ABSTRACT Native chemical ligation (NCL) and its modified versions (ligation-desulfurization chemistry) have revolutionized the way that large peptides and proteins are obtained by chemical synthesis. Ligation-desulfurization chemistry can generate thiol-derived peptide models, which can generate proteins through reductive desulfurization. The C-S bond cleavages are involved in the process. It is important for us to comprehend the strength of the C-S bond estimated by the homolytic bond dissociation enthalpies (BDEs). Therefore, 25 DFT methods were chosen to calculate the C-S BDEs of the 55 organic sulfides. It is reliable to predict C-S BDEs by M05-2X method with the corresponding root mean square error value of 6.2 kJ/mol. Then, the C-S BDEs of the thiol-derived peptide model and the structure-activity relationships were systematically researched by using this method. Besides, so as to comprehend the nature of the C-S BDE change mode, the analysis comprised of the natural bond orbit and the energies of frontier orbitals were studied. GRAPHICAL ABSTRACT

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硫醇衍生肽模型 CS 键解离焓的 DFT 研究

摘要 天然化学连接 (NCL) 及其改良版本（连接-脱硫化学）彻底改变了通过化学合成获得大肽和蛋白质的方式。连接脱硫化学可以生成硫醇衍生的肽模型，该模型可以通过还原脱硫生成蛋白质。CS 键断裂参与该过程。理解由均裂键解离焓 (BDE) 估计的 CS 键的强度对我们来说很重要。因此，选择了 25 种 DFT 方法来计算 55 种有机硫化物的 CS BDE。用M05-2X方法预测CS BDEs是可靠的，对应的均方根误差值为6.2 kJ/mol。然后，利用该方法系统地研究了硫醇衍生肽模型的CS BDEs及其构效关系。此外，为了理解CS BDE变化模式的性质，研究了由自然键轨道和前沿轨道能量组成的分析。图形概要