Design and Synthesis of Rhenium(I) Tricarbonyl Complexes and Scientific Education of Nuclear Chemistry PDF Download

Author: Chilaluck Charlene Konkankit
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Languages : en
Pages : 421

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Book Description
Despite significant advances in medicinal chemistry, cancer remains one of the leading causes of death worldwide. In conjunction with surgical resection and radiotherapy, chemotherapy is still the predominant strategy for cancer treatment. The current standard of care for this disease typically include the use of platinum-based drugs, such as cisplatin. Despite its widespread success and implementation, some patients experience relapse forms of the disease. For example, approximately 70% of ovarian cancer patients will experience relapse in which previous chemotherapy regimens are no longer effective. This platinum resistance is multifactorial, and the investigation of alternative anticancer metal complexes that lack cross resistance with cisplatin is a promising approach for developing new drug candidates. Among the potential alternative transition metals, complexes of rhenium have demonstrated their effectiveness at killing cancer. The most common class of rhenium compounds investigated for chemotherapy are the rhenium(I) tricarbonyl (Re(CO)3) structures, often bearing diimine ligands. Our lab has studied this class of compounds extensively, and here, I discuss our approaches for designing different structures of rhenium and our findings on their mechanisms of action. Chapter 1 is a comprehensive review of the anticancer activities of different drug candidates bearing the third row transition metals, rhenium, osmium, and iridium. Chapter 2 discusses the promising in vivo antitumor properties of a first-generation Re(CO)3 developed in our lab. Chapter 3 pursues a new route for generation a library of Re(CO)3 complexes in a quick, facile manner with studies on circumventing platinum resistance. Chapter 4 investigates how the lipophilicity of these structures affect the rate at which they induce cancer cell death. In Chapter 5, we discuss the addition of a covalently bound axial ligand, how its incorporation affects biological activity, and exploit the use of X-ray fluorescence microscopy to reveal the speciation of this class of rhenium isonitrile compounds. Appendix A reports a folate receptor targeting compound for treating ovarian cancer. In addition to my work on developing rhenium-based anticancer agents, I have also contributed significantly to the educational aspect of the Wilson Research Group. In this dissertation, I discuss the lack of tools and opportunities for teaching nuclear chemistry and radioactivity to students at the middle school, high school, and undergraduate levels. In Chapter 6, I discuss the design of workshop activities to provide tangible, hands-on activities for students to learn about radioactivity and isotopes. In Chapter 7 appears a new undergraduate laboratory experiment emphasizing radioactive safety including distance, shielding, and exposure time to radioactive sources. This research details synthetic protocols for developing rhenium compounds as well as novel approaches for teaching nuclear chemistry and radioactivity. As new complexes of rhenium are generated, we gain more insight on how to design future anticancer agents and what mechanisms of action contribute to circumventing cross resistance with platinum-based drugs. Additionally, the implementation of the activities and experiments outlined in Chapters 6 and 7 will give rise to a generation of scientists that have more knowledge and experience handling radioactive materials.