title: Protection of Endogenous Thiols against Methylmercury with Benzimidazole-Based Thione by Unusual Ligand-Exchange Reactions.
abstract: Organomercurials, such as methylmercury (MeHg+), are among the most toxic materials to humans. Apart from inhibiting proteins, MeHg+exerts its cytotoxicity through strong binding with endogenous thiols cysteine (CysH) and glutathione (GSH) to form MeHgCys and MeHgSG complexes. Herein, it is reported that the N,N-disubstituted benzimidazole-based thione 1 containing a N-CH2CH2OH substituent converts MeHgCys and MeHgSG complexes to less toxic water-soluble HgS nanoparticles (NPs) and releases the corresponding free thiols CysH and GSH from MeHgCys and MeHgSG, respectively, in solution by unusual ligand-exchange reactions in phosphate buffer at 37 °C. However, the corresponding N-substituted benzimidazole-based thione 7 and N,N-disubstituted imidazole-based thione 3, in spite of containing a N-CH2CH2OH substituent, failed to convert MeHgX (X=Cys, and SG) to HgS NPs under identical reaction conditions, which suggests that not only the N-CH2CH2OH moiety but the benzimidazole ring and N,N-disubstitution in 1, which leads to the generation of a partial positive charge at the C2 atom of the benzimidazole ring in 1:1 MeHg-conjugated complex of 1, are crucial to convert MeHgX to HgS NPs under physiologically relevant conditions.
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, NH91, Dadri, Gautam Buddha Nagar, UP, 201314, India.
authors.forename: Mainak
authors.initials: M
authors.lastname: Banerjee
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, NH91, Dadri, Gautam Buddha Nagar, UP, 201314, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Karri
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, NH91, Dadri, Gautam Buddha Nagar, UP, 201314, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Chalana
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, NH91, Dadri, Gautam Buddha Nagar, UP, 201314, India.
authors.forename: Ranajit
authors.initials: R
authors.lastname: Das
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, NH91, Dadri, Gautam Buddha Nagar, UP, 201314, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Rai
authors.affiliation: Discipline of Chemistry and Discipline of Metallurgy Engineering and Materials Science, Indian Institute of Technology (IIT) Indore, Indore, MP, 453552, India.
authors.forename: Kuber Singh
authors.initials: KS
authors.lastname: Rawat
authors.affiliation: Discipline of Chemistry and Discipline of Metallurgy Engineering and Materials Science, Indian Institute of Technology (IIT) Indore, Indore, MP, 453552, India.
authors.forename: Biswarup
authors.initials: B
authors.lastname: Pathak
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, NH91, Dadri, Gautam Buddha Nagar, UP, 201314, India.
authors.forename: Gouriprasanna
authors.identifier: http://orcid.org/0000-0002-0047-3575
authors.initials: G
authors.lastname: Roy
keywords: detoxification; methylmercury; nanochemistry; selenium; sulfur