Organometallic Complexes in Biological Applications: Synthesis, Mechanism, and In Vitro Behavior

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dc.contributor.advisorDo, Loi H.
dc.contributor.committeeMemberLee, T. Randall
dc.contributor.committeeMemberMay, Jeremy A.
dc.contributor.committeeMemberZastrow, Melissa L.
dc.contributor.committeeMemberUmetani, Michihisa
dc.contributor.committeeMemberDo, Loi H.
dc.creatorNguyen, Huong Thi Hoai
dc.creator.orcid0000-0001-8429-4365
dc.date.accessioned2022-06-29T23:30:52Z
dc.date.createdMay 2021
dc.date.issued2021-05
dc.date.submittedMay 2021
dc.date.updated2022-06-29T23:30:53Z
dc.description.abstractTransition metal complexes are attractive as bioactive compounds due to their structural complexity and ability to achieve high potency and selectivity. In recent years, the development of these complexes has gained much popularity due to their synthetically accessibility and tunable reactivity. However, creating complexes that are non-toxic and active inside biological environments is highly challenging. Herein, we describe the synthesis of new organometallic complexes and their possible application as anti-cancer agents. In the first project, a bifunctional complex featuring a quinone and picolinamide iridium moieties was synthesized as new transfer hydrogenation catalysts. We proposed that this catalyst design would enable more efficient generation of hydrogen peroxide by taking advantages of intramolecular reactivity. In the presence of sodium formate, our catalytic produced more hydrogen peroxide compared to that by the corresponding tandem catalysts under physiological conditions. We characterized several key reaction intermediates by VT NMR spectroscopy and determined catalyst stability over time. The biocompatibility of the complex toward cancer cell lines was also evaluated. The second project was performed in collaboration with Dr. Michihisa Umetani, in which we attempted to develop synthetic liver X receptor agonists (GW3965) that are nucleus impermeable and can selectively inhibit nuclear gene expression. Toward this goal, we covalently attached GW3965 to ruthenium/rhodium/iridium complexes using a variety of linkers. The fluorescent cyclometalated iridium complex bearing two GW3965 units showed extra-nuclear localization via live cell imaging. The distribution of Ru/Rh compounds is currently being investigated by Inductive coupled plasma-mass spectroscopy (ICP-MS). Further studies using qPCR, cell proliferation, and cytotoxicity assays would be conducted evaluate these complexes’ behavior inside cells. Our work had led to the first demonstration of using intramolecular transfer hydrogenation to enhance H2O2 generation at low catalyst concentrations. We also introduced a new approach for reducing the nuclear permeability of Liver X Receptor agonists. We believe the insights gained from the studies could be used to develop more biocompatible systems in the future.
dc.description.departmentChemistry, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.citationPortions of this document appear in: Nguyen, Dat P., Huong TH Nguyen, and Loi H. Do. "Tools and methods for investigating synthetic metal-catalyzed reactions in living cells." ACS catalysis 11, no. 9 (2021): 5148-5165; and in: Nguyen, Huong TH, and Loi H. Do. "Organoiridium–quinone conjugates for facile hydrogen peroxide generation." Chemical Communications 56, no. 87 (2020): 13381-13384.
dc.identifier.urihttps://hdl.handle.net/10657/10204
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjecttransfer hydrogenation
dc.subjectiridium
dc.subjectquinone, GW3965
dc.subjectliver X receptor agonist
dc.subjectruthenium
dc.subjecthydrogen peroxide
dc.subjectnucleus permeability
dc.subjectintramolecular
dc.subjectintracellular
dc.subjectfluorescence probe
dc.subjectbiocompatible systems
dc.titleOrganometallic Complexes in Biological Applications: Synthesis, Mechanism, and In Vitro Behavior
dc.type.dcmiText
dc.type.genreThesis
local.embargo.lift2023-05-01
local.embargo.terms2023-05-01
thesis.degree.collegeCollege of Natural Sciences and Mathematics
thesis.degree.departmentChemistry, Department of
thesis.degree.disciplineChemistry
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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