Identifier

etd-04122007-120024

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

Isoporphyrins are tautomers of porphyrins with an interrupted macrocyclic conjugation owing to the presence of a sp3 hybridized meso-carbon. Due to their absorption at long wavelengths (~800nm), isoporphyrins are potential candidates as photosensitizers in photodynamic therapy (PDT), a ternary modality of cancer treatment. They are also of biological interest due to their unique redox properties among porphyrin derivatives and could be a new class of near-IR dyes. Isoporphyrins are known to be unstable with respect to transformation back to the fully conjugated porphyrin chromophore except when the meso-carbon is geminally substituted and for this reason a detailed study of this macrocycle has previously been prevented. However, a better synthetic route (the main objective of this research project) by way of open-chain tetrapyrrole precursors has been developed to afford the target compound, zinc(II) isoporphyrin in better yields (28%) than previously reported (6%). No other metal isoporphyrin is known and a novel copper(II) isoporphyrin was synthesized and characterized. This was achieved by utilizing cuprous chloride as the metal ion donor. Stability studies have also been done to obtain stable metal-free isoporphyrins which have not previously been isolated and characterized. A detailed 1H and 13C NMR study allows their complete structural elucidation. Substitution of one of the meso-dimethyl groups for an ester using á,â-ketoesters as carbon-linking units in the cyclization reaction of b-bilenes, affords novel zinc isoporphyrins, whose preliminary chemical properties show that they can be used as intermediates to meso-monosubstituted porphyrins. However, during the synthesis, various intermediates were observed and studied. An interesting transformation – b-bilene, to a,b-biladine, to a,c-biladiene – was observed; this is the first example of such a transformation that we are aware of so far. This route has also been applied to synthesize meso-monosubstituted porphyrins in higher yields than previously reported. These compounds have also been studied for their biological properties applicable to photodynamic therapy, including dark- and phototoxicity, intracellular localization, and cell uptake. The preliminary results indicate that the compounds exhibit low dark toxicity and are phototoxic, they localize both in the mitochondria (major) and the lysosomes, and thus are very good candidates for tumor destruction in PDT.

Date

2007

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Kevin M. Smith

DOI

10.31390/gradschool_dissertations.1741

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