Abstract In the present research, we focus on the energetics and electronic aspects of enhanced reactivity in the regioselective bioorthogonal 1,3-dipolar cycloaddition reaction of various substituted cyclooctynes with methyl azide, applying quantum chemistry approaches. In this respect, we assessed the structural and energetic properties of regioisomeric products and their corresponded transition states and calculated the reaction electronic energy changes and energy barriers through the cycloaddition pathways. The obtained results revealed that the trifluoromethyl substitution and fluorination of cyclooctynes lead to improved reactivity, in conjunction with increased exothermicity and decreased activation energy values. On the other hand, quantum theory of atoms in molecules computations were performed on some key bond and ring critical points that demonstrated the stabilizing topological properties of electron density and its derivatives upon trifluoromethyl substitution and fluorination of propargylic carbon of cyclooctynes which can be regarded as the essential origin of enhanced reactivity.

中文翻译：

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取代环辛炔在生物正交环加成反应中促进反应性的量子化学研究

摘要 在目前的研究中，我们应用量子化学方法，重点研究了各种取代环辛炔与甲基叠氮化物的区域选择性生物正交 1,3-偶极环加成反应中增强反应性的能量学和电子学方面。在这方面，我们评估了区域异构产物的结构和能量特性及其相应的过渡态，并计算了通过环加成途径的反应电子能量变化和能垒。所得结果表明，环辛炔的三氟甲基取代和氟化导致反应性提高，同时放热增加和活化能值降低。另一方面，