Predictive multiscale free energy simulations of hybrid transition metal catalysts

催化是基础科学的一个关键领域，在制造业中占有很高的比重。催化科学和技术的发展对实现能源和环境的可持续性也至关重要。催化科学的进步需要对分子水平上的过程有详细的了解，在这方面计算现在起着至关重要的作用。当与实验结合使用时，计算模型能够表征结构、性质和过程，包括活性位点结构、反应机制以及越来越多的反应速率和产物分布。然而，尽管计算催化具有强大的功能，但目前可用的方法在准确性和模拟反应环境的能力方面都存在局限性。此外，实际上很难对混合催化剂进行建模，混合催化剂结合了不同类型的催化剂元素（例如，天然酶中掺入的非天然金属中心）。如果要实现设计催化的目标，技术的进步是必不可少的。量子力学/分子力学（QM/MM）方法为模拟催化过程提供了一种强大而实用的方法，其中反应和周围环境使用精确的量子力学方法进行描述，周围环境由更近似的经典力场建模。QM/MM已被广泛和成功地应用于模拟酶促反应（获得2013年诺贝尔化学奖），但在催化科学的其他领域也发挥着同样重要的作用。旗舰ChemShell代码，由STFC团队与UCL， Bristol和世界各地的其他团体合作开发，是一个高度灵活和适应性强的开源QM/MM软件包，允许在QM和MM区域使用一系列代码和技术（www.chemshell.org）。该软件已广泛并成功地用于模拟酶促反应和催化过程在沸石和氧化物表面。它将为我们提出的将计算催化提升到下一个水平的发展提供理想的平台。这些将包括使用高水平的QM技术来实现化学精度，溶剂效应的精确建模，允许与实验直接相互作用的光谱特征的计算，以及自由能模拟的动态方法。至关重要的是，我们将汇集不同领域的计算催化方法，以实现混合催化系统的建模。我们将开发灵活和严格的方法，以满足高水平质量管理处理的准确性和反应系统的采样动力学能力的双重挑战。总之，这些方法将允许在现实条件下的催化反应的准确和预测建模。该项目还将预测利用下一代百亿亿级高性能计算所需的软件开发。我们将应用这些新技术来模拟一系列工程多相、均相和生物分子催化剂的催化行为，这些催化剂目前正在英国催化中心进行研究。该中心支持整个英国催化社区的实验和计算应用。该项目将提供Hub未涵盖的方法开发和软件工程，因此将补充EPSRC在Hub的投资。特定的系统包括使用均相钌配合物合成甲醇，用于对映选择性frieel - crafts反应的cu基人工酶，用于烯烃氢甲酰化催化的氟磷酸盐修饰铑系统，以及用于C-H功能化的非血红素铁酶的非规范取代。这些高度热门和潜在的工业相关系统将使我们能够测试和利用新软件，这将使我们模拟催化系统和反应的能力发生重大变化。

Catalysis is a key area of fundamental science which underpins a high proportion of manufacturing industry. Developments in catalytic science and technology will also be essential in achieving energy and environmental sustainability. Progress in catalytic science requires a detailed understanding of processes at the molecular level, in which computation now plays a vital role. When used in conjunction with experiment, computational modelling is able to characterise structures, properties and processes including active site structures, reaction mechanisms and increasingly reaction rates and product distributions. However, despite the power of computational catalysis, currently available methods have limitations in both accuracy and their ability to model the reaction environment. Also, it is practically difficult to model hybrid catalysts, which combine elements of different types of catalyst (e.g. unnatural metal centres incorporated in natural enzymes). Advances in technique are essential if the goal of catalysis by design is to be achieved.A powerful, practical approach to modelling catalytic processes is provided by Quantum Mechanical/Molecular Mechanical (QM/MM) methods, in which the reaction and surroundings are described using an accurate quantum mechanical approach, with the surrounding environment modelled by more approximate classical forcefields. QM/MM has been widely and successfully employed in modelling enzymatic reactions (recognised in the 2013 Nobel prize for Chemistry) but has an equally important role in other areas of catalytic science.The flagship ChemShell code, developed by the STFC team in collaboration with UCL, Bristol and other groups around the world, is a highly flexible and adaptable open source QM/MM software package which allows a range of codes and techniques to be used in the QM and MM regions (www.chemshell.org). The software has been widely and successfully used in modelling enzymatic reactions and catalytic processes in zeolites and on oxide surfaces. It will provide the ideal platform for the developments we are proposing which will take computational catalysis to the next level. These will include the use of high level QM techniques to achieve chemical accuracy, accurate modelling of solvent effects, calculation of spectroscopic signatures allowing direct interaction with experiment, and dynamical approaches for free energy simulations. Crucially, we will bring together methods from different spheres of computational catalysis to enable modelling of hybrid catalytic systems. We will develop flexible and rigorous methods that meet the twin challenges of high-level QM treatment for accuracy with the ability to sample dynamics of the reacting system. Together these methods will allow accurate and predictive modelling of catalytic reactions under realistic conditions. The project will also anticipate the software developments needed to exploit the next generation of exascale high performance computing.We will apply these new techniques to model the catalytic behaviour of a range of engineered heterogeneous, homogeneous and biomolecular catalysts, currently under study in the UK Catalysis Hub. The Hub supports experimental and computational applications across the whole UK catalysis community. This project will provide method development and software engineering that is not covered by the Hub, and thus will complement EPSRC investment in the Hub. Specific systems include methanol synthesis using homogeneous ruthenium complexes, Cu-based artificial enzymes for enantioselective Friedel-Crafts reactions, fluorophosphite-modified rhodium systems for hydroformylation catalysis of alkenes, and non-canonical substitutions in non-heme iron enzymes for C-H functionalisations. These highly topical and potentially industrially relevant systems will allow us both to test and exploit the new software, which promises a step change in our ability to model catalytic systems and reactions.