Structures of Fe(II) Complexes with N,N,N'-Tris(2-pyridylmethyl)ethane-1,2-diamine Type Ligands. Bleomycin-like DNA Cleavage and Enhancement by an Alkylammonium Substituent on the N' Atom of the Ligand.

The complexes [L(5)Fe(II)Cl]BPh(4) and L(5)Fe(II)(H(2)O)(2) (L(5) = N,N,N'-tris(2-pyridylmethyl)-N'-methyl-ethane-1,2-diamine) have been isolated. Bernal et al. (Bernal, J.; et al. J. Chem. Soc., Dalton Trans. 1995, 3667-3675) have prepared this ligand and the corresponding complex [L(5)Fe(II)Cl]PF(6). We obtained the structural data of [L(5)Fe(II)Cl]BPh(4) by X-ray diffraction. It crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 17.645(7) Å, b = 16.077(6) Å, c = 13.934(5) Å, V = 3953(3) Å(3), and Z = 4. It presents Fe(II)-N bond lengths close to 2.2 Å, typical of high-spin Fe(II). In solution the L(5)Fe(II)(H(2)O)(2) complex showed a dependence of spin state upon the nature of the solvent. It was high spin in acetone and changed to low spin in acetonitrile. This was detected by UV-vis spectroscopy and by (1)H NMR. Bernal et al. (ibidem) showed that these complexes in the presence of an excess of H(2)O(2) give a purple species, very likely the L(5)Fe(III)(OOH) derivative, with spectroscopic signatures analogous to those of "activated bleomycin". The formation of L(5)Fe(III)(OOH) is confirmed here by electrospray ionization mass spectrometry. We found that a L(5)/Fe system gave single-strand breaks on plasmid DNA in the presence of either a reducing agent (ascorbate) and air or oxidants (H(2)O(2), KHSO(5), MMPP) at 0.1 &mgr;M concentration. The methyl group in L(5) was substituted by a (CH(2))(5)N(CH(3))(3)(+) group in order to get higher affinity with DNA. The corresponding ligand L(5)(+) was used to prepare the complexes [L(5)(+)Fe(II)Cl]Y(2) (Y = BPh(4)(-), PF(6)(-), ClO(4)(-)) and L(5)(+)Fe(II)Br(2). The crystal structure of L(5)(+)Fe(II)Cl(2) was solved. It crystallizes in the monoclinic space group P2(1)/a with a = 14.691(2) Å, b = 13.545(2) Å, c = 17.430(2) Å, beta = 93.43(1) degrees, V = 3462(1) Å(3), and Z = 4. The Fe(II)-ligand distances are similar to those of [L(5)Fe(II)Cl]BPh(4). At the relatively low concentration of 0.01 &mgr;M, L(5)(+)Fe(II)Br promoted DNA breaks. The reaction was not inhibited by hydroxyl radical scavengers. The reaction might involve a nondiffusible oxygen reactive species, either a coordinated hydroperoxide or a high-valent metal-oxo entity.