Tailored Force Fields for Modelling Transition-Metal-Mediated Reactions

过渡金属在具有巨大化学、工业和生物意义的各种过程中发挥着关键作用。对这些过程的理解和控制需要深入了解反应机理--将反应物连接到产物的途径。这条路径的关键特征是物种坐在山口--过渡态(TS)。如果你知道TS的结构和能量，你就可以预测反应的结果。但是，TS是一种瞬时的、不稳定的物种，很难用实验来表征。相比之下，TS的理论定义很简单。这只是势能(PE)表面上的另一个点。不幸的是，虽然定义可能很容易，但定位TS要困难得多，但由于TS是如此重要，理论化学家们越来越致力于开发新的、更好的方法来寻找它们。鉴于TS经常涉及成键/断键过程，理论建模通常集中在能够正确处理此类过程的全量子方法上。然而，所有的量子化学方法都相对较慢，这严重限制了我们可以在合理的时间框架内研究的分子体系的大小。另一种选择是使用快速的经典建模方法，如分子力学，前提是您可以解决MM通常不适用于TS位置的问题，并且在本提案的背景下，方法专门针对过渡金属介导的过程。然而，使过渡金属(TM)物种成为理想催化剂的特性也使它们难以计算。目前的建议描述了另一种经验方法：接缝搜索。接缝描述了描述反应物和产物状态的PE表面的交集。这种方法的巨大威力在于：1.Seam搜索是最小化的：所有标准的构象搜索工具都可以使用。SEAM只依赖于反应物和产物基态的合理模型。接缝上的最低能量点对起始几何形状不敏感。接缝上的最低能量点是真正的TSSeam搜索的一个很好的近似值，因此代表了一种强大的、通用的量子化学方法的替代方法，并代表了分子建模的下一次飞跃。

Transition metals play key roles in diverse processes of enormous chemical, industrial and biological significance. The understanding, and hence control, of these processes requires an intimate knowledge of the reaction mechanism - the pathway joining reactants to products. The key feature of this pathway is the species sitting at the mountain pass - the transition state (TS). If you know the structure and energy of the TS, you can predict the outcome of the reaction.However, the TS is a transient, unstable species which is difficult to characterise experimentally. In contrast, the theoretical definition of a TS is straightforward. It is just another point on the potential energy (PE) surface.Unfortunately, whilst the definition may be easy, locating the TS is much trickier but since the TS is so important, theoretical chemists are increasingly devoting themselves to developing new and better ways for finding them.Given that TSs often involve bond making/bond breaking processes, theoretical modelling has usually focussed on fully quantum methods which can treat such processes properly. However, all quantum chemical methods are relatively slow which severly limits the size of molecular system we can study in a reasonable timeframe. The alternative is to use fast classical modelling methods like molecular mechanics providing you can solve the issue that MM is not normally supposed for TS location and, in the context of this proposal, methods specifically targeted at transition-metal-mediated processes. However, the very features that make transition metal (TM) species ideal catalysts, also make them hard to calculate. The current proposal describes an alternative empirical approach: seam searching. The seam describes the intersection of the PE surfaces describing the reactant and product states. The enormous power of the approach is that:1. seam searching is minimisation: all the standard conformational search tools can be employed2. the seam depends only on a reasonable model for the ground states of the reactant and product3. the lowest energy point on the seam is not sensitive to the starting geometry4. the lowest energy point on the seam is a good approximation to the true TSSeam searching thus represents a powerful, general alternative to quantum chemical methods and represents the next leap forward in molecular modelling.