一个“水上”反应的概念用来描述不溶于水的有机反应物在水中高速搅拌下形成悬浮液而发生反应且与在有机溶剂中相比出现速率提升和反应选择性增强的现象。“水上”有机反应的发展是水相绿色合成反应研究领域中的一个突破。本项目将综合利用量子化学，QM/MM方法和Monte Carlo统计模拟方法以及自由能微扰理论，建立和完善有效的“双水平”计算策略来改进MC模拟方法的有效性，较为系统地研究几种重要的有机反应在“水上”和混合溶剂中的反应机理和反应选择性，定量地描述“水中”、“水上”和水-有机混合溶剂中溶质-溶剂氢键作用的微观结构，考察这种氢键作用对反应速率和选择性影响的规律，探索“水上”催化效应与溶剂环境及结构因素的内在联系，对一些实验现象作出更合理的解释。该项目的研究将有助于提高对水相非均相反应微观作用机制的认识，对于优化有机反应过程、设计更多高效的绿色合成路线具有非常重要的理论指导意义。

The concept of an "on water" reaction has been used to describe the phenomenon that the insoluble organic reactants in aqueous emulsions or suspensions formed under the high speed stirring react to give high yields of products with large rate acceleration and selectivity enhancement compared with in the organic solvent. The development of “on water” organic reaction is a breakthrough in the field of aqueous organic reactions for green synthesis. This project will comprehensively utilize quantum chemistry calculations, QM/MM method, Monte Carlo statistical simulation, and free energy perturbation theory to investigate systematically the mechanism and reaction selectivity of several important organic reactions "on water" and in mixed solvents after establishing and perfecting the effective "dual-level" computing strategy to improve the effectiveness of the MC simulation method. In this study, the microstructure of hydrogen bonding system between solute and solvent will be quantitatively described under the conditions of "in water", "on water" and the mixed water-organic solvent. We will inspect the crucial role law of the hydrogen bonding to the reaction rate and selectivity in the different solvent environments, explore the intrinsic relationship of the catalytic effect of "on water" with solvent environment and its structure factors, and make more reasonable explanation to the some experimental phenomena. The performance of this project will help us improve the understanding of the microscopic mechanism of aqueous heterogeneous reaction. For the optimization of organic reaction process and design of more efficient green synthetic route, it has very important theoretical guidance significance.