Complex Formation of Pb(II) with Cysteine, Penicillamine and N-acetylcysteine

The mechanism of lead poisoning and interest in metal toxicity has been a growing area of study since the late 1950s. In order to gain insight on how toxic metals behave physiologically, simple molecules can first be used to model the environments. Complex formation between Pb(II) and thiol-containing ligands D-penicillamine, L- cysteine and N-acetyl-L-cysteine were investigated in this study. The complexes formed were studied by 207Pb, 13C, 1H NMR, UV-Vis, ESI-MS, and X-ray absorption spectroscopy. The results of the study provide spectroscopic finger prints for Pb(II) coordination environments relevant to biological systems. The study revealed that small structural changes between each ligand, plays a large role in the manner at which they bind to the lead(II) centre

Similarities between <i>N</i>‑Acetylcysteine and Glutathione in Binding to Lead(II) Ions

<i>N</i>-Acetylcysteine is a natural thiol-containing antioxidant, a precursor for cysteine and glutathione, and a potential detoxifying agent for heavy metal ions. However, previous accounts of the efficiency of <i>N</i>-acetylcysteine (H₂NAC) in excretion of lead are few and contradicting. Here, we report results on the nature of lead­(II) complexes formed with <i>N</i>-acetylcysteine in aqueous solution, which were obtained by combining information from several spectroscopic methods, including ²⁰⁷Pb, ¹³C, and ¹H NMR, Pb L_III-edge X-ray absorption, ultraviolet–visible (UV–vis) spectroscopy, and electro-spray ionization mass spectrometry (ESI-MS). Two series of solutions were used containing <i>C</i>_Pb(II) = 10 and 100 mM, respectively, varying the H₂NAC/Pb­(II) mole ratios from 2.1 to 10.0 at pH 9.1–9.4. The coordination environments obtained resemble those previously found for the Pb­(II) glutathione system: at a ligand-to-lead mole ratio of 2.1, dimeric or oligomeric Pb­(II) <i>N</i>-acetylcysteine complexes are formed, while a trithiolate [Pb­(NAC)₃]^4– complex dominates in solutions with H₂NAC/Pb­(II) mole ratios >3.0

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