Insights into Thiol–Aromatic Interactions: A Stereoelectronic Basis for S–H/π Interactions

详细信息    查看全文

• 作者：Christina R. Forbes ; Sudipta K. Sinha ; Himal K. Ganguly ; Shi Bai ; Glenn P. A. Yap ; Sandeep Patel ; Neal J. Zondlo
• 刊名：Journal of the American Chemical Society
• 出版年：2017
• 出版时间：February 8, 2017
• 年：2017
• 卷：139
• 期：5
• 页码：1842-1855
• 全文大小：908K
• ISSN：1520-5126

文摘

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_thiol···C_aromatic 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.