Volumetric, acoustic, and computational investigation of l-threonine and glycyl-l-threonine interactions in aqueous 1-octyl-3-methylimidazolium bromide solutions

Abstract

The present study explores the thermodynamic and molecular interaction behaviour of L-threonine and its dipeptide glycyl-L-threonine in aqueous solutions of the ionic liquid 1-octyl-3-methylimidazolium bromide [OMIm][Br] across a temperature range of 288.15–318.15 K. Accurate measurements of solution density and ultrasonic velocity were undertaken to evaluate key thermodynamic parameters, including apparent molar volume, limiting partial molar properties, transfer volumes, and apparent molar isentropic compressibility. These parameters offer quantitative insights into solute–solvent and solute–solute interactions, highlighting the structure-making or structure-breaking tendencies of the solutes in the ionic liquid–water medium. Results show that both solutes act as structure-makers, with glycyl-L-threonine demonstrating stronger solute–solvent interactions than L-threonine, likely due to the presence of the peptide linkage and increased hydrogen-bonding ability. The effects of temperature and ionic liquid concentration further support the kosmotropic nature of [OMIm][Br], which stabilises hydrophilic and polar groups through hydrogen bonds and electrostatic interactions. To complement the experimental data, molecular docking, molecular dynamics simulations, and DFT-based quantum-chemical analyses were performed to reveal the electronic properties, interaction energies, and hydrogen-bonding patterns that control peptide–ionic liquid interactions. The combined experimental and computational results offer a clear understanding of the solvation dynamics and stabilisation mechanisms of peptides in ionic liquid–water systems. These findings enhance the fundamental understanding of biomolecular behaviour in engineered solvent environments and provide practical insights for developing IL-based platforms for peptide and protein drug-delivery formulations.