Conformationally restrained coumarin hemicyanines: Improved quantum yields and potential applications in bioimaging and photodynamic therapy

Abstract

In this work, by installing a bicyclic ring system into the skeleton of traditional coumarin-hemicyanines (CHCs), a new class of conformationally restrained coumarin-hemicyanines (RCHCs) were constructed, which showed dramatically improved fluorescence quantum yields (close to near-unity in CH2Cl2), while retaining the large Stokes shifts of CHCs. The feature was also reflected in living cell imaging, where the representative RCHCs, i.e. RCHC1 and RCHC2, showed significantly improved intracellular fluorescence brightness relative to control dye CHC1, along with excellent lysosome and mitochondria targetability. Based on RCHC1 platform, a carboxy-functionalized derivative, i.e., RCHC1-COOH, was developed, and its potential in fluorescently discriminating between cancer and normal cells was demonstrated in terms of its specific accumulation in lipid rafts localized in plasma membrane and enriched in cancer cells. Based on RCHC2 platform, a photosensitizer (PS) RCHC2-I was exploited for photodynamic therapy (PDT) of tumor, which exhibited markedly enhanced singlet oxygen generating ability due to its strong propensity to form aggregates. In vitro and in vivo PDT assays proved that RCHC2-I could cause extensive cancer cell death and tumor ablation upon light irradiation.