Chemical origins of enzymic catalysis

我已经发展了一种从相应的平衡常数来预测化学反应速率常数的一般方法。这不需要动力学信息，通常只需要相对较低水平的MO理论来计算畸变能。我的方法的关键假设是，如果一个分子只发生了一件事（几何变化而不改变成键，或者成键变化而不改变几何），那么能量是一个合适的反应坐标的二次函数。一个真实反应的动能障壁（内在障壁）产生于一个真实的化学转化需要发生不止一件事。这种方法在迄今为止的测试中非常成功，无论是已发表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，无机的和有机的，并开发和提供可用的软件，使其他人更容易应用这种方法。该方法不仅可以预测反应速率，而且还提供了一个通用的机理标准，允许对所提出的机理是否与观察到的速率常数相容进行明确的测试。此外，该方法作为一种思考反应的定性方法以及定量预测的价值。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未解决的问题。

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.