled, and e.g. by umbrella sampling the free energy profile for increased solvent loading can be computed. The approach is applied and validated for a purely organic porous solvent system and a palladium-based metal-organic cage compound. The influence of the smoothing parameter is tested and the results are com- pared to available experimental data as well as prior simulation results. The method is shown to be versatile and efficient in quantifying the loading of flexible and deforming molecular cages while monitoring the subsequent reactions of their hosts, with relevance for catalytic processes or separation using such tunable systems.