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Explicit Solvation Matters: Performance of QM/MM Solvation Models in Nucleophilic Addition
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2018-02-13 00:00:00 , DOI: 10.1021/acs.jctc.7b01206
Jelle M. Boereboom 1 , Paul Fleurat-Lessard 2 , Rosa E. Bulo 1
Affiliation  

Nucleophilic addition onto a carbonyl moiety is strongly affected by solvent, and correctly simulating this solvent effect is often beyond the capability of single-scale quantum mechanical (QM) models. This work explores multiscale approaches for the description of the reversible and highly solvent-sensitive nucleophilic N|···C═O bond formation in an Me2N–(CH2)3–CH═O molecule. In the first stage of this work, we rigorously compare and test four recent quantum mechanical/molecular mechanical (QM/MM) explicit solvation models, employing a QM description of water molecules in spherical regions around both the oxygen and the nitrogen atom of the solute. The accuracy of the models is benchmarked against a reference QM simulation, focusing on properties of the solvated Me2N–(CH2)3–CH═O molecule in its ring-closed form. In the second stage, we select one of the models (continuous adaptive QM/MM) and use it to obtain a reliable free energy profile for the N|···C bond formation reaction. We find that the dual-sphere approach allows the model to accurately account for solvent reorganization along the entire reaction path. In contrast, a simple microsolvation model cannot adapt to the changing conditions and provides an incorrect description of the reaction process.

中文翻译:

明确的溶剂化问题:亲核加成中的QM / MM溶剂化模型的性能

亲核加成到羰基部分上会受到溶剂的强烈影响,正确模拟这种溶剂效应通常超出了单尺度量子力学(QM)模型的能力。这项工作探索了多尺度方法来描述在Me 2 N–(CH 23中可逆和高度溶剂敏感的亲核N |··C═O键的形成–CH═O分子。在这项工作的第一阶段,我们使用溶质的氧和氮原子周围球形区域中水分子的QM描述,严格比较和测试了四个最新的量子力学/分子力学(QM / MM)显式溶剂化模型。 。模型的准确性以参考质量管理模拟为基准,重点是溶剂化的Me 2 N–(CH 23的性质-CH═O分子为闭环形式。在第二阶段,我们选择一种模型(连续自适应QM / MM),并使用它来获得可靠的N |··C键形成反应的自由能分布。我们发现,双球面方法使模型可以准确地说明整个反应路径中的溶剂重组。相反,简单的微溶剂化模型不能适应不断变化的条件,并且不能正确描述反应过程。
更新日期:2018-02-13
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