Thermodynamic investigation on acid-base equilibria of deferiprone and deferasirox at different ionic strengths and various temperatures

- Protonation constants of deferiprone and deferasirox were determined at different ionic strengths and various temperatures.
- Enthalpy, entropy, and Gibbs energy changes of protonation were determined at different ionic strengths of NaCl using modified van't Hoff method.
- The dependence of protonation constants of the drugs on ionic strength was modelled by seven different approaches at 25.0 °C.

The acid-base equilibria of two iron chelating drugs, deferiprone (DFP) and deferasirox (DFX), have been studied in aqueous solution using potentiometric and spectrophotometric methods at different ionic strengths (0.100-3.200 and 0.100-1.548 mol kg−1 NaCl for DFP and DFX, respectively) and various temperatures (293.15-310.15 K). Owing to the low solubility of DFX in aqueous medium, in this case, the experiments were performed in aqueous solution of 30% (v/v) DMSO. The results showed that by increasing of temperature, all the protonation constants of the both drugs decreased indicating exothermic reactions. The thermodynamic functions of protonation including ΔG°, ΔH° and ΔS° at the mean temperature (301.15 K) were determined at different ionic strengths using a modified van't Hoff equation. The relative contributions of enthalpy (ζH) and entropy (ζTS) were also calculated for the protonation steps of the drugs. The dependence of protonation constants of DFP and DFX on ionic strength was modelled by seven different approaches at 298.15 K. The log Ko values (at zero ionic strength) of the drugs were also determined. Finally, the experimental protonation constants of DFP were compared with the literature data and comparison has been made and discussed between the different models.

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