Lead(II) Binding to the Chelating Agent d‑Penicillamine in Aqueous Solution

A spectroscopic investigation of the complexes formed between the Pb­(II) ion and d-penicillamine (H₂Pen), a chelating agent used in the treatment of lead poisoning, was carried out on two sets of alkaline aqueous solutions with <i>C</i>_Pb(II) ≈ 10 and 100 mM, varying the H₂Pen/Pb­(II) molar ratio (2.0, 3.0, 4.0, 10.0). Ultraviolet–visible (UV-vis) spectra of the 10 mM Pb­(II) solutions consistently showed an absorption peak at 298 nm for S^– → Pb­(II) ligand-to-metal charge-transfer. The downfield ¹³C NMR chemical shift for the penicillamine COO^– group confirmed Pb­(II) coordination. The ²⁰⁷Pb NMR chemical shifts were confined to a narrow range between 1806 ppm and 1873 ppm for all Pb­(II)-penicillamine solutions, indicating only small variations in the speciation, even in large penicillamine excess. Those chemical shifts are considerably deshielded, relative to the solid-state ²⁰⁷Pb NMR isotropic chemical shift of 909 ppm obtained for crystalline penicillaminatolead­(II) with Pb­(<i><i>S,N,O</i></i>-Pen) coordination. The Pb L_III-edge extended X-ray absorption fine structure (EXAFS) spectra obtained for these solutions were well-modeled with two Pb–S and two Pb-(N/O) bonds with mean distances 2.64 ± 0.04 Å and 2.45 ± 0.04 Å, respectively. The combined spectroscopic results, reporting δ­(²⁰⁷Pb) ≈ 1870 ppm and λ_max ≈ 298 nm for a Pb^IIS₂NO site, are consistent with a dominating 1:2 lead­(II):penicillamine complex with [Pb­(<i><i>S,N,O</i></i>-Pen)­(<i>S</i>-H_<i>n</i>Pen)]^2–<i>n</i> (<i>n</i> = 0–1) coordination in alkaline solutions, and provide useful structural information on how penicillamine can function as an antidote against lead toxicity <i>in vivo</i>

Lead(II) Complex Formation with l‑Cysteine in Aqueous Solution

The lead­(II) complexes formed with the multidentate chelator l-cysteine (H₂Cys) in an alkaline aqueous solution were studied using ²⁰⁷Pb, ¹³C, and ¹H NMR, Pb L_III-edge X-ray absorption, and UV–vis spectroscopic techniques, complemented by electrospray ion mass spectrometry (ESI-MS). The H₂Cys/Pb^II mole ratios were varied from 2.1 to 10.0 for two sets of solutions with <i>C</i>_Pb^II = 0.01 and 0.1 M, respectively, prepared at pH values (9.1–10.4) for which precipitates of lead­(II) cysteine dissolved. At low H₂Cys/Pb^II mole ratios (2.1–3.0), a mixture of the dithiolate [Pb­(<i>S</i>,<i>N</i>-Cys)₂]^2– and [Pb­(<i>S</i>,<i>N</i>,<i>O</i>-Cys)­(<i>S</i>-HCys)]⁻ complexes with average Pb–(N/O) and Pb–S distances of 2.42 ± 0.04 and 2.64 ± 0.04 Å, respectively, was found to dominate. At high concentration of free cysteinate (>0.7 M), a significant amount converts to the trithiolate [Pb­(<i>S</i>,<i>N</i>-Cys)­(<i>S</i>-HCys)₂]^2–, including a minor amount of a PbS₃-coordinated [Pb­(<i>S</i>-HCys)₃]⁻ complex. The coordination mode was evaluated by fitting linear combinations of EXAFS oscillations to the experimental spectra and by examining the ²⁰⁷Pb NMR signals in the chemical shift range δ_Pb = 2006–2507 ppm, which became increasingly deshielded with increasing free cysteinate concentration. One-pulse magic-angle-spinning (MAS) ²⁰⁷Pb NMR spectra of crystalline Pb­(aet)₂ (Haet = 2-aminoethanethiol or cysteamine) with PbS₂N₂ coordination were measured for comparison (δ_iso = 2105 ppm). The UV–vis spectra displayed absorption maxima at 298–300 nm (S^– → Pb^II charge transfer) for the dithiolate PbS₂N­(N/O) species; with increasing ligand excess, a shoulder appeared at ∼330 nm for the trithiolate PbS₃N and PbS₃ (minor) complexes. The results provide spectroscopic fingerprints for structural models for lead­(II) coordination modes to proteins and enzymes