| dc.description.abstract | Corroles are ring-contracted, triprotic analogues of porphyrins. This PhD study expands earlier knowledge in particular on ReO corroles. Early on, it became apparent that ReO corroles exhibit the highest phosphorescence quantum yields among all metallocorroles. They also sensitize singlet oxygen formation and serve as oxygen sensors and as triplet-triplet annihilation upconverters. I accordingly wanted to synthesize new classes of functionalized 5d corroles as well as to examine ReO corroles as photosensitizers in in vitro photodynamic therapy experiments. I found that amphiphilic meta/para-carboxyl-appended ReO triphenylcorroles exhibit high photocytotoxicity against multiple cancer cell lines. In the synthetic realm, one study examined electrophilic chlorination and bromination of ReO corroles. X-ray structures of ReO octachloro- and octabromocorroles yielded a host of insights into the conformational preferences of sterically hindered corrole derivatives. Another synthetic study afforded an innovative approach to water-soluble iridium corroles, involving the use of water-soluble axial ligands. I also undertook extensive studies of formylation of ReO and Au triarylcorroles, arriving at the rather elegant conclusion that whereas the former largely afford 3-monoformyl products, the latter preferentially yield 3,17-diformylproducts, presumably reflecting the higher nucleophilicity of the Au complexes. The formylcorrole products could be readily postfunctionalized, such as via the Knoevenagel reaction. The 5d formylcorroles should serve as valuable starting materials for bio- and nanoconjugated 5d metallocorroles for advanced, targeted cancer therapies. I feel privileged to have developed a new class of triplet photosensitizers – the ReO corroles – that to this day remain unique to our Tromsø laboratory. I am confident, however, that we shall soon see exciting applications of these compounds as advanced photodynamic, photothermal and multimodal cancer therapeutics. | en_US |
| dc.description.popularabstract | The bright colours of life such as the red colour of blood and the green of plants are due to a class of ring-shaped molecules called porphyrins, which bind metal atoms such as iron or magnesium at their centres. As part of my PhD studies, I have worked on a similar, but smaller ring-shaped molecule called corrole and managed to coordinate larger precious metals such as rhenium, iridium, and gold into their central cavities. Although these unusual molecules might have been expected to be unstable, on account of the size mismatch between the corrole ring and the large central metal, they are actually remarkably stable. What is more, they exhibit remarkable light absorption and emission properties, which in turn allows them to convert regular atmospheric oxygen to a high-energy state called singlet oxygen. Singlet oxygen is the key agent that kills cancer cells and tumours in the light-mediated cancer therapy called photodynamic therapy. Excitingly, my rhenium corroles have proven exceedingly affective at killing two lines of cancer cells under blue light irradiation. I feel privileged to have discovered a class of compounds that hold significant promise as a new class of cancer photodrugs. | en_US |
| dc.relation.haspart | <p>Paper A: Borisov, S.M., Einrem, R.F., Alemayehu, A.B. & Ghosh, A. (2019). Ambient-temperature near-IR phosphorescence and potential applications of rhenium-oxo corroles. <i>Photochemical and Photobiological Sciences, 18</i>, 1166-1170. Also available at <a href=https://doi.org/10.1039/c8pp00473k> https://doi.org/10.1039/c8pp00473k</a>.
<p>Paper B: Einrem, R.F., Ghosh, A., Alemayehu, A.B., Borisov, S.M. & Gederaas, O.A. (2020). Amphiphilic Rhenium-Oxo Corroles as a New Class of Sensitizers for Photodynamic Therapy. <i>ACS Omega, 5</i>, 10596 – 10601. Also available in Munin at <a href=https://hdl.handle.net/10037/18426> https://hdl.handle.net/10037/18426</a>.
<p>Paper C: Alemayehu, A.B., Einrem, R.F., McCormick, L.J., Settineri, N.S. & Ghosh, A. (2020). Synthesis and Molecular Structure of Perhalogenated Rhenium-Oxo Corroles. <i>Scientific Reports, 10</i>, 19727. Also available in Munin at <a href=https://hdl.handle.net/10037/20414>https://hdl.handle.net/10037/20414</a>.
<p>Paper D: Higashino, T., Kurumisawa, Y., Alemayehu, A.B., Einrem, R.F., Sahu, D., Packwood, D.M., … Imahori, H. (2020). Heavy Metal Effects on the Photovoltaic Properties of Metallocorroles in Dye- Sensitized Solar Cell. <i>ACS Applied Energy Materials, 3</i>(12), 12460-12467. Also available at <a href=https://doi.org/10.1021/acsaem.0c02427>https://doi.org/10.1021/acsaem.0c02427</a>.
<p>Paper E: Einrem, R.F., Jonsson, E.T., Teat, S.J., Settineri, S.S., Alemayehu, A.B. & Ghosh, A. (2021). Regioselective formylation of rhenium-oxo and gold corroles substituent effects on optical spectra and redox potentials. <i>RSC Advances, 11</i>(54), 34086-34094. Also available in Munin at <a href=https://hdl.handle.net/10037/23887>https://hdl.handle.net/10037/23887</a>.
<p>Paper F: Thomassen, I.K., Rasmussen, D. Einrem, R.F. & Ghosh, A. (2021). Simple, Axial Ligand-Mediated Route to Water-Soluble Iridium Corroles. <i>ACS Omega, 6</i>(25), 16683-16687. Also available in Munin at <a href=https://hdl.handle.net/10037/23641>https://hdl.handle.net/10037/23641</a>. | en_US |
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