ROY Reclaims Its Crown: New Ways To Increase Polymorphic Diversity

Abstract

Chemical compounds that exist in multiple crystalline forms are said to exhibit polymorphism. Polymorphs have the same composition, but their structures and properties can vary markedly. In many fields, conditions for crystallizing compounds of interest are screened exhaustively to generate as many polymorphs as possible, from which the most advantageous form can be selected. We report new ways to search for polymorphs and increase polymorphic diversity, based on crystallization induced by suitably designed mixed-crystal seeds. The potential of the strategy has been demonstrated by using it to produce new polymorphs of the benchmark compound ROY as single crystals structurally characterized by X-ray diffraction. This allows ROY to reclaim its crown as the most polymorphic compound in the Cambridge Structural Database. More generally, the methods promise to become valuable tools for polymorphic screening in all fields where crystalline solids are used.

Thermally Activated Delayed Fluorescence: Beyond the Single Molecule

“…This framework will facilitate the development and understanding of functional materials that are sensitive to mechanical and thermal energy while opening up pathways to AIE-based, non-doped OLEDs (Furue et al, 2016;Liu et al, 2018a;Cai et al, 2020;Yang et al, 2020). It will also help unify the study of intramolecular TADF emitters with the studies of polymorphism (Chung and Diao, 2016;Bernstein, 2020;Levesque et al, 2020) exciplexes (Kim et al, 2016;Sarma and Wong, 2018;Tang et al, 2020) and hostguest interactions (Matsunaga and Yang, 2015;Feng et al, 2017;Ono et al, 2018).…”

“…This blue shift was attributed to polymorphism of the compound and shows that very small changes in structure between a set of similar compounds can have significant effects on their aggregation properties. As polymorphism is a common explanation for many of these observed properties in the solid-state, knowledge of polymorphism and crystallography is crucial to understanding the fundamental origins of this functional behavior (Chung and Diao, 2016;Bernstein, 2020;Levesque et al, 2020). The importance of knowing the crystal structures of the compounds for understanding the packing and intermolecular interactions is demonstrated in the work by Klimash et al (2018) In this work they uncovered differences in the molecular crystal structures and how these relate to differences in the TADF efficiency.…”

Minimizing Polymorphic Risk Through Cooperative Computational and Experimental Exploration

“…6 Indeed, there are many compounds for which an extraordinary number of forms have been discovered. For instance, the tenth form of galunisertib 7 , the twelfth form of aripiprazole 8 and sixteenth polymorph of ROY 9,10 have all been reported. Such a high degree of polymorphism is uncommon, however, and some compounds are monomorphic, i.e.…”

Crystal forms in pharmaceutical applications: olanzapine, a gift to crystal chemistry that keeps on giving

“…1(a). OZPN is not just known to crystal chemists and crystallographers for having given us the spectacularly polymorphic molecule, ROY, a synthetic precursor characterized by its red, orange and yellow coloured crystals (Yu, 2002(Yu, , 2010Yu et al, 2005;Gushurst et al, 2019;Lé vesque et al, 2020;Tyler et al, 2020;Nyman et al, 2019;Li et al, 2020). The drug compound, having been crystallized in 60+ forms (not including salts and co-crystals) over the course of more than two decades, is famous in its own right.…”