XAFS studies on metal complexes of small biological molecules

XAFS 对生物小分子金属配合物的研究

• 批准号: 250406-2008
• 负责人: Jalilehvand, Farideh
• 金额: $ 2.19万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=426380
• 关键词: XAFS; studies; metal; complexes; small

Exposure to heavy metal ions has profound health effects. Only a few are positive, such as the therapeutic effects of some platinum, bismuth and gold compounds, but accumulation of heavy metals in the environment is causing severe problems. Uptake via food, drinking water and the atmosphere of e.g., lead (dust from previous lead-based paint and leaded gasoline), cadmium (smoking and food) and mercury (in fish), can affect the human metabolism by replacing zinc and calcium in enzymes. Most heavy metal ions show high affinity to thiol (-SH) groups, which, in physiological systems, mostly occur in cysteine residues e.g., in enzymes, hormones or cell receptors. The tripeptide glutathione (Glutamyl-Cysteine-Glycine), the most abundant cellular thiol in the body, is important for protection against heavy metal ions. Its metal complexes form part of enzymes with dominant roles in protein metabolism. N-acetyl cysteine (NAC), a natural antioxidant, has long been used in several treatments, from heart diseases to HIV-1 retardation. NAC improves the efficiency of clinical chelating agents and facilitates detoxification of Cr, Cd and Pb. Recent bio-tests on NAC complexes with transition biometals (Zn, Co, Fe) showed significant anti-inflammatory activity. Therefore, the nature of the coordination of metal ions to N-acetyl cysteine and glutathione is needed for better understanding of such reaction mechanisms and also for improving specific cysteine based clinical detoxification agents. We will prepare such complexes with NAC and glutathione in solution and in the solid state, and use synchrotron-based X-ray absorption, vibrational, and NMR spectroscopic methods to study the local structure around the metal atoms for systems where crystallography cannot be applied. By establishing the bonding environment around the metal ions in these complexes as models for in-vivo conditions, and correlating their structures to their clinical properties, more efficient chelating agents for detoxification can be designed. Training of highly qualified researchers in applying synchrotron radiation methods is part of this project, and is required for efficient use of the advanced Canadian Light Source facility, the largest scientific project in Canada.

暴露在重金属离子中会对健康产生深远的影响。只有少数是积极的，如一些铂、铋和金化合物的治疗效果，但环境中重金属的积累正在造成严重的问题。通过食物、饮用水和大气摄取铅(以前含铅油漆和含铅汽油中的粉尘)、镉(吸烟和食物)和汞(鱼中的汞)可通过取代酶中的锌和钙来影响人体新陈代谢。大多数重金属离子对硫醇(-SH)基团表现出很高的亲和力，在生理系统中，这些基团大多存在于半胱氨酸残基中，例如酶、激素或细胞受体中。三肽谷胱甘肽(谷氨酰半胱氨酸-甘氨酸)是体内含量最丰富的细胞硫醇，对抵御重金属离子具有重要作用。它的金属络合物形成酶的一部分，在蛋白质代谢中起主导作用。N-乙酰半胱氨酸(NAC)是一种天然抗氧化剂，长期以来一直被用于多种治疗，从心脏病到HIV-1延迟。NAC可提高临床螯合剂的使用效率，促进铬、镉、铅的解毒。最近的生物实验表明，NAC与过渡金属(锌、钴、铁)形成的络合物具有显著的抗炎活性。因此，需要了解金属离子与N-乙酰半胱氨酸和谷胱甘肽配位的性质，以便更好地了解这种反应机理，也为了改进基于半胱氨酸的临床解毒剂。我们将在溶液和固态中制备这种与NaC和谷胱甘肽的配合物，并使用基于同步加速器的X射线吸收、振动和核磁共振光谱方法来研究不能应用结晶学的体系中金属原子周围的局域结构。通过建立这些络合物中金属离子周围的键合环境作为体内条件的模型，并将它们的结构与其临床性质相关联，可以设计出更有效的解毒螯合剂。培训高素质的研究人员应用同步辐射方法是该项目的一部分，也是有效利用加拿大最大的科学项目--先进的加拿大光源设施所必需的。