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 photophysical properties of a series of chlorin-based symmetrical and unsymmetrical dimers with amide linkages. All compounds exhibited strong absorption maxima at wavelengths ranging between λmax 660 and 702 nm. Compared with 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 unsymmetrical dimer 12 in which the chlorin e6 and 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide a moieties are linked with amide bonds, produced high fluorescence yields. For all photosensitizers, energy transfer from the sensitizer triplet to the ground state of oxygen is irreversible with rate constants kTΣ ≈ 2 × 109 M−1 s−1, a value in the diffusion-limited rate range. This energy transfer resulted in relatively high singlet oxygen quantum yields (ΦΔ ≈ 0.50 for compounds 12 and 8; and ΦΔ ≈ 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 (ΦΔ 0.06). The in vivo PDT efficacy of these compounds was evaluated in DBA/2 mice bearing SMT/F tumors. Among all the dimers, the unsymmetrical dimer 12 was found to be most effective, but it was significantly less active than the related monomer 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide a2.