Competing protonation sites in sulfadiazine: answers from chemistry and electron density

Abstract

Sulfadiazine, a common drug, has been studied as anion in its Zn(II) salt, as a neutral compound and as hydrochloride. An unexpected protonation pattern was encountered in the cation of the latter, with a coexisting protonated anilinium and pyridinium functionality and a deprotonated amide group. Experimental charge density provides conclusive evidence about the position of the hydrogen atoms, and these results match the hydrogen bond requirements.