Interactions of Cu(I) with Selenium-Containing Amino Acids Determined by NMR, XAS, and DFT Studies

Abstract

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.

Synthesis and Characterization of Copper(I) Halide Complexes with N‐(2, 6‐Diisopropylphenyl)‐N′‐benzoylthiourea: Monomeric, Dimeric, and Cage Structures

“…The product in 50 mmol scale synthesis was recrystallized from acetone to give a moderate yield (13.79 2 stirring. An additional 6 h was allowed to insure completion of complexation.…”

“…40 [LICu(μ-L)] 2 (5): The procedure for the preparation of 5 was similar to that described for compound 2 using 1 (0.85g, 2.5 mmol) in THF (20 mL) and CuI (0.25 g, 1.3 mmol) in ethanol (20 mL) to afford a yellow precipitate. The solid was separated by filtration and washed with n-hexane (0.4 g, 0.23 mmol, 37 % 2 X-ray Crystallography: Data were collected with a Bruker SMART APEX II CCD diffractometer for 1·THF, 2-5, and 2Ј·2tol and an Oxford Gemini S Ultra system for 1. The diffraction data were obtained by using graphite monochromated Mo-K α radiation with a ω-2θ scan technique at room temperature.…”

“…[2] Among these sulfur containing ligands, thiourea and its derivatives have been frequently reported to support Cu I complexes.…”

“…[6] Another appealing feature of acylthioureas is the structural diversity of of adamantanoid cage (LCu) 2 (μ-L) 2 Cu 2 (μ-Br) 4 (4) containing enantiomeric couple. The product of 1 and CuI was found to be dimeric [LICu(μ-L)] 2 (5), which is isomorphous to 3.…”

Selenium Metabolism in Cancer Cells: The Combined Application of XAS and XFM Techniques to the Problem of Selenium Speciation in Biological Systems

“…In some cancer cells, MeSeCys was largely unmetabolised, with the generation of dimethyldiselenide (DMeDSe) alone suggesting the generation of MeSe – , although MeSeCys was comparatively non-toxic to the cells [13,56]. Tsuji et al [31,57] found that long-term ingestion of MeSeCys by rats led to Se accumulation in the kidney, liver and testes, selenoprotein synthesis and the excretion of TMSe + and selenosugars in urine, in accordance with the prevailing model of Se metabolism [34].…”