Very Strong Hydrogen Bond in Nitrophthalic Cocrystals

Area of Science:

• Supramolecular Chemistry
• Biophysical Chemistry
• Organic Chemistry

Background:

• Very strong hydrogen bonds (VSHB) play a critical role in numerous biological processes.
• Understanding VSHB formation is key to designing biologically active molecules.

Purpose of the Study:

• To model and synthesize complexes of phthalic acids with specific amines to achieve VSHB.
• To investigate the influence of steric and electronic factors on hydrogen bond strength.

Main Methods:

• Synthesis of four phthalic acid-amine complexes.
• Experimental characterization using X-ray diffraction, IR, and Raman spectroscopy.
• Theoretical calculations including Car-Parrinello Molecular Dynamics (CP-MD) and Density Functional Theory (DFT).

Main Results:

• Successfully synthesized complexes exhibiting VSHB.
• DFT calculations revealed low energy barriers for proton transfer in intermolecular hydrogen bonds.
• CP-MD simulations showed significant proton dynamics in intermolecular hydrogen bonds.
• Crystallographic and spectroscopic data confirmed OHO intramolecular hydrogen bonds as VSHB in 4-nitrophthalic acid cocrystals.

Conclusions:

• Achieved very strong intramolecular hydrogen bonds in phthalic acid complexes.
• Demonstrated the significant impact of steric effects and basicity on hydrogen bond geometry and dynamics.
• VSHB formation was confirmed through a combination of experimental and computational approaches.