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Abstract：
This study investigates the application of quantum mechanical (QM) and multiscale computational methods in understanding the reaction mechanisms and kinetics of SN2 reactions involving methyl iodide with NH2OH and NH2O-, as well as the Claisen rearrangement of 8-(vinyloxy)dec-9-enoate. Our aim is to evaluate the accuracy and effectiveness of these methods in predicting experimental outcomes for these organic reactions. We achieve this by employing QM-only calculations and several hybrids of QM and molecular mechanics (MM) methods, namely QM/MM, QM1/QM2, and QM1/QM2/MM methodologies. For the SN2 reactions, our results demonstrate the importance of explicitly including solvent effects in the calculations to accurately reproduce the transition state geometry and energetics. The multiscale methods, particularly QM/MM and QM1/QM2, show promising performance in predicting activation energies. Moreover, we observe that the size of the MM active region significantly affects the accuracy of calculated activation energies, highlighting the need for careful consideration during the setup of multiscale calculations. In the case of the Claisen rearrangement, both QM-only and multiscale methods successfully reproduce the proposed reaction mechanism. However, the activation free energies calculated using a continuum solvation model, based on single-point calculations of QM-only structures, fail to account for solvent effects. On the other hand, multiscale methods more accurately capture the impact of solvents on activation free energies, with systematic error correction enhancing the accuracy of the results. Furthermore, we introduce a Python code for setting up multiscale calculations with ORCA, which is available on GitHub at https://github.com/iranimehdi/pdbtoORCA .
摘要：
这项研究调查了量子力学（QM）和多尺度计算方法在理解涉及甲基碘与NH2OH和NH2O-的SN2反应的反应机理和动力学中的应用，以及8-（乙烯氧基）十二-9-烯酸的克莱森重排。我们的目的是评估这些方法在预测这些有机反应的实验结果方面的准确性和有效性。我们通过使用仅QM计算以及QM和分子力学（MM）方法的几种混合方法来实现这一目标，即QM/MM，QM1/QM2和QM1/QM2/MM方法。对于SN2反应，我们的结果证明了在计算中明确包括溶剂效应以准确再现过渡态几何形状和能量学的重要性。多尺度方法，特别是QM/MM和QM1/QM2，在预测活化能方面显示出有希望的性能。此外，我们观察到MM活性区的大小显着影响计算的活化能的准确性，强调在多尺度计算的设置过程中需要仔细考虑。在克莱森重新安排的情况下，仅QM和多尺度方法都成功地再现了所提出的反应机理。然而,使用连续溶剂化模型计算的活化自由能，基于仅QM结构的单点计算，没有考虑到溶剂的影响。另一方面,多尺度方法更准确地捕获溶剂对活化自由能的影响，通过系统的误差校正，提高了结果的准确性。此外，我们介绍了一个Python代码，用于使用ORCA设置多尺度计算，它可在GitHub上获得，网址为https://github.com/iranimehdi/pdbtoORCA。
