Photodynamic studies of metallo 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin: Photochemical characterization and biological consequences in a humancarcinoma cell line

The photodynamic activities of the free-base 5,10,15,20-tetrakis(4-methoxyp henyl)porphyrin (TMP) and their metal complexes with zinc(II) (ZnTMP), copp er(II) (CuTMP) and cadmium(II) (CdTMP) have been compared in two systems: r everse micelle of n-heptane/sodium his(2-ethylhexyl)sulfosuccinate/water be aring photooxidizable substrates and Hep-2 human larynx carcinoma cell Line . The quantum yields of singlet molecular oxygen, O-2((1)Delta (g)), produc tion (Phi (Delta)) of TMP, ZnTMP and CdTMP in tetrahydrofuran, were determi ned yielding values of 0.65, 0.73 and 0.73, respectively, while O-2((1)Delt a (g)) formation was not detected for CuTMP, In the reverse micellar system , the amino acid L-tryptophan (Trp) was used as biological substrate to ana lyze the O-2((1)Delta (g))-mediated photooxidation, The observed rate const ants for Trp photooxidation (k(obs)(Trp)) were proportional to the sensitiz er quantum yield of O-2((1)Delta (g)). A value of similar to2 x 10(7) s(-1) M-1 was found for the second-order rate constant of Trp (k(r)(Try)) in thi s system, The response of Hep-2 cells to cytotoxicity photoinduced by these agents in a biological medium was studied. The Hep-2 cultures were treated with 1 muM of porphyrin for 24 h at 37 degreesC and the cells exposed to v isible light. The cell survival at different light exposure levels was depe ndent on Phi (Delta). Under these conditions, the cytotoxic effect increase s in the order: CuTMP much less than TMP < ZnTMP similar to CdTMP, correlat ing with the production of O-2((1)Delta (g)), A similar behavior was observ ed in both the chemical and biological media indicating that the O-2((1)Del ta (g)) mediation appears to be mainly responsible for the cell inactivatio n.