The effect of solvent heterogeneity on the solvation and complexation of alkali cations by 18-crown-6: a simulation study in the 90 : 10 chloroform/methanol mixture

Abstract

We studied by molecular dynamics “MD” and potential of mean force “PMF” simulations the complexation of M⁺ alkali picrates by 18C6 in the 90 : 10 chloroform/methanol mixture and in its neat solvent components, for comparison. The mixture is found to be microscopically heterogeneous, owing to self-aggregation of methanol molecules into labile nano-domains. It thus displays dual “amphiphilic” solvation properties: the free or complexed M⁺ and Pic⁻ ions are mainly solvated by the methanol molecules, while 18C6 prefers chloroform. As a result, although chloroform is in excess in the mixture, the predicted thermodynamics of complexation (absolute binding free energies and selectivities) is more methanol-like than chloroform-like, with the selectivity order K⁺ > Cs⁺ > Na⁺. In pure chloroform, it would be: Na⁺ > K⁺ > Cs⁺, as in the gas phase. The results point to the analogy between preferential solvation in the studied mixture and at water/oil interfaces. Beyond the prototypical case studied here, understanding the subtle factors that determine the thermodynamics of binding and recognition in solvent mixtures, from traces to co-solvents, is crucial in many processes in chemistry and biology.