Preferential solvation and solvation shell composition of sunitinib malate, an anti-tumor compound, in some binary mixed
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ORIGINAL PAPER
Preferential solvation and solvation shell composition of sunitinib malate, an anti‑tumor compound, in some binary mixed solvents at 298.15 K Mohsen Padervand1 · Shima Naseri1 · Sima Hajiahmadi2 Received: 30 July 2020 / Accepted: 18 September 2020 © Institute of Chemistry, Slovak Academy of Sciences 2020
Abstract Preferential solvation of sunitinib malate (STM) was investigated in the binary mixtures of water, ethanol, ethylene glycol (EG), and propylene carbonate (PC) solvents at 298.15 K. Similar to its pharmaceutical formulation steps, dimethyl sulfoxide (DMSO) was used as the base solvent during our experiments. Bosch–Rose model was utilized to estimate the electronic transition energies, ET, and other preferential solvation parameters, demonstrating solute–solvent and solute–solute interactions. Shifting λmax situation with respect to the dielectric constant of the pure solvents was carefully monitored indicating that STM had the lowest λmax in water and PC among HBD and HBA solvents, respectively. Moreover, ET showed positive deviation with respect to ideality for ethanol–EG, ethanol–PC, and ethanol–DMSO binary systems while negative deviation was obtained for the others which was explainable based on the model assumptions. According to the results, STM molecules preferred to be solvated by PC, ethanol, EG, and DMSO solvent molecules rather than water in the binary mixtures of the aforementioned solvents, meaning that the presence of water in the cybotactic region is least probable compared to the others. Based on the local mole fractions, the abundance of pure solvents and/or complex solvent molecules in the cybotactic region around the solute was discussed in detail, illustrating the specific and non-specific interactions between solute and solvent molecules. Keywords Sunitinib malate · Bosch–Rose model · Preferential salvation · Mixed solvents
Introduction S u n i t i n i b m a l a t e , t h e m o l e c u l a r fo r m u l a o f C22H27FN4O2·C4H6O5 and the molecular weight of 532.6 Daltons, is chemically defined as Butanedioic acid, hydroxy-, (2S)-, compound with N-[2-(diethylamino)ethyl]5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidine) methyl]-2,4dimethyl-1H-pyrrole-3-carboxamide (1:1) (Gan et al. 2009). As a multi-targeted tyrosine kinase receptor inhibitor, the efficacy of STM for the treatment of renal cell carcinoma and gastrointestinal stromal tumor has received FDA approved on January 2006 (Ishihara et al. 2011). STM * Mohsen Padervand [email protected]; [email protected] 1
Department of Chemistry, Faculty of Science, University of Maragheh, Maragheh, Iran
Department of Biochemistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2
is sparingly soluble in aqueous buffers but soluble in the inert gas-purged organic solvents such as DMF and DMSO. Its solubility and solvation behavior in the solvent mixtures have not been reported yet. Poor aqueous solubility of some Active Pharmaceutical Ingredients (APIs), as one of the most important obst
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