title: 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···Caromaticdistance 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Christina R
authors.initials: CR
authors.lastname: Forbes
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Sudipta K
authors.initials: SK
authors.lastname: Sinha
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Himal K
authors.initials: HK
authors.lastname: Ganguly
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Shi
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Glenn P A
authors.initials: GP
authors.lastname: Yap
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Neal J
authors.identifier: 0000-0002-7417-8085
authors.initials: NJ
authors.lastname: Zondlo
mesh_terms: D018360:Crystallography, X-Ray; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D006841:Hydrocarbons, Aromatic; D013438:Sulfhydryl Compounds