Towards deracemization in the absence of grinding through crystal transformation, ripening, and racemization

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Xiouras, Christos and Van Cleemput, Emma and Kumpen, Andries and Ter Horst, Joop H. and Van Gerven, Tom and Stefanidis, Georgios D. (2017) Towards deracemization in the absence of grinding through crystal transformation, ripening, and racemization. Crystal Growth and Design, 17 (2). pp. 882-890. ISSN 1528-7483 (https://doi.org/10.1021/acs.cgd.6b01758)

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Abstract

New insights into the obscure mechanisms of solid-state deracemization phenomena are obtained by crystal ripening experiments that, contrary to standard techniques, exclude attrition enhancement (grinding). The results point out that small particles and an initial size imbalance between the two enantiomeric crystal populations can intensify the rate of solidstate enantiomeric enrichment even in the absence of intermediate actions (e.g., grinding or thermal cycling). On this ground, a new process that creates such initial conditions is designed and exemplified for the proteinogenic glutamic acid. As a first step, racemic compound solvate (DL-glutamic acid monohydrate) crystals are completely converted to small-sized conglomerate anhydrate crystals, in the presence of larger seeds of a single chirality. After the transformation is complete and the racemization catalyst is added, the suspension contains an equal number of small-sized conglomerate crystals of both enantiomers together with the larger seeds of the preferred enantiomer. Over time, the large crystals of the preferred enantiomer tend to grow at the expense of smaller ones, which dissolve. This, combined with the fast racemization, leads to enantiomeric enrichment. The possible occurrence of enantioselective agglomeration between small and seed crystals speeds up this process by removing small crystals of the preferred enantiomer. Since most amino acids and several other pharmaceutical compounds are known to form metastable racemic hydrate crystals, it is expected that this new method is readily applicable to a variety of compounds. In addition, the process provides a technically simpler and more scalable route to enantiomeric enrichment compared to attritionenhanced deracemization, and its applicability extends to the wider pool of compounds that crystallize as racemic crystals.

ORCID iDs

Xiouras, Christos, Van Cleemput, Emma, Kumpen, Andries, Ter Horst, Joop H. ORCID logoORCID: https://orcid.org/0000-0003-0118-2160, Van Gerven, Tom and Stefanidis, Georgios D.;
  • Item type:Article
    ID code:59914
    Dates:
    Date
    Event
    1 February 2017
    Published
    15 December 2016
    Published Online
    31 December 2015
    Accepted
    Notes:“This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.cgd.6b01758
    Subjects:Science > Chemistry
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:22 Feb 2017 10:23
    Last modified:11 Nov 2024 11:38
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/59914
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