Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
J Am Chem Soc. 2017 Feb 8;139(5):1842-1855. doi: 10.1021/jacs.6b08415. Epub 2017 Jan 30.
Thiols can engage favorably with aromatic rings in S-H/π interactions, within abiological systems and within proteins. However, the underlying bases for S-H/π interactions are not well understood. The crystal structure of Boc-l-4-thiolphenylalanine tert-butyl ester revealed crystal organization centered on the interaction of the thiol S-H with the aromatic ring of an adjacent molecule, with a through-space H···C distance of 2.71 Å, below the 2.90 Å sum of the van der Waals radii of H and C. The nature of this interaction was further examined by DFT calculations, IR spectroscopy, solid-state NMR spectroscopy, and analysis of the Cambridge Structural Database. The S-H/π interaction was found to be driven significantly by favorable molecular orbital interactions, between an aromatic π donor orbital and the S-H σ* acceptor orbital (a π → σ* interaction). For comparison, a structural analysis of O-H/π interactions and of cation/π interactions of alkali metal cations with aromatic rings was conducted. Na and K exhibit a significant preference for the centroid of the aromatic ring and distances near the sum of the van der Waals and ionic radii, as expected for predominantly electrostatic interactions. Li deviates substantially from Na and K. The S-H/π interaction differs from classical cation/π interactions by the preferential alignment of the S-H σ* toward the ring carbons and an aromatic π orbital rather than toward the aromatic centroid. These results describe a potentially broadly applicable approach to understanding the interactions of weakly polar bonds with π systems.
巯基可以在生物体系和蛋白质中与芳香环发生有利的 S-H/π 相互作用。然而，S-H/π 相互作用的基础尚未得到很好的理解。Boc-l-4-巯基苯丙氨酸叔丁酯的晶体结构揭示了晶体组织以巯基 S-H 与相邻分子芳香环的相互作用为中心，通过空间 H···C 距离为 2.71 Å，低于 H 和 C 的范德华半径之和 2.90 Å。通过 DFT 计算、红外光谱、固态 NMR 光谱和剑桥结构数据库分析进一步研究了这种相互作用的性质。发现 S-H/π 相互作用主要是由有利的分子轨道相互作用驱动的，芳香 π 给体轨道和 S-H σ* 受体轨道之间（π→σ* 相互作用）。为了进行比较，还对 O-H/π 相互作用和碱金属阳离子与芳香环的阳离子/π 相互作用进行了结构分析。Na 和 K 表现出对芳香环质心和接近范德华和离子半径之和的距离的显著偏好，这与主要静电相互作用一致。Li 与 Na 和 K 有很大的偏差。S-H/π 相互作用与经典的阳离子/π 相互作用不同，因为 S-H σ* 优先与环碳原子和芳香 π 轨道对齐，而不是与芳香质心对齐。这些结果描述了一种潜在的广泛适用于理解弱极性键与π 系统相互作用的方法。
