Characterizing N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) binding for lead poisoning treatment.

Abstract

Using antioxidants is an important means of treating lead poisoning. Prior in vivo studies showed marked differences between various chelator antioxidants in their ability to decrease both blood Pb(II) levels and oxidative stress resulting from lead poisoning. The comparative abilities of NAC and NACA to Pb(II) were studied in vitro, for the first time, to examine the role of the -OH/-NH(2) functional group in antioxidant binding behavior. To assay the antioxidant-divalent metal interaction, the antioxidants were probed as solid surfaces, adsorbing Pb(II) onto them. Surface characterization was carried out using X-ray photoelectron spectroscopy (XPS) analysis to quantify Pb(II) in the resulting adducts. XPS of the Pb 4f orbitals showed that more Pb(II) was chemically bound to NACA than NAC. In addition, the antioxidant surfaces probed via point-of-zero charge (PZC) measurements of NAC and NACA were obtained to gain further insight into the Pb-NAC and Pb-NACA binding, showing that Coulombic interactions played a partial role in facilitating complex formation. The data correlated well with solution analysis of metal-ligand complexation. UV-vis spectroscopy was used to probe complexation behavior. NACA was found to have the higher binding affinity as shown by free Pb(II) available in the solution after complexation from HPLC data. Electrospray ionization mass spectrometry (ESI-MS) was applied to delineate the structures of Pb-antioxidant complexes. Experimental results were further supported by density functional theory (DFT) calculations of supermolecular interaction energies (E(inter)) showing a greater interaction of Pb(II) with NACA than NAC.

• Authors: Weiqing Chen, Nuran Ercal, Tien Huynh, Anatoliy Volkov, Charles C Chusuei
• Journal: Journal of colloid and interface science (J Colloid Interface Sci) Vol. 371 Issue 1 Pg. 144-9 (Apr 01 2012) ISSN: 1095-7103 [Electronic] United States
• PMID: 22284448 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Free Radical Scavengers
• Lead
• N-Acetylcysteinamide
• Acetylcysteine

Topics

• Acetylcysteine (analogs & derivatives, chemistry, metabolism, pharmacology)
• Chromatography, High Pressure Liquid
• Free Radical Scavengers (chemistry, pharmacology)
• Lead (chemistry, metabolism)
• Lead Poisoning (drug therapy)
• Photoelectron Spectroscopy
• Spectrometry, Mass, Electrospray Ionization