Synthesis, characterization and cytotoxicity studies of Co(III)-flavonolato complexes

Hypoxia activated Co(III) complexes as prodrugs may provide with a selective delivery of cytotoxic or antibacterial compounds. Whithin this field sixteen novel Co(III) ternary complexes with the general formula [Co(4N)(flav)](ClO4)(2), where 4N = tris(2-aminoethyl)amine (tren) or tris(2-pyridylmethyl)amine (tpa) and flav = deprotonated form of differently substituted flavonols have been synthesized, characterized, and their cytotoxicity assayed under both normoxic and hypoxic conditions. Molecular structures of two free flavonols and seven complexes are also reported. In all the complexes the bioligands exhibited the expected (O,O) coordination mode and the complexes showed a slightly distorted octahedral geometry. Cyclic voltammetric studies revealed that both the substituents of the flavonoles and the type of 4N donor ligands had an impact on the reduction potential of the complex. The ones containing tren demonstrated significantly higher stability than the tpa analogues, making these former compounds promising candidates for the development of hypoxia-activated prodrug complexes. Tpa complexes showed higher activity against both selected human cancer cell lines (A549, A431) than their free ligand flavonols, indicating that the anticancer activity of the bioligand can be enhanced upon complexation. However, slight hypoxia-selectivity was found only for a tren complex (11) with moderate cytotoxicity.Metals in Catalysis, Biomimetics & Inorganic Material

CHIRAL QUADRIDENTATE LIGANDS BASED ON AMINO-ACIDS - TEMPLATE SYNTHESES AND PROPERTIES OF THE FREE LIGANDS AND THEIR TRANSITION-METAL COMPLEXES

The copper(II)-directed condensation of amino acids with formaldehyde and nitroethane has produced new open-chain quadridentate ligands stereoselectively and in generally high yield. The free ligands with pendant amine substituents may be isolated by zinc reduction of the copper(II) complexes. The reactions studied employed optically pure L-amino acids with non-co-ordinating side chains, racemic amino acids with non-co-ordinating side chains, amino acid mixtures and beta-amino acids. The quadri- and quinquedentate ligands form very stable complexes with transition-metal ions, with their copper(II) complexes being generally stable down to pH almost-equal-to 1. The isolation and spectroscopic properties (UV/VIS, IR, NMR and EPR) of cobalt(III) and copper(II) complexes of some of the amino acid-based ligands are reported. Condensation of racemic and mixed amino acids led to one out of three possible quadridentate ligands, and this stereoselectivity is interpreted based on a model involving the co-ordination of an organic nitro group. This mechanism is supported by qualitative molecular mechanics calculations. The crystal structures of the condensation products with beta-alanine, ([Cu(mnp-beta-ala)].5H2O (mnp-beta-ala = 6-methyl-6-nitro-4,8-diazaundecanedioate), and the Zn-HCI reduction product of the condensation with glycine [Cu(Hampgly)Cl].2H2O (ampgly = 5-amino-5-methyl-3,7-diazanonanedioate), have been determined. In the former structure the Cu(II) is in a distorted trigonal-bipyramidal environment with the fifth site being a co-ordinated carboxylate oxygen from an adjacent molecule, while in the latter Cu(II) has a square-pyramidal co-ordination with an apical chloride ligand

An Iron-Based Molecular Redox Switch as a Model for Iron Release from Enterobactin via the Salicylate Binding Mode

The iron release mechanism from protonated ferric enterobactin [FeIII(enterobactinH3)] via the salicylate binding mode was probed. For this purpose, a tripodal dodecadentate ligand incorporating three salicylamide (OO) and three bipyridine (NN) binding sites was synthesized as well as iron complexes thereof. It was shown that a ferric ion coordinates selectively to the hard salicylamides and a ferrous ion binds to the softer bipyridines. Upon reduction or oxidation, the iron translocates reversibly and intramolecularly from one site to the other, thus displaying switchlike properties. Both states were characterized by cyclic voltammetry and visible and Mössbauer spectroscopy. The Mössbauer spectrum for the ferric complex is fully consistent with that obtained by Pecoraro et al. upon lowering the pH of [FeIII(enterobactin)]3- solutions (Pecoraro, V. L., et al. J. Am. Chem. Soc. 1983, 105, 4617), thus supporting the alternative iron release mechanism from enterobactin via the salicylate binding mode