| Abstract
| - Reductive nitrosylation of Fe(III) complexes of bleomycin (Blm) and a cationic porphyrin (TMpyP) took place in situ on B-form DNA fibers. The angles β between the fiber axis and the gz axis and γ that determines the orientation of gx and gy axes were estimated by computer simulations of the electron paramagnetic resonance spectra.The NO was held rigidly in place as the temperature increased from 123 K to room temperature for ON−Fe(II)Blm but not for ON−Fe(II)TMpyP or ON−Fe(II)TMpyP−Im.
- Bleomycin (Blm) is an antitumor agent that requires iron and oxygen for strand cleavage of DNA. In this study,ferric bleomycin, Fe(III)Blm, or the nitric oxide adduct of ferrous bleomycin, ON−Fe(II)Blm, were bound toone-dimensionally oriented DNA fibers. Reductive nitrosylation of Fe(III) complexes took place in situ on B-formDNA fibers. Electron paramagnetic resonance (EPR) spectra were obtained as a function of the angle Φ betweenthe magnetic field B and the fiber axis Zf. For comparison, EPR spectra were acquired for ON−Fe(II)TMpyP andON−Fe(II)TMpyP−Im on oriented DNA fibers, where TMpyP is 5,10,15,20-tetrakis(1-methyl-4-pyridino)porphyrin and Im is imidazole. EPR spectra showed both low-spin Fe(III)Blm and ON−Fe(II)Blm bound to B-formDNA in two slightly different binding orientations in the ratio of 1:0.2. With A-form DNA, a fraction ofbound Fe(III)Blm was high spin. Specifically, the angle β between the fiber axis Zf and the g axis, gz, perpendicular to or nearly perpendicular to the equatorial plane of the iron complex was estimated as 20° and 25° forON−Fe(II)Blm and 30° and 25° for Fe(III)Blm, respectively. The angle γ that determines the orientation of gxand gy axes was estimated as 90° for the two ON−Fe(II)Blm species and 10° for the two Fe(III)Blm species,respectively. The NO was held rigidly in place as the temperature increased from 123 K to room temperature forON−Fe(II)Blm but not for ON−Fe(II)TMpyP or ON−Fe(II)TMpyP−Im. It is hypothesized that the NO isstructurally oriented by hydrogen bonding like the peroxide is held in HO2-−Co(III)Blm (Wu et al. J. Am.Chem. Soc.1996, 118, 1281−1294). The EPR parameters are consistent with a six-coordinate complex forON−Fe(II)Blm, although the superhyperfine structure from the trans nitrogen was not detected. The increase ing value anisotropy upon binding ON−Fe(II)Blm to DNA fiber may be caused by an increase in the overlap ofdπ and 2pπ* orbitals induced by an interaction of NO with DNA and/or by a perturbation of d orbitals due to thepyrimidine−guanine interaction. It is concluded that the EPR parameters of ON−Fe(II)Blm and Fe(III)Blm boundto oriented DNA support the hypothesis that FeBlm species bind to DNA with adduct structures similar to thoseformed by related CoBlm species and DNA.
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