New thermodynamic insights into pregabalin interactions with H+, Na+, Mg2+, Ca2+, Cu2+, Zn2+: Equilibrium constants, enthalpy changes and sequestering ability

Abstract

The thermodynamics of the interaction between (S)-(+)-3-aminomethyl-5-methylhexanoic acid (pregabalin) and protons was studied potentiometrically at different temperatures (288.15 ≤ T/K ≤ 310.15), ionic strengths (0.16 ≤ I/mol kg⁻¹(H₂O) ≤ 0.97, NaCl), (0.11 ≤ I/mol kg⁻¹(H₂O) ≤ 1.11, (C₂H₅)₄NI), (0.10 ≤ I/mol kg⁻¹(H₂O) ≤ 1.03, NaClO₄, only at T = 298.15 K). The protonation constants at infinite dilution and the corresponding enthalpy change values were determined, as well as their parameters for the dependence on the temperature and ionic strength. The results showed that the protonation reactions are exothermic, and that the entropic contribution is the driving force of the processes. Formation constants of pregabalin (L) with Zn²⁺, Cu²⁺, Ca²⁺, and Mg²⁺ were determined in NaCl(aq) at different ionic strength values, at 298.15 K. Different speciation models were proposed for the various metal/Pregabalin systems: ZnHL²⁺, ZnLOH⁰_(aq), CuL⁺, CuL₂⁰_(aq), CaL⁺, CaHL²⁺, and MgL⁺, depending on the different acid–base properties of the metals and the possible formation of sparingly soluble species. The modelling of the thermodynamic formation parameters respect to the temperature and ionic strength variation was carried out by using both the Specific Ion Interaction Theory (SIT) and an extended Debye-Hückel type equation. Being Pregabalin an emerging contaminant, it was interesting to investigate its distribution in presence of the investigated metal cations in aqueous solution simulating both biological fluid (urine) and natural water (seawater).