Ionic Analysis

Figure 1 shows the synthesized ionic liquid of CVD with studied acidic compounds (white crystalline materials) in 1:1 molar ratio after dissolving them in methanol and complete solvent evaporation after five days. CVD with CA, TA and SAC convert to a viscous yellow liquid form. This method was used to preparation of different ionic liquid form of drugs such as ketoconazole with TA and CA (24) and sulfasalazine and acyclovir with choline (28).

****Fig 1****

The DSC thermograms of CVD, CA, TA and their ionic liquid forms have been demonstrated in Figure 2. They shows that CVD and studied acidic compounds are crystalline and they have a distinct endothermic peaks corresponding to the melting of solid forms. The DSC curve of CA exhibits a broad

According to the simulated NMR spectra of CA, TA and saccharin by ACD-ilab software (34), hydroxyl functional groups of them have a single peak at ~10 ppm which in is upfield to ~6 ppm in ionized from whenever the first carboxylic acids was converted to carboxylate (COO−). In SAC, disappearance of a single peak at 8.1 ppm of saccharin confirm ionization of 1,2-benzisothiazole ring of SAC. CVD has no peak in the studied regions (8 ppm and ~6 ppm for ionized form of SAC and studied carboxylic acid, respectively).

Similar spectra (Figure S1 in supplementary information) of CVD-CA and CVD-TA show the appearance of a peak at ~6 ppm. It established the ionization of the first carboxylic acid of CA and TA and salt formation. In CVD-SAC, disappearance of a single peak at 8.1 ppm of SAC in ionized form confirm ionization of 1,2-benzisothiazole

The solubility of CVD-ILs with CA and TA is less than CVD. This observation could be related with pH of final solution. pHs of final solution for CVD-ILs in HCl 0.2 M are 2.5-3 for IL-CA and IL-TA. According to the pKa of CA and TA (Table 1), they are partially in non-ionized form and synthesized ionic liquid cannot increase the CVD’s solubility against of the ionic liquid’s solubility in acetate buffer solution. Nevertheless a high concentration of chloride ion in solution because of fully ionization of counter-ions, the solubility improved in compared with CVD. Moreover, based on previous study by Hamed et al. a change in CVD solubility could be related to ionic strength of solution. It is another important parameter in evaluating solubility of CVD and it decreases solubility (14). Ionic liquids can produce higher ionic strength in solution medium and it is a possible reason for decreasing of solubility in acidic medium whenever CVD is fully ionized.

Similar pattern is observed in solubility studies of CVD and corresponding IL forms in HCl 0.1 M and 0.01 M. However, solubility was considerably improved in compared with HCl 0.1 M, 0.2 M). It could be related to the low concentration of chloride ion. The maximum solubility was observed in CVD because in this pH, it is fully ionized and ionic strength in compared with CVD is less than CVD’s ionic