Computational NanoBio Technology Laboratory, School of Materials Science and Engineering, ‡School of Chemical & Biomolecular Engineering, §Institute for Electronics and Nanotechnology, and ∥Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology , 771 Ferst Drive NW, Atlanta, Georgia 30332-0245, United States.
J Am Chem Soc. 2016 Jun 22;138(24):7664-72. doi: 10.1021/jacs.6b03309. Epub 2016 Jun 10.
Molecular dynamics simulations are performed to investigate the cooperatively catalyzed aldol condensation between acetone and 4-nitrobenzaldehyde on alkylamine (or alkylenamine)-grafted silica surfaces, focusing on the mechanism of the catalytic activation of the acetone and 4-nitrobenzaldehyde by the acidic surface silanols followed by the nucleophilic attack of the basic amine functional group toward the activated reactant. From the analysis of the correlations between the catalytically active acid-base sites and reactants, it is concluded that the catalytic cooperativity of the acid-base pair can be affected by two factors: (1) the competition between the silanol and the amine (or enamine) to form a hydrogen bond with a reactant and (2) the flexibility of the alkylamine (or alkylenamine) backbone. Increasing the flexibility of the alkylamine facilitates the nucleophilic attack of the amine on the reactants. From the molecular dynamics simulations, it is found that C3 propylamine and C4 butylamine linkers exhibit the highest probability of reaction, which is consistent with the experimental observation that the activity of the aldol reaction on mesoporous silica depends on the length of alkylamine grafted on the silica surface. This simulation work serves as a pioneering study demonstrating how the molecular simulation approach can be successfully employed to investigate the cooperative catalytic activity of such bifunctional acid-base catalysts.
采用分子动力学模拟方法研究了在烷基胺（或亚烷基胺）接枝硅胶表面上丙酮与 4-硝基苯甲醛之间协同催化的羟醛缩合反应，重点研究了酸性表面硅醇对丙酮和 4-硝基苯甲醛的催化活化以及碱性胺官能团对活化反应物的亲核攻击的机制。通过分析催化活性酸碱位与反应物之间的相关性，得出结论，酸碱对的催化协同作用可以受到两个因素的影响：（1）硅醇和胺（或亚胺）与反应物形成氢键的竞争，以及（2）烷基胺（或亚烷基胺）主链的柔韧性。增加烷基胺的柔韧性有利于胺对反应物的亲核攻击。从分子动力学模拟中可以发现，C3 丙基胺和 C4 丁基胺连接基表现出最高的反应概率，这与实验观察到的在介孔硅上羟醛反应的活性取决于接枝在硅表面上的烷基胺的长度一致。这项模拟工作是一项开创性的研究，证明了分子模拟方法如何成功地用于研究这种双功能酸碱催化剂的协同催化活性。
