Conglomerate Crystallization in the Cambridge Structural Database (2020-2021).

Conglomerate crystals are materials capable of undergoing spontaneous resolution and were responsible for the discovery of molecular chirality. Their relevance to modern chemical and crystallographic sciences has been hindered by the difficulty in identifying and searching materials with this characteristic ability to spontaneously bias their own enantioenrichment. With the release of the November 2021 distribution of the Cambridge Structural Database (CSD) (version 5.43), a fresh quantity of chiral conglomerate crystals is expected to have been published in the CSD without identification. Indeed, no crystals in the CSD have been identified as a spontaneously resolving conglomerate crystal in their crystallographic information file since the 2019 release, despite the deposition of over 108,000 new crystal structures into the database over the same time period. A manual inspection of crystals deposited between 2020 and 2021 was conducted to identify 343 new chiral materials which exhibit conglomerate crystallization behavior. It is hoped that the continued manual curation of this list will aid those in the crystallographic and synthetic communities to study and exploit this spontaneous enantioenrichment behavior.

Identifying a Hidden Conglomerate Chiral Pool in the CSD.

Conglomerate crystallization is the spontaneous generation of individually enantioenriched crystals from a nonenantioenriched material. This behavior is responsible for spontaneous resolution and the discovery of molecular chirality by Pasteur. The phenomenon of conglomerate crystallization of chiral organic molecules has been left largely undocumented, with no actively curated list available in the literature. While other crystallographic behaviors can be interrogated by automated searching, conglomerate crystallizations are not identified within the Cambridge Structural Database (CSD) and are therefore not accessible by conventional automated searching. By conducting a manual search of the CSD and literature, a list of over 1800 chiral species capable of conglomerate crystallization was curated by inspection of the racemic synthetic routes described in each publication. The majority of chiral conglomerate crystals are produced and published by synthetic chemists who seldom note and rarely exploit the implications this phenomenon can have on the enantiopurity of their crystalline materials. With their structures revealed, we propose that this list of compounds represents a new chiral pool which is not tied to biological sources of chirality.