Thioamide, a Hydrogen Bond Acceptor in Proteins and Nucleic Acids

Area of Science:

• Biochemistry
• Structural Biology
• Computational Chemistry

Background:

• Thioamides serve as potential surrogates for amides in studying biomolecular structure and dynamics.
• Incorporation of thioamides can alter biomolecular structures due to the unique properties of the amide-N-H···S═C hydrogen bond.

Purpose of the Study:

• To investigate the strength of the amide-N-H···S═C hydrogen bond in thioamides.
• To determine if thioamides can form strong hydrogen bonds comparable to conventional amide bonds.
• To precisely quantify the enthalpy of the amide-N-H···S═C hydrogen bond.

Main Methods:

• Analysis of Protein Data Bank (PDB) structures.
• Nuclear Magnetic Resonance (NMR) spectroscopy.
• Quantum chemistry calculations.

Main Results:

• Thioamides form strong hydrogen bonds, similar to their amide counterparts, in unconstrained environments.
• The enthalpy (ΔH) of the amide-N-H···S═C hydrogen bond was precisely determined to be approximately -30 kJ/mol.
• This indicates that the amide-N-H···S═C hydrogen bond is a strong interaction.

Conclusions:

• The amide-N-H···S═C hydrogen bond is a strong interaction, contrary to some previous assumptions.
• These findings support the inclusion of amide-N-H···S═C hydrogen bonds in computational force fields for biomolecular simulations.
• Accurate modeling of these bonds is crucial for understanding nucleobase pairing and protein folding.