Amphiphilic Porphyrins as Possible Photodynamic Therapy Sensitizers

Although photodynamic therapy with porphyrinic
pigments as photosensitizers has emerged as promising
modality for disease treatment, there remains a great
need for the preparation of more selective
sensitizers. Thus, the synthesis of amphiphilic
porphyrins bearing fluoro and carboxy substituents
was attempted. The most successful were the synthesis
of three para-phenyl substituted
tetraphenylporphyrins (TPPs) using both rational and
statistical methodology. The porphyrins of greatest
interest, where carboxy and fluoro substituents were
placed at the para positions of opposite or adjacent
phenyl rings, were either not obtained or only in
small yields. However,
5,10,15-tri(4-fluorophenyl)-20(4-carboxyphenyl)porphyrin
was synthesized in higher yields. To derive
information on the factors that govern the permeation
of this porphyrin across cell membrane mimics and its
localization patters, it was allowed to diffuse into
unilamellar vesicles at pH 2,7 and 10. The porphyrin
incorporated in vesicles only to a small extent at pH
10 demonstrating that a proper amphiphilicity balance
is required for porphyrins to incorporate into cell
membrane mimics.

Autorentext

Carina Peritore received her B.S. from UCSC with ProfessorBakthan Singaram in Organic Chemistry. She went on to work forProfessor Tony Fink in a Biochemistry Lab at UCSC and thenreceived her M.S. with Professor Ursula Simonis in BioorganicChemistry at SFSU. She is currently a PhD Candidate withProfessor Scott Schaus in Organic Synthesis at BU.

Klappentext

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.