Photosensitized biological processes, as applied in photodynamic therapy, are based on light-triggered generation of molecular singlet oxygen by a membrane-residing sensitizer. Most of the sensitizers currently used are hydrophobic or amphiphilic porphyrins and their analogs. The possible activity of the short-lived singlet oxygen is limited to the time it is diffusing in the membrane, before it emerges into the aqueous environment. In this paper we demonstrate the enhancement of the photosensitization process that is obtained by newly synthesized protoporphyrin derivatives, which insert their tetrapyrrole chromophore deeper into the lipid bilayer of liposomes. The insertion was measured by fluorescence quenching by iodide and the photosensitization efficiency was measured with 9,10-dimethylanthracene, a fluorescent chemical target for singlet oxygen. We also show that when the bilayer undergoes a melting phase transition, or when it is fluidized by benzyl alcohol, the sensitization efficiency decreases because of the enhanced diffusion of singlet oxygen. The addition of cholesterol or of dimyristoyl phosphatydilcholine to the bilayer moves the porphyrin deeper into the bilayer; however, the ensuing effect on the sensitization efficiency is different in these two cases. These results could possibly define an additional criterion for the choice and design of hydrophobic, membrane-bound photosensitizers.
Previous literature work has assumed that the metal ion in metal-assisted a, c-biladiene cyclizations serves as a chelator as well as an oxidant. New results suggest that the metal is not of primary importance in aligning the tetrapyrroles into the proper cyclic conformation prior to cyclization. Though the metal insertion into the tetrapyrrole can take place at any stage in the reaction sequence, it appears only to be essential after formation of the 1,20-dihydroporphyrin intermediate, wherein it serves to facilitate the elimination of the 1-substituent to produce porphyrin.
Porphyrinyl beta-ketoesters dimerize to afford novel bistetrapyrrole systems by way of a radical process; the X-ray structure of one such bistetrapyrrole 14 is reported.
