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DNA cleavage activity with a novel pentadentate iron(II) complex and spectroscopic property of its active intermediate
Journalof
Inorganic Biochemistry
M 18
NON-HEME
IRON
329
DNA C L E A V A G E A C T I V I T Y W I T H A NOVEL P E N T A D E N T A T E IRON(II) COMPLEX AND SPECTROSCOPIC PROPERTY OF ITS
ACTIVE INTERMEDIATE Y. Ishikawa, a T. Ishihara, a Y. Modshita, a A. Yamamoto, a H. Kurosaki, a H. Mod, a M. Goto, a H. Matsuo b and M. Sugiyama b
a Faculty of Pharmaceutical Sciences, Kumamoto University, 5-10e-honmachi, Kumamoto 862, Japan b Department of Medicinal Chemistry, Hiroshima University, School of Medicine, Kasumi, Minami-ku, Hiroshima 734, Japan In recent years, mononuclear non-heme iron complexes related to iron-bleomycin (Fe-BLM) have been increasingly noted. Fe-BLM is known to cause oxidative DNA cleavage and to catalyze the oxidation of hydrocarbons. It is also supposed that the five nitrogen donors, a part of metal-chelating portion of BLM, are essential for activation of dioxygen. We recently reported that the reaction of the tetradentate iron(H) complex, 1, containing 1,3-diimine moiety with acetonitrile in the presence of triethylamine afforded a novel pentadentate iron(l/) complex, 2.1
activated
CHs
methylene proton
Ni
CH3
_
H÷
< _
.N 9
el.13
(I)
e CH3
(2)
2 is analogous to Fe-BLM in that it bears a pentadentate ligand and has shown high activity toward degradation of plasmid DNA in the presence of H202 and that the extent of DNA strand scission has little affected by addition of hydroxyl radical scavenger such as dimethylsulfoxide. Like Fe-BLM, 2 is able to oxidize hydrocarbons with 50eq. H202. When cyclohexane is used as the substrate, for example, cyclohexanol (130%) and cyclohexanone (80%) (yield based on 2) are obtained. Mixture of 2 and 50eq. I-I~O2 in acetonitrile produces a transient purple species (~, = 580 nm) at 298K and the EPR spectra of the intermediate at 77K exhibit signals for a low-spin iron(HI) species (g = 2.16, 2.10 and 1.98). 1. M. Goto et al., J. Chem~ Soc. Chent Commun., in press
Inorganic Biochemistry
M 18
NON-HEME
IRON
329
DNA C L E A V A G E A C T I V I T Y W I T H A NOVEL P E N T A D E N T A T E IRON(II) COMPLEX AND SPECTROSCOPIC PROPERTY OF ITS
ACTIVE INTERMEDIATE Y. Ishikawa, a T. Ishihara, a Y. Modshita, a A. Yamamoto, a H. Kurosaki, a H. Mod, a M. Goto, a H. Matsuo b and M. Sugiyama b
a Faculty of Pharmaceutical Sciences, Kumamoto University, 5-10e-honmachi, Kumamoto 862, Japan b Department of Medicinal Chemistry, Hiroshima University, School of Medicine, Kasumi, Minami-ku, Hiroshima 734, Japan In recent years, mononuclear non-heme iron complexes related to iron-bleomycin (Fe-BLM) have been increasingly noted. Fe-BLM is known to cause oxidative DNA cleavage and to catalyze the oxidation of hydrocarbons. It is also supposed that the five nitrogen donors, a part of metal-chelating portion of BLM, are essential for activation of dioxygen. We recently reported that the reaction of the tetradentate iron(H) complex, 1, containing 1,3-diimine moiety with acetonitrile in the presence of triethylamine afforded a novel pentadentate iron(l/) complex, 2.1
activated
CHs
methylene proton
Ni
CH3
_
H÷
< _
.N 9
el.13
(I)
e CH3
(2)
2 is analogous to Fe-BLM in that it bears a pentadentate ligand and has shown high activity toward degradation of plasmid DNA in the presence of H202 and that the extent of DNA strand scission has little affected by addition of hydroxyl radical scavenger such as dimethylsulfoxide. Like Fe-BLM, 2 is able to oxidize hydrocarbons with 50eq. H202. When cyclohexane is used as the substrate, for example, cyclohexanol (130%) and cyclohexanone (80%) (yield based on 2) are obtained. Mixture of 2 and 50eq. I-I~O2 in acetonitrile produces a transient purple species (~, = 580 nm) at 298K and the EPR spectra of the intermediate at 77K exhibit signals for a low-spin iron(HI) species (g = 2.16, 2.10 and 1.98). 1. M. Goto et al., J. Chem~ Soc. Chent Commun., in press