Transformation kinetics and pathways of tetracycline antibiotics with manganese oxide

Tetracycline antibiotics including tetracycline (TTC), oxytetracycline (OTC) and chlorotetracycline (CTC) undergo rapid transformation to yield various products in the presence of MnO(2) at mild conditions (pH 4-9 and 22 degrees C). Reaction rates follow the trend of CTC > TTC > OTC, and are affected by pH and complexation of TCs with Mg(2+) or Ca(2+). Experimental results of TTC indicate that MnO(2) promotes isomerization at the C ring to form iso-TTC and oxidizes the phenolic-diketone and tricarbonylamide groups, leading to insertion of up to 20 most likely at the C9 and C2 positions. In contrast, reactions of OTC with MnO(2) generate little iso-OTC, but occur mainly at the A ring's dimethylamine group to yield N-demethylated products. CTC yields the most complicated products upon reactions with MnO(2), encompassing transformation patterns observed with both Tit and OTC. The identified product structures suggest lower antibacterial activity than that of the parent tetracyclines. (C) 2011 Elsevier Ltd. All rights reserved.