Date Available
6-8-2018
Year of Publication
2016
Degree Name
Doctor of Philosophy (PhD)
Document Type
Doctoral Dissertation
College
Arts and Sciences
Department/School/Program
Chemistry
First Advisor
Dr. Edith C. Glazer
Abstract
Current chemotherapeutics exhibit debilitating side effects as a result of their toxicity to healthy tissues. Reducing these side effects by developing chemotherapeutics with selectivity for cancer cells is an active area of research. Phototherapy is one promising modality for selective treatment, where drug molecules are “turned on” when irradiated with light, reducing damage to healthy tissues by spatially restricting the areas exposed to irradiation. A second approach to improve selectivity is to exploit the differences in cancerous versus healthy cells, such as increased metabolism and/or upregulation of cell surface receptors. Ruthenium(II) polypyridyl complexes are candidates for phototherapy due to their highly tunable photophysical and photochemical properties. The addition of strain to the metal center is a general approach used to render complexes susceptible to light-induced ligand loss. Upon ejection of a ligand, the Ru(II) center is capable of covalently binding biomolecules within cells to produce a cytotoxic effect. The ligands surrounding the metal center are amenable to chemical modification through the incorporation of pendent functional groups as chemical “handles”, allowing for different directing molecules to be attached.
Nucleic acids are important targets for drug discovery, and the development of selective probes to either visualize or selectively damage nucleic acids within the cell is an ongoing area of research. Specifically, G-rich regions are abundant in the human genome, and the presence of G-quadruplexes in telomeres and promoter regions of oncogenes make them potential therapeutic targets. Ru(II) complexes are known to bind nucleic acids, and some have been shown to induce and/or stabilize G-quadruplex Structures. Multiple series of Ru(II) compounds have been synthesized and tested to improve the functional range for Ru(II) complexes for in vivo applications, where they act as “light switches” for DNA. These molecules are “off” when in an aqueous environment but turned “on” in the presence of DNA. Several hit compounds were identified that showed selectivity for specific G-quadruplex structures.
Digital Object Identifier (DOI)
http://dx.doi.org/10.13023/ETD.2016.229
Recommended Citation
Wachter, Erin Melissa, "Design, Synthesis and Physicochemical Analysis of Ruthenium(II) Polypyridyl Complexes for Application in Phototherapy and Nucleic Acid Sensing" (2016). Theses and Dissertations--Chemistry. 60.
https://uknowledge.uky.edu/chemistry_etds/60
