First-Principles Modeling of Preferential Solvation in Mixed-Modifier Differential Mobility Spectrometry.

Differential mobility spectrometry (DMS) separates ions based on mobility differences between high and low electric field conditions. To enhance resolution, solvents such as water and acetonitrile are often used to modify the collision environment and take advantage of differing dynamic clustering behavior between analytes that coelute in hard-sphere environments (., N). When binary solvent mixtures are used to modify the DMS environment, one solvent can have a dominant influence over the other with respect to ion trajectories. For example, for quinoline derivatives, a 9:1 water:acetonitrile solvent mixture exhibited identical behavior to an environment containing only acetonitrile as a modifier. It was hypothesized that this effect arises due to the significantly different binding strengths of the two solvents. Here, we utilize a first-principles model of DMS to study analytes in single and binary solvent mixtures and explore the effects governing the dominance of one solvent over the other. Computed DMS dispersion curves of quinoline derivatives are in excellent agreement with those measured experimentally. For mixed-modifier environments, the predicted cluster populations show a clear preferential solvation of ions with the stronger binding solvent. The influence of ion-solvent binding energies, solvent concentration, and solvent molecule size is discussed in the context of the observed DMS behavior. This work can guide the usage of binary solvent mixtures for improving ion separations in cases where compounds coelute in pure N and in single-solvent modifier environments. Moreover, our results indicate that binary solvent mixtures can be used to create a relative scale for solvent binding energies.