Expanding the Arsenal : Developing Novel PhotoCORMs and Delivery Systems Tailored for Biological Applications
- Degree Grantor:
- University of California, Santa Barbara. Chemistry and Biochemistry
- Degree Supervisor:
- Peter C. Ford
- Place of Publication:
- [Santa Barbara, Calif.]
- Publisher:
- University of California, Santa Barbara
- Creation Date:
- 2014
- Issued Date:
- 2014
- Topics:
- Chemistry, Inorganic
- Keywords:
- Carbon Monoxide,
PhotoCORM, and
Photochemistry - Genres:
- Online resources and Dissertations, Academic
- Dissertation:
- Ph.D.--University of California, Santa Barbara, 2014
- Description:
Carbon monoxide (CO) is an endogenously produced bioactive small molecule whose biological role has not yet been completely elucidated. It has, however, been implicated in having anti-inflammatory, anti-proliferative, and wound healing properties, as well as a dose-dependent cytotoxicity. To exploit these properties, a reliable method to deliver CO must be developed. A key requirement of any pharmaceutical agent is that it must be able to deliver its drug to a specific target in a controllable fashion, and a CO releasing moiety (CORM) is no different. Photochemical activation is uniquely suited for this application because it provides excellent control over the timing, dosage, and location of CO release.
To be used as a pharmaceutical agent, a photochemical CO releasing moiety (photoCORM) must exhibit certain desirable properties, all of which revolve around their biological compatibility. They must be stable to air and water in the dark, soluble in aqueous media, and photochemically active with red or near-infrared (NIR) light where light penetration is maximized in biological systems. Ideally, they would also exhibit some targeting properties, enhancing their role as pharmaceutical agents. Metal carbonyls are ideal photoCORMs because their photochemistry is well understood and can be controlled easily. However, photochemical CO release from these complexes is notoriously wavelength dependent and typically requires UV or near-UV activation, wavelengths that have minimal biological transmission.
This work presents several novel approaches using group VII metal carbonyls as photoCORMs that are each uniquely well-suited for use in biological applications. One multi-functional complex incorporates luminescent properties so that it can both serve as a photochemical CO releaser and as an imaging agent to help elucidate the fate and transport of photoCORMs in biological systems. Another system incorporates a NIR harvester, enabling photochemical activation at biologically suitable wavelengths while also providing an in vivo imaging agent. This work also introduces a novel photoCORM delivery framework capable of indirect activation using long-wavelength red light and can hijack existing immune system responses to effectively deliver the photoCORM to biological targets.
- Physical Description:
- 1 online resource (216 pages)
- Format:
- Text
- Collection(s):
- UCSB electronic theses and dissertations
- Other Versions:
- http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3682958
- ARK:
- ark:/48907/f33x84tg
- ISBN:
- 9781321568417
- Catalog System Number:
- 990045118770203776
- Copyright:
- Agustin Pierri, 2014
- Rights:
- In Copyright
- Copyright Holder:
- Agustin Pierri
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