Unraveling Glycine and Glycylglycine Dynamics in Aqueous 4-AP Solutions: A Combined Experimental and DFT Study Across Temperatures

In the present investigation, aqueous solutions of 4-aminopyridine (4-AP) at molalities of 0.001, 0.003, and 0.005 mol·kg^–1 were utilized as solvent media to explore the physicochemical properties of the amino acids (AAs) glycine and glycylglycine across a temperature span of 293.15 to 313.15 K under ambient pressure. Experimental determinations of density and viscosity facilitated the evaluation of critical thermodynamic and transport parameters, including apparent molar volumes (V_ϕ), limiting partial molar volumes (V_ϕ⁰), transfer volumes (Δ_trV_ϕ⁰), Jones–Dole viscosity B-coefficients, and the activation free energies for viscous flow (Δμ₁^0# and Δμ₂^0#), interpreted through the framework of Transition State Theory. The obtained data indicated stronger intensification of solute–solvent interactions with increasing concentrations of 4-AP, consistent with the Co-sphere Overlap Model. Both glycine and glycylglycine were found to exhibit structure-disrupting effects on the aqueous medium in the presence of 4-AP, suggesting a perturbation of the inherent water structure. Complementary fluorescence spectroscopic analysis, through systematic variation in AA concentration, enabled the estimation of association constants, while ¹H NMR spectroscopy provided insights into the presence of hydrophobic interactions between 4-AP and the AAs. These experimental insights were further substantiated through computational modeling, offering a coherent and molecular-level perspective on the interaction dynamics governing these systems.