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.
Quantum-chemistry-aided identification, synthesis and experimental validation of model systems for conformationally controlled reaction studies: Separation of the conformers of 2,3-dibromobuta-1,3-diene in the gas phase
Reactive atomistic simulations of Diels-Alder-type reactions: Conformational and dynamic effects in the polar cycloaddition of 2,3-dibromobutadiene radical ions with maleic anhydride
用多表面绝热反应分子动力学方法对顺丁烯二酸酐与2，3-二溴丁二烯自由基离子的离子Diels-Alder反应（极性环加成）的动力学、动力学和构象特异性进行了理论研究.发现了协同和分步反应途径的竞争，并且二烯的s-顺式和s-反式构象都是反应性的。对反应最小动力学路径的分析表明，反应物分子的转动和振动对驱动体系向过渡态的转变都是重要的。在300 K的内部温度下，速率计算为2，3-二溴丁二烯的s-顺式构象的$k = 5.1 \times 10^{-14}$ s $^{-1}$和s-反式构象的$k = 3.8 \times 10^{-14}$ s $^{-1}$。目前的结果是要与标题系统的中性变体，其中只有二烯的笨拙构象被发现进行一个相当慢的，一致的，大多是同步的反应驱动的激励旋转。这里提出的结果通知详细的实验研究极性环加成反应的动力学在气相中的单碰撞条件下。
State-of-the-Art Quantum Chemistry Meets Variable Reaction Coordinate Transition State Theory to Solve the Puzzling Case of the H2S + Cl System
本文重新研究了H $_2$ S与Cl的大气反应，以检验是否如前所述，由于强烈的再交叉效应和过渡态理论的变分扩展的崩溃，只有明确的动力学计算才能得到反应速率的准确估计。为此，相应的势能面已被彻底研究，从而导致所有驻点的准确表征，其能量已被计算在最先进的状态。为此，耦合团簇理论，包括高达四重激发，连同外推到完整的基组极限，并结合核心价相关，自旋轨道，标量相对论效应以及对角玻恩-奥本海默修正。这种高精度的复合方案也已被更便宜但有前途的计算方法所验证。移动到动力学，变分过渡态理论和它的可变反应坐标扩展的无势垒步骤已被利用，从而获得反应速率常数（8.16 × 10 $^{-11}$ cm $^3$分子$^{-1}$ s $^{-1}$在300 K和1大气压）在显着的协议与实验对应。因此，与前面的权利要求相反，只要进行足够精确的量子化学计算，就不需要援引过渡态理论的任何失败。对H $_2$ S + Cl系统这一令人困惑的案例的研究，使我们能够提出一种强有力的方法来揭示大气和天体物理学感兴趣的反应的热化学和动力学。
HIP: Hessian Interatomic Potentials without derivatives
University of Toronto（多伦多大学）；Vector Institute for Artificial Intelligence（向量人工智能研究所）；Technical University of Denmark（丹麦技术大学）；CAPeX Pioneer Center for Accelerating P2X Materials Discovery（CAPeX加速P2X材料发现先锋中心）；Acceleration Consortium（加速联盟）；Canadian Institute for Advanced Research (CIFAR)（加拿大高等研究院）；NVIDIA（英伟达）
