Establishing the Analogy between Hydrates and Peroxosolvates: Cambridge Structural Database Analysis of Pyridyl Hydrates Yields New Peroxosolvates

Adiscovery strategy for new pyridine peroxosolvates iscritically evaluated. Using the Cambridge Structural Database, eightcommercially available hydrates were identified based on their hydrogenbonding motif featuring hydrogen bond acceptance. This led to thediscovery of peroxosolvates for six of the compounds. Competitionbetween cocrystallization and oxidative reactivity was observed asa critical factor for success. Non-covalent interactions are critical components inthe synthetictoolbox to modulate self-assembly processes and molecular recognition.Hydrogen bonding is most commonly employed because of the strong anddirectional interactions that can be designed. In recent years, studiesto improve the properties of active pharmaceutical ingredients (APIs)and energetic materials have explored incorporating hydrogen peroxideinto molecular design strategies to improve physical and chemicalproperties relative to hydrates. Herein, the structural similaritiesbetween water and hydrogen peroxide were leveraged using hydrate identificationfrom the Cambridge Structural Database (CSD) to identify hydrogenperoxide solvate (peroxosolvate) formation with pyridines. The CSDsearch yielded eight commercially available pyridine hydrates that,under various crystallization conditions, successfully produced eightnew peroxosolvates (pyridyl or derived from the corresponding N-oxides). The obtained solvates were characterized by Ramanspectroscopy, and for six peroxosolvates the structures were determinedby single-crystal X-ray diffraction. The peroxosolvate structuraldata were compared with the known hydrate structures to analyze hydrogenbonding and packing motifs. The success in obtaining new peroxosolvatesvalidates the predictive power of hydrate structures for identifyingpotential peroxosolvate formation.

Automated summary

A discovery strategy for new pyridine peroxosolvates is evaluated by using the Cambridge Structural Database. Hydrogen bonding motif featuring hydrogen bond acceptance was used to identify eight commercially available hydrates, leading to the discovery of peroxosolvates for six compounds. The competition between cocrystallization and oxidative reactivity was found to be a critical factor for success.