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

Area of Science:

• Biochemistry
• Chemical Physics
• Structural Biology

Background:

• S-H/π interactions between thiols and aromatic rings are observed in biological systems but poorly understood.
• Understanding these interactions is crucial for various chemical and biological processes.

Purpose of the Study:

• To elucidate the fundamental nature of S-H/π interactions.
• To compare S-H/π interactions with other non-covalent interactions like O-H/π and cation/π.

Main Methods:

• Crystal structure analysis of Boc-l-4-thiolphenylalanine tert-butyl ester.
• Density Functional Theory (DFT) calculations.
• Infrared (IR) spectroscopy and solid-state Nuclear Magnetic Resonance (NMR) spectroscopy.
• Cambridge Structural Database analysis.

Main Results:

• S-H/π interactions are characterized by a short H···C distance (2.71 Å).
• These interactions are driven by π → σ* molecular orbital interactions, with the S-H σ* orbital acting as an acceptor.
• Unlike cation/π interactions, S-H/π interactions show preferential alignment toward ring carbons, not the centroid.

Conclusions:

• S-H/π interactions are distinct from electrostatic cation/π interactions.
• A π → σ* orbital interaction model explains the driving forces of S-H/π bonding.
• This provides a framework for understanding interactions involving weakly polar bonds and π systems.