Polyphenol prevention of iron-mediated DNA damage occurs primarily through iron binding. Once bound, iron in the Fe(2+)-polyphenol complex autooxidizes to Fe(3+) in the presence of O(2). To determine the correlation between the rate of Fe(2+)-polyphenol autooxidation and polyphenol antioxidant ability, kinetic studies at pH = 6.0 in the presence of oxygen were performed using UV-vis spectrophotometry. Initial rates of iron-polyphenol complex oxidation for epigallocatechin gallate (EGCG), methyl-3,4,5-trihydroxybenzoate (MEGA), gallic acid (GA), epicatechin (EC), and methyl-3,4-dihydroxybenzoate (MEPCA) were in the range of 0.14-6.7 min(-1). Polyphenols with gallol groups have faster rates of iron oxidation than their catechol analogs, suggesting that stronger iron binding results in faster iron oxidation. Concentrations of polyphenol, Fe(2+), and O(2) were varied to investigate the dependence of the Fe(2+)-polyphenol autooxidation on these reactants for MEGA and MEPCA. For these analogous gallate and catecholate complexes of Fe(2+), iron oxidation reactions were first order in Fe(2+), polyphenol, and O(2), but gallate complexes show saturation behavior at much lower Fe(2+) concentrations. Thus, gallol-containing polyphenols promote iron oxidation at a significantly faster rate than analogous catechol-containing compounds, and iron oxidation rate also correlates strongly with polyphenol inhibition of DNA damage for polyphenol compounds with a single iron-binding moiety.

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.

Cu(I) coordination by organoselenium compounds was recently reported as a mechanism for their prevention of copper-mediated DNA damage. To establish whether direct Se-Cu coordination may be involved in selenium antioxidant activity, Cu(I) coordination of the selenoamino acids methyl-Se-cysteine (MeSeCys) and selenomethionine (SeMet) was investigated. NMR results in D2O indicate that Cu(I) binds to the Se atom of both MeSeCys and SeMet as well as the carboxylic acid oxygen atom(s) or amine nitrogen atoms. X-ray absorption spectroscopy (XAS) and density functional theory (DFT) results confirm Se-Cu coordination, with the identification of a 2.4 Å Se-Cu vector in both the Se- and Cu-EXAFS data. XAS studies also show Cu(I) in an unusual three-coordinate environment with the additional two ligands arising from O/N (2.0 Å). DFT models of 1:1 Cu-selenoamino acid complexes suggest that both selenoamino acids coordinate Cu(I) through the selenium and amino groups, with the third ligand assumed to be water. These compounds represent the first structurally characterized copper(I) complexes with sulfur or selenium-containing amino acids.

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