LE3 .A278

2015

Lukeman, Matthew

Acadia University

Bachelor of Science

Honours

Biology

Biology

Photoremovable protecting groups (PPGs) are compounds capable of protecting molecules of interest and later releasing them upon irradiation allowing for spatial and temporal control of the substrate. A series of three different PPGs were studied: salicylaldehyde, 2-hydroxynaphthaldehyde, and pyridoxal for their applications as potential agents for photo-activated drug release substrates. Salicylaldehyde is a simple molecule that resembles the o-hydroxybenzyl alcohol based PPGs that have been previously studied. Compounds 22, 23, and 24 were successfully synthesized and photochemical studies determined 22 and 23 to be photostable compounds. The lack of photochemistry exhibited in these compounds is believed to be due to the formation of a highly unstable quinone methide intermediate that is capable of a reverse reaction leading back to the starting materials. 24 was synthesized, but thorough photochemical studies could not be completed due to the compound’s short lifetime. The short half-life was attributed to the instability of a 5- membered acetal ring. The 2-hydroxynaphthalene chromophore has previously been studied by this group and shown to efficiently release 1,3-propandiol upon irradiation of 300 nm of light. Compound 26 was successfully synthesized, but the 5-membered ring showed the same instability exhibited in compound 24 and thorough photochemical analysis could not be completed. Compound 25 was successfully synthesized and photochemically characterized. UV-Vis spectroscopy showed clean conversion of the compound based on the observed change in absorbance and the clean isosbestic points. The mechanism for this reaction is believed to proceed through the formation of a quinone methide intermediate upon irradiation and an ESIPT reaction. Lastly, pyridoxal, an interchangeable form of vitamin B6, was proposed as a potential PPG. Applications of a vitamin chromophore as a drug-release substrate are favourable because of their known biochemistry compared to synthetic chromophores typically used. The synthesis of these derivatives, 31, 32, and 33, was unsuccessful and is being further investigated.

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https://scholar.acadiau.ca/islandora/object/theses:1272