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Synthesis and photochemistry of AZO-type derivitized porphyrins with crosslinking applications

University of British Columbia

The objective of this work was to synthetically modify porphyrins such that they would possess a functionality that would crosslink within its biological environment upon photoactivation, in photodynamic therapy applications. The reaction of diazomethane and protoporphyrin dimethylester (9) yielded a series of three novel pyrazoline porphyrins (10 - 12) that were isolated and characterized. These were investigated for their ability to extrude molecular nitrogen on thermal and photochemical activation with both near-UV and long wavelength light to yield a 1,3- biradical intermediate that may provide a site for potential crosslinking. Upon activation three cyclopropane derivatives (15 - 17) were formed in high yield, presumably through the 1,3 biradical intermediate. These novel cyclopropane porphyrin derivatives were purified and characterized. The optimized diazomethane reaction was then carried out on a chlorin (18), a photosensitizer currently undergoing clinical trials for PDT, to yield the first example of a pyrazoline derivatized methylpyropheophorbide (MePPP, 19). Activation with heat, U V light or long wavelength light yielded the cyclopropane product of MePPP (20), analogous to the photoreaction described for the model PPDME pyrazoline reactions. These studies represent the first example of long wavelength activation of a photoactive functionality at the porphyrin periphery. Attempts to trap the biradical intermediates produced on photoactivation of the pyrazolines were carried out in solution. Unfortunately, no trapped products were isolated, presumably because the lifetimes of these intermediates proved to be too short due to efficient formation of the cyclopropane. The second photoactive functionality that was pursued is anticipated to yield a much longer lived carbene intermediate that should be more effective in cross-linking studies. The synthetic target was the diazirine of TPP (25). Five of the eight reactions planned in the synthesis of (25) were optimized, and scaled-up. Each of the intermediates (21, 22, 23, 24) were isolated and characterized. The reactions leading up to the novel trifluoroacetyl-TPP (23) provide the first example of introducing a trifluoroacetyl group at the β position of the porphyrin.

Thesis/Dissertation

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2009-07-20

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http://hdl.handle.net/2429/10946

Chemistry

University of British Columbia

UBCV

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