Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals

Natalia Tumanova; Nikolay Tumanov; Koen Robeyns; Franziska Fischer; Luca Fusaro; Fabrice Morelle; Voraksmy Ban; Geoffroy Hautier; Yaroslav Filinchuk; Johan Wouters; Tom Leyssens; Franziska Emmerling

doi:10.1021/acs.cgd.7b01436

Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals

Natalia Tumanova, Nikolay Tumanov, Koen Robeyns, Franziska Fischer, Luca Fusaro, Fabrice Morelle, Voraksmy Ban, Geoffroy Hautier, Yaroslav Filinchuk, Johan Wouters, Tom Leyssens, Franziska Emmerling

Research output: Contribution to journal › Article › peer-review

Abstract

Proline has been widely used for various cocrystallization applications, including pharmaceutical cocrystals. Combining enantiopure and racemic flurbiprofen and proline, we discovered 18 new crystal structures. Liquid-assisted grinding proved highly efficient to explore all the variety of crystal forms. A unique combination of state-of-the-art characterization techniques, comprising variable temperature in situ X-ray diffraction and in situ ball-milling, along with other physicochemical methods and density functional theory calculations, was indispensable for identifying all the phases. Analyzing the results of in situ ball-milling, we established a stepwise mechanism for the formation of several 1:1 cocrystals via an intermediate 2:1 phase. The nature of the solvent in liquid-assisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.

Original language	English
Pages (from-to)	954-961
Number of pages	8
Journal	Crystal Growth & Design
Volume	18
Issue number	2
DOIs	https://doi.org/10.1021/acs.cgd.7b01436 https://doi.org/10.1021/acs.cgd.7b01436
Publication status	Published - 4 Jan 2018

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Tumanova, N., Tumanov, N., Robeyns, K., Fischer, F., Fusaro, L., Morelle, F., Ban, V., Hautier, G., Filinchuk, Y., Wouters, J., Leyssens, T., & Emmerling, F. (2018). Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals. Crystal Growth & Design, 18(2), 954-961. https://doi.org/10.1021/acs.cgd.7b01436, https://doi.org/10.1021/acs.cgd.7b01436

@article{65e1fe7c8ee24e958accef2cd0a636d1,

title = "Opening Pandora{\textquoteright}s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals",

abstract = "Proline has been widely used for various cocrystallization applications, including pharmaceutical cocrystals. Combining enantiopure and racemic flurbiprofen and proline, we discovered 18 new crystal structures. Liquid-assisted grinding proved highly efficient to explore all the variety of crystal forms. A unique combination of state-of-the-art characterization techniques, comprising variable temperature in situ X-ray diffraction and in situ ball-milling, along with other physicochemical methods and density functional theory calculations, was indispensable for identifying all the phases. Analyzing the results of in situ ball-milling, we established a stepwise mechanism for the formation of several 1:1 cocrystals via an intermediate 2:1 phase. The nature of the solvent in liquid-assisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.",

author = "Natalia Tumanova and Nikolay Tumanov and Koen Robeyns and Franziska Fischer and Luca Fusaro and Fabrice Morelle and Voraksmy Ban and Geoffroy Hautier and Yaroslav Filinchuk and Johan Wouters and Tom Leyssens and Franziska Emmerling",

note = "Funding Information: The authors thank UCL, FNRS, FRIA (scholarship allocated to N.T.), and COST Action (CM1402) for the financial support; PC2 platform (UNamur) for the equipment; ESRF, PSI, and BESSY II for the beam time; Dr. D. Waroquiers, Dr. G. Yu, Prof. R. Cerny, Prof. J. van de Streek, L. Baulard, and P. Van Velthem for their help and advice; and CISM/UCL and C{\'E}CI for providing computational resources. Funding Information: The authors thank UCL, FNRS, FRIA (scholarship allocated to N.T.), and COST Action (CM1402) for the financial support; PC2 platform (UNamur) for the equipment; ESRF, PSI, and BESSY II for the beam time; Dr. D. Waroquiers, Dr. G. Yu, Prof. R. Cerny, Prof. J. van de Streek L. Baulard, and P. Van Velthem for their help and advice; and CISM/UCL and CECI for providing computational resources. Publisher Copyright: {\textcopyright} 2018 American Chemical Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2018",

month = jan,

day = "4",

doi = "10.1021/acs.cgd.7b01436",

language = "English",

volume = "18",

pages = "954--961",

journal = "Crystal Growth and Design",

issn = "1528-7483",

publisher = "American Chemical Society",

number = "2",

}

Tumanova, N, Tumanov, N, Robeyns, K, Fischer, F, Fusaro, L, Morelle, F, Ban, V, Hautier, G, Filinchuk, Y, Wouters, J, Leyssens, T & Emmerling, F 2018, 'Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals', Crystal Growth & Design, vol. 18, no. 2, pp. 954-961. https://doi.org/10.1021/acs.cgd.7b01436, https://doi.org/10.1021/acs.cgd.7b01436

