MOLECULAR STRUCTURE OF N-ACETYL CYSTEINE METAL COMPLEXES

N-乙酰半胱氨酸金属配合物的分子结构

• 批准号: 8362319
• 负责人: FARIDEH JALILEHVAND
• 金额: $ 0.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362319
• 关键词: Acetylcysteine; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Chelating Agents; Complex; Cysteine; Data Analyses; Drug Metabolic Detoxication; Excretory function; Funding; Goals; Grant; Heavy Metals; Ions; Metals; Methods; Molecular Structure; National Center for Research Resources; Nuclear; Penicillamine; Physiological; Principal Component Analysis; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Solutions; Source; Structure; Techniques; Testing; Trace Elements; United States National Institutes of Health; absorption; aqueous; base; cost; improved; metal complex; metal poisoning; solid state; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. N-acetyl-L-cysteine (NAC), a natural antioxidant, improves the efficiency of chelating agents used against heavy metal poisoning and facilitates the excretion of Cr(III), Cd(II) and Pb(II), but not of Hg(II). Recent bio-tests on NAC complexes with transition biometals (Zn2+, Co2+, Co3+, Fe2+) showed significant anti-inflammatory activity. The goal of our proposed research is to study the structure of NAC complexes with heavy metals, and transition biometals, in solid state and in aqueous solution at physiological pH and pH = 8.5, using different [NAC]/[Mn+] ratios and [Mn+] = 10 and 100 mM. In this study, we will combine the results from different spectroscopic techniques, such as extended x-ray-absorption fine structure (EXAFS), multi-nuclear NMR, Raman and IR, to identify the local structure around the central metal ion in these complexes. We will use the method that we have developed for EXAFS data analysis of mixtures for similar Cd(II), Hg(II) and Pb(II) complexes with cysteine and penicillamine (3,3'-dimethyl cysteine), including Principal Component Analysis (PCA) of the EXAFS spectra. The aim of the current study is to provide a basis for better understanding of the detoxification treatments and the anti-inflammatory activities with the use of cysteine derivatives as complex-forming agents.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 N-乙酰-L-半胱氨酸（NAC）是一种天然抗氧化剂，可提高螯合剂抗重金属中毒的效率，促进Cr（III）、Cd（II）和Pb（II）的排泄，但对Hg（II）无影响。最近的生物测试表明，NAC与过渡金属（Zn 2+，Co 2+，Co 3+，Fe 2+）的配合物具有显著的抗炎活性。我们提出的研究的目标是研究NAC与重金属和过渡生物金属的络合物的结构，在固态和生理pH和pH = 8.5的水溶液中，使用不同的[NAC]/[Mn+]比和[Mn+] = 10和100 mM。在这项研究中，我们将联合收割机不同光谱技术的结果，如扩展的X射线吸收精细结构（EXAFS）、多核NMR、拉曼和IR，以确定这些配合物中中心金属离子周围的局部结构。我们将使用的方法，我们已经开发了类似的镉（II），汞（II）和铅（II）与半胱氨酸和青霉胺（3，3 '-二甲基半胱氨酸）配合物的混合物的EXAFS数据分析，包括EXAFS光谱的主成分分析（PCA）。本研究的目的是为更好地了解使用半胱氨酸衍生物作为复合物形成剂的解毒治疗和抗炎活性提供基础。