Date of Degree
PhD (Doctor of Philosophy)
Leonard R. MacGillivray
The research presented in this thesis is founded upon the ability to mimic Nature by using highly directional forces to influence self-assembly, while achieving the formation of desired supramolecular structures. The successful engineering of such solids relies upon a full comprehension of supramolecular synthons, so as to apply them to design complex architectures. We have studied synthon formation in multifunctional pharmaceutical solids. Through the formation of salts and co-crystals, we uncovered a role of tautomers in the salt – co-crystal continuum. From a solid-state perspective, one can envisage that tautomers could promote co-crystal formation since an inherent flexibility to interconvert can accommodate geometries of different co-formers, as well as increase the number of synthons able to support a multicomponent solid. We have also employed co-crystallization to ibuprofen as a means to exploit solid-state properties. We have shown that co-crystallization with bipyridines can result in the formation of both co-crystal solid solutions and co-crystal conglomerates.
Supramolecular chemistry can also be utilized to construct target organic and metal-organic frameworks. Solid-state synthesis has emerged as a means to achieve the formation of molecular targets that are usually inaccessible via solution phase synthesis through the exploitation of molecular recognition and self-assembly. In particular, utilizing a combinatorial template strategy can facilitate a [2+2] photodimerization in the solid state. Although the template-directed strategy has helped circumvent problems associated with crystal packing, the solid state is still not routinely used for synthesis, owing, in part, to a lack of expansion to multifunctional olefins and molecular targets.
We have introduced a method to direct the reactivity of multifunctional olefins that contain two robust hydrogen bonding elements to produce heteropolytopic molecules that are of interest for the formation of metal-organic frameworks. Specifically, we developed a protecting group strategy that affords a supramolecular regiochemistry to attain the desired self-assembly. We have also extended our template approach to more conformationally-complex molecules to gain a further understanding of the rules regarding reactivity in highly substituted systems.
The end of this thesis is focused upon the solid-state synthesis of a series of molecular targets known as cyclophanes. Cyclophanes have a very rich history however, their immersion in all aspects of chemistry has suffered from a lack of high yielding synthetic techniques, as well as novel methodologies that target substitution on the aliphatic bridges. We have shown that a series of laterally-substituted [2.2]cyclophanes can be synthesized in quantitative yields utilizing template-directed self-assembly. The cyclophanes also exhibit optical properties that are influenced by a nonconventional internal charge transfer process, stemming from the strained cyclobutane core. We have also developed a sonochemical method to produce nanocrystals of cyclophanes, resulting in enhanced and red-shifted emissions.
Overall, the results described herein detail the use of supramolecular chemistry to achieve the formation of target architectures that differ in topology, connectivity, and/or physiochemical properties. The entirety of this thesis represents the undeveloped interplay between traditional synthetic organic chemistry and supramolecular solid-state chemistry. While the precision afforded by the crystalline phase provides access to molecular targets with high fidelity, expansion to multifunctional molecules that are desirable in the context of emergent properties bodes well for the continued development and exploitation of molecular recognition to generate novel functional materials.
Copyright 2012 Elizabeth Elacqua
Elacqua, Elizabeth. "Supramolecular chemistry of molecular concepts: tautomers, chirality, protecting groups, trisubstituted olefins, cyclophanes, and their impact on the organic solid state." dissertation, University of Iowa, 2012.