Synthesis Of Unsymmetrical Core Modified Porphyrins

Water-soluble core-modified porphyrins have been designed as photosensitizers for the use in Photodynamic Therapy, a cancer treatment regime introduced over 100 years ago. These photosensitizers are recognized by the substitution in the porphyrin chromophore with different chalcogens, providing longer wavelengths. Substitutions at the meso - positions of the chromophore, however, have shown to correlate to the solubility of the molecule. Dicarboxylic and monocarboxylic acid derivatives have been reported as potent photosensitizers, where the dicarboxylic acid has been furthered investigated with varying substituents located at the other meso - positions. These studies showed that the symmetrical dicarboxylic acid molecules were prone to aggregate in polar solvents, believed to lead to low cellular uptake or a false positive activity result in the tumor cells. The following chapters will discuss background work leading to the design and synthesis of unsymmetrical core-modified porphyrins as photosensitizers. The major impetus in the design of these compounds is to examine (1) whether the unsymmetrical structures would have a positive effect on the aggregation issues observed with the dicarboxylic acid derivatives, and (2) whether increasing the log P values would affect the cellular uptake significantly. The major isomer of 20(4- tert -butylphenyl)-5,10-diphenyl-15-(4-methoxy)phenyl-21,23-dithiaporphyrin was successfully isolated and identified as the cis -isomer by X-ray crystallography.