engleski

Synthesis of meso-tetrasubstituted porphyrins bearing epoxide unit on the long alkyl chain

Photodynamic therapy (PDT) is a method that uses a therapeutic photosensitizer (PS), combined with light irradiation of an appropriate wavelength and molecular oxygen to generate singlet oxygen and other reactive oxygen species (ROS) to destroy tumour cells. Some advantages of PDT are selective cell targeting, localised impact, tumor vasculature destruction, and potential immunostimulation. Future progress of PDT requires design of new PSs with improved selectivity, bioavailability, and lesser dark toxicity. Porphyrins and their derivatives are often used as PSs for their photophysical properties, tumour tissue accumulation, and high singlet oxygen yield. Amphiphilic cationic tetraaryl porphyrins are convenient for therapeutic use since their cationic moiety enables water solubility and easier drug administration, whereas lipophilic portion induces absorption into the cell. Porphyrins with long alkyl chain (18C) have shown to successfully enter the cell and achieve photodynamic action, but they were shown to have dark toxicity and are unstable in biological medium. Overcoming those disadvantages is attempted by adding an epoxide group on the alkyl chain, while achieving additional cytotoxic and proapoptotic action of epoxidized alkyl chain against cancer cells. The aim of this master thesis was to optimize the synthesis of two tripyridyl-porphyrins with long alkyl chains (C18), of which one has a saturated alkyl chain, while other has a chain with epoxide unit on 9, 10-position. Porphyrin with saturated chain was methylated to improve its polarity and amphiphilic properties. Different routes of epoxidation and activation of carboxylic group of the alkyl chain were examined, as well as its conjugation onto the porphyrin. Activation of carboxylic acid by N-hydroxysuccinimide (NHS) has shown to be a successful method. Photophysical properties and fluorescence quantum yield of synthesized porphyrins were examined, and high quantum yield of fluorescence was measured for all compounds.

Photodynamic therapy ; Porphyrins ; Epoxidation ; NHS activation ; Quantum yield of fluorescence

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