Competitive Intramolecular Hydrogen Bonding: Offering Molecules a Choice

Area of Science:

• Chemical Physics
• Molecular Dynamics
• Supramolecular Chemistry

Background:

• Acyl thiourea derivatives exhibit diverse conformational behaviors.
• Intramolecular hydrogen bonds (IHBs) significantly influence molecular conformation.
• Understanding conformational dynamics is crucial for molecular design.

Purpose of the Study:

• To investigate the conformational preferences of N-((6-methylpyridin-2-yl)carbamothioyl)benzamide.
• To elucidate the role of solvent polarity on molecular conformation.
• To explore the dynamic nature of intramolecular hydrogen bonds in this system.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy.
• Density Functional Theory (DFT) calculations.
• Single crystal X-ray diffraction.

Main Results:

• The molecule adopts two low-energy conformations stabilized by distinct 6-membered intramolecular hydrogen bond (IHB) pseudorings.
• Conformational preference is polarity-dependent, with polar solvents favoring the NH⋅⋅⋅N IHB conformer.
• Calculated interconversion barriers suggest dynamic behavior at room temperature.

Conclusions:

• Competitive IHB pathways can enhance the dynamic nature of otherwise static IHBs.
• This conformational plasticity suggests potential applications as "chameleons" in drug design.
• The study highlights the interplay between molecular structure, solvent environment, and hydrogen bonding dynamics.