Date of Award

2017

Degree Type

Thesis

Degree Name

Master of Science (MS)

Author's Department

Chemistry

First Advisor

Kraig A. Wheeler

Abstract

The manner in which molecules recognize each other holds critical importance to nearly every area of science. This significance stems from the key underpinning of molecular assembly to our most basic understanding of chemical processes. Whether these interactions relate to small-molecule catalytic transformations or complex physiological processes, the structural features responsible for molecular association play into the well-known adage that form follows function where material property arises from the collective structural features of the molecular components. Because the form of chemical systems is derived from a complex blend of covalent and non-bonded contacts, codifying each contributor has become essential for recognizing the functions and potential applications of materials. While considerable progress in this area has been realized by isolating and identifying molecular contacts and the structural details of their conditional exceptions, insight to the entire landscape of molecular associations remains an ongoing effort. This thesis explores the molecular recognition process from two uniquely different perspectives. The first is from cocrystalizing a variety of benzoic acids with the pharmaceutical agent sulfamethazine and the second area investigates how molecular shape controls quasiracemate formation.

Sulfamethazine is an active pharmaceutical ingredient (API) with a strong ability to form hydrogen bonds due to its donor and acceptor groups. The chemical structure of this API allows it to exist in more than one tautomer. The cocrystallization of this molecule with a coformer has the ability to influence which tautomer is present in the crystal structure. This thesis provides data that defines the relationship of coformer acidity to tautomer formation in sulfamethazine. A total of eighteen cocrystals of sulfamethazine with benzoic acid derivatives were synthesized and the tautomeric form to coformer acidity was analyzed.

The cocrystallization of APis is a classic example of molecular recognition between two or more compounds. Studies that seek to design these materials and others often focus on strong non-bonded contacts (e.g. hydrogen bonds) as a means to generate desired supramolecular architectures. Less well studied, but no less important to the overall molecular recognition process, are chemical features that produce less manageable motifs via ill-defined or weak contacts. Molecular shape is one such feature. This thesis exploits quasiracemates — i.e., near racemic materials — to probe the role molecular topology plays in the recognition process. A diverse set of diarylamide quasienantiomers that differ incrementally in substituent size and molecular framework has been prepared. Mixing of pairs of these quasienantiomers in the melt using video-assisted host stage microscopy provided a robust diagnostic tool for detecting new quasiracemic crystalline phases. Data retrieved using this virtual melting-point phase method not only draws considerable attention to the role of topological features to supramolecular assemblies, but also the structural boundaries of these co-crystalline systems. This investigation synthetically explores the broad structure space towards the identification of new isostructural building blocks and highlights important molecular relationships responsible for molecular recognition that may serve in the design of new functional materials.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Sunday, June 09, 2019

Included in

Chemistry Commons

Share

COinS