(374g) Understanding the Molecular Origin of Polymorphic Transition Mechanisms in Molecular Crystals

Crystallization and Evaporation

Solid Form Selection: Cocrystals, Salts, Solvates, Polymorphs, and Beyond (02B08)

Understanding the Molecular Origin of Polymorphic Transition Mechanisms in Molecular Crystals

Hyunjoong Chung; Ying Diao

In the pharmaceuticals field, controlling and accessing different polymorphs of drugs is important for drug efficacy and bioavailability¹. In addition, during the drug development process, the exact polymorph used for production and how its transition might affect the performance or stability must be known. Therefore it is imperative to understand the specific route of polymorphic transitions, such as the energy barriers and the mechanism of transition. This understanding can further provide insight on molecule design and help establish processes that stabilize a particular polymorph. In our study, we focus on a system of molecules with an identical conjugated core, but various side chains to investigate the impact of molecular structure on polymorphic transition. By direct observation and various molecular characterization methods, we discover that subtle changes in the side chains can lead to drastically different phase transition behaviors from cooperative transition^2,3 to nucleation and growth. We believe this type of systematic study can pinpoint the exact molecular design criteria for polymorphic transitions, and be extended to the initial stages of molecular design in the pharmaceutical field. In this way, we can successfully drive or eliminate preferred polymorphic transitions in pharmaceutical compounds.

References

1. Chung, H.; Diao, Y., Polymorphism as an emerging design strategy for high performance organic electronics. Journal of Materials Chemistry C 2016, 4 (18), 3915-3933.
2. Chung, H.; Ruzié, C.; Geerts, Y.; Diao, Y. “Investigation of the three-step mechanism and the role of defects in cooperative single-crystal-to-single-crystal transition of a molecular crystal”. Submitted to Crystal Growth & Design, 2018.

3. Chung, H.; Dudenko, D.; Zhang, F. J.; D'Avino, G.; Ruzie, C.; Richard, A.; Schweicher, G.; Cornil, J.; Beljonne, D.; Geerts, Y.; Diao, Y., Rotator side chains trigger cooperative transition for shape and function memory effect in organic semiconductors. Nature Communications 2018, 9.