INVESTIGATION OF KETO-ENOL-TAUTOMERISM AND IONIZATION OF DOXYCYCLINE IN AQUEOUS-SOLUTIONS

The keto and enol tautomers of doxycycline were separated by liquid ch romatography on poly(styrene-divinylbenzene). The keto-enol tautomeris m occurred between C-11a and C-12. The chemical structure of the tauto mers was elucidated by on-line and off-line UV spectrophotometry and b y C-13-NMR spectrometry. The kinetics of the equilibrium were investig ated in the pH range 1-12. The equilibrium was subject to base catalys is. The tautomerism was enhanced by protonation of doxycycline. The as signment of the groups responsible for the micro-ionization of doxycyc line was discussed. Activation parameters were determined at pH 4.0.