Equilibrium characterization of the As(III)-cysteine and the As(III)-glutathione systems in aqueous solution

Sulfhydryl groups as targets of mercury toxicity.

The metal ion coordination abilities of reduced and oxidized glutathione are reviewed. Reduced glutathione (GSH) is a very versatile ligand, forming stable complexes with both hard and soft metal ions. Several general binding modes of GSH are described. Soft metal ions coordinate exclusively or primarily through thiol sulfur. Hard ones prefer the amino acid-like moiety of the glutamic acid residue. Several transition metal ions can additionally coordinate to the peptide nitrogen of the gamma-Glu-Cys bond. Oxidized glutathione lacks the thiol function. Nevertheless, it proves to be a surprisingly efficient ligand for a range of metal ions, coordinating them primarily through the donors of the glutamic acid residue.

/pdf/coordination-chemistry-of-glutathione-16fpeyx4nr.pdf

Coordination chemistry of glutathione.

Cadmium is a heavy metal and a pollutant that can be found in large quantities in the environment from industrial waste. Its toxicity for living organisms could arise from its ability to alter thiol-containing cellular components. Glutathione is an abundant tripeptide (γ-Glu-Cys-Gly) that is described as the first line of defence against cadmium in many cell types. NMR experiments for structure and dynamics determination, molecular simulations, competition reactions for metal chelation by different metabolites (γ-Glu-Cys-Gly, α-Glu-Cys-Gly and γ-Glu-Cys) combined with biochemical and genetics experiments have been performed to propose a full description of bio-inorganic reactions occurring in the early steps of cadmium detoxification processes. Our results give unambiguous information about the spontaneous formation, under physiological conditions, of the Cd(GS)2 complex, about the nature of ligands involved in cadmium chelation by glutathione, and provide insights on the structures of Cd(GS)2 complexes in solution at different pH. We also show that γ-Glu-Cys, the precursor of glutathione, forms a stable complex with cadmium, but biological studies of the first steps of cadmium detoxification reveal that this complex does not seem to be relevant for this purpose.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2010.07913.x

Cadmium-glutathione solution structures provide new insights into heavy metal detoxification.

The complex formation between cadmium(II) and the ligands cysteine (H(2)Cys) and penicillamine (H(2)Pen = 3,3'-dimethylcysteine) in aqueous solutions, having C(Cd(II)) approximately 0.1 mol dm(-3) and C(H(2)L) = 0.2-2 mol dm(-3), was studied at pH = 7.5 and 11.0 by means of (113)Cd NMR and Cd K- and L(3)-edge X-ray absorption spectroscopy. For all cadmium(II)-cysteine molar ratios, the mean Cd-S and Cd-(N/O) bond distances were found in the ranges 2.52-2.54 and 2.27-2.35 A, respectively. The corresponding cadmium(II)-penicillamine complexes showed slightly shorter Cd-S bonds, 2.50-2.53 A, but with the Cd-(N/O) bond distances in a similar wide range, 2.28-2.33 A. For the molar ratio C(H(2)L)/C(Cd(II)) = 2, the (113)Cd chemical shifts, in the range 509-527 ppm at both pH values, indicated complexes with distorted tetrahedral CdS(2)N(N/O) coordination geometry. With a large excess of cysteine (molar ratios C(H(2)Cys)/C(Cd(II)) >or= 10), complexes with CdS(4) coordination geometry dominate, consistent with the (113)Cd NMR chemical shifts, delta approximately 680 ppm at pH 7.5 and 636-658 ppm at pH 11.0, and their mean Cd-S distances were 2.53 +/- 0.02 A. At pH 7.5, the complexes are almost exclusively sulfur-coordinated as [Cd(S-cysteinate)(4)](n-), while at higher pH, the deprotonation of the amine groups promotes chelate formation. At pH 11.0, a minor amount of the [Cd(Cys)(3)](4-) complex with CdS(3)N coordination is formed. For the corresponding penicillamine solutions with molar ratios C(H(2)Pen)/C(Cd(II)) >or= 10, the (113)Cd NMR chemical shifts, delta approximately 600 ppm at pH 7.5 and 578 ppm at pH 11.0, together with the average bond distances, Cd-S 2.53 +/- 0.02 A and Cd-(N/O) 2.30-2.33 A, indicate that [Cd(penicillaminate)(3)](n-) complexes with chelating CdS(3)(N/O) coordination dominate already at pH 7.5 and become mixed with CdS(2)N(N/O) complexes at pH 11.0. The present study reveals differences between cysteine and penicillamine as ligands to the cadmium(II) ion that can explain why cysteine-rich metallothionines are capable of capturing cadmium(II) ions, while penicillamine, clinically useful for treating the toxic effects of mercury(II) and lead(II) exposure, is not efficient against cadmium(II) poisoning.

Cadmium(II) Complex Formation with Cysteine and Penicillamine

Potentiometrically determined formation constants are reported for cadmium(II), lead(II), and zinc(II) with ethylenediaminetetra-acetic acid, 1,2,di(2-aminoethoxy)ethanetetra-acetic acid, glutathione, cysteine, and D-penicillamine at 25 °C, I= 3.00M(NaClO4). Computer-simulated models of blood plasma conditions were used to examine the complexing competition between cadmium(II) and zinc(II), and lead(II) and zinc(II), with these ligands. It was concluded that glutathione is the most promising ligand for future clinical studies.

Thermodynamic considerations in co-ordination. Part XXII. Sequestering ligands for improving the treatment of plumbism and cadmiumism

Premature ejaculation is a common male condition worldwide with prevalence estimates varying from 30% to 85%. Owing to the lack of a clear definition and a clear understanding of the potentially multifactorial pathophysiology, treatment remains challenging. The aim of this systematic review was to evaluate the non‐pharmacological treatment modalities for PE to inform clinical practice and patients.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/tre.903

Anna M. Carrie

Papers

Thermodynamic considerations in co-ordination. Part XXII. Sequestering ligands for improving the treatment of plumbism and cadmiumism

Non‐pharmacological approaches for treatment of premature ejaculation: a systematic review