Electron Spin Resonance Studies of 1:1:1 Bleomycin-Cobalt(II)-Qxygen Adduct Complex

Abstract

Bleomycin has been used extensively in the chemotherapy and radiodiagnosis of cancer ⁽¹⁾. One of the most important aspects of its chemistry is its ability to coordinate a variety of metals. Recently, bleomycin-metal complexes have attracted particular attention because of their interesting behavior: (i) the copper(II) complex is a metabolic form of bleomycin (2), (ii) γ-emitting metal complexes such as ⁵⁷CO, ^99mTc, and ¹¹¹In have been investigated as a means of visualizing tumors⁽³⁾, and (iii) an oxygen-labile iron(II) complex may play an important role in DNA degradation by bleomycin^(4,5). Sausville et al. reported that the conversion of SV40 DNA to acid-soluble products occurs at approximately equimolar levels of Fe(II), bleomycin, and DNA⁽⁴⁾. Takita et al. have proposed that an oxygen activated by the bleomycin-Fe(II) complex is involved in the action of bleomycin on DNA⁽⁵⁾. Additionally, it has been suggested that superoxide radical is one of the chemical mediators responsible for the enhancement of DNA chain breakage by bleomycin ⁽⁶⁾. Herein, the 1:1 bleomycin A₂-Co(II) complex and its oxygen adduct complexes have been characterized by electron spin resonance (ESR) spectroscopy; the present results should serve to facilitate an understanding of the degradation of DNA by the bleomycinFe(II)-0₂ complex.