Chlorin-based symmetrical and unsymmetrical dimers with amide linkages: effect of the substituents on photodynamic and photophysical properties

In this study, we report syntheses, in vivo biological activity, and photop hysical properties of a series of chlorin-based symmetrical and unsymmetric al dimers with amide linkages. All compounds exhibited strong absorption ma xima at wavelengths ranging between lambda(max) 660 and 702 nm. Compared wi th the formylpyropheophorbide a dimer 7 and purpurin 18 dimer 9 containing electron-withdrawing substituents at peripheral positions, pyropheophorbide a dimer 6, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide a dimer 8, and un symmetrical dimer 12 in which the chlorin e(6) and 3-devinyl-3-(1-hexyloxye thyl)pyropheophorbide a moieties are linked with amide bonds, produced high fluorescence yields. For all photosensitizers, energy transfer from the se nsitizer triplet to the ground state of oxygen is irreversible with rate co nstants k(T Sigma)approximate to 2x10(9) M-1 s(-1), a value in the diffusio n-limited rate range. This energy transfer resulted in relatively high sing let oxygen quantum yields (Phi(Delta)approximate to 0.50 for compounds 12 a nd 8; and Phi(Delta)approximate to 0.30 for compounds 6 and 7). Among these dimers, compound 9 with a six-membered anhydride ring system produced the lowest singlet oxygen quantum yield (Phi(Delta) 0.06). The in vivo PDT effi cacy of these compounds was evaluated in DBA/2 mice bearing SMT/F tumors. A mong all the dimers, the unsymmetrical dimer 12 was found to be most effect ive, but it was significantly less active than the related monomer 3-deviny l-3-(1-hexyloxyethyl)pyropheophorbide a 2.