Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Pollum_M-Thesis-FINAL.pdf (11 MB)

ETD Abstract Container

Abstract Header

Applying Fundamental Photochemistry to Drive Drug Development: The Photo-Dynamics and Reactions of Sulfur-Substituted Nucleic Acids

Pollum, Marvin
http://orcid.org/0000-0002-9826-3225
http://rave.ohiolink.edu/etdc/view?acc_num=case1481287737895585

Abstract Details

2017, Doctor of Philosophy, Case Western Reserve University, Chemistry.
Sulfur-substituted purine and pyrimidine nucleobases—also known as thiobases—are among the world’s leading prescriptions for chemotherapy and immunosuppression. Long-term treatment with some of the purine derivatives of these drugs has recently been correlated with the photo-induced formation of carcinomas. Establishing an in-depth understanding of the photochemical properties of these thiobase drugs may provide a route to overcoming these carcinogenic side effects, or, alternatively, may provide a basis for developing highly-effective compounds for targeted photochemotherapy. In this thesis work, a broad investigation is undertaken, surveying the excited-state dynamics and photochemical reactions of nearly every sulfur-substituted analog of the canonical DNA and RNA nucleobases. The thiobase derivatives are investigated using time-resolved absorption and emission spectroscopies in the femtosecond (10-15 s) to microsecond (10-6 s) time window. Coupling these experiments with quantum chemical calculations, we have developed a molecular-level understanding of how sulfur-substitution so drastically perturbs the photochemical properties of the nucleobases. The structure-property relationships established by this work demonstrate the impact of site-specific sulfur substitution on the population and reaction dynamics of the excited triplet state. Some of the most photoreactive derivatives identified are applied to human epidermoid carcinoma cells and shown to effectively decrease their proliferation upon exposure to a low dose of light. The results presented in this body of work demonstrate the utility of fundamental photochemical investigations for driving the development of next-generation photochemotherapeutics, while simultaneously elucidating overarching principles for the impact of sulfur substitution (thionation) on the photochemical properties of organic chromophores.
Carlos Crespo-Hernández (Advisor)
Mary Barkley (Committee Chair)
Clemens Burda (Committee Member)
Geneviève Sauvé (Committee Member)
Nancy Oleinick (Committee Member)
392 p.
Analytical Chemistry; Biochemistry; Chemistry; Experiments; Molecules; Pharmaceuticals; Physical Chemistry; Quantum Physics
sulfur-substituted nucleobases; thiobases; photosensitizer; excited-state dynamics; femtosecond; intersystem crossing; triplet state; triplet yield; reactive oxygen species; singlet oxygen; photocrosslinking; photochemotherapy; photodynamic therapy

Recommended Citations

Citations

  • Pollum, M. (2017). Applying Fundamental Photochemistry to Drive Drug Development: The Photo-Dynamics and Reactions of Sulfur-Substituted Nucleic Acids [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1481287737895585

    APA Style (7th edition)

  • Pollum, Marvin. Applying Fundamental Photochemistry to Drive Drug Development: The Photo-Dynamics and Reactions of Sulfur-Substituted Nucleic Acids . 2017. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1481287737895585.

    MLA Style (8th edition)

  • Pollum, Marvin. "Applying Fundamental Photochemistry to Drive Drug Development: The Photo-Dynamics and Reactions of Sulfur-Substituted Nucleic Acids ." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1481287737895585

    Chicago Manual of Style (17th edition)

case1481287737895585
906
© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.