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

Abstract

Non-covalent interactions are critical components in the synthetic toolbox to modulate self-assembly processes and molecular recognition. Hydrogen bonding is most commonly employed because of the strong and directional interactions that can be designed. In recent years, studies to improve the properties of active pharmaceutical ingredients (APIs) and energetic materials have explored incorporating hydrogen peroxide into molecular design strategies to improve physical and chemical properties relative to hydrates. Herein, the structural similarities between water and hydrogen peroxide were leveraged using hydrate identification from the Cambridge Structural Database (CSD) to identify hydrogen peroxide solvate (peroxosolvate) formation with pyridines. The CSD search yielded eight commercially available pyridine hydrates that, under various crystallization conditions, successfully produced eight new peroxosolvates (pyridyl or derived from the corresponding N-oxides). The obtained solvates were characterized by Raman spectroscopy, and for six peroxosolvates the structures were determined by single-crystal X-ray diffraction. The peroxosolvate structural data were compared with the known hydrate structures to analyze hydrogen bonding and packing motifs. The success in obtaining new peroxosolvates validates the predictive power of hydrate structures for identifying potential peroxosolvate formation.

Probing Short-Range Interactions in Isostructural Hydrate and Perhydrate of Dabrafenib by Magic-Angle Spinning Solid-State NMR

“…The XRD data of DBF⊃H 2 O 2 show a residual peak of electron density (∼0.4 e Å –3 ) at the center of the O–O bond after anisotropic refinement of oxygen atoms . This is not a reliable method to quantify the water content, but the additional electron density suggests the feasibility of residual crystallized water in DBF⊃H 2 O 2 at H 2 O 2 crystal sites. , Additionally, the DSC-TGA data of DBF⊃H 2 O show that water loss (∼3.35%) occurs at ∼150–160 °C with a solid–solid phase transition at ∼140 °C (Figure S2a in SI). However, the same data for DBF⊃H 2 O 2 (mixed hydrate/perhydrate) show a broad endotherm between ∼140 and 170 °C in DSC, and TGA shows continuous weight loss from ∼130 to 225 °C (Figure S2b in SI).…”

“…However, achieving pure peroxosolvate is challenging due to the unavailability and hazards of absolute H 2 O 2, which is sold as a 35% solution in water. Previous studies indicate that maximizing hydrogen bonding (up to 6 bonds) with H 2 O 2 molecules can lead to stable peroxosolvates even from dilute solutions. , However, isostructural cocrystallization with water molecules complicates structural characterization, often resulting in solid solutions with low water occupancy (<15%) . The utilization of encapsulated H 2 O 2 in biocompatible polymers in photodynamic therapy for hypoxia tumors − encouraged us to cocrystallize H 2 O 2 with an anticancer drug and evaluate their stability through proper solid-form characterization.…”

Polymorphism and Peroxomorphism in Peroxosolvates of Zwitterionic Sulfonic Acids: Features of H-Bonding and Crystal Packing

“…5.43, September 2022), in the last decade the number of structurally characterized metal-free (true) peroxosolvates exceeded this value for the whole previous century (67 vs 43). That was due to growing concernment in prospective multicomponent materials, where hydrogen peroxide can sufficiently change physicochemical properties of parent coformers , or cooperatively increase their beneficial action. − The efforts were mainly focused on (1) peroxosolvates acting as stable and efficient oxidizing agents for organic synthesis; − (2) peroxosolvates of energetic materials with improved detonation properties (velocity and pressure) and oxygen balance; − and (3) peroxosolvates of active pharmaceutical ingredients with enhanced biological activity. − As a result, a large number of hydrogen peroxide adducts with organic coformers bearing functional groups were synthesized and their crystal structures (usually built by hydrogen bonds of H 2 O 2 with these specific fragments) were determined: −NO 2 – , − −CO 2 – , − N + → O – , ,− PO, ,− −NH 2 , ,,, −NH 3 + , − , −OH, , Alk 2 O, −CO 2 H, −C(O)–N<, ,, >N–N<, , −SO 2 – , pyridyl, , pyridylH + , , furyl, H 2 O 2 , ,,,, Hal – , , etc. Surprisingly, peroxosolvates containing sulfonate groups −SO 3 – were not reported to date despite the extreme significance of sulfonates in indus...…”