Prediction and screening of solubility of pharmaceuticals in single‐ and mixed‐ionic liquids using COSMO‐SAC model

Molecular dynamics simulations were performed to study combinations of [AcO]−, [TfO]−, [BF4]−, and [PF6]− anions paired with imidazolium cations of increasing alkyl chain length to elucidate the roles of anions and cations in solvating ibuprofen. Our simulation results revealed that ionic liquids (ILs) with strong ibuprofen solvation capacity should possess strong van der Waals force from cations and strong hydrogen bond (HB) from anions. Accordingly, it was found that ILs containing anions with strong HB acceptability, such as [AcO]− anion, were the best effective solvent for ibuprofen solvation, while the longer alkyl chain in the imidazolium cations decrease the polarity, thus increasing the affinity with ibuprofen. Therefore, it was suggested that the heterocyclic structure of imidazolium cation with moderate polarity and longer alkyl chain is a promising cation candidate, whereas the anions which have a strong HB acceptability and substituents without electron withdrawing groups are beneficial. The obtained results can provide useful information for rational design and selection of new ILs to dissolve insoluble drugs.

Section: Resultsmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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How imidazolium‐based ionic liquids solubilize the poorly soluble ibuprofen? A theoretical study

Huang

Zhang

et al. 2020

Section: Introductionmentioning

confidence: 99%

“…Moving beyond two‐ion ILs, several researchers have recently turned their attention to double salt ionic liquids (DSILs) which are composed of more than one cation and/or anion . As the most straightforward approach to obtain such DSILs is mixing two different ILs together, they are treated as “IL mixtures” in many studies (in the following all ILs refer to two‐ion ones if they are not particularly specified) . However, through an elaborate review, Rogers and co‐workers suggested the concept of DSILs as they found that the “mixture” of ILs is quite different from the mixture of molecular solvents: (a) the ionic associations in the individual ILs are lost and one cannot identify which ion is from which IL; (b) the overall properties of the “mixture” are derived from the ion identities and ion ratios in it, not necessarily derived from the individual ILs (also named as IL parents of DSIL) used for its preparation …”

Section: Introductionmentioning

confidence: 99%

Rational design of double salt ionic liquids as extraction solvents: Separation of thiophene/n‐octane as example

Song

Zhou

et al. 2019

Although double salt ionic liquids (DSILs) offer significant advantages over classical twoion ionic liquids as separation solvents, relevant studies are still scarce and a systematic DSIL selection method is thus highly desirable. In this contribution, a rational method for designing DSILs as extraction solvents is proposed and exemplified by the thiophene/ n-octane separation. The effects of additional degrees of freedom for DSIL design (i.e., double cations and/or anions and the ion ratio) on the thermodynamic properties are first analyzed by COSMO-RS. Then, a multilevel DSIL design method combining the prediction of infinite dilution thermodynamic properties, the estimation of physical properties, the evaluation of phase equilibrium behavior, and the experimental validation is proposed. By applying this method, [C 2 MIm][OAc] x [NO 3 ] 1-x (x = [0, 1]) and [C 2 MIm] [OAc] x [SCN] 1-x (x = [0.70, 1]) are identified as promising DSIL solvents for the thiophene/ n-octane separation. Correspondingly, the liquid-liquid equilibria of {DSILs + thiophene + n-octane} with the designed DSILs are experimentally studied. K E Y W O R D S COSMO-RS, double salt ionic liquids, liquid-liquid equilibrium, solvent design, thiophene/ n-octane separation 1 | INTRODUCTION During the past decades, ionic liquids (ILs) have sparked significant interest for application in various separation processes due to their overwhelming advantages over conventional organic solvents, such as negligible vapor pressure, broad liquid range, designable and tunable character, and so on. 1-10 However, as known to all, various cationanion combinations can lead to very different physical and thermodynamic properties, making the selection of ILs the most crucial task for the development of IL-based separation processes. 4-10 A large number of experimental and theoretical studies have been reported on the identification of suitable ILs for different separation processes. 7-25 Particularly, several research groups have employed COSMO-based activity coefficient models 12-19 or the UNIFAC-IL model 20-25 to perform computational screening and design of ILs as separation solvents. Because of the predictive character of these thermodynamic models, the separation performance of ILs that have not been experimentally covered can be estimated and thus the identification of suitable solvent candidates in a large range is possible. Despite the progress made, the selection of practically attractive IL for a specific process is still challenging as in many cases very few ILs can satisfy different desirable properties simultaneously. For instance, when screening ILs as extractive desulfurization solvent, Song et al found that only 831 of the initial 36,260 cation-anion combinations meet the thermodynamic property requirements, among which only 15 satisfy the physical property constraints. 16 Conceivably, if more restrictions such as easy preparation, commercial availability, low cost, and so on of ILs are considered, the number of feasible solvents will be further reduced...

Predictive molecular thermodynamic models for ionic liquids

Wei

Chen

et al. 2022

Predictive molecular thermodynamic models can bridge the gap between the microscopic molecular level and macroscopic system scale. Over the past few decades, ionic liquids (ILs), as a class of green solvents and functional materials, have received widespread research interest in the field of chemical processing owing to their unique physicochemical merits. This review aims to provide an easy‐to‐read and exhaustive reference regarding state‐of‐the‐art predictive thermodynamic models for ILs, with more focuses on UNIFAC‐ and COSMO‐based models and various applications involving phase equilibrium prediction, guidance for IL screening and design, and building equilibrium stage models for separation processes. This review provides a theoretical perspective on the structure–property relationships between molecular structures and phase behaviors for the systems and the constituted components covering a multi‐scale viewpoint from molecular level to industrial scale. Moreover, the predictive capacities of different thermodynamic models are comprehensively compared.