Insights into Thiol-Aromatic Interactions: A Stereoelectronic Basis for S-H/? Interactions.

ABSTRACT: Thiols can engage favorably with aromatic rings in S-H/? interactions, within abiological systems and within proteins. However, the underlying bases for S-H/? 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/? interaction was found to be driven significantly by favorable molecular orbital interactions, between an aromatic ? donor orbital and the S-H ?* acceptor orbital (a ? ? ?* interaction). For comparison, a structural analysis of O-H/? interactions and of cation/? 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/? interaction differs from classical cation/? interactions by the preferential alignment of the S-H ?* toward the ring carbons and an aromatic ? orbital rather than toward the aromatic centroid. These results describe a potentially broadly applicable approach to understanding the interactions of weakly polar bonds with ? systems.

SUBMITTER: Forbes CR 

PROVIDER: S-EPMC5890429 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature