Molecular properties impact on bioavailability of second generation triazoles antifungal agents.

The bioavailability of active compounds depends on their two main features: solubility and permeability. The experimental determination of these factors is rather cumbersome. The free enthalpies of salvation deltaG in water and chloroform, and the electrostatic potential surface around examined molecules were ab initio calculated by HF method for voriconazole, posaconazole and ravuconazole. These quantities are assumed to be the new determinants correctly describing both solubility and the affinity of biologically active compounds to lipophilic tendency to cross cellular membranes. The values of deltaG were compared to the theoretically and experimentally determined partition coefficients. The calculated values of deltaG and electrostatic potentials appeared to be consistent with these partition coefficients. It leads to conclusion that these theoretically derived parameters deltaG and electrostatic potential could be useful tools for fast and precise classification of chemical substances within the Biopharmaceutics Classification System (BCS).