Probing the Antioxidant Action of Selenium and Sulfur Using Cu(I)-Chalcogenone Tris(pyrazolyl)methane and -borate Complexes

Abstract

Hydroxyl radical generated from the reaction of Cu(+) with hydrogen peroxide results in oxidative DNA damage, and this damage is implicated in aging, cancer, and many other diseases. Selenium- and sulfur-containing compounds can act as antioxidants, and coordination of selenium and sulfur to copper is one explanation for this antioxidant activity. To determine how copper coordination results in antioxidant activity, biologically relevant tris(pyrazolyl)methane and borate Cu(+) complexes of the formulas Tp*Cu(L) and [Tpm(R)Cu(L)](+), where (L = N, N'-dimethylimidazole selone, dmise; N, N'-dimethylimidazole thione, dmit; Tp* = hydrotris(3,5-dimethylpyrazolyl)borate; Tpm(R) = tris(pyrazolyl)methane, R = H; Tpm, R = Me; Tpm*, R = iPr; Tpm(iPr)), have been synthesized and characterized. The structures of complexes Tp*Cu(Dmit), Tp*Cu(dmise), [Tpm(R)Cu(dmise)][BF(4)], and [Tpm(R)Cu(Dmit)][BF(4)] (where R = H; Tpm, R = Me; Tpm*, R = iPr; Tpm(iPr)) were determined by X-ray crystallography. All the Cu(+) centers adopt distorted tetrahedral coordination geometry, and Cu-Se and Cu-S distances for all the complexes are approximately 2.30 Å, and 2.20 Å, respectively. The effects of counterion and steric bulk at the 3 and 5 positions of the pyrazolyl ring on the structural and spectroscopic properties are discussed. Selone or thione coordination to copper significantly alters the Cu(+/2+) redox potential: Cu-selone complexes have Cu(2+/+) potentials from -283 to -390 mV, whereas those of Cu-thione complexes range from 70 to -232 mV versus NHE. The Cu-selone complexes have Cu(2+/+) potentials near or below that of the cellular reductant NADH (-324 mV). Thus, selenium and sulfur coordination to copper in biological systems may prevent the Cu(2+) reduction by NADH required for the catalytic formation of damaging hydroxyl radical.

2-Seleno-1-alkylbenzimidazoles and their diselenides: Synthesis and structural characterization of a 2-seleno-1-methylbenzimidazole complex of mercury

“…Thus, upon coordination, the 13 C NMR spectroscopic signal shifts upfield by 11 ppm (from δ 162.8 to 151.8), while the 77 Se NMR spectroscopic signal shifts upfield by 63 ppm (from 83 ppm to 20 ppm). Similar trends have been observed in related systems, 32,50 including thione counterparts. 51 Also of note, 1 J Se-C is reduced from a value of 230 Hz for H(sebenzim Me ) to a value of 204 Hz upon coordination.…”

Dinuclear copper(i) complexes with N-heterocyclic thione and selone ligands: synthesis, characterization, and electrochemical studies

“…27,28 Notably, the Cu(II/I) reduction potential of the dinuclear copper chalcogenone complexes 1 to 10 can be tuned in a 470 mV window from 102 mV to -369 mV by simply changing the nature of the chalcogen donor and the denticity of thione and selone ligands. The reduction potentials from the bidentate chalcogenones indicate that increasing the length of the linker from methylene to ethylene results in more negative reduction potentials.…”

New Selenoderivatives as Antitumoral Agents

“…The Se and sulfur antioxidant activity has been explained using copper-mediated DNA damage studies and UV-vis spectroscopy that have allowed identifying a copper coordination through a novel metal bond. For this reason has been described the synthesis of relevant copper selone complexes with tris(pyrazolyl)methane or tris(pyrazolyl)borate ligands ( Figure 7) (Kimani et al, 2010). The determination of redox potential for Cu-Selone complexes indicated that Se coordination to copper in biological systems may prevent the reduction of Cu 2+ by NADH required for the catalytic formation of damaging hydroxyl radical.…”