Characterization of pharmacologically important prototropic species derived from a pyridinemethanol antimalarial by...

Variations of the absorption and fluorescence spectra of the experimental antimalarial drug, alpha-dibutylaminomethyl-2,6-bis(p-trifluoromethylphenyl)-4-pyridinemethanol, were investigated throughout the pH region in concentrated sulfuric acid media and in n-hexane. The predominant prototropic species at physiological pH is the singly charged cation. In the pH 6--12 region, the structured fluorescence of the monocation is quenched with the concomitant appearance of a diffuse, long wavelength emission while the corresponding absorption spectra shift only slightly to longer wavelengths. Furthermore, the dibutylamino group exhibits an unusually low basicity. This behavior is explained as due to the formation of an intramolecular hydrogen bond in the neutral molecule in the ground and lowest excited singlet states. A similar intramolecular hydrogen bond in the monocation is not spectroscopically visible.