Amphiphilic Porphyrins as Possible PhotodynamicTherapy Sensitizers

Although photodynamic therapy with porphyrinicpigments as photosensitizers has emerged as promisingmodality for disease treatment, there remains a greatneed for the preparation of more selectivesensitizers. Thus, the synthesis of amphiphilicporphyrins bearing fluoro and carboxy substituentswas attempted. The most successful were the synthesisof three para-phenyl substitutedtetraphenylporphyrins (TPPs) using both rational andstatistical methodology. The porphyrins of greatestinterest, where carboxy and fluoro substituents wereplaced at the para positions of opposite or adjacentphenyl rings, were either not obtained or only insmall yields. However,5,10,15-tri(4-fluorophenyl)-20(4-carboxyphenyl)porphyrinwas synthesized in higher yields. To deriveinformation on the factors that govern the permeationof this porphyrin across cell membrane mimics and itslocalization patters, it was allowed to diffuse intounilamellar vesicles at pH 2,7 and 10. The porphyrinincorporated in vesicles only to a small extent at pH10 demonstrating that a proper amphiphilicity balanceis required for porphyrins to incorporate into cellmembrane mimics.