Quantitative structure-activity and structure-property relationship (QSAR/QSPR) studies are unquestionably of great importance in modern chemistry and biochemistry. The concept of QSAR/QSPR is to transform searches for compounds with desired properties using chemical intuition and experience into a mathematically quantified and computerized form. 1
Solvent polaritySimplistically, "solutions" can be defined as homogeneous liquid phases consisting of more than one substance in variable ratios, where one of the substances, the so-called "solvent" (which could itself be a mixture), is treated differently from the other substances, which are called "solutes". Usually, the solute(s) is/are the minor component(s) and the solvent is the component in excess. The term "polarity" is usually related to the capacity of a solvent for solvating dissolved charged or dipolar species.2 Solvent polarity defined as the overall solvation capability (or solvation power) for reactants and activated complexes as well as for molecules in the ground and excited states, which in turn depends on the action of all possible, specific and nonspecific, intermolecular forces between solvent and solute molecules, including Coulomb interactions between ions, directional interactions between dipoles, and inductive, dispersion, hydrogen-bonding, and charge-transfer forces, as well as solvophobic interactions. Only those interactions leading to definite chemical alterations of the solute molecules through protonation, oxidation, reduction, complex formation, or other chemical processes are excluded. 3 A number of general empirical solvent scales have been reported. [3][4][5] In earlier reports, a unified solvation model was offered to treat both specific and non specific effects. 5,6-10 In 1992, Drago 5 developed the "unified solvent polarity", also called the "S′ scale" by using a least-squares minimization program 11 to fit a series of physico-chemical properties (χ) for systems where specific interactions with the solvents were excluded to the equation:In this equation, Δχ is the solvent-dependent physicochemical property, P is the susceptibility of the solute probe to polarity, S′ is the solvent polarity derived from experimental observations, EA and EB are the electrostatic specific interaction parameters of the acid and base, CA and CB are the covalent parameters of the acid and base and W is a constant that is the value of Δχ when EA = CA = P = 0. This model separates solvent effects into non specific (PS′) and specific (EAEB + CACB) interactions. The former arises from non specific electrostatic forces involving bulk and internal solvent permittivity influences on charged ions, non polar and dipolar solutes. The latter comprises electron-pair, donor-acceptor interactions including hydrogenbonding and π-π* charge transfer.
12Katritzky and co-workers 13 developed a three-parameter QSPR model (N = 25 solvents, R 2 = 0.936), and Mu and coworkers 14 developed a two-parameter MQSPR (model-based QSPR) model for a unified solvent polarity scale (S′...