当前位置：
X-MOL 学术
›
Org. Process Res. Dev.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Toward a Combined Molecular Dynamics and Quantum Mechanical Approach to Understanding Solvent Effects on Chemical Processes in the Pharmaceutical Industry: The Case of a Lewis Acid-Mediated SNAr Reaction
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2023-03-29 , DOI: 10.1021/acs.oprd.3c00010 Gerald J. Tanoury 1 , Satish Kumar Iyemperumal 2 , Elaine C. Lee 1
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2023-03-29 , DOI: 10.1021/acs.oprd.3c00010 Gerald J. Tanoury 1 , Satish Kumar Iyemperumal 2 , Elaine C. Lee 1
Affiliation
|
Solvation effects on chemical reactions can have a significant impact on the development of chemical processes in the pharmaceutical industry. Evaluating solvation effects at the atomic level would provide greater insight and understanding into their impact on chemical transformations. However, modeling complex reaction systems at this level of detail is challenging and a consistent approach of evaluation has not been established. Herein, we describe our initial results on the development of a practical solvation modeling protocol, which combines classical/ab initio molecular dynamics and density functional theory-based techniques with trajectory clustering, identification of solvent shells, and subsequent wave function analysis for characterizing a range of diverse interactions in the multicomponent solvation system. We describe how our solvation modeling protocol attempts to capture and describe these interactions objectively and simultaneously in the drug substance-forming step for the manufacture of 3, an SNAr reaction of aryl chloride 1 and pyrrolidine 2.
中文翻译：
结合分子动力学和量子力学方法来理解溶剂对制药行业化学过程的影响：以路易斯酸介导的 SNAr 反应为例
溶剂化对化学反应的影响可能对制药工业中化学工艺的发展产生重大影响。在原子水平上评估溶剂化作用将有助于更深入地了解和理解它们对化学转化的影响。然而，在这种详细程度下对复杂的反应系统进行建模具有挑战性，并且尚未建立一致的评估方法。在此，我们描述了我们在开发实用溶剂化建模协议方面的初步结果，该协议将经典/从头算分子动力学和基于密度泛函理论的技术与轨迹聚类、溶剂壳的识别以及随后的波函数分析相结合以表征范围多组分溶剂化系统中的不同相互作用。图3 ，芳基氯1和吡咯烷2的S N Ar反应。
更新日期：2023-03-29
中文翻译：
结合分子动力学和量子力学方法来理解溶剂对制药行业化学过程的影响：以路易斯酸介导的 SNAr 反应为例
溶剂化对化学反应的影响可能对制药工业中化学工艺的发展产生重大影响。在原子水平上评估溶剂化作用将有助于更深入地了解和理解它们对化学转化的影响。然而，在这种详细程度下对复杂的反应系统进行建模具有挑战性，并且尚未建立一致的评估方法。在此，我们描述了我们在开发实用溶剂化建模协议方面的初步结果，该协议将经典/从头算分子动力学和基于密度泛函理论的技术与轨迹聚类、溶剂壳的识别以及随后的波函数分析相结合以表征范围多组分溶剂化系统中的不同相互作用。图3 ，芳基氯1和吡咯烷2的S N Ar反应。
京公网安备 11010802027423号