The ‐N+(CH3)3 residue is present in acetylcholine (ACh) and in many of its analogues which are used as selective ACh agonist or antagonists for human therapy. The X‐ray structures of four ACh derivatives show the presence of short and linear contacts between the C atoms of ‐N+(CH3)3 groups and lone pair possessing atoms. These contacts can be rationalized as tetrel bonds (TtBs) thanks to their geometric features. Interrogation of the Protein Data Bank suggests that similar ‐N+‒C···nucleophile contacts affect the details of the binding of ACh and its derivatives to proteins. Quantum theory of atoms in molecules, noncovalent interaction plot, and natural bond orbital analyses consistently confirm that the ‐N+‒C···nucleophile contacts observed in small molecule crystals and in substrate/protein complexes are attractive in nature and can be rationalized as TtBs. TtBs involving methyl groups of the –N+(CH3)3 moiety can be proposed as a new item in the palette of interactions allowing the compounds containing this pharmacophoric unit to bind to their target protein and/or to express their biological/pharmacological properties.

中文翻译：

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Tetrel 键影响乙酰胆碱及其类似物的自组装，是蛋白质结合中的辅助相互作用


‐N+(CH3)3 残基存在于乙酰胆碱 (ACh) 及其许多类似物中，这些类似物被用作人类治疗的选择性 ACh 激动剂或拮抗剂。四种ACh衍生物的X射线结构显示-N+(CH3)3基团的C原子和孤对电子原子之间存在短的线性接触。由于其几何特征，这些接触可以合理化为四重键（TtB）。对蛋白质数据库的询问表明，类似的-N+-C···亲核体接触会影响乙酰胆碱及其衍生物与蛋白质的结合细节。分子中原子的量子理论、非共价相互作用图和自然键轨道分析一致证实，在小分子晶体和底物/蛋白质复合物中观察到的-N+-C...亲核接触在本质上是有吸引力的，可以合理化为TtBs 。涉及 –N+(CH3)3 部分甲基的 TtB 可以被提议作为相互作用调色板中的一个新项目，允许含有该药效单元的化合物与其靶蛋白结合和/或表达其生物/药理学特性。