A proton nuclear magnetic resonance study of the interaction of zinc(II) with the antitumour drug streptonigrin

Abstract

The interaction of zinc(II) with the antitumour drug streptonigrin in [²H₈]tetrahydrofuran has been studied by 400 MHz variable-temperature ¹H NMR spectroscopy. At 190 K, and in the presence of an excess of zinc(II) trifluoromethanesulfonate (triflate)(10–15 equivalents), streptonigrin forms a 1 : 1 complex 1a(6%) and two diastereomeric 2 : 1 complexes, 1b(15%) and 1c(79%). The relative concentrations of these complexes are highly temperature dependent and at room temperature only 1a is detected. A fourth minor complex 1d was detected (<5%) in the range 240–260 K. In CD₃CN and less than 5 equivalents of zinc(II) triflate, 1a–1d are detected, but in the presence of 10–15 equivalents of zinc(II) triflate 1a is the predominant complex (>93%) in the range 235–300 K. Implications for the role of metal ions in the mechanism of the antitumour action of streptonigrin are discussed.