NMR studies of the paramagnetic complex Fe(II)-bleomycin

The coordination chemistry of the iron(II) complex of the antitumor drug bleomycin has been extensively investigated with a number of spectroscopic and chemical techniques. However, the actual structure of this complex is not established. In this report, we present NMR studies of the paramagnetic Fe(II)BLM and use one- and two-dimensional methods to assign the paramagnetically shifted features to particular protons. The data analysis points toward the primary and secondary amines of the β-aminoalanine fragment, the pyrimidine and imidazole rings, and the amide nitrogen of the β-hydroxyhistidine fragment as ligands to the metal center. Correlation of the T₁ values with the metal-proton distances derived from the NMR-generated solution structure of HOO-Co(III)BLM [Wu, W., Vanderwall, D. E., Lui, S. M., Tang, X.-J., Turner, C. J., Kozarich, J. W., and Stubbe, J. (1996) J. Am. Chem. Soc. 118, 1268-1280] indicates that the two metallobleomycins share similar structures. The chemical shifts as well as the T₁ values of the sugar protons indicate that these fragments are close but not bound to the metal in Fe(II)BLM.