Dissertation
Advancements in sulfide technologies as hydrogen sulfide donors, biological materials, and radioactive tracers
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2021
DOI: 10.17077/etd.006347
Abstract
Sulfide technologies are a rapidly growing field that leverage the unique chemical properties of sulfur bonds for a variety of applications. One of the most prevalent is the developments of hydrogen sulfide (H2S) releasing technologies. This thesis focuses on three main areas for the improvement of sulfide technologies. First, water-soluble heterosubstituted disulfides, diaminodisulfide (NSSN) and dialkoxydisulfide (OSSO), were synthesized from commercially available sulfur monochloride or simple disulfur transfer reagents. Both the NSSN and OSSO functional groups were found to have rapid rates of H2S release in the presence of excess intracellular thiols. The by-products were investigated to prove decomposition pathways and real-time HRMS analysis was used to track postulated intermediates. These results add heterosubstituted disulfides as a class of H2S donors with unique, rapid release profiles. These functional groups are easy to synthesize and functionalizable, which can allow for more rigorous design of byproduct co-drug release schemes. Chemicals with the diaminodisulfide and dialkoxydisulfide functional groups may find applications in medicine where a controlled, burst release of H2S is needed. Second, these same heterosubstituted sulfides were then developed into materials for further study. Polymerizations of substituted phenylamines with a disulfide transfer reagent (S2Cl2) to yield poly[N,N-(phenylamino)disulfides] (poly-NADs) were investigated due to their unique repeat units that resulted in complete N-S conjugation along the backbone, perturbed by the aromatic rings, and gave different colors for the polymers depending on the substituent. Ten polymers were reported from this step-growth polymerization. The polymers were characterized by nuclear magnetic resonance spectroscopy, size exclusion chromatography-multiangle light scattering, and UV-Vis spectroscopy. These polymers possessed a polymeric backbone solely consisting of nitrogen and sulfur [-N(R)SS-] which was conjugated and yielded polymers of moderate molecular weight. Synthetic studies were performed to block positions on the ring and increase equivalence of the S2Cl2 to show the lack of aromatic substitution side reactions. Furthermore, crosslinking studies were done to show increased yield and Mw with phenylene diamine. Finally, synthetic methods to improve H2S tracking were considered. Advancements in accessing radioactive H2(35)S donors is shown, which would allow for more accurate tracking in complex biological systems and likely be distinguishable from endogenously produced H2(32)S. Incorporating radioactive sulfur into known organic H2S donors could help track the effects and improve the physiological understanding of this therapeutic gasotransmitter. Pathways to radioactive H2(35)S donors was investigated from commercially available 35S-enriched sodium sulfate. It was found that access to one synthetic precursor to an H2S donor could be achieved from sulfate in a 3-step synthesis followed by conversion into amino acid based trisulfides as known, thiol-mediated H2S donors.
Details
- Title: Subtitle
- Advancements in sulfide technologies as hydrogen sulfide donors, biological materials, and radioactive tracers
- Creators
- James Phillip Grace
- Contributors
- Ned B Bowden (Advisor)Allan C Guymon (Committee Member)Amanda J Haes (Committee Member)Louis Messerle (Committee Member)Gregory K Friestad (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Chemistry
- Date degree season
- Autumn 2021
- DOI
- 10.17077/etd.006347
- Publisher
- University of Iowa
- Number of pages
- xxi, 182 pages
- Copyright
- Copyright 2021 James Phillip Grace
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 161-182).
- Public Abstract (ETD)
My research expands the field of available sulfur technologies that are usefully in many biological applications. Particularly, this thesis builds on the improved delivery, detection and quantification of the therapeutic gas hydrogen sulfide (H2S). If H2S concentrations are too high, it can be highly toxic. Therefore, it is necessary to have rigorous control of H2S when being used as a therapeutic. Alternative methods to administer H2S in biological systems is a large area of study and has given rise to a variety of chemicals which can break down to release H2S over time in a controlled manner to impart the desired therapeutic effects. My preliminary aims were to develop new synthetic chemicals which could deliver this therapeutic drug at known quantities and study the release rates and degradation of these drugs to avoid toxic by-products. A new class of H2S donor compounds were developed and similar technologies were then applied to synthesize polymeric materials.
Polymeric materials have the advantage of higher stabilities and can be implemented in a variety of alternative applications such as medical device coatings, early-stage seed protection in plants, organo-electronics, and even biodegradable materials. Therefore, I demonstrated the efficacy of making colorful polymers from this same technology and reported their stabilities and chemical proclivities.
Lastly, I developed new molecular technologies that will help solve why H2S is such a potent therapeutic. I accomplished this by using radioactive sulfur-35 which can be tracked by known techniques and could be applied to biological systems.
- Academic Unit
- Chemistry
- Record Identifier
- 9984210641902771
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