Phosphate Diester Hydrolysis and DNA Damage Promoted by New cis-Aqua/Hydroxy Copper(II) Complexes Containing Tridentate Imidazole-rich Ligands

The tridentate Schiff base [(2-(imidazol-4-yl)ethyl)(1-methylimidazol-2-yl)methyl)imine (HISMIMI) and its reduced form HISMIMA were synthesized and characterized, as well their mononuclear cis-dihalo copper(II) complexes 1 and 2, respectively. In addition, the dinuclear [CuII(μ-OH)2CuII]2+ complexes (3) and (4) obtained from complexes 1 and 2, respectively, were also isolated and characterized by several physicochemical techniques, including magnetochemistry, electrochemistry, and EPR and UV−vis spectroscopies. The crystal structures of 1 and 2 were determined by X-ray crystallography and revealed two neutral complexes with their tridentate chelate ligands meridionally coordinated. Completing the coordination spheres of the square-pyramidal structures, a chloride ion occupies the apical position and another is bonded in the basal plane. In addition, complexes 1 and 2 were investigated by infrared, electronic, and EPR spectroscopies, cyclic voltammetry, and potentiometric equilibrium studies. The hydrolytic activity on phosphate diester cleavage of 1 and 2 was investigated utilizing 2,4-BDNPP as substrate. These experiments were carried out at 50 °C, and the data treatment was based on the Michaelis−Menten approach, giving the following kinetic parameters (complex 1/complex 2): v max (mol L-1 s-1) = 16.4 × 10-9/7.02 × 10-9; K M (mol L-1) = 17.3 × 10-3/3.03 × 10-3; k cat (s-1) = 3.28 × 10-4/1.40 × 10-4. Complex 1 effectively promoted the hydrolytic cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions, with a rate constant of 0.28 h-1 for the decrease of form I, which represents about a 107 rate increase compared with the estimated uncatalyzed rate of hydrolysis.