Porphyrin Dimers as Photosensitizers in Photodynamic Therapy

Porphyrin dimers 9 with ether linkages and possible isomers bis[l-[6,7-bis[2-(methoxycarbonyl)ethyl]-l,3,5,8-tetramethyl-2-vinylporphin-4-yl]ethyl] ether (10) bis[l-[6,7-bis[2-(methoxycarbonyl)ethyl]-l,3,5,8-tetramethyl-4-vinylporphin-2-yl]ethyl] ether (11), and l-[6,7-bis[2-(methoxycarbonyl)ethyl]-l,3,5,8-tetramethyl-2-vinylporphin-4-yl]ethyl l-[6,7-bis[2-(methoxycarbonyl)ethyl]-l,3,5,8-tetramethyl-4-vinylporphin-2-yl]ethyl ether (12) were synthesized from the corresponding (l-hydroxyethyl)vinyldeuteroporphyrin IX dimethyl esters (Hvd). The pure Hvd isomers 2-(l-hydroxyethyl)-4-vinyldeuteroporphyrin IX dimethyl ester (7) and 4-(l-hydroxyethyl)-2-vinyldeuteroporphyrin IX dimethyl ester (8) were obtained from 2-acetyl-4-(l-hydroxyethyl)deuteroporphyrin IX dimethyl ester (3) and 4-acetyl-2-(l-hydroxyethyl)deuteroporphyrin IX dimethyl ester (4). Porphyrins 3 and 4 were prepared either by partial reduction of 2,4-diacetyldeuteroporphyrin IX dimethyl ester (2) or by oxidation of hematoporphyrin IX dimethyl ester (1) by using tetra-n-propylammonium perruthenate (Prⁿ₄N)(Ru0₄) with N-methylmorpholine N-oxide as an oxidizing agent. The in vivo photosensitizing ability and therapeutic ratios of dimers 912 were compared with that of Photofrin II in the SMT-F tumor growing subcutaneously in DBA/2 Ha mice. These dimers were found to have better tumorcidal activity than Photofrin II with reduced skin phototoxicity.