Site-specific protonation microequilibria of penicillin and cephalosporin beta-lactam core molecules.
Acid-base chemistry of 6-aminopenicillanic acid (6-APA) and 7-aminocephalosporanic acid (7-ACA), the fundamental units of the two classical antibiotic families is characterised at the macroscopic and microscopic levels. (1)H NMR-pH and pH-potentiometric titrations were combined to monitor the previously unreported extent of the site-specific protonation of 6-APA and 7-ACA. Microscopic protonation constants were derived either from direct multiple fittings of NMR-pH titration curves of adjacent carbon-bound (1)H nuclei, using in situ pH-indicator molecules, or from newly synthesised methyl ester derivatives. The results indicate that even the amino protonation of both structures occurs well below pH 5, the major protonation route includes the zwitterionic forms, and protonation at the carboxylate site brings about a three-fold diminish in the amino basicity and vice versa.
Kóczián
Kristóf
K
Department of Pharmaceutical Chemistry, Semmelweis University, Research Group for Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, H-1092 Budapest, Hogyes Endre u. 9, Hungary.
Szakács
Zoltán
Z
Kökösi
József
J
Noszál
Béla
B
D002511:Cephalosporins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009994:Osmolar Concentration; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D010406:Penicillins / Q000737:chemistry; D011199:Potentiometry; D011522:Protons; D047090:beta-Lactams / Q000737:chemistry
D002511:Cephalosporins; D007477:Ions; D010406:Penicillins; D011522:Protons; D047090:beta-Lactams; D010397:Penicillanic Acid; C030735:7-aminocephalosporanic acid; C004408:aminopenicillanic acid