Title: Reaction profiles for quantum chemistry-computed [3 + 2] cycloaddition reactions Show Chinese title

Title: 量子化学计算的[3 + 2]环加成反应的反应轮廓

Abstract: Bio-orthogonal click chemistry based on [3 + 2] dipolar cycloadditions has had a profound impact on the field of biochemistry and significant effort has been devoted to identify promising new candidate reactions for this purpose. To gauge whether a prospective reaction could be a suitable bio-orthogonal click reaction, information about both on- and off-target activation and reaction energies is highly valuable. Here, we use an automated workflow, based on the autodE program, to compute over 5000 reaction profiles for [3 + 2] cycloadditions involving both synthetic dipolarophiles and a set of biologically-inspired structural motifs. Based on a succinct benchmarking study, the B3LYP-D3(BJ)/def2-TZVP//B3LYP-D3(BJ)/def2-SVP level of theory was selected for the DFT calculations, and standard conditions and an (aqueous) SMD model were imposed to mimic physiological conditions. We believe that this data, as well as the presented workflow for high-throughput reaction profile computation, will be useful to screen for new bio-orthogonal reactions, as well as for the development of novel machine learning models for the prediction of chemical reactivity more broadly. Show Chinese abstract

Abstract: 基于[3 + 2]偶极环加成的生物正交点击化学对生物化学领域产生了深远影响，人们已投入大量努力以确定适用于此目的的有前景的新候选反应。 为了评估一个潜在反应是否可能成为合适的生物正交点击反应，了解其在靶标和非靶标上的活化能及反应能是非常有价值的。 在此，我们使用基于autodE程序的自动化工作流，计算了涉及合成偶极亲合物和一组生物启发结构基序的[3 + 2]环加成的5000多个反应路径。 根据一项简洁的基准研究，选择了B3LYP-D3(BJ)/def2-TZVP//B3LYP-D3(BJ)/def2-SVP理论水平进行DFT计算，并施加了标准条件和（水相）SMD模型以模拟生理条件。 我们认为，这些数据以及所展示的用于高通量反应路径计算的工作流，将有助于筛选新的生物正交反应，并有助于开发更广泛的化学反应性预测的新型机器学习模型。