Design, Synthesis, and Pharmacological Screening of Novel Porphyrin Derivatives

A series of porphyrin derivatives 2a-f was synthesized, namely, 5,10,15,20-mesotetrakis[p-methoxyphenyl]-21H,23H-porphyrin (2a), 5,10,15,20-mesotetrakis[2,6-dichloro-phenyl]dimethoxyphenyl-21H,23H-porphyrin (2b), 5,10,15,20-mesotetrakis[4-hydroxy-3,5-dimethoxyphenyl]-21H, 23H-porphyrin (2c), 5,10,15,20-mesotetrakis[3,4-dimethoxyphenyl]-21H, 23H-porphyrin (2d), 5,10, 15,20-mesotetrakis[2,4-dichlorophenyl]-21H,23H-porphyrin (2e), and 5,10,15,20-mesotetrakis[3,4,5-trimethoxyphenyl]-21H,23H-porphyrin (2f), in high yields using a new method via a capping mechanism. These dyes were used as a model to study the free radical-induced damage of biological membranes and the protective effects of these porphyrins. It was demonstrated that these dyes were effective in the inhibition of the free radical-induced oxidative haemolysis of rat blood cells. Dyes 2d and 2f which bear methoxy functionality exhibited markedly higher antihaemolysis activity than the other analogs. Molecular modeling methods using ZINDO/INDO-1, with a configuration interaction of 26, and TD-DFT using the energy functional B3LYP and the basis set DGTZVP were used to study the vertical electronic excitations of porphyrins 2a-f and it was shown that the lambda(max) calculated using TD-DFT method was in excellent agreement with the experimental results, while the ZINDO method was inferior. Moreover, excellent correlation between the LUMO energy and cytotoxicity of dyes 2a-f was found.