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

Abstract

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(mu-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 degrees C, and the data treatment was based on the Michaelis-Menten approach, giving the following kinetic parameters (complex 1/complex 2): vmax (mol L(-1) s(-1))=16.4x10(-9)/7.02x10(-9); KM (mol L(-1))=17.3x10(-3)/3.03x10(-3); kcat (s(-1))=3.28x10(-4)/1.40x10(-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 10(7) rate increase compared with the estimated uncatalyzed rate of hydrolysis.

Binuclear CuII complexes as catalysts for hydrocarbon and catechol oxidation reactions with hydrogen peroxide and molecular oxygen

“…This fact suggests a slight increase of the ligand field strength around the metal center for complex 2 compared to complex 1. In fact, as imidazole is a better s-donor than pyridine, [19][20][21]23,56 it was expected that HL1 presented higher ligand field strength than HL2, which is exactly the opposite behavior of the observed here. …”

“…8), 19,36,40 reveals that these pK a values are much higher. This fact can be tentatively explained by the existence of a weak metal-water interaction, as observed in the crystal structure of complex 1, in which the water molecule is 2.899 Å away from the Cu(02) center.…”

“…16 It is a matter of great concern to understand how small changes on the ligand scaffold can interfere in the reactivity of copper-containing coordination complexes, in order to improve their efficiency. 17 In view of our previous interest in copper model complexes and in polipodal ligands, [18][19][20][21][22] we present here two new binuclear Cu II complexes (1 and 2, Figure 1) employing the tridentate N,O-donor ligands HL1, [(2-hydroxybenzyl) (2-(imidazol-2-yl)ethyl)]amine, and HL2, [(2-hydroxybenzyl) (2-(pyridil-2-yl)ethyl]amine. These complexes were designed intending to develop new catalysts for oxidative processes, and their reactivity towards cyclohexane and catechol oxidation reactions were investigated using hydrogen peroxide or molecular oxygen as oxidants.…”

“…In fact, these Cu-Cl bond distances are longer than those reported for coordinated chloride anions. 19,40,41 The geometries adopted by the Cu II centers are both distorted square-planar, with angles varying from 76.8(2) Å to 95.7(2) Å, for Cu(01), and from 77.9(2) Å to 96.9(2) Å, for Cu(02).In both Cu II centers, the shorter bond distances are Cu-N imidazole [Cu (01) . 24,[44][45][46] Finally, the Cu … Cu distance is 3.043(10) Å and is in the range observed for other binuclear Cu II complexes bridged by two phenoxo groups.…”

Electronic Structure and Spectro-Structural Correlations of FeIIIZnII Biomimetics for Purple Acid Phosphatases: Relevance to DNA Cleavage and Cytotoxic Activity

“…The ability of 1-4 to cleave DNA was examined by following the conversion of supercoiled plasmid DNA (F I) to open circular DNA (F II) or linear DNA (F III) using agarose gel electrophoresis to separate the cleavage products. 41,44 In general, 400 ng of pBSK II (∼30 mmol L -1 bp) buffered with PIPES (10 mmol L -1 , pH 6.5) were treated with 1-4 in CH 3 CN (25% reaction volume) for different time reactions at 50°C. Thereafter, each reaction was quenched adding 5 μL of a loading buffer solution (0.25% bromophenol blue, 50% glycerol and 250 mmol L -1 ethylenediamine tetraacetic acid (EDTA) at pH 8.0) and then subjected to electrophoresis on a 0.8% agarose gel containing 0.3 mg mL -1 of ethidium bromide in 0.5x TBE buffer (44.5 mmol L -1 TRIS, 44.5 mmol L -1 boric acid and 1 mmol L -1 EDTA) at 90 V for approximately 1.5 h. The resulting gels were visualized and digitized using a DigiDoc-It gel documentation system (UVP, U.S.A.).…”