Ionic Co‐Crystal Formation as a Path Towards Chiral Resolution in the Solid State

Shemchuk, Oleksii; Tsenkova, Boryana K.; Braga, Dario; Duarte, M. Teresa; André, Vânia; Grepioni, Fabrizia

doi:10.1002/chem.201802446

Cited by 22 publications

(44 citation statements)

References 61 publications

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“…The cocrystals obtained by reacting the amino acids L-and DL-histidine and L-and DL-proline with lithium [33,35] and calcium [34] halides are model compounds of the effect of metal coordination on chiral selection.…”

Section: Cocrystallization Of L-and Dl-histidine With Lithium Halidesmentioning

confidence: 99%

Chiral Resolution via Cocrystallization with Inorganic Salts

Shemchuk

Grepioni

Leyssens

et al. 2021

Israel Journal of Chemistry

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The coordination mode to lithium, magnesium, calcium and zinc cations of racemic vs. enantiopure amino acids and racetam APIs is analysed and its effect on chiral selection critically reviewed. It is shown that chiral resolution in the solid state can be obtained via cocrystallization of racemic compounds with an achiral inorganic salt coformer, such as LiX (X = Cl, Br, I) or ZnCl 2 , which favour tetrahedral coordination in the solid state. The chiral selection may take the form of conglomerate crystal formation or of selective homochiral aggregation in racemic crystals. When cocrystallization involves alkaline earth metal cations, such as Ca 2 + and Mg 2 + , which favour octahedral coordination, heterochiral complexation is observed in most cases, with formation of racemic crystals.

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Section: Cocrystallization Of L-and Dl-histidine With Lithium Halidesmentioning

confidence: 99%

Chiral Resolution via Cocrystallization with Inorganic Salts

Shemchuk

Grepioni

Leyssens

et al. 2021

Israel Journal of Chemistry

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“…The presence of pyrrolidine groups in L-proline contributes to its good stabilization ability [ 73 ]. Hence, l -proline is a stabilizer for both non-salt mixtures such as co-amorphous systems [ 66 ] and ionic/salt co-crystal [ 17 , 22 , 85 ] by increasing the interaction between components.…”

Section: Amino Acids As Co-formersmentioning

confidence: 99%

“…Those solid phases consisted of the inorganic element with this amino acid formed conglomerates (with Cl and Br) and racemates (with Cl and I), which produced distinct crystal layers between the opposite chirality. Hence, this developed method offers an advantage to chiral resolution [ 17 ].…”

Section: Amino Acids As Co-formersmentioning

confidence: 99%

“…In that kind of co-crystal development, amino acids become the main co-former, i.e., in the ionic co-crystal formation of levodopa with LiCl and l -tyrosine and l -phenylalanine as the biological precursors [ 16 ]. The hydrated ionic co-crystals from enantiopure l -proline and racemic dl -proline with LiX (X=Cl, Br, I) were also reported can increase chiral resolution [ 17 ], as well as dl -amino acids alanine, valine, leucine, and isoleucine with LiCl [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Here, this article dealt with reviewing the amino acid-based co-crystals and their opportunities. l -proline is discussed in depth due to it becoming the most used co-former with some advantages over the other amino acids [ 17 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Nugrahani

Jessica

2021

Molecules

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Co-crystals are one of the most popular ways to modify the physicochemical properties of active pharmaceutical ingredients (API) without changing pharmacological activity through non-covalent interactions with one or more co-formers. A “green method” has recently prompted many researchers to develop solvent-free techniques or minimize solvents for arranging the eco-friendlier process of co-crystallization. Researchers have also been looking for less-risk co-formers that produce the desired API’s physicochemical properties. This review purposed to collect the report studies of amino acids as the safe co-former and explored their advantages. Structurally, amino acids are promising co-former candidates as they have functional groups that can form hydrogen bonds and increase stability through zwitterionic moieties, which support strong interactions. The co-crystals and deep eutectic solvent yielded from this natural compound have been proven to improve pharmaceutical performance. For example, l-glutamine could reduce the side effects of mesalamine through an acid-base stabilizing effect in the gastrointestinal fluid. In addition, some amino acids, especially l-proline, enhances API’s solubility and absorption in its natural deep eutectic solvent and co-crystals systems. Moreover, some ionic co-crystals of amino acids have also been designed to increase chiral resolution. Therefore, amino acids are safe potential co-formers, which are suitable for improving the physicochemical properties of API and prospective to be developed further in the dosage formula and solid-state syntheses.

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Recent advances in the field of chiral crystallization

Putman

Armstrong

2022

Chirality

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Crystallization is one of the largest and most economical bulk purification techniques used in industry today. There has been an increase in demand for enantiomerically pure compound production for research, organic synthesis, pharmaceutical drug production, and other applications. Even after asymmetric synthesis, chiral purification will always be necessary. The focus of this review is on recent advances in chiral crystallization for the purification of enantiomers. A comprehensive discussion of three techniques and their mechanisms is provided, namely: attrition‐enhanced deracemization, cocrystallization, and inorganic ionic cocrystallization. Several examples of attrition‐enhanced deracemization are discussed. The key advantage of this technique is that it eliminates enantiomeric waste and can be used to produce enantiomeric excesses of greater than 99% from racemic mixtures. Chiral cocrystallization is examined, with over 60 cocrystallizing compounds, as an excellent means for enantiomeric enrichment. Selective chiral inclusion complexation was shown to be a novel approach for the formation of cocrystals. Chiral inorganic ionic cocrystallization is a new technique involving the formation of cocrystals between chiral ligands and certain metal salts in order to produce conglomerate crystal behavior in otherwise racemic compounds.

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Ionic Co‐Crystal Formation as a Path Towards Chiral Resolution in the Solid State

Cited by 22 publications

References 61 publications

Chiral Resolution via Cocrystallization with Inorganic Salts

Chiral Resolution via Cocrystallization with Inorganic Salts

Amino Acids as the Potential Co-Former for Co-Crystal Development: A Review

Recent advances in the field of chiral crystallization

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