Solvent Effects on Protonation Process of Clindamycin in Mixed Solvents

Clindamycin is used in the treatment of bacterial infections. The protonation constant of this drug was determined in mixed solvents of water and methanol as well as water and ethanol in the volume range 0–50 (% v/v) at 298.15 K and 0.1 M NaClO₄ as the inert electrolyte. The results show that in both mixed solvents, pK_a decreases when the volume fraction of alcohols increases. We considered the effect of the solvent on equilibrium constants using the electrostatic model of Born and the linear solvation energy relationship model developed by Kamlet and Taft. The results indicate that both hydrogen-bonding interactions and electrostatic interactions give rise to the observed changes. Using the derived equations, it is possible to determine pK_a of clindamycin in the desired composition throughout the studied range.