The Correlated States Theory of the Hydrophobic Effect.

Abstract

Starting from Frank and Evans' "iceberg" model of hydrophobic hydration of small molecules (the "microscopic" hydrophobic effect, HE) published in 1945, much has been done with respect to understanding the nature of HE and elaborating a quantitative theory able to describe the thermodynamic profile (the "signature" of HE) for the large volume of experimental data accumulated to date. Generally, three sets of approaches addressing this issue were suggested, ranging from the approval of the central role of the water shell to the complete denial of its role, with the focus placed on the solute and its interactions with surrounding water. For this reason, some controversy is still present in understanding the fundamental nature of HE, even at the "microscopic" scale. Nevertheless, the general tendency of the past decade seems to have shifted toward a greater role of the water environment in determining the thermodynamic profile of HE, with a designated place for solute-water interactions as a fine-tuning of thermodynamic observables. In the present work, we developed a novel view on HE at the microscopic scale, appearing as a consequence of solute-water correlated translational and orientational vibration motion, emerging as a new property of hydrophobic hydration/solvation (the Correlated States Theory of HE). We built a fully analytical description of this process, which has enabled us to quantify the "signature" of HE for extended thermodynamic data sets without employing molecular simulations or any numerical functions in the core of the theory. As a consequence, our approach provides a self-consistent view on the known major experimental manifestations of HE across an extended temperature range, addresses some controversial issues existing to date, and creates a new augmentation to current knowledge. Most importantly, the suggested approach offers a paradigm shift from the currently dominating views on HE as a consequence of water-water interactions and the "excluded volume effect" toward the central role of solute-water interactions, and provides the first nonempirical proof of the validity of SASA-based computational models of hydrophobic hydration/solvation, which have been utilized on an empirical basis for more than 40 years.