Chemical origins of enzymic catalysis

我已经开发了一种根据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分子轨道理论来计算扭曲能。我方法中的关键假设是，如果一个分子只发生了一件事(几何变化而不改变成键或成键变化而不改变几何结构)，那么能量是合适的反应坐标的二次函数。真正反应的动力学障碍(内在障碍)源于需要发生一件以上的事情才能实现真正的化学转化。到目前为止，这种方法在测试中非常成功，无论是已经发表的还是仍在进行中的。他说，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，无论是无机的还是有机的，并开发和提供软件，使其他人更容易应用这种方法。该方法不仅允许预测反应速率，还通过允许清楚地测试所提出的机理是否与观察到的速率常数相容来提供一般的机理准则。此外，该方法作为一种思考反应的定性方法以及定量预测都具有价值。重要的近期目标是将这种方法扩展到分子内反应，并在一系列溶剂中进行测试。最终，人们希望该方法能够用于解释酶催化反应中的速度提高，这些反应仍然是物理有机化学面临的最大一组未解决的问题。

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.