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

Abstract

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 Hthiol...Caromatic 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.

A Conditionally Fluorescent Peptide Reporter of Secondary Structure Modulation

“…[18] Consistent with this model, alkylation of the cysteine residue with iodoacetamide caused a 4.8-fold decrease in peptide fluorescence, which was not altered with 50 % TFE (Figure 3 B). Importantly, these results were corroborated by CD spectroscopy (Figure 3 C).…”

The role of metals in mammalian olfaction of low molecular weight organosulfur compounds

“…64a Perforated patch-clamp recordings were performed on dissected septal organs from SR1-IRES-tauGFP mice, and MTMT responses among the non-SR1 cells were examined. Of 132 cells recorded, 76 cells (58%) responded to MTMT in a dose-dependent manner.…”

“…These interactions were reported 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. 64b …”

“…It should also be noted that human OR2T11 and mouse MOR244-3 are not orthologous (Fig 34). As noted above (Section 6.2), it would be of interest to determine if S–H/π-interactions with receptor aromatic rings 64b play a role in docking of thiols with these ORs.…”

The mechanism research for the surface plasmon-catalysed reaction of the mercapto group substituted benzoic acid

“…The self-assembled monolayer, with organic small molecules that contain the mercapto group on the surface of the metal film, has been widely used in embellishing electrodes, biological sensors and other research fields [15][16][17]. Furthermore, thiol molecules along with some other molecules with specific functional groups were usually regarded as the superior substance for SERS recognition, as the formation of Au-MBA@SiO 2 nanoparticles was achieved on the basis of Stöber's method by the hydrolysis of TEOS.…”