Cocrystal formation between chiral compounds: How cocrystals differ from salts

Géraldine Springuel, Koen Robeyns, Bernadette Norberg, Johan Wouters, Tom Leyssens

Research output: Contribution to journalArticle

Abstract

A cocrystal screening of a series of chiral target compounds was performed in order to investigate the propensity for two optically active compounds to cocrystallize in an enantiospecific manner. Thirteen novel cocrystal systems were identified, out of which 11 are enantiospecific and two present a diastereomeric cocrystal pair, yielding a total of 15 novel cocrystals. Six of these are structurally characterized in this study. A meticulous search in the Cambridge Structural Database (CSD) has allowed expanding this study. The results led us to the conclusion that enantiospecific cocrystallization seems to be the common rule of thumb, as over 85% of cocrystal systems behave enantiospecifically. Directionality of the hydrogen bonding motifs is likely responsible for the cocrystals' predilection toward enantiospecificity, while salts are mainly stabilized by less directional electrostatic interactions, leading to the formation of diastereomeric pairs.

Original languageEnglish
Pages (from-to)3996-4004
Number of pages9
JournalCrystal Growth and Design
Volume14
Issue number8
DOIs
Publication statusPublished - 6 Aug 2014

Fingerprint

Coulomb interactions
Hydrogen bonds
Screening
screening
Salts
electrostatics
salts
hydrogen
interactions

Cite this

Springuel, Géraldine ; Robeyns, Koen ; Norberg, Bernadette ; Wouters, Johan ; Leyssens, Tom. / Cocrystal formation between chiral compounds: How cocrystals differ from salts. In: Crystal Growth and Design. 2014 ; Vol. 14, No. 8. pp. 3996-4004.
@article{a24f78c11cd442f69a0459f1deb53b9d,
title = "Cocrystal formation between chiral compounds: How cocrystals differ from salts",
abstract = "A cocrystal screening of a series of chiral target compounds was performed in order to investigate the propensity for two optically active compounds to cocrystallize in an enantiospecific manner. Thirteen novel cocrystal systems were identified, out of which 11 are enantiospecific and two present a diastereomeric cocrystal pair, yielding a total of 15 novel cocrystals. Six of these are structurally characterized in this study. A meticulous search in the Cambridge Structural Database (CSD) has allowed expanding this study. The results led us to the conclusion that enantiospecific cocrystallization seems to be the common rule of thumb, as over 85{\%} of cocrystal systems behave enantiospecifically. Directionality of the hydrogen bonding motifs is likely responsible for the cocrystals' predilection toward enantiospecificity, while salts are mainly stabilized by less directional electrostatic interactions, leading to the formation of diastereomeric pairs.",
author = "G{\'e}raldine Springuel and Koen Robeyns and Bernadette Norberg and Johan Wouters and Tom Leyssens",
year = "2014",
month = "8",
day = "6",
doi = "10.1021/cg500588t",
language = "English",
volume = "14",
pages = "3996--4004",
journal = "Crystal Growth and Design",
issn = "1528-7483",
publisher = "American Chemical Society",
number = "8",

}

Cocrystal formation between chiral compounds: How cocrystals differ from salts. / Springuel, Géraldine; Robeyns, Koen; Norberg, Bernadette; Wouters, Johan; Leyssens, Tom.

In: Crystal Growth and Design, Vol. 14, No. 8, 06.08.2014, p. 3996-4004.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cocrystal formation between chiral compounds: How cocrystals differ from salts

AU - Springuel, Géraldine

AU - Robeyns, Koen

AU - Norberg, Bernadette

AU - Wouters, Johan

AU - Leyssens, Tom

PY - 2014/8/6

Y1 - 2014/8/6

N2 - A cocrystal screening of a series of chiral target compounds was performed in order to investigate the propensity for two optically active compounds to cocrystallize in an enantiospecific manner. Thirteen novel cocrystal systems were identified, out of which 11 are enantiospecific and two present a diastereomeric cocrystal pair, yielding a total of 15 novel cocrystals. Six of these are structurally characterized in this study. A meticulous search in the Cambridge Structural Database (CSD) has allowed expanding this study. The results led us to the conclusion that enantiospecific cocrystallization seems to be the common rule of thumb, as over 85% of cocrystal systems behave enantiospecifically. Directionality of the hydrogen bonding motifs is likely responsible for the cocrystals' predilection toward enantiospecificity, while salts are mainly stabilized by less directional electrostatic interactions, leading to the formation of diastereomeric pairs.

AB - A cocrystal screening of a series of chiral target compounds was performed in order to investigate the propensity for two optically active compounds to cocrystallize in an enantiospecific manner. Thirteen novel cocrystal systems were identified, out of which 11 are enantiospecific and two present a diastereomeric cocrystal pair, yielding a total of 15 novel cocrystals. Six of these are structurally characterized in this study. A meticulous search in the Cambridge Structural Database (CSD) has allowed expanding this study. The results led us to the conclusion that enantiospecific cocrystallization seems to be the common rule of thumb, as over 85% of cocrystal systems behave enantiospecifically. Directionality of the hydrogen bonding motifs is likely responsible for the cocrystals' predilection toward enantiospecificity, while salts are mainly stabilized by less directional electrostatic interactions, leading to the formation of diastereomeric pairs.

UR - http://www.scopus.com/inward/record.url?scp=84905715680&partnerID=8YFLogxK

U2 - 10.1021/cg500588t

DO - 10.1021/cg500588t

M3 - Article

VL - 14

SP - 3996

EP - 4004

JO - Crystal Growth and Design

JF - Crystal Growth and Design

SN - 1528-7483

IS - 8

ER -