Demystifying Preferential Solvation Phenomena

In this work we identify and derive the rigorous formal signature and unique molecular-based expression for the unambiguous assessment of the preferential solvation phenomena involving any type of dilute solute in any mixed binary-solvent system. In particular, we formulate the rigorous assessment of preferential solvation in ternary system involving a combination of dissociative and nondissociative species. Our goal comprises the characterization of a universal representation for the <i>preferential solvation function</i> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>P</mml:mi><mml:mi>S</mml:mi><mml:mrow><mml:mo>(</mml:mo><mml:mi>T</mml:mi><mml:mo>,</mml:mo><mml:mi>P</mml:mi><mml:mo>,</mml:mo><mml:msub><mml:mrow><mml:mi>x</mml:mi></mml:mrow><mml:mrow><mml:mi>j</mml:mi></mml:mrow></mml:msub><mml:mo>)</mml:mo></mml:mrow></mml:math> according to fundamental molecular scale-to-macroscopic relationships between the differential microstructural perturbation of the mixed-solvent environments and the thermodynamic responses of the solute's standard chemical potential to changes in the mixed-solvent composition. For that purpose, we first derive the formal expressions to make feasible the inversion of the Kirkwood-Buff approach for these types of systems, to determine the required total correlation function integrals, and then to assess the resulting solvation behavior. Further linking of the <i>universal preferential solvation function</i> to precisely defined <i>fundamental structure-making/-breaking functions</i> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mrow><mml:mi>S</mml:mi></mml:mrow><mml:mrow><mml:mi>α</mml:mi><mml:mi>β</mml:mi></mml:mrow></mml:msub><mml:mrow><mml:mo>(</mml:mo><mml:mi>T</mml:mi><mml:mo>,</mml:mo><mml:mi>P</mml:mi><mml:mo>,</mml:mo><mml:msub><mml:mrow><mml:mi>x</mml:mi></mml:mrow><mml:mrow><mml:mi>α</mml:mi></mml:mrow></mml:msub><mml:mo>)</mml:mo></mml:mrow></mml:math> facilitates the explicit interpretation of a variety of preferential solvation phenomena including the cosolvent effects on the conformational equilibrium of proteins, on the kinetic rate constant of chemical reactions, as well as the interplay between cosolvency and co-nonsolvency processes in mixed-solvent environments.