Physical organic studies of metal ion catalyzed acyl and phosphoryl transfer reactions in alcohols

金属离子催化醇中酰基和磷酰基转移反应的物理有机研究

• 批准号: 183939-2009
• 负责人: Brown, Robert
• 金额: $ 7.65万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=522990
• 关键词: Physical; organic; studies; metal; ion

Due to the far reaching consequences of the recent research results, the proposed research program we will continue to explore over the next five year deals with exploitation of an area virtually exclusively developed in our labs. In what appears to be a simple extension of metal ion catalyzed acyl and phosphoryl transfer processes, we have studied metal catalyzed alcoholysis reactions of carboxylate and phosphate esters in the light alcohols, notably methanol and ethanol. Metal ions such as Zn^2+, Cu^2+ and lanthanides such as La3+ as well as complexes of these greatly accelerate the methanolysis of esters, activated amides, phosphate diesters and phosphate triesters at room temperature and essentially neutral pH in alcohol. This has led to the development of effective, patented methods for decontamination of organophosphorus based pesticides and chemical weapons. In addition, recent results have shown that various dinuclear Zn(II) complexes provide accelerations of 10^12-10^14-fold for the cleavage of two series of phosphate diesters that are commonly used as simple models for RNA and DNA. In the proposed work we intend to investigate the mechanism of these very fast reactions using solvent deuterium kinetic isotope studies for the cleavage of the RNA and DNA models promoted by a set of mono and di-Zn(II) containing complexes in deuterio-methanol and ethanol. We will mount a major effort to understand a very recent finding in our labs where one of our dinuclear Zn(II) complexes, in ethanol containing small amounts of water, can accelerate the hydrolysis of a phosphate diester by ~10^17-fold. We will investigate the catalysis of cleavage of a series of beta-lactams afforded by these di- and mononuclear Zn(II) complexes as models for the Zn(II) class B1 metallo-beta-lactamases, which are currently of interest as pathogenic bacteria that produce these enzymes have a great resistance to therapeutic treatment with beta-lactam antibiotics. This research program will provide training for several students and post-doctoral persons, and at the same time will lay the foundation for the development of several new catalytic systems that may find practical use for transformation of important biological and industrial materials.

由于最近的研究成果的深远影响，我们将在未来五年内继续探索的拟议研究计划涉及开发一个几乎完全在我们实验室开发的领域。在金属离子催化的酰基和磷酰基转移过程的简单延伸中，我们研究了羧酸酯和磷酸酯在轻质醇，特别是甲醇和乙醇中的金属催化的醇解反应。金属离子如Zn^2+、Cu^2+和镧系元素如La 3+以及这些的络合物在室温和基本中性的pH下在醇中大大加速酯、活化酰胺、磷酸二酯和磷酸三酯的甲醇分解。这导致了有效的专利方法的发展，用于有机磷农药和化学武器的去污。此外，最近的研究结果表明，各种双核Zn（II）配合物对两个系列的磷酸二酯的裂解提供了10^12-10^14倍的加速，这两个系列的磷酸二酯通常用作RNA和DNA的简单模型。在拟议的工作中，我们打算调查这些非常快的反应的机制，使用溶剂氘动力学同位素研究的切割的RNA和DNA模型促进了一组单和二锌（II）含配合物在氘甲醇和乙醇。我们将投入大量精力来理解我们实验室最近的一项发现，即我们的一种双核Zn（II）配合物在含有少量水的乙醇中可以将磷酸二酯的水解加速约10^17倍。我们将研究由这些二-和单核Zn（II）络合物作为Zn（II）B1类金属-β-内酰胺酶的模型提供的一系列β-内酰胺的裂解的催化作用，所述Zn（II）B1类金属-β-内酰胺酶是目前感兴趣的，因为产生这些酶的病原菌对β-内酰胺抗生素的治疗性治疗具有很大的抗性。 该研究计划将为几名学生和博士后提供培训，同时将为开发几种新的催化体系奠定基础，这些催化体系可能用于重要生物和工业材料的转化。