From Binary to Higher-Order Organic Cocrystals: Design Principles and Performance Optimization

Angew Chem Int Ed Engl. 2025 Jul 7;64(28):e202507102. doi: 10.1002/anie.202507102. Epub 2025 Jun 16.

Abstract

Organic cocrystals, particularly the evolution from binary to higher-order structures, have garnered considerable attention due to their tunable intermolecular interactions and unique material properties. Binary cocrystals, formed through π-π stacking, charge transfer, and hydrogen/halogen bonding, allow for precise control over molecular packing and enhanced optoelectronic properties. In contrast, higher-order cocrystals, incorporating three or more components, enable greater complexity and functional diversity. Strategies such as homologation via isostructural substitution, hierarchical intermolecular interactions, and long-range Synthon Aufbau Modules facilitate the synthesis of these advanced materials. The shift toward higher-order cocrystals paves the way for novel applications in fields such as deep learning for cocrystal prediction, drug design, organic solar cells, and NIR-II photothermal conversion. However, challenges related to molecular screening, ratio optimization, scalable synthesis, and long-term stability remain critical hurdles for the broader implementation of these materials in practical applications.

Keywords: Deep learning; Intermolecular interactions; Isostructural substitution; Molecular packing; Organic cocrystals.

Publication types

  • Review