Towards a custom chelator for mercury: evaluation of coordination environments by molecular modeling

Fu, Juxia; Hoffmeyer, Ruth E.; Pushie, M. Jake; Singh, Satya Pal; Pickering, Ingrid J.; George, Graham N.

doi:10.1007/s00775-010-0695-1

Cited by 16 publications

(19 citation statements)

References 43 publications

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“…11 and 12). 5 As expected for an increased spacer length [25], the S–Hg–S bond angles for the 1,3-derivatives are larger than those for the 1,2-derivatives, in various protonation states (Tables 2 and 3). The bond angles for the 1,3-derivatives are, however, far from linear, such that the molecules studied in silico are unlikely to correspond to stable species that would exist in solution [7].…”

Section: Resultssupporting

confidence: 57%

Structural characterization of 1,3-propanedithiols that feature carboxylic acids: Homologues of mercury chelating agents

et al. 2013

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The molecular structures of a series of 1,3-propanedithiols that contain carboxylic acid groups, namely rac- and meso-2,4-dimercaptoglutaric acid (H4DMGA) and 2-carboxy-1,3-propanedithiol (H3DMCP), have been determined by X-ray diffraction. Each compound exhibits two centrosymmetric intermolecular hydrogen bonding interactions between pairs of carboxylic acid groups, which result in a dimeric structure for H3DMCP and a polymeric tape-like structure for rac- and meso-H4DMGA. Significantly, the hydrogen bonding motifs observed for rac- and meso-H4DMGA are very different to those observed for the 1,2-dithiol, rac-2,3-dimercaptosuccinic acid (rac-H4DMSA), in which the two oxygen atoms of each carboxylic acid group hydrogen bond to two different carboxylic acid groups, thereby resulting in a hydrogen bonded sheet-like structure rather than a tape. Density functional theory calculations indicate that 1,3-dithiolate coordination to mercury results in larger S–Hg–S bond angles than does 1,2-dithiolate coordination, but these angles are far from linear. As such, κ2-S2 coordination of these dithiolate ligands is expected to be associated with mercury coordination numbers of greater than two. In vivo studies demonstrate that both rac-H4DMGA and H3DMCP reduce the renal burden of mercury in rats, although the compounds are not as effective as either 2,3-dimercaptopropane-1-sulfonic acid (H3DMPS) or meso-H4DMSA.

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Section: Resultssupporting

confidence: 57%

Structural characterization of 1,3-propanedithiols that feature carboxylic acids: Homologues of mercury chelating agents

et al. 2013

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“…Conversely, the affinity of mercury toward the thiol group is important in developing chelating agents and for mercury detoxification. 7 …”

Section: Introductionmentioning

confidence: 99%

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

Warner

Jalilehvand

2016

Can. J. Chem.

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Mercury(II) ions precipitate from aqueous cysteine (H2Cys) solutions containing H2Cys/Hg(II) mole ratio ≥ 2.0 as Hg(S-HCys)2. In absence of additional cysteine, the precipitate dissolves at pH ~12 with the [Hg(S,N-Cys)2]2− complex dominating. With excess cysteine (H2Cys/Hg(II) mole ratio ≥ 4.0), higher complexes form and the precipitate dissolves at lower pH values. Previously, we found that tetrathiolate [Hg(S-Cys)4]6− complexes form at pH = 11.0; in this work we extend the investigation to pH values of physiological interest. We examined two series of Hg(II)-cysteine solutions in which CHg(II) varied between 8 – 9 mM and 80 – 100 mM, respectively, with H2Cys/Hg(II) mole ratios from 4 to ~20. The solutions were prepared in the pH range 7.1 – 8.8, at the pH at which the initial Hg(S-HCys)2 precipitate dissolved. The variations in the Hg(II) speciation were followed by 199Hg NMR, X-ray absorption and Raman spectroscopic techniques. Our results show that in the dilute solutions (CHg(II) = 8 – 9 mM), mixtures of di-, tri- (major) and tetrathiolate complexes exist at moderate cysteine excess (CH2Cys ~ 0.16 M) at pH 7.1. In the more concentrated solutions (CHg(II) = 80 – 100 mM) with high cysteine excess (CH2Cys > 0.9 M), tetrathiolate [Hg(S-cysteinate)4]m-6 (m = 0 – 4) complexes dominate in the pH range 7.3 – 7.8, with lower charge than for the [Hg(S-Cys)4]6− complex due to protonation of some (m) of the amino groups of the coordinated cysteine ligands. The results of this investigation could provide a key to the mechanism of biosorption and accumulation of Hg(II) ions in biological / environmental systems.

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“…The primary toxicological target of CH 3 Hg + is the neurological system; therefore, prenatal exposure to this metal can have serious neurological consequences in the fetus. These include reduced cognitive function, dysarthria, strabismus, and cerebral palsy [10-13]. Because CH 3 Hg + is a prevalent environmental toxicant which humans are exposed to frequently and owing to its propensity to negatively affect fetal health, it is important that we understand completely the handling of mercuric ions by placental and fetal tissues.…”

Section: Introductionmentioning

confidence: 99%

Placental and fetal disposition of mercuric ions in rats exposed to methylmercury: Role of Mrp2

Bridges

Joshee

Zalups

2012

Reproductive Toxicology

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Methylmercury is a prevalent environmental toxicant that can have deleterious effects on a developing fetus. Previous studies indicate that the multidrug resistance-associated protein 2 (Mrp2) is involved in renal and hepatic export of mercuric ions. Therefore, we hypothesize that Mrp2 is also involved in export of mercuric ions from placental trophoblasts and fetal tissues. To test this hypothesis, we assessed the disposition of mercuric ions in pregnant Wistar and TR– (Mrp2-deficient) rats exposed to a single dose of methylmercury. The amount of mercury in renal tissues (cortex and outer stripe of outer medulla), liver, blood, amniotic fluid, uterus, placentas and fetuses was significantly greater in TR– rats than in Wistar rats. Urinary and fecal elimination of mercury was greater in Wistar dams than in TR– dams. Thus, our findings suggest that Mrp2 may be involved in the export of mercuric ions from maternal and fetal organs following exposure to methylmercury.

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Towards a custom chelator for mercury: evaluation of coordination environments by molecular modeling

Cited by 16 publications

References 43 publications

Structural characterization of 1,3-propanedithiols that feature carboxylic acids: Homologues of mercury chelating agents

Structural characterization of 1,3-propanedithiols that feature carboxylic acids: Homologues of mercury chelating agents

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

Placental and fetal disposition of mercuric ions in rats exposed to methylmercury: Role of Mrp2

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