Banana-shaped biphotonic quadrupolar chromophores: from fluorophores to biphotonic photosensitizers

Abstract

This study aims at designing dual-role biphotonic chromophores that could be used for photodynamic therapy (PDT) while maintaining some fluorescence in order to locate them, thus allowing selective irradiation of cancer cells when combined with targeting. Quadrupolar two-photon absorbing fluorophores were synthesized from the symmetrical functionalization of a fluorene core bearing elongated conjugated rods made from arylene–vinylene or arylene–ethynylene building blocks in order to test modifications which could increase singlet oxygen production ability while retaining some fluorescence and high two-photon absorption (TPA) cross-sections in the biological spectral range of interest. All chromophores show a polar emissive excited state whose dipole moment is highly dependent on the nature of the conjugated linker. Interestingly, the largest TPA responses in the NIR region as well as singlet oxygen quantum yield are correlated with the smallest dipole moment of the emissive excited-state. The molecular optimization study led to a multifunctional biphotonic chromophore combining high TPA cross-sections in the whole spectral range of interest (700–900 nm), reasonable singlet oxygen production efficiency, significant remaining fluorescence, and alcohol end-groups for further covalent grafting. This compound offers thus interesting potentialities for highly selective spatially-resolved two-photon PDT by incorporation in nanostructures.