Expansions of supramolecular chemistry: nanocrystals, pharmaceutical cocrystals, imaging, and decorated olefins

Crystal engineering has matured into a design-driven field based on the exploitation of reliable interactions between the functional groups of molecules so as to achieve desired properties. The utility of crystal engineering has been realized in a breadth of fields and, as a microcosm of crystal engineering, this thesis will explore the application of crystal engineering in the pharmaceutical sciences, nanotechnology, synthetic chemistry, materials science, and biomedical imaging.

As the trend in drug development continues to skew towards molecules with poor aqueous solubility the ability improve the physicochemical properties of a pharmaceutical agent, especially via non-covalent means, has become crucial. One method to impart improved physiochemical properties to pharmaceutical agents is through cocrystallization. A portion of this thesis will focus on the design-driven development of pharmaceutical cocrystals so as to impart improved mechanical properties to acetaminophen. As part of our investigation, we observed unexpected intermolecular interactions between the constituents of our cocrystals, which will contribute to the continued development of crystal engineering. In addition, we are interested in developing a methodology for the reliable fabrication of organic nanocrystals based on multi-component solids. Whereas the field of inorganic nanocrystals has blossomed, organic nanocrystals have remained largely underdeveloped. To expand the field of organic nanocrystals we turned to the synthesis of pharmaceutical nano-cocrystals. Specifically, we determined a sonochemical approach combined with multiple solvents and a surfactant could effectively synthesize pharmaceutical nano-cocrystals. As part of our desire to synthesize complex, multi-component, organic nanocrystals we also investigated the ability of a sonochemical approach to synthesize host-guest nanocrystals. In particular, the results demonstrated that sonochemistry successfully fabricates nano- and micrometer sized crystals of a host-guest solid and affords rhombic-dodecahedral crystals of a hollow topology.

This thesis will also examine [2+2] photodimerizations in the solid-state. Previous work has successfully established the application of a template-directed solid-state approach to the photodimerization of olefins in the solid-state. However, these studies have largely focused on the reactivity of symmetric bipyridines. Thus, we have expanded the functional group diversity associated with [2+2] photodimerizations to include the cyano moiety. We have shown the template approach successfully aligns our targeted cyano-substituted olefins to enable photodimerizations in the solid-state.

In addition, we have investigated the ability to synthesize cocrystals based on iodinated contrast agents. We believe the cocrystal approach could afford contrast agents with tailored properties based on the selected cocrystal former. The results of our investigation include five cocrystals and five salts composed of iodinated contrast agents. The results help to establish a knowledge base to be exploited in the design of future contrast agent based cocrystals with tailored properties.