Deciphering the stabilization mechanism of L-arginine and glycyl-L-arginine in an imidazolium-based ionic liquid through thermodynamic and computational approaches.

This study examines the thermodynamic behavior and molecular interactions of L-arginine and the dipeptide glycyl-L-arginine in aqueous solutions of the ionic liquid 1-octyl-3-methylimidazolium bromide ([OMIm][Br]) across the temperature range 288.15-318.15 K. Solution density and ultrasonic velocity were measured with high precision to derive key thermodynamic parameters including apparent molar volumes, limiting partial molar properties, transfer volumes, and apparent molar isentropic compressibilities which together provide quantitative insight into solute-solvent and solute-solute interactions and allow assessment of the structure-making or structure-breaking character of each solute in the ionic liquid-water medium. Both solutes were found to act as structure-makers; however, glycyl-L-arginine exhibited markedly stronger solute-solvent interactions than L-arginine, an effect attributed to its peptide linkage and highly polar guanidinium side chain, which promote extensive hydrogen bonding and electrostatic interactions. The systematic dependence of these parameters on temperature and ionic liquid concentration further supports the kosmotropic character of [OMIm][Br] and its capacity to stabilize charged and polar functional groups in aqueous media. To complement the experimental findings, molecular docking and density functional theory (DFT) calculations were performed to elucidate the electronic properties, interaction energies, and hydrogen-bonding networks governing peptide-ionic liquid interactions. The integrated experimental and computational results yield a coherent mechanistic picture of peptide solvation and stabilization in ionic liquid-water systems, advancing fundamental understanding of biomolecular behavior in engineered solvent environments and underscoring, providing molecular-level insight into peptide solvation and stabilization in aqueous ionic liquid systems.