Thermodynamic,Transport, and Spectroscopic Characterizationof Nicotinamide–Caffeine Aqueous Systems

Abstract A holistic understanding of molecular interplay in multicomponent aqueous systems is crucial for developing the applications in pharmaceutical and biochemical domains. In the current research, the thermodynamic and transport properties and spectroscopic characteristics of nicotinamide (NA)–caffeine (CAF) aqueous systems have been investigated in a queue using specific volumetric, viscometric, and UV–visible spectroscopic approaches over a wide range of concentrations and temperatures (293.15 K–313.15 K). To elucidate the nature and strength of solute–solute, solute–cosolute, and solute–solvent interactions some of the parameters were evaluated such as apparent molar volumes, viscosity coefficients, activation parameters, and many more. The positive values of apparent molar volumes, together with transfer parameters, reveal the predominance of strong solute–solvent and solute–cosolute interactions mediaated through hydrogen bonding, dipole–dipole attractions, π–π stacking, and hydration cosphere overlap effects. Increasing CAF concentration enhances volumetric expansion and promotes molecular association, while elevated temperatures weaken the hydrogen-bonded water network and facilitate desolvation. Positive Jones–Dole coefficients and their temperature dependence indicate significant solvation accompanied by the structure-breaking behavior of NA in both binary and ternary systems. Thermodynamic activation parameters derived from Eyring’s treatment demonstrate that viscous flow proceeds through an activated process involving highly solvated transition states, with increasing free energy of activation reflecting enhanced molecular organization and restricted mobility in the mixed solvent environment. UV–visible spectroscopic observations further support the existence of intermolecular association between NA and CAF. Collectively, the results provide molecular level insights into hydration, solvation, and transport phenomena in biologically relevant aqueous systems, offering valuable information for the rational design of pharmaceutical, nutraceutical, and drug-delivery formulations containing NA and CAF.