Kryptoracemic compound hunting and frequency in the Cambridge Structural Database

Abstract

<p>Determination of kryptoracemic compound frequency in the Cambridge Structural Database using CCDC Python API script.</p>

Symmetry and chirality in crystals

“…racemic structures crystallizing in a Sohncke-type space group (Bernal, 1995). To explain their existence, the condition Z 0 > 1 was introduced when surveys of the CSD were run to identify the occurrence of kryptoracemates (Fa ´bia ´n & Brock, 2010; Bernal & Watkins, 2015;Clevers & Coquerel, 2020). It was assumed that the two enantiomers must occur in the asymmetric unit and be approximately related by an isometry of the second kind, often an inversion.…”

“…It was assumed that the two enantiomers must occur in the asymmetric unit and be approximately related by an isometry of the second kind, often an inversion. This mapping being only approximate, the corresponding operation is only a pseudo-symmetry operation, sometimes incorrectly called 'non-crystallographic' (Clevers & Coquerel, 2020) instead of partial or pseudo or pseudo-partial (Nespolo et al, 2008). This operation does not appear in the space group, allowing for a racemic compound in a Sohncke-type space group.…”

“…The disordered arrangement of enantiomers in a type I solid solution prevents any restriction on the type of space group (Clevers & Coquerel, 2020). However, because of the statistical distribution of enantiomers the crystal structure cannot be chiral.…”

Howard Flack and the Flack Parameter

“…Materials exhibiting this phenomenon have subsequently been termed kryptoracemates, as their racemic nature is hidden by the space group symmetry. A recent survey identified 724 examples in the crystallographic literature [14].…”

Broken symmetry between RNA enantiomers in a crystal lattice

“…A survey of ‘small molecule’ structures in the Cambridge Structural Database ( 13 ) reveals that racemic compounds generally cocrystallize in centrosymmetric space groups (over 90% of cases) or as separate l - and d -crystals (ca 6%). In approximately 1% of cases they crystallize as ‘kryptoracemates’ in chiral space groups, in which the enantiomers are not constrained by crystallographic symmetry ( 14 ). The conformations of the enantiomers in kryptoracemates are usually very similar, although differences have been noted.…”