Searching for stereoisomerism in crystallographic databases: algorithm, analysis and chiral curiosities

Abstract

The automated identification of chiral centres in molecular residues is a non-trivial task. Current tools that allow the user to analyze crystallographic data entries do not identify chiral centres in some of the more complex ring structures, or lack the possibility to determine and compare the chirality of multiple structures. This article presents an approach to identify asymmetric C atoms, which is based on the atomic walk count algorithm presented by Rücker & Rücker [(1993), J. Chem. Inf. Comput. Sci. 33, 683-695]. The algorithm, which we implemented in a computer program named ChiChi, is able to compare isomeric residues based on the chiral centres that were identified. This allows for discrimination between enantiomers, diastereomers and constitutional isomers that are present in crystallographic databases. ChiChi was used to process 254 354 organic entries from the Cambridge Structural Database (CSD). A thorough analysis of stereoisomerism in the CSD is presented accompanied by a collection of chiral curiosities that illustrate the strength and versatility of this approach.

Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients

“…Surprisingly, R,S-carnitinenitrile chloride crystallized with two S-carnitinenitrile and one R-carnitinenitrile cations in the asymmetric unit of the chiral space group P2 1 . Such a rare system has been described in the literature either as a pseudo unbalanced crystallization, co-crystals of a racemate or unbalanced chiral packing (Fá biá n & Brock, 2010; Albrecht et al, 2010;Wachter et al, 2016;Kotelnikova et al, 2017;Grothe et al, 2017). The remaining observed negative crystallization results were either mixtures of NaCl (Fig.…”

Chirality and stereoisomerism of organic multicomponent crystals in the CSD

“…We exported the entries to files with pdb and mol2 format and for repeated refcodes discarded all but the highest sequential number, and passed these files to our in-house program ChiChi. 26 The majority of the discarded refcodes are redeterminations, however, some polymorphs will inevitably also be discarded with this selection. 27 The multicomponent classification is based on the types of residue in an entry: ion, solvent molecule, or coformer, and follows the rules outlined in Table 1.…”

“…Its methods have been described in detail previously. 26 The algorithm is limited to carbon stereocenters; other types of chirality (e.g. P or S stereocenters and axial chirality) are not considered.…”

Crystallization of chiral molecular compounds: what can be learned from the Cambridge Structural Database?

“…Meso-compounds are molecules that contain chiral centres but are achiral due to symmetry. Such structures should preferably be excluded from the dataset; however, it seems to be a complicated task (Grothe et al, 2017). This is another weakness of the Python API that there is no convenient way to identify such structures.…”