Equilibrium studies on tetracycline-metal ion systems

Protonation and equilibrium constant for oxytetracycline (OTC) and doxycycline (DOX) with Zn2+, Ca2+ and Mg2+ ions have been determined with Calvin-type pH-metric titrations under physiological conditions (37 degrees C, 0.15 M NaCl ionic strength). Even though OTC and DOX are similar in structure, major differences were found in complex composition with regard to the protonation state: OTC generally formed species with less protons compared to those with DOX. Studies of parent complexes were followed by investigations of ternary complexes where ascorbic acid was used as a secondary ligand. Again, OTC showed a tendency to form complexes in which fewer protons are bound than in those with DOX. This equilibrium difference between OTC and DOX might be because DOX has a better pharmacodynamic effect relative to that of OTC.