In
this work, interactions occurring among solute, solvent, and
cosolute in aqueous solutions containing caffeine (CAF) as the solute
and protic ionic liquid (ethanolammonium butyrate; [EABu]) as the
cosolute was studied experimentally (viz. volumetric properties and
spectroscopic analysis) and theoretically (using density functional
theory). Density, ρ, and speed of sound, u,
of CAF in mixed aqueous solutions of protic ionic liquid (PIL) with
concentration (0.05, 0.10, 0.15, and 0.20) mol·kg–1 were measured at temperatures (298.15–313.15 K) and at 0.1
MPa. The data was used to calculate apparent molar volume, apparent
molar isentropic compressibility, and transfer volumes to understand
the type of interactions present between CAF and PIL in water. Further,
the interactions were studied by density functional theory and spectroscopic
analysis (UV–visible and 1H NMR). Hyperchromic shift
in the UV–visible absorption spectra of ternary solutions signifies
the presence of hydrogen bonding interactions. Such hydrophilic types
of interactions were also observed from chemical shift (Δδ)
in 1H NMR spectra of CAF in the ternary system. The structure
of CAF and ionic liquid were optimized in the gas and solvent phase
by employing density functional theory, indicating hydrogen bond interactions
between these molecules. For drug delivery, physicochemical studies
of such PIL-CAF systems are pivotal in understanding the kind of interactions
possible in liquid mixtures.