ACID-BASE PROPERTIES AND PROTON-SPECIATION OF VANCOMYCIN

The protonation-deprotonation equilibria of the glycopolypeptide antibiotic vancomycin are characterized in terms of protonation macroconstants, isoelectric point and diagram of pH-dependent species distribution. Vancomycin contains two-basic and four acidic groups. Of these, dissociation of the C-terminal carboxyl group takes place separately at low pH, whereas proton binding of the two amino sites and deprotonation of the three phenolic hydroxyl groups occur between pH 5 and 13, in a highly overlapping fashion. Our study indicates for an isoelectric point of 8.30 the vancomycin molecule and an average charge of +0.67, with the predominant existence of penta- and tetraprotonated species at physiological pH.