Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS(3) Coordination Environment Imitating Metalloid Binding Sites in Proteins

[Image: see text] The As(III) binding of two NTA-based tripodal pseudopeptides, possessing three cysteine (ligand L(1)) or d-penicillamine residues (ligand L(2)) 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 As(III):ligand concentration ratios or pH values in some instances, evidence the exclusive formation of species with an AsS(3)-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 (AsL(1)) and logK′ = 3.04 (AsL(2))) 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 (1)H NMR data, indicate a preference for the all-endo conformers resembling the As(III) environment at the semimetal binding sites in various metalloproteins.