19 Kryptoracemates
383
related to close-packing considerations: it is well established that 83% of all structures included in the CSD [4] crystallise in one of six space-groups out of a possible
230 space-groups (or 219 when the 11 pairs of enantiomorphic space-groups are
counted once only), i.e. P2 1 /c (34.6%), P ¯
1 (24.5%), C2/c (8.4%), P2 1 2 1 2 1 (7.2%),
P2 1 (5.2%) and Pbca (3.3%), or alternative settings of these [9, 10]. The common
feature of the indicated space-groups is that they are all are conducive to closepacking arrangements, which is optimised for spherical molecules. Thus, an oddshaped molecule crystallising about a centre of inversion inherently becomes more
spherical in shape. When enantiophilic behaviour [8] no longer prevails, enantiophobic behaviour comes to the fore resulting in the formation of conglomerates or,
more rarely, kryptoracemates.
In terms of space-group symmetry, kryptoracemates are restricted in the adoption
of these. As mentioned above, kryptoracemates can only crystallise in space-groups
not having symmetry operators of the second kind. Thus, a kryptoracemate must
crystallise in one of the 65 Sohncke space-groups (non-enantiogenic groups) which
are characterised as not having a centre of inversion, rotary-inversion axes or glide
planes, i.e. only have symmetry operations of the first kind; crystals adopting Sohncke
space-groups are chiral. Further, the number of molecules in the crystallographic
asymmetric unit, i.e. Z
(equals the number of formula units in a unit cell divided by
the number of general positions for that unit cell), is greater than unity unless the
molecule itself lies on a rotation axis [11].
The purpose of this overview is not to give a comprehensive list of all known
kryptoracemates but rather to highlight the different classes of kryptoracemates
that have been described in the crystallographic literature. As a starting point, a
clarification of the term kryptoracemic compound is made, analogous to that now
adopted for supramolecular isomers [12, 13]. A supramolecular isomer (SI) is a
molecule/framework that can adopt a different structure, including with a different
atomic connectivity, as opposed to a polymorph [14]. Often, this phenomenon was
accompanied by a change in the counter-ion and/or solvent occluded in the crystal
[12]. Subsequently, the term was modified to refer to a genuine SI [13], whereby the
molecular formula was exactly the same, rather than the generic, all-encompassing
SI [12]. Following this precedent, herein, kryptoracemates are divided into “genuine kryptoracemates”, with only one type of species (molecule or zwitterion)
in the crystal, and “more loosely defined kryptoracemates”, which may include
counter-ions, solvent, etc., in their crystals.
With the above division in mind, the following survey is arranged in terms of
the number of chiral centres in the molecule and highlights different issues associated with the examples, for example, polymorphism, the availability of crystals
of diastereoisomers, etc. The images herein are original, being generated from
the Crystallographic Information Files (CIFs) [15] available through the CSD [4]
employing DIAMOND [16] and QMol [17]. The chemical diagrams were drawn
with ChemDraw
™ , and data analysis was aided by Mercury [18] and PLATON [19].
383
related to close-packing considerations: it is well established that 83% of all structures included in the CSD [4] crystallise in one of six space-groups out of a possible
230 space-groups (or 219 when the 11 pairs of enantiomorphic space-groups are
counted once only), i.e. P2 1 /c (34.6%), P ¯
1 (24.5%), C2/c (8.4%), P2 1 2 1 2 1 (7.2%),
P2 1 (5.2%) and Pbca (3.3%), or alternative settings of these [9, 10]. The common
feature of the indicated space-groups is that they are all are conducive to closepacking arrangements, which is optimised for spherical molecules. Thus, an oddshaped molecule crystallising about a centre of inversion inherently becomes more
spherical in shape. When enantiophilic behaviour [8] no longer prevails, enantiophobic behaviour comes to the fore resulting in the formation of conglomerates or,
more rarely, kryptoracemates.
In terms of space-group symmetry, kryptoracemates are restricted in the adoption
of these. As mentioned above, kryptoracemates can only crystallise in space-groups
not having symmetry operators of the second kind. Thus, a kryptoracemate must
crystallise in one of the 65 Sohncke space-groups (non-enantiogenic groups) which
are characterised as not having a centre of inversion, rotary-inversion axes or glide
planes, i.e. only have symmetry operations of the first kind; crystals adopting Sohncke
space-groups are chiral. Further, the number of molecules in the crystallographic
asymmetric unit, i.e. Z
(equals the number of formula units in a unit cell divided by
the number of general positions for that unit cell), is greater than unity unless the
molecule itself lies on a rotation axis [11].
The purpose of this overview is not to give a comprehensive list of all known
kryptoracemates but rather to highlight the different classes of kryptoracemates
that have been described in the crystallographic literature. As a starting point, a
clarification of the term kryptoracemic compound is made, analogous to that now
adopted for supramolecular isomers [12, 13]. A supramolecular isomer (SI) is a
molecule/framework that can adopt a different structure, including with a different
atomic connectivity, as opposed to a polymorph [14]. Often, this phenomenon was
accompanied by a change in the counter-ion and/or solvent occluded in the crystal
[12]. Subsequently, the term was modified to refer to a genuine SI [13], whereby the
molecular formula was exactly the same, rather than the generic, all-encompassing
SI [12]. Following this precedent, herein, kryptoracemates are divided into “genuine kryptoracemates”, with only one type of species (molecule or zwitterion)
in the crystal, and “more loosely defined kryptoracemates”, which may include
counter-ions, solvent, etc., in their crystals.
With the above division in mind, the following survey is arranged in terms of
the number of chiral centres in the molecule and highlights different issues associated with the examples, for example, polymorphism, the availability of crystals
of diastereoisomers, etc. The images herein are original, being generated from
the Crystallographic Information Files (CIFs) [15] available through the CSD [4]
employing DIAMOND [16] and QMol [17]. The chemical diagrams were drawn
with ChemDraw
™ , and data analysis was aided by Mercury [18] and PLATON [19].