Mercury(ii) complex formation with N-acetylcysteine

Abstract

N-Acetylcysteine (H2NAC) is a potent antioxidant, a precursor for cysteine and glutathione, and a potential antidote against certain metal ions such as cadmium and mercury. Little is known about the structural aspects of complexes formed between Hg(II) and N-acetylcysteine, despite many biological tests on its ability to bind to organic and inorganic mercury, and a few reports on formation constants for Hg(NAC)n (n = 1-3) complexes. We have combined several techniques, including Hg L3-edge EXAFS (extended X-ray absorption fine structure), (199)Hg NMR and Raman spectroscopy, to investigate the nature and structure of Hg(II) N-acetylcysteine complexes formed in aqueous solution at pH 7.5 and 10.5. To allow measurements on the same samples, rather concentrated solutions containing CHg(II) = 0.1 M and variable H2NAC/Hg(II) mole ratios = 2.0-10.0 were used. At physiological pH, Hg(NAC)2(2-) and Hg(NAC)3(4-) complexes form, while in ligand excess and at alkaline pH (H2NAC/Hg(II) > 4), a novel tetra-thiolate species Hg(NAC)4(6-) dominates. Comparison between the Hg(II) complex formation with cysteine, penicillamine and N-acetylcysteine in alkaline aqueous solution has been made to elucidate the influence of the blocked amino group of N-acetylcysteine.

Formation of Hg(II) tetrathiolate complexes with cysteine at neutral pH

“…10, 22 This observation supports our fitting of linear combinations of model oscillations to the experimental EXAFS spectra, which resulted in HgS 4 coordination for at least 70% of the Hg(II) species in these solutions (Tables 3 and S-2).…”

“…10, 21 The average Hg-S distance for the Hg(cysteinate) 3 species (2.44 ± 0.02 Å) is comparable to the average crystallographic distance 2.446 Å ± 0.018 Å for trithiolate Hg(SR) 3 complexes, 3 and that of the [Hg( S -cysteinate) 4 ] m -6 species (2.52 ± 0.02 Å) 10 is similar to those of the [Hg( S -NAC) 4 ] 6− and [Hg( S -GSH) 4 ] 10− complexes, all with HgS 4 coordination. 22, 23 …”

“…The 199 Hg chemical shifts observed for these solutions can be compared with those of Hg( S -GSH) 2 (HgS 2 ; δ Hg = −960 ~ −993 ppm; R Hg-S = 2.32 ± 0.02 Å), 23-25 [Hg( S,N -Pen) 2 ] 2− (HgS 2 N 2, δ Hg = −619 ppm) and [Hg( S,N -Cys) 2 ] 2− (HgS 2 N 2 ; δ Hg = −609 ~ −656 ppm; R Hg-S = 2.34 ± 0.02 Å), 10, 21 Hg(SCH 2 CH 2 NH 2 ) 2 (HgS 2 N 2 ; δ Hg = −608), 17 [Hg(Pen) 3 ] 4− (HgS 3 N 2 ; δ Hg = −390 ppm; R Hg-S = 2.44 ± 0.02 Å), 21 the estimated δ( 199 Hg) values for Hg( S -GSH) 3 and [Hg( S -NAC) 3 ] 4− (HgS 3 ; δ Hg ~ −170 ppm; R Hg-S = 2.42 ± 0.02 Å), 22, 23 as well as [Hg( S -Cys) 4 ] 6− and [Hg( S -NAC) 4 ] 6− (HgS 4 ; δ Hg = −340 ~ − 350 ppm; R Hg-S = 2.52 ± 0.02 Å). 10, 22 ( abbreviations: GSH = glutathione; H 2 Pen = penicillamine; H 2 NAC = N -acetylcysteine). For trigonal planar HgS 3 coordination in Hg( S -cysteinate) 3 the experimental δ( 199 Hg) = −185 ppm was reported.…”

Synthesis, Characterization of Some Ferrocenoyl Cysteine and Histidine Conjugates, and Their Interactions with Some Metal Ions

“…[11] The thiol group also has a high affinity for toxic heavy metals including Hg 2+ , Pb 2+ , Cd 2+ , [12] and has, for example, enabled the removal of Pb 2+ from dithiocarbamate-capped Ag nanoparticles. [13] Jalilehvand and co-workers [14][15][16][17] have investigated the potential for Hg 2+ complex formation with Cys and other thiolate-containing biological molecules at both physiological and alkaline pH, with the aim of [a] 5337 taining peptides involved the imidazole group. Metal coordination affects the structural properties of the ferrocene (Fc) conjugates, as judged by CD spectroscopy, and also the redox properties of the Fc group.…”

“…Examples are the FeMo-cofactor in nitrogenase, in which the metal cluster is linked to the protein via cysteine thiols, [3] or other Fc-S clusters, [4][5][6][7] which play important roles in electron transfer reactions, such as aerobic respiration, photosynthesis, and biodegradation of various alkene and aromatic compounds. [13] Jalilehvand and co-workers [14][15][16][17] have investigated the potential for Hg 2+ complex formation with Cys and other thiolate-containing biological molecules at both physiological and alkaline pH, with the aim of [a] 5337 taining peptides involved the imidazole group. [11] The thiol group also has a high affinity for toxic heavy metals including Hg 2+ , Pb 2+ , Cd 2+ , [12] and has, for example, enabled the removal of Pb 2+ from dithiocarbamate-capped Ag nanoparticles.…”