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 [(L5FeCl)-Cl-II]BPh4 and [L5FeII(H2O)](BPh4)(2) (L-5 = N,N,N'-tris(2-pyridylmethyl)-N'-methyl-ethane-1,2-diamine) have been isolated. Bemal et al. (Bernal, J.; et al. J. Chem. Soc., Dalton Trans. 1995, 3667-3675) have prepared this ligand and the corresponding complex [(L5FeCl)-Cl-II]PF6. We obtained the structural data of [(L5FeCl)-Cl-II]BPh4 by X-ray diffraction. It crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 17.645(7) Angstrom, b = 16.077(6) Angstrom, c = 13.934(5) Angstrom, V = 3953(3) Angstrom(3), and Z = 4. It presents Fe(II)-N bond lengths close to 2.2 Angstrom, typical of high-spin Fe(II). In solution the [L5FeII(H2O)](BPh4)(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 H-1 NMR. Bernal et al. (ibidem) showed that these complexes in the presence of an excess of H2O2 give a purple species, very likely the [L5FeIII(OOH)](2+) derivative, with spectroscopic signatures analogous to those of "activated bleomycin". The formation of [L5FeIII(OOH)](2+) 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 (H2O2, KHSO5, MMPP) at 0.1 mu M concentration. The methyl group in L-5 was substituted by a (CH2)(5)N(CH3)(3)(+) group in order to get higher affinity with DNA. The corresponding ligand L-5(+) was used to prepare the complexes [(L5+FeCl)-Cl-II]Y-2 (Y = BPh4-, PF6-, ClO4-) and [(L5+FeBr)-Br-II](PF6)(2). The crystal structure of [(L5+FeCl)-Cl-II](ClO4)(2) was solved. It crystallizes in the monoclinic space group P2(1)/a with a = 14.691(2) Angstrom, b = 13.545(2) Angstrom, c = 17.430(2) Angstrom, beta = 93.43(1)degrees, V = 3462(1) Angstrom(3), and Z = 4. The Fe(II)-ligand distances are similar to those of [(L5FeCl)-Cl-II]BPh4. At the relatively low concentration of 0.01 mu M, [(L5+FeBr)-Br-II](2+) 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.