Synthesis and characterisation of porphyrazines with chiral recognition motifs.

Increased interest in porphyrazines is due to the role they play as photosensitisers in tumour therapy. A continuing problem in photodynamic therapy is selective uptake of the photosensitiser into cancerous tissue versus healthy tissue. A potential solution would be to functionalise the photosensitiser with biological molecules to assist in its selective uptake and for enhanced water solubility. The main objective of the project was the synthesis, deprotection, metalation and characterisation of peripherally carbohydrate substituted porphyrazines. A succesful synthetic pathway for the incorporation of carbohydrate moeities into porphyrazine systems in the form of 1:3, where 1 represents the carbohydrate-substituent and 3 represents the propyl-substituted pyrrole unit, has been demonstrated by this study. To this end, a range of selectively protected monosaccharide precursors was coupled to a small variety of phthalonitriles in nucleophilic aromatic substitution reactions. The products were co-macrocyclised to form hybrid porphyrazines via Linstead macrocyclisation reactions to form the desired 1:3 cyclisation products. Similarly, two protected disaccharides were synthesised de novo, coupled with the phthalonitriles and macrocyclised into their porphyrazine derivatives. Several problems were encountered in the latter set of reactions, but various methods were devised to overcome these issues. Demetalation of the porphyrazine products mentioned above was effected with relative ease using glacial acetic acid to afford the free-base pigments, which were subsequently converted into their zinc or nickel complexes. One of the problems encountered with some of the metalated products was poor solubility in spectroscopic solvents used for their characterisation. The UV-visible spectra revealed some features related to those of free-base porphyrazines or phthalocyanines but demonstrated diagnostic unsplit Q-bands confirming the success of each metalation reaction. In the second part of this investigation, some of the porphyrazines were deprotected of their isopropylidene groups of the carbohydrates to increase their hydrophilicity. This was done by using a catalytic amount of p-TsOH acid in the presence of a nucleophilic solvent. This extraction coefficients were determined as measured between 2-octanol and PBS solution. Comparison of the partition coefficients of the carbohydrate-substituted porphyrazines and their deprotected counterparts to those of non-carbohydrate substituted pigments showed that the structural alteration offers a way to significantly increase the hydrophilicity of substituted porphyrazines. Finally, photophysical studies on the porphyrazine products were performed, and these include singlet oxygen generation, triplet lifetimes and -yields, etc. The results of this part of study showed that the products are good candidates for PDT and that the nature of the carbohydrate played an insignificant role in the activity of the pigments. Rather, the position of attachment and the presence/absence of a metal in the core cavity were found to be more important.Prof. D.B.G. William