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http://hdl.handle.net/11375/18064
Title: | Fluorous Supports and Oxidants for Radiochemistry, Tetrazine Synthesis, and Hydrogen Sulfide Processing |
Authors: | Dzandzi, James P. K. |
Advisor: | Valliant, John F. |
Department: | Chemistry and Chemical Biology |
Keywords: | Radioiodination; Fluorous oxidant; Tetrazine; Labelling methods; 125I; instant kits; fluorous |
Publication Date: | Nov-2015 |
Abstract: | A new class of fluorous materials was developed to create a hybrid solid-solution phase strategy for the expedient preparation of 125I-labelled compounds, without the need of HPLC purification. The system is referred to as a hybrid platform in that it combines solution phase labelling and fluorous solid-phase purification in one step as opposed to two separate individual processes. Initial success was achieved by treating fluorous stannanes, coated on fluorous silica, with [125I]NaI and chloramine-T (CAT) as the oxidant, where the desired nonfluorous radiolabelled products were isolated in minutes in biocompatible solutions in high purity (>98%) free from excess starting material and unreacted radioiodine. This platform was initially developed through a model system based on a fluorous benzoic acid derivative. The platform was then validated with simple aryl and heterocyclic derivatives, known radiopharmaceuticals including meta-iodobenzylguanidine (MIBG) and iododeoxyuridine (IUdR), and a new agent with high affinity for prostate-specific membrane antigen (PSMA). The limitation of the platform was the presence of non-radioactive UV impurities which came from the oxidants employed. To resolve this issue a new class of fluorous oxidants based on chloramine-T (CAT, F-CAT) were prepared. F-CAT, was prepared in 87% overall synthesis yield from commercially available starting materials and found to be effective in labelling arylstannanes and proteins with [125I]NaI. The utility of the oxidant was further demonstrated in successfully preparing a radioiodinated tetrazine (125I-Tz) through a concomitant oxidation-halodemetallation reaction. 125I-Tz can be used to label biomolecules through bioorthogonal coupling reactions with prosthetic groups containing strained alkenes including norbornene and trans-cyclooctene (TCO). The reported hybrid platform labelling approach is readily accessible and requires minimal radiochemistry expertise and should therefore find widespread use. It is also noteworthy that a second generation of the fluorous oxidant, F-CAT2, was also prepared with the aim of obtaining an oxidant which has a higher solubility in perfluorinated solvents. Application of F-CAT2 for oxidation of hydrogen sulfide to elemental sulphur in a fluorous-aqueous biphasic system was demonstrated. This approach offers a new metal-free approach to scrubbing sour gas wells and demonstrates that the fluorous oxidants developed here have utility beyond radiochemistry. |
URI: | http://hdl.handle.net/11375/18064 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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James Dzandzi PhDThesis, June 2015..pdf | 6.06 MB | Adobe PDF | View/Open |
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