pKa Calculation of Coumarin Derivatives in Aqueous Solution: A Theoretical Approach

In this work, calculation of pKa values has been performed on the 3-hydroxycoumarin, 4-hydroxycoumarin, 6-hydroxycoumarin and 7-hydroxycoumarin drugs in aqueous solution. Gas-phaseenergies were calculated at the B3LYP/6-31+G(d) level of theory. Free energies of solvation werecalculated by applying the conductor-like polarizable continuum model (CPCM) solvation model at thePBE1PBE/6-31G(d) level of theory. The CPCM calculations were employed with the UAHF, UAKS, Bondiand Pauling atomic radii. By comparing the calculated pKa’s for 3-hydroxycoumarin, 4-hydroxycoumarin,6-hydroxycoumarin and 7-hydroxycoumarin drugs from various methods to their experimental values, itwas found an optimal combination of methods for gas and solution phase energies.

Keywords:

Thermodynamic cycle , Coumarin derivatives , pKa , Solvation models , Cavity models