Mitochondria targeting by guanidine- and biguanidine-porphyrin photosensitizers

We report the syntheses of three new amphiphilic porphyrin derivatives, containing a guanidine, a biguanidine, or an MLS peptide, that were designed to target the cell mitochondria. The guanidine- and biguanidine-porphyrins are poorly soluble in water, forming J-type aggregates in aqueous solutions. On the other hand, the porphyrin-MLS peptide conjugate bearing a low molecular weight PEG spacer is highly water-soluble and does not aggregate in aqueous media. The fluorescence quantum yields determined for all porphyrins were higher at low pH (\u3c6) and the porphyrin-peptide conjugate had the highest quantum yields in aqueous media. All porphyrins showed low dark toxicity toward human carcinoma HEp2 cells, and the guanidine-porphyrin was the most phototoxic (IC50 = 4.8 μM at 1 J cm-2), followed by the biguanidine-porphyrin and the porphyrin-MLS (IC50 = 8.2 μM and 9.8 μM at 1 J cm -2, respectively). The porphyrin-MLS peptide conjugate accumulated the most within cells of all porphyrins at all times investigated and the biguanidine-porphyrin accumulated the least. Both the guanidine-and biguanidine-porphyrins localized within cell mitochondria and, in addition, were found in the lysosomes and the ER (in the case of the guanidine-porphyrin). In contrast, the porphyrin-MLS peptide conjugate localized mainly within the cell lysosomes. © 2008 American Chemical Society