DOI

10.17077/etd.2pc1-tags

Document Type

Dissertation

Date of Degree

Summer 2019

Access Restrictions

Access restricted until 09/04/2021

Degree Name

PhD (Doctor of Philosophy)

Degree In

Chemistry

First Advisor

MacGillivray, Leonard R.

First Committee Member

Tivanski, Alexei V.

Second Committee Member

Arnold, Mark A.

Third Committee Member

Gloer, James B.

Fourth Committee Member

Quinn, Daniel M.

Abstract

Supramolecular chemistry and crystal engineering seek to control molecular packing in the solid state to influence the physical and chemical properties of crystalline solid materials. A goal of supramolecular chemistry that seeks to control molecular packing in the solid state focuses on exploiting non-covalent interactions to assemble molecules into desirable arrangements. Strategies implemented to control molecular packing rely on strong, directional interactions such as hydrogen bonding, halogen bonding, and metal coordination to direct localized arrangement of molecules in solids. In this context, small molecules can be used as linear templates in co-crystals to assemble reactive alkenes into specific geometries allowing reactivity in the solid state. A linear template method has been used to achieve [2+2] photocycloadditions of discrete assemblies containing alkenes to afford cyclobutanes in high stereospecificity and in quantitative yield.

Herein, we describe the use of a nonlinear template, in the form of 1,4-butynediol (1,4-bd), to pre-organize alkenes in the solid state. The nonlinear template of 1,4-bd hydrogen-bonds to the alkene 1,2-bis(N-pyridyl)ethene (where N = 3 or 4) to form 1D hydrogen-bonded polymers. The hydrogen-bonded polymer chains form infinite stacks which are sustained by C-H···O interactions occurring between polymer chains. The stacked alkenes undergo a UV-induced [2+2] photocycloaddition to produce rctt-tetrakis(N-pyridyl)cyclobutane photoproducts (where N = 3 and 4) in non-quantitative yields. The yield of the photoreaction is increased to nearly quantitative by applying a supramolecular catalysis approach with the 1,4-bd template.

Functional groups on reactant molecules can compete via non-covalent interactions with templates employed for the self-assembly process. One method to inhibit competition between functional groups involves chemically modifying a functional group employing a supramolecular protecting group. Here, we describe an acetyl supramolecular protecting group approach employed to mask alkenes containing phenolic and pyridyl functional groups. The acetyl protecting group prevents the phenolic substituents of the targeted alkene from participating in non-covalent interactions employed for the template-mediated self-assembly process. Thus, a cyclobutane molecule was obtained using the novel acetyl supramolecular protecting group strategy applied to a solid-state [2+2] photodimerization that affords a head-to-head cyclobutane. After deprotection, the resulting cyclobutane possessed tetrahedrally-disposed cis-hydrogen-bond-donor and cis-hydrogen-bond-acceptor groups. Thus, a purely organic three-dimensional hydrogen-bonded network based on a rare Michael O'Keeffe (mok) topology was constructed using an organic molecule synthesized in the organic solid state. The phenolic substituents of the cyclobutane adopt different orientations (syn-, anti-, and gauche-) to conform to the structural requirements of the mok net.

A challenge surrounding template-directed solid-state reactivity requires alkenes to be lined with functional groups that coordinate (or bind through other non-covalent interactions) to the template. Herein, we describe a dual approach of supramolecular assistance to covalent bond formation that utilizes a combination of imine and metal-organic chemistry to generate cyclobutanes lined with aldehyde groups. Specifically, dynamic imine chemistry was implemented to install a temporary recognition site on an aldehyde-containing alkene of cinnamaldehyde for a template-directed [2+2] photocycloaddition in the solid state. The resulting modified alkene aligns using Ag(I) ions into desirable arrangements for the covalent-bond-forming [2+2] photocycloaddition. The result is a 1D coordination polymer undergoes a UV-induced, regio-controlled [2+2] photocycloaddition in the solid state. The photoreaction proceeds stereospecifically with quantitative yield of the corresponding aldehyde-functionalized photodimer, α-truxilaldehyde. Additionally, we investigate the influence of the Ag(I) counterions on the assembly of imine containing alkenes to generate reactive assemblies for the purpose of producing aldehyde-containing cyclobutanes.

This dissertation also encompasses research pertaining to pharmaceutical solids and mechanical properties of organic molecular crystals. Specifically, we describe the discovery of two polymorphic co-crystals containing acetylsalicylic acid (aspirin) combined with 4,4’-bipyridine. The initial discovery of the form I polymorph was aided by mechanical dry-grinding, while an additional form II polymorph was revealed by rapid cooling in ethanol. The polymorphs differ by relative twists of carboxylic acid groups of the aspirin molecules and of the pyridyl rings of 4,4’-bipyridine. Additionally, the form I polymorph contains aspirin molecules that are linked via discrete catemeric methyl C-H···O interactions, while the form II polymorph is linked via both infinite methyl C-H···O catemers and centrosymmetric dimers. These results demonstrate the importance of dry mechanical grinding for the discovery of pharmaceutical co-crystals and polymorphs.

Keywords

aspirin, mechanical properties, pharmaceutical cocrystal, photodimerization, polymorphism, supramolecular

Pages

xxv, 234 pages

Bibliography

Includes bibliographical references (pages 164-185).

Comments

This thesis has been optimized for improved web viewing. If you require the original version, contact the University Archives at the University of Iowa: https://www.lib.uiowa.edu/sc/contact/.

Copyright

Copyright © 2019 Shalisa M. Oburn

Available for download on Saturday, September 04, 2021

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Chemistry Commons

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