Interactions of Gallium(III) with Bleomycin Antibiotics

The addition of Ga(III) to an aqueous solution of bleomycin results in the observation of several new peaks in the ¹H NMR spectrum, concomitant with the reduction in intensity of several of the peaks of the antibiotic. By measuring the relative intensity of the resonance of the C₄ proton of the imidazole at various Ga(III) concentrations, we have found that the Ga(III)- bleomycin complex has a 1:1 stoichoimetry. The lifetime of the Ga(III)-bleomycin complex was found to be ca. 15 s at 343 K (70 °C) from NMR transfer of magnetization and spin-lattice relaxation time measurements. On the basis of a combination of fluorescence binding studies and proton-displacement experiments, we conclude that the binding of Ga(lll) to the bleomycins (As and Bs) displaces a single proton from the -amino group of the diaminopropionamide moiety of the drugs. This evidence implicates this portion of the molecule directly in metal binding.