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 beta-aminoalanine fragment, the pyrimidine and imidazole rings, and the amide nitrogen of the beta-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., & 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.