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Chemistry at the porphyrin periphery

University of British Columbia

The objective of this work was to synthesize novel aromatic compounds based on tetraphenylporphyrins. These compounds are potential photosensitizers for use in photodynamic therapy. Several approaches were employed towards this goal. Numerous tetraphenylporphyrins possessing a variety of substituents were synthesized, characterized and used as starting materials to prepare the analogous diol chlorins via the patented osmium tetroxide oxidation. Compounds possessing hydroxy, methoxy, alkyl and halogen substituents were prepared. Studies involving the syntheses of these variously substituted meso-tetraphenyl- vic-2,3-dihydroxy-2,3-chlorins and analysis of their in vitro biological test results are presented and discussed. A number of these compounds appear very promising, particularly diphenyl-2,3-dihydroxy-2,3-chlorin (125) which had an LD50 value of 0.0024 µM - 450 times as potent as the commercially available standard Photofrin. [Figure.] Attempts to improve the oxidation reaction via the reversible modification of starting materials and the use of other substrates as starting materials are also discussed. The use of electronically activated N-alkylated tetraphenylporphyrins as starting materials was attempted. This reaction was successful for N-methyl TPP (131) but failed when N-phenyl TPP (132) was employed. Additionally, the osmium tetroxide mediated oxidation of octaethyltetraphenylporphyrin (137) was attempted. (meso-Tetraphenyl-2,3-dihydroxy-2,3-chlorinato)nickel (106) can be oxidized to form (meso-tetraphenyl- 2,3-dialdehyde-2,3-secochlorinato)nickel (145). An investigation of the reactivity of this novel compound (145) is presented. A wide variety of reactions were performed including reactions with acids, bases, alcohols, amines and reducing agents. Over 30 interesting and novel compounds were synthesized from nickel bisaldehyde secochlorin (145) such as the doubly cyclized diketo product (182) from reaction of (145) with TFA followed by base, and the unsubstituted secochlorin (191) from the decarbonylation of (145) with Wilkinson's catalyst. [Figures.] Finally, a relatively unexplored field of porphyrin research was investigated. Studies probed the reactivity of both tetra- and diphenylporphyrins in a number of different 1,3-dipolar cycloaddition reactions. Although this initial investigation was met with limited success overall, reactions with mesitaldehyde oxide, tetracyanoethylene oxide (TCNEO) and diazomethane were fruitful, forming products (226), (213) and (223) respectively. [Figures.]

Thesis/Dissertation

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2009-07-20

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http://hdl.handle.net/2429/10944

Chemistry

University of British Columbia

UBCV

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