Acidity constants of cefetamet, cefotaxime and ceftriaxone; the effect of the substituent at C3 position

Abstract

Ionization constants of three cephalosporin antibiotics, cefetamet (CEF), cefotaxime (CFX) and ceftriaxone (CFTR) are determined using pH-potentiometric titrations at I= 0.1 M (NaCl) and t = 25 degrees C. Cefetarnet and cefotaxime have three ionization groups: carboxylic, amide and aminothiazole. Besides those three, ceftriaxone possesses an hydroxytriazi none group as new and additional ionization center. In acid medium two overlapping acid-base processes are occuring with acidity constants being: pK(1) 2.93 (COOH) and PK2 3.07 (amin nothiazole) for cefetamet, and pK(1) 2.21 (COOH) and pK(2) 3.15 (aminothiazole) for cefotaxime. In the case of ceftriaxone the situation is even more complicated, three overlapping processes coexist with pK(1) 2.37 (COOH), pK(2) 3.03 (aminothiazole) and pK(3) 4.21 (hydroxytriazinone). Protolysis of amide group is happening in the alkaline medium as completely separated process from those in acid medium. The acidity constants which correspond to amide group are pK(3) 10.65 (CEF), pK(3) 10.87 (CFX) and pK(4) 10.74 (CFTR). The influence of the C3 substituent on the dissociation process of the neighboring ionization group, particularly carboxylic group, was considered. The differences in acidity of CEF, CFX and CFFR pK(1): 2.93, 2.21 and 2.37, respectively) are likely to be caused by the stereoelectronic properties of substituents in the P-position to the carboxylic group due to the combined inductive, hyperconjugative and resonance effects.