Linear Free-Energy Relationships (LFER) and Solvation Thermodynamics: The Case of Water and Aqueous Systems

Abstract

The Abraham solvation parameter model, known alternatively as the Linear Solvation-Energy Relationships (LSER) model, is critically examined for its capacity to predict the hydration free-energy for a variety of solutes. The very linearity of the LSER approach is reconsidered as regards the hydrogen-bonding contribution to solvation free energy. This is done by combining the equation-of-state solvation thermodynamics with the statistical thermodynamics of hydrogen bonding. Thus, this hydrogen-bonding contribution is placed on a firm thermodynamic basis and the predictive calculations are now possible with known acidity and basicity, A and B, molecular descriptors. The LFER coefficients are now expressed in terms of the A and B descriptors. The methodology for the derivation of the new linear equations for the hydrogen-bonding contribution to solvation free energy is presented along with examples of calculations. The implication for the exchange of information on intermolecular interactions between diverse Quantitative Structure–Property Relationships (QSPR) and other approaches is discussed. The proposed changes and descriptor adjustments augments the LSER capacity for solvent screening and use in numerous applications in the broader chemical, biochemical and environmental sector. A critical discussion of perspectives and the challenging issues is also presented. Keywords: Abraham LSER model, Hydrogen-bonding, Molecular descriptors, Hydration, COSMO-RS