Title

Synthesis and Characterization of Novel Ru(II) Dipyrrin Complexes for Use as Photodynamic Therapy Agents in Cancer Treatments

Author

Max Tsao

Date of Award

1-1-2019

Degree Name

M.S. in Chemistry

Department

Department of Chemistry

Advisor/Chair

Advisor: Shawn Swavey

Second Advisor

Advisor: Mark Masthay

Third Advisor

Advisor: Angela Mammana

Abstract

Cancer remains a significant obstacle in modern healthcare, and efforts are needed to discover and advance new treatment methods and compounds. Accordingly, two novel dipyrrin compounds, consisting of a heteroleptic monometallic ruthenium(II) complex and a heteroleptic trimetallic ruthenium(II) complex, were synthesized and characterized for use as photosensitizers in photodynamic therapy of cancer. In the monometallic complex, a ? to ?* transition is observed originating from the bipyridyl groups along with overlapping MLCT from Ru(d?) to bpy(?*) and ligand centered transition occurring at a range between 520 nm and 600 nm. The trimetallic complex contains an expected ? to ?* dipyrrin transition at 294 nm and Ru(d?) to bpy(?*) MLCT transitions at 355 nm and 502 nm. An intense transition occurring at 578 nm from overlapping dipyrrin ? to ?* and Ru(d?) to dipyrrin(?*) is also observed. These transitions were predominantly analyzed through electrochemical and spectroelectrochemical experiments. Performance of the complexes was initially tested through irradiation in the 600 to 850 nm photodynamic therapy window while in the presence of plasmid DNA, with both complexes showing the ability to cause photo-damage to the DNA backbone. However, in the absence of oxygen, the trimetallic Ru(II) complex also generated photo-induced DNA damage, which is suggestive of a photo-oxidative Type I process. Cytotoxicity of the complexes up to 50 ╡M concentration towards A549 lung cancer cells was negligible in the absence of light. The trimetallic complex demonstrated significantly greater photo-cytotoxicity compared to the monometallic analog upon irradiation of the cells with a 420 nm low power light source. A dose dependent response curve results in an IC50 value of 92 ╡M for complex B.

Keywords

Biochemistry, Chemistry, Photodynamic therapy, PDT, Ruthenium complexes, Dipyrrin, Cancer, Synthesis, Characterization, A549, pUC18

Rights Statement

Copyright 2019, author

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