Characterization of Amino Acid–Drug Interactions in Aqueous Tetracycline Hydrochloride Systems Using Volumetric, Acoustic, and Viscometric Approaches

This study investigates the molecular interactions between amino acids, l-serine, l-valine, and l-histidine, and aqueous solutions of tetracycline hydrochloride (TCH, C22H25ClN2O8) at varying concentrations (0.0005, 0.0007, and 0.0009 mol·kg–1) and temperatures (293.15–313.15 K) at standard atmospheric conditions. Experimental data for density (ρ), absolute viscosity (η), and ultrasonic velocity (u) were employed to derive key thermodynamic and acoustic parameters, including the apparent molar volume (V2,ϕ) and apparent molar isentropic compression (K2,ϕ,S), along with their respective limiting values (Vϕ0, and Kϕ,S0). The absolute viscosity data were analyzed using the Jones–Dole equation to obtain A and B coefficients. Transfer properties (ΔtrVϕ0, ΔtrB, and ΔtrKϕ,S0), hydration number (nH), molar expansivity (E2,ϕ0), and Hepler’s constant (∂E2,ϕ0/∂T)p were calculated to assess solute–solvent interactions. Group contribution analysis revealed the influence of zwitterionic moieties (NH3+, COO–), methylene (−CH2−) units, and alkyl chain length on Vϕ0 and Kϕ,S0. The results elucidate the role of amino acid structure, temperature, and solute concentration in modulating interionic interactions with TCH, offering insights into drug–biomolecule compatibility and solvation dynamics in aqueous media.