Iron-bleomycin interactions with oxygen and oxygen analogues. Effects on spectra and drug activity.
Despite extensive structural dissimilarities, iron . bleomycin complexes and heme-containing oxygenases display remarkable similarities in binding oxygen antagonists and in spectral properties deriving from bound iron. Fe(II)-bleomycin reversibly forms a complex with either CO or isocyanide (lambda max = 384 and 497 nm, respectively), either of which interfere with its oxygen-dependent cleavage of DNA. A similar but paramagnetic complex forms with NO (lambda max = 470 nm; AN = 24 G). In contrast, cyanide enhances bleomycin activity against DNA. Complexes of bleomycin and FE(III), formed either by direct association or by autoxidation of the Fe(II) . bleomycin complex, exhibit indistinguishable EPR and visible spectra, which change characteristically with pH. At neutral pH, Fe(III) . bleomycin is a low spin complex (g = 2.45, 2.18, 1.89; lambda max = 365, 384 nm) and, at low pH, it is a high spin rhombic complex (geff = 9.4, 4.3; lambda max = 430 nm). These complexes are interconvertible (pK 4.3). Fe(II) . bleomycin oxidation, although reversible by spectral criteria, is accompanied by drug inactivation unless DNA is present.
D000818:Animals; D001386:Azides; D001761:Bleomycin; D002248:Carbon Monoxide; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D003486:Cyanides; D004247:DNA; D004578:Electron Spin Resonance Spectroscopy; D007501:Iron; D008315:Malondialdehyde; D009569:Nitric Oxide; D010084:Oxidation-Reduction; D010100:Oxygen; D013053:Spectrophotometry
D001386:Azides; D003486:Cyanides; D001761:Bleomycin; D009569:Nitric Oxide; D008315:Malondialdehyde; D002248:Carbon Monoxide; D004247:DNA; D007501:Iron; D010100:Oxygen