Mercury-Sequestering Pseudopeptides with a Tris(cysteine) Environment in Water

Abstract

The three pseudopeptides L^1–3 having three converging cysteine arms anchored on a nitrilotriacetic acid scaffold, are demonstrated to be efficient sulfur-based Hg^II chelating agents. The three ligands differ by the nature of the carbonyl group of the cysteine moieties, ester, amide, and carboxylate for L¹, L², and L³, respectively. The coordination chemistry of the mercury thiolate complexes was characterized in water by acid–base titration and several spectroscopic methods, including UV, ¹H, and ¹⁹⁹Hg NMR spectroscopy and Hg-L_III EXAFS. At alkaline pH, they form monometallic complexes with typical signatures of a trigonal HgS₃ coordination site, which is uncommon, as Hg^II usually prefers a coordination number of two. The digonal HgS₂ structure is formed at acidic pH, where one cysteine group is protonated (HgLH complex). EXAFS spectra at liquid He temperature and alkaline pH are nearly identical for the three HgL complexes. Their analysis reveals an asymmetrical HgS₃ binding environment with three S atoms at 2.38, 2.51, and 2.67 Å. This suggests that the C₃-symmetrical species detected by ¹H NMR spectroscopic analysis at 298 K are averages of nonsymmetrical complexes that rapidly equilibrate on the NMR time-scale at ambient temperature. At acidic pH, Hg^II is coordinated in a linear configuration to the two sulfur atoms from the thiolate groups at a distance of 2.36 Å, and in a T-shaped geometry to the third sulfur atoms from the protonated cysteine at 3.07 Å. The three pseudopeptides have high affinities for Hg^II and are interesting alternatives for the design of efficient water-soluble mercury-sequestering agents that favor an uncommon tris(thiolato)mercury environment.