Mitochondria-Targeted Anticancer Activity of BODIPY-Appended Iron(III) Catecholates in Red Light

Abstract

Iron(III) catecholates of dipicolylamine (dpa) bases having appended Benzyl (in bzdpa) or BODIPY (borondipyrromethene) moiety (in L1 and L2), viz. [Fe(Bzdpa)(cat)Cl] (1), [Fe(L1)(cat)Cl] (2) and [Fe(L2)(cat)Cl] (3), were prepared and characterized (H2cat=catechol). The iron(III) complexes with a ligand-to-metal charge transfer (LMCT) band within 600–800 nm were studied for their photocytotoxicity in visible (400–700 nm) and red (600–720 nm) light. Complex 2 with a BODIPY fluorophore in L1 gave IC50 values of 2.2±0.5 and 15.0±0.7 μM in visible and red light, respectively, in HeLa cells. Complex 3 with a diiodo-BODIPY moiety showed excellent PDT activity giving respective IC50 values of 0.8±0.2 and 12.6±1.1 μM. They are less toxic in dark (IC50: ≥85 μM). A similar activity was observed in MCF-7 cancer cells. The BODIPY complexes showed significant mitochondrial localization. Annexin FITC assay showed apoptotic cell death involving reactive oxygen species (ROS). Photo-generation of ROS was evidenced from dichlorofluorescein diacetate (DCFDA) assay. Mechanistic studies on DNA photocleavage reactions showed the presence of two types of ROS. Singlet oxygen formation from BODIPY was evidenced from the 1,3-diphenylisobenzofuran (DPBF) experiments. Hydroxyl radical was generated on red light photo-activation of the LMCT band within photodynamic therapy (PDT) spectral window.