Towards polynuclear metal complexes with enhanced bioactivities: Synthesis, crystal structures and DNA cleaving activities of CuII, NiII, ZnII, CoII and MnII complexes derived from 4-carboxy-1-(4-carboxybenzyl) pyridinium bromide

Six transition metal complexes, that is, {[Cu(Ccbp)2]·4H2O}n (1), [Ni(H2O)6](Ccbp)2·4H2O (2), [M(Ccbp)2(H2O)4]·2H2O·2MeOH (M = ZnII (3), CoII (4), MnII (5)), and [Cu(Cbp)2(H2O)2](NO3)2·4H2O (6) were synthesized from the reaction of 4-carboxy-1-(4-carboxybenzyl)pyridinium bromide (H2CcbpBr) and N-(4-carboxybenzyl)pyridinium bromide (HCbpBr) with the corresponding metal salts in the presence of NaOH, respectively. All these metal complexes were characterized by IR, elemental analyses and single crystal X-ray crystallography. In complex 1, every two Ccbp− ions bridge two Cu2+ ions through four terminal carboxylate ions in a monodentate coordination mode, thus forming a one-dimensional polymer structure. Complex 2 is an ionic metal complex consisting of isolated [M(H2O)6]2+ dications and Ccbp− anions. Complexes 3–5 have similar structures, in which the central metal atom in [M(Ccbp)2(H2O)4] unit adopts a slightly distorted octahedral geometry. In complex 6, the central Cu atom adopts a distorted tetrahedral coordination geometry that is formed from two unidentate Cbp ligands and two H2O molecules. Agarose gel electrophoresis studies on the cleavage of plasmid pBR322 DNA by complexes 1–6 indicated that only complex 1 was capable of efficiently cleaving DNA, most probably via an oxidative mechanism. Kinetic assay of complex 1 afforded the maximal catalytic rate constant kmax of 0.50 h−1 and Michaelis constant KM of 0.60 mM, respectively. Ethidium bromide displacement experiments indicated that complex 1 had a binding affinity of (3.10 ± 0.90) × 105 M−1 toward calf-thymus DNA, 10- to 55-fold higher than those shown by H2CcbpBr and complexes 2–5. The high cleaving efficacy of complex 1 is thought to be due to its polynuclear structure.