Synthesis of novel asymmetrically substituted phthalocyanines

• Main Author: Sharman, Wesley Milton
• Other Authors: Van Lier, J.E.
• Language: English
• Published: Université de Sherbrooke 2005
• Online Access: http://savoirs.usherbrooke.ca/handle/11143/4220

Phthalocyanines are among the more promising second generation photosensitizers for photodynamic therapy. Our research group has consistently shown that the more amphiphilic of these compounds display improved biological properties as photosensitizers for photodynamic therapy. However, synthetic approaches towards such asymmetrically substituted amphiphilic phthalocyanines are quite limited. As such, we have examined different methodologies for imparting amphiphilicity to phthalocyanine-based photosensitizers. Boron subphthalocyanines are the lower homologs of phthalocyanines and the reactivity of boron subphthalocyanines allows them to react with 1,3-diiminoisoindolines in a Kobayashi ring expansion reaction to give 3:1 asymmetrically substituted phthalocyanines. While several literature examples demonstrate that this protocol can lead to a mixture of substituted phthalocyanine products, the ring expansion reaction of halogenated boron subphthalocyanines in the current study has proven to proceed smoothly to selectively produce the desired 3:1 asymmetrically substituted products. Fluorinated photosensitizers have been previously demonstrated to have interesting properties for PDT and a series of 3:1 asymmetrically substituted dodecafluorinated phthalocyanines have been synthesized by the Kobayashi ring expansion reaction of (dodecafluorosubphthalocyaninato)boron(III) bromide. The asymmetry in these lipophilic compounds improves the photodynamic efficiency of these photosensitizers compared to previously examined symmetrically substituted fluorinated phthalocyanine derivatives. The chemical versatility of aryl iodides, in particular towards palladium-catalyzed reactions, allows for the controlled addition of novel functionality to 3:1 asymmetrically substituted iodinated phthalocyanines prepared by the Kobayashi ring expansion reaction of iodinated boron subphthalocyanines. Palladium-catalyzed reactions have thus been employed in the preparation of new amphiphilic anionic and cationic water-soluble photosensitizers. These compounds should have interesting properties for photodynamic therapy. Lastly, boron subnaphthalocyanines absorb light at a wavelength around 660-680 nm. Their cone-shaped structure prevents aggregation and may impart amphiphilicity to the molecule depending on the nature of the substituents on the subnaphthalocyanine macrocycle and the axial ligand on the central boron. A series of boron subnaphthalocyanines has been synthesized and this class of photosensitizers has been shown to effectively generate singlet oxygen in an aqueous, biologically relevant environment while undergoing rapid photobleaching.