Through-Space Polar-pi Interactions in 2,6-Diarylthiophenols.

Molecular recognition between polar groups and aromatic molecules is fundamentally important to rational drug design. Although it has been well established that many polar functionalities interact with electron-rich aromatic residues via energetically favorable polar-pi interactions, there is a limited understanding of the association between thiols and aromatic systems. Here we report physical-organic chemistry studies on 2,6-diarylthiophenols that possess the central thiophenol ring and two flanking aromatic rings with tunable electronic properties caused by substituents at distant para position. Hammett analysis revealed that p K a values and proton affinities correlate well with Hammett sigma values of substituents. Additional energy decomposition analysis supported the conclusion that both through-space SH-pi interactions and S - -pi interactions contribute to intramolecular stabilization of 2,6-diarylthiophenols.