Temperature dependence of the acid dissociation constants of chloroquine

The pKa values of the conjugate acids of the antimalarial drug chloroquine were determined at various temperatures using fluorescence spectrophotometry and nonlinear regression in the data analysis. Both pKa values decreased by approximately one unit with increasing temperature over the range 0-37 degrees C with enthalpy changes of 46 and 49 kJ X mol-1. The ionization of chloroquine was found to be mainly controlled by the change in enthalpy. The chloroquine monocation was shown to be almost exclusively in the alkylamino protonated form at all temperatures studied.