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 L 1 , L 2 , and L 3 , respectively. The coordination chemistry of the mercury thiolate complexes was characterized in water by acid-base titration and several spectroscopic methods, including UV, 1 H, and 199 Hg NMR spectroscopy and Hg-L III EXAFS. At alkaline pH, they form monometallic complexes with typical signatures of a trigonal HgS 3 coordination site, which is uncommon, as Hg II usually prefers a coordination number of two. The digonal HgS 2 structure is formed at acidic pH, where one cysteine group is protonated (HgLH complex). EXAFS spectra at liquid He temperature and alk-

Mercury Complexes with Tripodal Pseudopeptides Derived from D‐Penicillamine Favour a HgS3 Coordination

“…Indeed, low temperature Hg L III -edge extended X-ray absorption fine structure (EXAFS) data have previously evidenced highly distorted HgS 3 coordination modes with three sulfur shells for the parent complexes HgL 1 and HgL 2 . [26] These results are in contrast with spectroscopic data acquired at 298 K, which are fully consistent with C 3 -symmetrical species as seen for the mercury complexes with the two d-Pen pseudopeptides. The C 3 -symmetrical species detected at room temperature may thus be the average of the nonsymmetrical complexes.…”

“…The pK a value of the HgL 5 complex was determined in water (pK a HgL 5 = 5.5) and is more than one pH unit lower than the value measured for the cysteine analogue L 2 (pK a HgL 2 = 6.8). [26] This suggests that the gemdimethyl groups borne by L 5 reinforce the stability of the HgS 3 trigonal coordination of mercury. Water-soluble Hg binding three helical bundles show even higher pK a values ranging from 7.1 to 7.7 depending on the peptide sequence.…”

“…[22][23][24][25][26] These scaffolds were functionalized with d-Pen, which is a bulkier analogue of cysteine with the β-methylene hydrogen atoms replaced by larger methyl groups. [31] d-Pen is an interesting unnatural amino acid that provides more steric bulk in peptide sequences and has been demonstrated to favour a MS 3 coordination of Cd II [28] or Co II .…”

“…Following the latter strategy we developed tripodal ligands derived from nitrilotriacetic acid (NTA) and extended them with three converging cysteine units to give L 1 and L 2 ( Figure 1). [22][23][24][25][26] These sulfur pseudopeptides have been demonstrated to bind tightly both Cu I and Hg II in trithiolato coordination modes. [27] d-Penicillamine (d-Pen) has also been chosen as a favoured building block: it looks like cysteine but bears extra gem dimethyl groups close to the coordinating thiolate functions.…”

A Trishistidine Pseudopeptide with Ability to Remove Both CuΙ and CuΙΙ from the Amyloid‐β Peptide and to Stop the Associated ROS Formation

“…The nitrilotriacetic (NTA) scaffold is a perfect candidate to anchor three amino acids that can be grafted to the three acidic functions with peptide amide bonds. Moreover, bioinspired pseudopeptides built up on the NTA template and extended with three sulfur amino acids such as cysteines[25] d -penicillamine[26] or methionine,[27] have proven their capacity to tightly bind Cu i in trigonal planar coordination sites, Cu i S 3 , with three sulfur donors in the first sphere. Therefore the novel ligand L (Scheme 1), based on a similar design with His is expected to make the N-donors of the three amino acids converge to the metal center.…”