Exploring the role of ionic liquids to tune the polymorphic outcome of organic compounds

Zeng, Qingying; Mukherjee, Arijit; Müller, Péter; Rogers, Robin D.; Myerson, Allan S.

doi:10.1039/c7sc04353h

Cited by 34 publications

(32 citation statements)

References 37 publications

(40 reference statements)

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“…At present, the structural relevance between solute selfassemblies in solution and molecular synthons in the resultant crystals is of great interest (Parveen et al, 2005;Burton et al, 2010;Tang et al, 2017;Zeng et al, 2018) and could shed light on how nucleation proceeds. For instance, it was found that the formation of two conformational polymorphs of Nphenylhydroxamic acid had direct correspondence with the dominant conformers in two different solvents (Yamasaki et al, 2006;Ischenko et al, 2005), which suggested a simple nucleation pathway.…”

Section: Introductionmentioning

confidence: 99%

Probing the structural pathway of conformational polymorph nucleation by comparing a series of α,ω-alkanedicarboxylic acids

Shi

et al. 2020

IUCrJ

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Herein the nucleation pathway of conformational polymorphs was revealed by studying the relationships and distinctions among a series of α,ω-alkanedicarboxylic acids [HOOC–(CH2) n−2–COOH, named DAn, where n = 5, 7, 9, 11, 13, 15] in the solid state and in solution. Their polymorphic outcomes, with the exception of DA5, show solvent dependence: form I with conformation I crystallizes from solvents with hydrogen-bond donating (HBD) ability, whereas form II with conformation II crystallizes preferentially from solvents with no HBD ability. In contrast, form II of DA5 does not crystallize in any of the solvents used. Quantum mechanical computation showed that there is no direct conformational link between the solvents and the resultant polymorphic outcomes. Surprisingly, solute aggregates were found in no-HBD solvents by Fourier transform infrared spectroscopy, and only monomers could be detected in HBD solvents, suggesting stronger solvation. Furthermore, it was found that all six compounds including DA5 followed the same pattern in solution. Moreover, crystal-packing efficiency calculations and stability tests stated that dimorphs of DA5 bear a greater stability difference than others. These suggest that the rearrangement from conformation II to I could not be limited by hard desolvation in HBD solvents, where form I was also obtained. In other systems, metastable II was produced in the same solvents, probably as a result of the rearrangement being limited by hard desolvation. In this work, a comparative study uncovers the proposed nucleation pathway: difficulty in desolvation has a remarkable effect on the result of rearrangement and nucleation outcome.

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Section: Introductionmentioning

confidence: 99%

Probing the structural pathway of conformational polymorph nucleation by comparing a series of α,ω-alkanedicarboxylic acids

Shi

et al. 2020

IUCrJ

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“…To counteract the disadvantages of solid drugs, new ILs could be linked with pharmacologically active ingredients, forming API-ILs, an alternative to common crystalline salts [ 24 , 27 , 28 , 31 , 38 , 40 , 43 ]. The possibility to eliminate or reduce the negative side effects of an active compound by delivering it as an API–IL is attractive for pharmaceutical, environmental, and medical applications.…”

Section: Discussionmentioning

confidence: 99%

“…The nearly infinite combinations of suitable cations and anions allow for a wide range of modulation of the IL properties [ 39 , 40 , 41 , 42 ]. The anion is usually responsible for characteristics such as air and water stability, and the cation is usually responsible for the melting temperature and organic solubility [ 43 ].…”

Section: Ionic Liquids and Active Pharmaceutical Ingredients (Apismentioning

confidence: 99%

Recycling Old Antibiotics with Ionic Liquids

et al. 2020

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Antibiotics are considered one of the great “miracles” of the 20th century. Now in the 21st century in the post-antibiotic era, the miracle is turning into a nightmare, due to the growing problem of the resistance of microorganisms to classic antimicrobials and the non-investment by the pharmaceutical industry in new antimicrobial agents. Unfortunately, the current COVID-19 pandemic has demonstrated the global risks associated with uncontrolled infections and the various forms of impact that such a pandemic may have on the economy and on social habits besides the associated morbidity and mortality. Therefore, there is an urgent need to recycle classic antibiotics, as is the case in the use of ionic liquids (ILs) based on antibiotics. Thus, the aim of the present review is to summarize the data on ILs, mainly those with antimicrobial action and especially against resistant strains. The main conclusions of this article are that ILs are flexible due to their ability to modulate cations and anions as a salt, making it possible to combine the properties of both and multiplying the activity of separate cations and anions. Also, these compounds have low cost methods of production, which makes it highly attractive to explore them, especially as antimicrobial agents and against resistant strains. ILs may further be combined with other therapeutic strategies, such as phage or lysine therapy, enhancing the therapeutic arsenal needed to fight this worldwide problem of antibacterial resistance. Thus, the use of ILs as antibiotics by themselves or together with phage therapy and lysine therapy are promising alternatives against pathogenic microorganisms, and may have the possibility to be used in new ways in order to restrain uncontrolled infections.

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“…17 Although these types of interactions are complex in nature, recently we have shown that the effect of certain ILs can be studied with respect to crystallization and polymorphism. 18,19 In analogy with the POLAG approach as mentioned above, we hypothesized that changing the structural variables of suitable ILs by changing either of the components may give us access to desirable cocrystals. While the chain length of the EG derivatives could be only variable in POLAG, the structural variables of ILs can be controlled either by individual tuning of the components or in a dual manner, increasing the number of variables in the grinding process.…”

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confidence: 99%

“…We chose imidazolium-based ILs with relatively inert anions as grinding liquids because of their utility in crystallization of small molecules in previous studies. 19 While previous studies employed different solvents or polymers of varying chain lengths, the focus of our strategy involved tuning the ILs either by modifying the substitution on the imidazolium cation or by changing the anions. The ILs studied, 26 ).…”

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confidence: 99%

Cocrystal formation by ionic liquid-assisted grinding: case study with cocrystals of caffeine

2018

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Exploring the role of ionic liquids to tune the polymorphic outcome of organic compounds

Abstract: The adoption of ionic liquids as crystallization solvents for polymorphic screening opens a new window for the applications of ILs, which may allow one to access the forms difficult to crystallize from organic solvents.

Cited by 34 publications

References 37 publications

Probing the structural pathway of conformational polymorph nucleation by comparing a series of α,ω-alkanedicarboxylic acids

Probing the structural pathway of conformational polymorph nucleation by comparing a series of α,ω-alkanedicarboxylic acids

Recycling Old Antibiotics with Ionic Liquids

Cocrystal formation by ionic liquid-assisted grinding: case study with cocrystals of caffeine

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