British anti-Lewisite (2,3-dimerkaptopropan-1-ol, dimercaprol, BAL) is one of the best-known chelator-type therapeutic agents against toxic metal ions and metalloids, especially arsenicals. Surprisingly, the mechanisms of action at the molecular level, as well as the coordination features of this traditional drug toward various arsenicals, are still poorly revealed. The present study on the interaction of arsenous acid (HAsO) with BAL, involving UV and NMR titrations, electrospray ionization mass spectrometry, and 2D NMR experiments combined with MP2 calculations, demonstrates that the reaction of HAsO with BAL at pH = 7.0 results in a more complex speciation than was assumed before. The three reactive hydroxyl groups of HAsO allow for interaction with three thiol moieties via condensation reaction, leading to the observed AsBAL and AsBAL complexes besides the AsBAL species. This indicates the strong propensity of inorganic As(III) to saturate its coordination sphere with thiolate groups. The alcoholic hydroxyl group of the ligand may also directly bind to As(III) in AsBAL. Compared to dithiothreitol or dithioeritritol, the preference of BAL to form complexes with such a tridentate binding mode is much lower owing to the more strained bridged bicyclic structure with an α < 90° bond angle and an unfavorable condensed boat-type six-membered ring. On the basis of the NMR data, the predominating, bidentately bound AsBAL species, including a five-membered chelate ring, exists in rapidly interconverting envelope forms of E and Z stereoisomers. The conditional stability constants calculated for the three macrospecies from a series of UV data [log β = 6.95 (AsBAL), 11.56 (AsBAL), and 22.73 (AsBAL)] reflect that BAL is still the most efficient, known, dithiol-type chelator of HAsO.

Cys-Tyr-(YY), targeting Cd(II) ion sensing, was synthesized on various solid supports including two resins, as well as glass and quartz surfaces. The synthesis was based on the Fmoc (9-fluorenylmethoxycarbonyl) and the APTES (3-aminopropyltriethoxysilane) methodologies on the resin and silica supports, respectively. The immobilized ligand, except when coupled to a hydrophobic benzhydrylamine resin, showed a remarkably efficient, pHdependent Cd(II) capturing ability with a maximum binding capacity around neutral pH. The effect of contact time and metal ion concentration was also studied with a hydrophilic resin supported peptide (YY-NTG). The interaction of YY-NTG with Cd(II) was investigated by pH-potentiometric titrations in aqueous samples containing the resin beads and Cd(II). These studies, together with metal ion capturing experiments under buffer-controlled pH, prove that each immobilized peptide can bind one Cd(II) ion at pH=7.0 in the presence of one equivalent metal ion or metal ion excess. For Cd(II) binding to YY-NTG a notably high, K=1.310 10 apparent stability constant was determined (1:1 metal-to-ligand ratio, pH=7.0). Analytical results suggests that the concentration of Cd(II) can be measured below 200 nM with this silica-supported peptide. The usefulness of the probe was demonstrated by fluorescence spectroscopy.

The AsIII binding of two NTA-based tripodal pseudopeptides, possessing three cysteine (ligand L1 ) or d-penicillamine residues (ligand L2 ) as potential coordinating groups for soft semimetals or metal ions, was studied by experimental (UV, CD, NMR, and ESI-MS) and theoretical (DFT) methods. All of the experimental data, obtained with the variation of the AsIII:ligand concentration ratios or pH values in some instances, evidence the exclusive formation of species with an AsS3-type coordination mode. The UV-monitored titration of the ligands with arsenous acid at pH = 7.0 provided an absorbance data set that allowed for the determination of apparent stability constants of the forming species. The obtained stabilities (logK′ = 5.26 (AsL1 ) and logK′ = 3.04 (AsL2 )) reflect high affinities, especially for the sterically less restricted cysteine derivative. DFT calculated structures correlate well with the spectroscopic results and, in line with the 1H NMR data, indicate a preference for the all-endo conformers resembling the AsIII environment at the semimetal binding sites in various metalloproteins.

Efficient and selective Hg2+ binding of a hexapeptide containing two cysteine residues is demonstrated both in solution and immobilized forms.

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