Metal complexes of anhydrotetracycline. 1. A spectrometric study of the Cu(II) and Ni(II) complexes.

Anhydrotetracycline (AHTC), one of the major toxic decomposition products of the antibiotic tetracycline, contains several potential binding sites to metal ions. The acidity constants of the ligand were calculated in aqueous medium (I = 0.1 M) at 25 and 37 degrees C. We found pKa1 = 3.23 +/- 0.08, pKa2 = 5.94 +/- 0.09, and pKa3 = 8.48 +/- 0.02 at 25 degrees C and pKa1 = 3.12 +/- 0.09, pKa2 = 5.86 +/- 0.03, and pKa3 = 8.38 +/- 0.04 at 37 degrees C. The coordination of AHTC to Cu(II) and Ni(II) ions was studied in the solid state as well as in buffered aqueous solution at pH 10.0. At this pH, the formation of the two CuL2 and CuL species was indicated (log beta 1 = 8.41 +/- 0.04 and log beta 2 = 12.55 +/- 0.05), but only the formation of the NiL complex (log beta = 5.74 +/- 0.04) was identified. Spectroscopic data confirm the previous assignment of the C11 and C12 oxygens as the coordination sites, yielding six-membered ring chelates and excluding complexation through any of the potential binding positions on ring A.