title: 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.
abstract: The complexes [L(5)Fe(II)Cl]BPh(4) and [L(5)Fe(II)(H(2)O)](BPh(4))(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)](BPh(4))(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)](2+) derivative, with spectroscopic signatures analogous to those of "activated bleomycin". The formation of [L(5)Fe(III)(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 (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](PF(6))(2). The crystal structure of [L(5)(+)Fe(II)Cl](ClO(4))(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](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.
authors.affiliation: Laboratoire de Chimie Inorganique, URA CNRS 420, Institut de Chimie Moléculaire d'Orsay, Université Paris-Sud, 91405 Orsay, France, Institut de Chimie des Substances Naturelles, UPR CNRS 2301, 91198 Gif-sur-Yvette, France, Laboratoire de Chimie de Coordination du CNRS, 31077 Toulouse, France, and Laboratoire des Mécanismes Réactionnels, UMR CNRS 7651, Ecole Polytechnique, 91128 Palaiseau, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mialane
authors.forename: Alexander
authors.initials: A
authors.lastname: Nivorojkine
authors.forename: Geneviève
authors.initials: G
authors.lastname: Pratviel
authors.forename: Laurent
authors.initials: L
authors.lastname: Azéma
authors.forename: Michaela
authors.initials: M
authors.lastname: Slany
authors.forename: Frédéric
authors.initials: F
authors.lastname: Godde
authors.forename: Ariane
authors.initials: A
authors.lastname: Simaan
authors.forename: Frédéric
authors.initials: F
authors.lastname: Banse
authors.forename: Taraneh
authors.initials: T
authors.lastname: Kargar-Grisel
authors.forename: Guy
authors.initials: G
authors.lastname: Bouchoux
authors.forename: Joelle
authors.initials: J
authors.lastname: Sainton
authors.forename: Olivier
authors.initials: O
authors.lastname: Horner
authors.forename: Jean
authors.initials: J
authors.lastname: Guilhem
authors.forename: Lyuba
authors.initials: L
authors.lastname: Tchertanova
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Girerd