Tautomerism of Singly Protonated Chloroquine and Quinacrine

Differential absorptiometric pH titrations of the antimalarials chloroquine and quinacrine, employing the respective uncharged species at pH12.5 in the reference cell, show that protolytic dissociation from the heterocyclic ring nitrogen atoms occurs over pH6–12. This finding indicates that the singly charged cations of the drugs exist measurably in two tautomeric forms. The tautomeric equilibrium constants were calculated from the titration data. The existence of these tautomeric equilibria may have significance in the pharmacodynamics of chloroquine and quinacrine.