Synthesis and Characterization of a New Cocrystal of Glycylglycine and Glutaric Acid

High Resolution Image Download MS PowerPoint Slide Peptides have attracted growing interest in therapeutic development due to their high target specificity and biocompatibility, driving the need to understand and control their solid-state structures and intermolecular interactions. In this work, a new 1:1 cocrystal of glycylglycine (GG) and glutaric acid (GA) was produced. The structure of the GG-GA cocrystal was determined by single-crystal X-ray diffraction. Cocrystallization in liquid-assisted grinding or slow cooling was used to produce the peptide cocrystal, which was characterized with scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, and Fourier transform infrared spectroscopy (FT-IR). The melting point of the cocrystal is 450 K. The structure is stabilized by hydrogen bonds between the carboxylic acid of GA and the carboxylate group of zwitterionic GG. Solubility and dissolution studies demonstrate that the GG–GA cocrystal significantly enhances the dissolved concentration of glycylglycine compared with pure GG, while maintaining a stable solid-state form after equilibration. Computational analysis using density functional theory supports the experimental structure determination is consistent with the vibrational assignments obtained from spectroscopy. Furthermore, Hirshfeld surface analysis supports that O–H···O hydrogen bonds are the dominant intermolecular interactions, contributing 56.2% of the total contacts. Overall, this work provides a comprehensive experimental and computational framework for understanding peptide–organic acid cocrystals, offering insights that can guide the rational design of new solid-state peptide materials with tailored properties.