Metal coordination environment and dynamics in (113)cadmium bleomycin: Relationship to zinc bleomycin

The C-13 chemical shifts of Cd- and ZnBlm A(2) are almost identical throughout the entire molecule, suggesting that these structures adopt similar conformations. Nuclear magnetic resonance experiments with Cd-113-bleomycin have defined part of the metal-ligand environment of the molecule. Nitrogen atoms from the primary amine, pyrimidine, and imidazole are bound to Cd-113 according to C-13 spectra showing Cd-113-C-13 spin-spin couplings. Bound and free forms of the secondary amine nitrogen may be in equilibrium, as suggested by temperature-dependent C-13 studies With Cd-bleomycin. In addition, a number of other carbon resonances are in chemical exchange over the temperature range 5-54 degrees C. The temperature dependence of the line widths of carbon atoms of Zn-bleomycin strongly resembles that of Cd-bleomycin. Examination of the Cd-113 resonance as a function of temperature also supports the presence of at least two differently coordinated forms of cadmium in the molecule. According to the position of the Cd-113 chemical shift, at most four nitrogen atoms are bound to Cd at low temperature. Titrations of Cd-113-bleomycin with chloride or acetate demonstrate that these anions can bind to major and minor forms of the structure and that a minor species exists which does not associate with chloride.