TY - JOUR

T1 - Opening Pandora’s Box

T2 - Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals

AU - Tumanova, Natalia

AU - Tumanov, Nikolay

AU - Robeyns, Koen

AU - Fischer, Franziska

AU - Fusaro, Luca

AU - Morelle, Fabrice

AU - Ban, Voraksmy

AU - Hautier, Geoffroy

AU - Filinchuk, Yaroslav

AU - Wouters, Johan

AU - Leyssens, Tom

AU - Emmerling, Franziska

N1 - Funding Information: The authors thank UCL, FNRS, FRIA (scholarship allocated to N.T.), and COST Action (CM1402) for the financial support; PC2 platform (UNamur) for the equipment; ESRF, PSI, and BESSY II for the beam time; Dr. D. Waroquiers, Dr. G. Yu, Prof. R. Cerny, Prof. J. van de Streek, L. Baulard, and P. Van Velthem for their help and advice; and CISM/UCL and CÉCI for providing computational resources. Funding Information: The authors thank UCL, FNRS, FRIA (scholarship allocated to N.T.), and COST Action (CM1402) for the financial support; PC2 platform (UNamur) for the equipment; ESRF, PSI, and BESSY II for the beam time; Dr. D. Waroquiers, Dr. G. Yu, Prof. R. Cerny, Prof. J. van de Streek L. Baulard, and P. Van Velthem for their help and advice; and CISM/UCL and CECI for providing computational resources. Publisher Copyright: © 2018 American Chemical Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2018/1/4

Y1 - 2018/1/4

N2 - Proline has been widely used for various cocrystallization applications, including pharmaceutical cocrystals. Combining enantiopure and racemic flurbiprofen and proline, we discovered 18 new crystal structures. Liquid-assisted grinding proved highly efficient to explore all the variety of crystal forms. A unique combination of state-of-the-art characterization techniques, comprising variable temperature in situ X-ray diffraction and in situ ball-milling, along with other physicochemical methods and density functional theory calculations, was indispensable for identifying all the phases. Analyzing the results of in situ ball-milling, we established a stepwise mechanism for the formation of several 1:1 cocrystals via an intermediate 2:1 phase. The nature of the solvent in liquid-assisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.

AB - Proline has been widely used for various cocrystallization applications, including pharmaceutical cocrystals. Combining enantiopure and racemic flurbiprofen and proline, we discovered 18 new crystal structures. Liquid-assisted grinding proved highly efficient to explore all the variety of crystal forms. A unique combination of state-of-the-art characterization techniques, comprising variable temperature in situ X-ray diffraction and in situ ball-milling, along with other physicochemical methods and density functional theory calculations, was indispensable for identifying all the phases. Analyzing the results of in situ ball-milling, we established a stepwise mechanism for the formation of several 1:1 cocrystals via an intermediate 2:1 phase. The nature of the solvent in liquid-assisted grinding was found to significantly affect the reaction rate and, in some cases, the reaction pathway.

UR - http://www.scopus.com/inward/record.url?scp=85041915775&partnerID=8YFLogxK

U2 - 10.1021/acs.cgd.7b01436

DO - 10.1021/acs.cgd.7b01436

M3 - Article

SN - 1528-7483

VL - 18

SP - 954

EP - 961

JO - Crystal Growth and Design

JF - Crystal Growth and Design

IS - 2

ER -

Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals

Abstract

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High Performance Computing Technology Platform

Physical Chemistry and characterization(PC2)

CCDC 1537416: Experimental Crystal Structure Determination

CCDC 1537413: Experimental Crystal Structure Determination

CCDC 1537403: Experimental Crystal Structure Determination

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Opening Pandora’s Box: Chirality, Polymorphism, and Stoichiometric Diversity in Flurbiprofen/Proline Cocrystals

Abstract

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High Performance Computing Technology Platform

Physical Chemistry and characterization(PC2)

Datasets

CCDC 1537416: Experimental Crystal Structure Determination

CCDC 1537413: Experimental Crystal Structure Determination

CCDC 1537403: Experimental Crystal Structure Determination

Cite this