Studies of metallobleomycins by electronic spectroscopy, electron spin resonance spectroscopy, and potentiometric titration.

Abstract

The 1:1 bleomycin-A2-Cu(II) complex shows an absorption maximum at 595 nm (.epsilon. 120), circular dichroism extrema at 555 nm (.delta..epsilon. + 1.21) and 665 nm (-0.61), and ESR signal with g.dblvert. = 2.211, g.perp. = 2.055 and A.dblvert. = 178 .times. 10-4 cm-1. The formation constant (log K = 12.630) and deprotonation constant (pKc = 3.585) of the 1:1 bleomycin-Cu(II) complex were determined by computer analysis of potentiometric data. The results of potentiometric titration also indicate that the stability of bleomycin-metal complexes is in the order Fe(II) < Co(II) < Ni(II) < Cu(II) > Zn(II) and that these divalent metal complexes have a similar coordination environment. The bleomycin-Cu(II) complex has substantially a square-pyramidal configuration in which the secondary amine N, pyrimidine(N-1) ring N, deprotonated peptide N of histidine residue and histidine imidazole(N-1) N coordiante to Cu(II) as planar ligand donors and the .alpha.-amino N as axial donor. The specific Cu(II)-binding site of bleomycin was compared with that of human serum albumin.