New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles
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 for...
Main Author: | |
---|---|
Format: | Doctoral or Postdoctoral Thesis |
Language: | English |
Published: |
UiT Norges arktiske universitet
2023
|
Subjects: | |
Online Access: | https://hdl.handle.net/10037/28538 |
id |
ftunivtroemsoe:oai:munin.uit.no:10037/28538 |
---|---|
record_format |
openpolar |
institution |
Open Polar |
collection |
University of Tromsø: Munin Open Research Archive |
op_collection_id |
ftunivtroemsoe |
language |
English |
topic |
VDP::Mathematics and natural science: 400::Chemistry: 440::Inorganic chemistry: 442 VDP::Matematikk og Naturvitenskap: 400::Kjemi: 440::Uorganisk kjemi: 442 DOKTOR-004 |
spellingShingle |
VDP::Mathematics and natural science: 400::Chemistry: 440::Inorganic chemistry: 442 VDP::Matematikk og Naturvitenskap: 400::Kjemi: 440::Uorganisk kjemi: 442 DOKTOR-004 Einrem, Rune Finsås New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles |
topic_facet |
VDP::Mathematics and natural science: 400::Chemistry: 440::Inorganic chemistry: 442 VDP::Matematikk og Naturvitenskap: 400::Kjemi: 440::Uorganisk kjemi: 442 DOKTOR-004 |
description |
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. |
format |
Doctoral or Postdoctoral Thesis |
author |
Einrem, Rune Finsås |
author_facet |
Einrem, Rune Finsås |
author_sort |
Einrem, Rune Finsås |
title |
New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles |
title_short |
New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles |
title_full |
New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles |
title_fullStr |
New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles |
title_full_unstemmed |
New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles |
title_sort |
new building blocks for cancer phototherapeutics: 5d metallocorroles |
publisher |
UiT Norges arktiske universitet |
publishDate |
2023 |
url |
https://hdl.handle.net/10037/28538 |
geographic |
Tromsø |
geographic_facet |
Tromsø |
genre |
Tromsø |
genre_facet |
Tromsø |
op_relation |
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. Photochemical and Photobiological Sciences, 18 , 1166-1170. Also available at https://doi.org/10.1039/c8pp00473k . 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. ACS Omega, 5 , 10596 – 10601. Also available in Munin at https://hdl.handle.net/10037/18426 . 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. Scientific Reports, 10 , 19727. Also available in Munin at https://hdl.handle.net/10037/20414 . 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. ACS Applied Energy Materials, 3 (12), 12460-12467. Also available at https://doi.org/10.1021/acsaem.0c02427 . 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. RSC Advances, 11 (54), 34086-34094. Also available in Munin at https://hdl.handle.net/10037/23887 . Paper F: Thomassen, I.K., Rasmussen, D. Einrem, R.F. & Ghosh, A. (2021). Simple, Axial Ligand-Mediated Route to Water-Soluble Iridium Corroles. ACS Omega, 6 (25), 16683-16687. Also available in Munin at https://hdl.handle.net/10037/23641 . 978-82-8236-511-6 (electronic/pdf version). 978-82-8236-510-9 (printed version) https://hdl.handle.net/10037/28538 |
op_rights |
openAccess Copyright 2023 The Author(s) |
_version_ |
1766219735073030144 |
spelling |
ftunivtroemsoe:oai:munin.uit.no:10037/28538 2023-05-15T18:34:48+02:00 New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles Einrem, Rune Finsås 2023-02-24 https://hdl.handle.net/10037/28538 eng eng UiT Norges arktiske universitet UiT The Arctic University of Norway 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. Photochemical and Photobiological Sciences, 18 , 1166-1170. Also available at https://doi.org/10.1039/c8pp00473k . 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. ACS Omega, 5 , 10596 – 10601. Also available in Munin at https://hdl.handle.net/10037/18426 . 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. Scientific Reports, 10 , 19727. Also available in Munin at https://hdl.handle.net/10037/20414 . 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. ACS Applied Energy Materials, 3 (12), 12460-12467. Also available at https://doi.org/10.1021/acsaem.0c02427 . 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. RSC Advances, 11 (54), 34086-34094. Also available in Munin at https://hdl.handle.net/10037/23887 . Paper F: Thomassen, I.K., Rasmussen, D. Einrem, R.F. & Ghosh, A. (2021). Simple, Axial Ligand-Mediated Route to Water-Soluble Iridium Corroles. ACS Omega, 6 (25), 16683-16687. Also available in Munin at https://hdl.handle.net/10037/23641 . 978-82-8236-511-6 (electronic/pdf version). 978-82-8236-510-9 (printed version) https://hdl.handle.net/10037/28538 openAccess Copyright 2023 The Author(s) VDP::Mathematics and natural science: 400::Chemistry: 440::Inorganic chemistry: 442 VDP::Matematikk og Naturvitenskap: 400::Kjemi: 440::Uorganisk kjemi: 442 DOKTOR-004 Doctoral thesis Doktorgradsavhandling 2023 ftunivtroemsoe 2023-02-16T00:04:07Z 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. Doctoral or Postdoctoral Thesis Tromsø University of Tromsø: Munin Open Research Archive Tromsø |