Investigating the copper coordination, electrochemistry, and Cu(ii) reduction kinetics of biologically relevant selone and thione compounds

Abstract

Selenium- and sulfur-containing compounds can act as antioxidants by binding copper. To determine how this copper coordination results in the observed antioxidant activity, biologically relevant Cu(+) and Cu(2+) complexes with the formulae [Cu(dmit)(3)](+) (3), [Cu(dmise)(4)](+) (4a), and [Tpm(iPr)Cu(MISeox)](2+) (6) (dmise = N,N'-dimethylimidazole selone; dmit = N,N'-dimethylimidazole thione; MISeox = bis(1-methylimidazolyl)diselenide; Tpm(iPr) = tris(1,3-diisopropylpyrazolyl)methane) were synthesized, characterized, and their structures determined by single-crystal X-ray crystallography. In addition, kinetic studies using UV-vis spectroscopy indicate that dmise reduces Cu(2+) to Cu(+) three times faster than dmit. Coordination of dmise and MISeox to copper also results in more negative Cu(2+/+) reduction potentials (-373 mV and -503 mV) compared to dmit (-217 mV). These results highlight the different complexation behaviors and reactivities of analogous selone- and thione-containing compounds, traits which likely influence their antioxidant activity.

A Computational Investigation of the Binding of the Selenium Analogues of Ergothioneine and Ovothiol to Cu(I) and Cu(II) and the Effect of Binding on the Redox Potential of the Cu(II)/Cu(I) Redox Couple

“…us, the Cu(II)(OSe) 2 /Cu(I)(OSeH) 3 + and Cu(II)(ESe) 2 /Cu(I)(E-SeH) 3 + redox couples are 0.17 V and 0.15 V more reducing than their respective sulfur analogues. While the sulfur compounds have the more positive potential and therefore suggests a greater protection from the recycling of Cu(I) to Cu(II) from past experiments into the binding of N,N′dimethylimidazole selone and N,N′-dimethylimidazole thione to Cu, similar differences in reduction potentials were observed [36,40]. In particular, the reduction potentials for the Cu(II)-selone complexes were more negative than the Cu(II)-thione analogues by an average of 0.11 V [36,40].…”

“…While the sulfur compounds have the more positive potential and therefore suggests a greater protection from the recycling of Cu(I) to Cu(II) from past experiments into the binding of N,N′dimethylimidazole selone and N,N′-dimethylimidazole thione to Cu, similar differences in reduction potentials were observed [36,40]. In particular, the reduction potentials for the Cu(II)-selone complexes were more negative than the Cu(II)-thione analogues by an average of 0.11 V [36,40]. While both the thione and selone prevented copper redox cycling and copper-mediated DNA damage, it was found that the selone did so where the reduction of Cu(II) to Cu(I) occurred 3x faster than in the presence of the thione [36].…”

“…In particular, the reduction potentials for the Cu(II)-selone complexes were more negative than the Cu(II)-thione analogues by an average of 0.11 V [36,40]. While both the thione and selone prevented copper redox cycling and copper-mediated DNA damage, it was found that the selone did so where the reduction of Cu(II) to Cu(I) occurred 3x faster than in the presence of the thione [36]. Moreover, other experimental work has shown that the introduction of the selenium atom in ovothiol-derived 4mercaptoimidazoles resulted in antioxidants that were approximately 8x more effective at a 5x lower dosage [24,45,46].…”

“…Like sulfurcontaining compounds, selenium-containing compounds have shown the ability to inhibit copper-mediated DNA damage metal through the formation of Cu-Se complexes [4,26,[33][34][35]. For instance, the binding of methyl-Secysteine and selenomethionine to Cu(I) was looked at, and it was concluded that these selenium-containing compounds prevent the oxidation of Cu(I), thus preventing copper-mediated DNA damage [35,36]. Moreover, Kimani et al [36] investigated the binding of N,N′-dimethylimidazole selone and N,N′-dimethylimidazole thione to copper and found that the selone-containing compound reduced Cu(II) to Cu(I) three times faster than thione containing compound.…”

“…For instance, the binding of methyl-Secysteine and selenomethionine to Cu(I) was looked at, and it was concluded that these selenium-containing compounds prevent the oxidation of Cu(I), thus preventing copper-mediated DNA damage [35,36]. Moreover, Kimani et al [36] investigated the binding of N,N′-dimethylimidazole selone and N,N′-dimethylimidazole thione to copper and found that the selone-containing compound reduced Cu(II) to Cu(I) three times faster than thione containing compound. However, it is noted that for N,N′dimethylimidazole selone and N,N′-dimethylimidazole thione both nitrogens of the imidazole ring are methylated; thus, the possible binding of the nitrogens to the Cu center is not possible.…”