Chemical origins of enzymic catalysis

酶催化的化学起源

• 批准号: 5779-2007
• 负责人: Guthrie, Peter
• 金额: $ 2.77万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=362377
• 关键词: Chemical; origins; enzymic; catalysis

I have developed a general approach to predicting rate constants for chemical reactions from the corresponding equilibrium constants. This requires no kinetic information and generally requires only relatively low levels of MO theory to calculate distortion energies. The key assumption in my approach is that if only one thing happens to a molecule (geometry change with no change in bonding or bonding change with no change in geometry) then the energy is a quadratic function of a suitable reaction coordinate. The kinetic barrier (intrinsic barrier) for a real reaction arises from the need for more than one thing to happen for a real chemical transformation. This approach has been very successful in tests to date, both published and still in progress.     The goal of my research program is to test this approach over the widest possible range of reactions, inorganic as well as organic, and to develop and make available software which will make it easy for others to apply the method. Not only does the method allow prediction of rates of reaction, it also provides a general mechanistic criterion by allowing a clear test of whether or not a proposed mechanism is compatible with the observed rate constant. Furthermore the approach has value as a qualitative way of thinking about reactions as well as for quantitative predictions. Important near term goals are to extend this approach to intramolecular reactions and to test it in a range of solvents. Ultimately it is hoped that the method can be applied to explaining the rate enhancements in enzyme catalyzed reactions, which continue to represent the largest unsolved set of problems facing physical organic chemistry.

我开发了一种从相应的平衡常数预测化学反应速率常数的通用方法。这不需要动力学信息，并且通常只需要相对较低水平的MO理论来计算扭曲能。在我的方法中，关键的假设是，如果一个分子只发生一件事（几何形状改变而键没有改变，或者键改变而几何形状没有改变），那么能量是一个合适的反应坐标的二次函数。真实的反应的动力学势垒（内禀势垒）来自于真实的化学转化需要不止一件事发生。这种方法在迄今为止的测试中非常成功，无论是已发布的还是仍在进行中的。 我的研究计划的目标是在尽可能广泛的反应范围内测试这种方法，无机的以及有机的，并开发和提供软件，使其他人很容易应用这种方法。该方法不仅允许预测反应速率，还通过允许明确测试所提出的机制是否与观察到的速率常数相容来提供一般的机制标准。此外，这种方法作为一种定性的思考反应的方法以及定量预测的方法都有价值。重要的近期目标是将这种方法扩展到分子内反应，并在一系列溶剂中对其进行测试。最终，希望该方法可以应用于解释酶催化反应的速率增强，这仍然是物理有机化学面临的最大的未解决的问题。