Aqueous Solubilities, Infinite Dilution Activity Coefficients and Octanol-Water Partition Coefficients of Tricyclic Analogs of Acyclovir*

Abstract

Solubilities of tricyclic analogs of acyclovir have been determined in water at 25, 35, and 45°C and in octanol, water-saturated octanol, and octanol-saturated water at 25°C. Octanol-water partition coefficients were determined at 25°C. Melting temperatures and molar enthalpies of fusion were measured. Activity coefficients in water, octanol, and in aqueous octanol solutions were determined and are discussed. The effect of hydrophilic and hydrophobic substituents in the tricyclic analogs on their thermodynamic properties are discussed. The standard Gibbs energy of transfer between the saturated phases were found to correlate with known values of the melting point of the solvents and the solubilities of the solute. For a number of the compounds examined, correlations between the minimum inhibitory concentration against the herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), thymidine kinase-deficient (TK−) strains of VZV and \(\Delta G_{{\text{W}} \to {\text{0}}}^0 ;\Delta G_{{\text{tr}}}^0\) were established. Detailed conclusions have been derived concerning the relationships between the structure and the thermodynamic parameters of the compounds examined.