Curcumin “Drug” Stabilized in Oxidovanadium(IV)-BODIPY Conjugates for Mitochondria-Targeted Photocytotoxicity

Abstract

Ternary oxidovanadium(IV) complexes of curcumin (Hcur), dipicolylamine (dpa) base, and its derivatives having pendant noniodinated and di-iodinated boron-dipyrromethene (BODIPY) moiety (L1 and L2, respectively), namely, [VO(dpa)(cur)]ClO4 (1), [VO(L1)(cur)]ClO4 (2), and [VO(L2)(cur)]ClO4 (3) and their chloride salts (1a–3a) were prepared, characterized, and studied for anticancer activity. The chloride salts were used for biological studies due to their aqueous solubility. Complex 1 was structurally characterized by single-crystal X-ray crystallography. The complex has a VO2+ moiety bound to dpa ligand showing N,N,N-coordination in a facial mode, and curcumin is bound in its mono-anionic enolic form. The V–O(cur) distances are 1.950(18) and 1.977(16) Å, while the V–N bond lengths are 2.090(2), 2.130(2), and 2.290(2) Å. The bond trans to V═O is long due to trans effect. The complexes are stable in a solution phase over a long period of time of 48 h without showing any apparent degradation of the curcumin ligand. The diiodo-BODIPY ligand (L2) or Hcur alone showed limited solution stability in dark. The emissive BODIPY (L1) containing complex 2a showed preferential mitochondrial localization in MCF-7 cells in cellular imaging experiments. The cytotoxicity of the complexes was studied by MTT assay. The BODIPY complex 3a showed excellent photodynamic therapy effect in visible light (400–700 nm) giving IC50 values of 2–6 μM in HeLa and MCF-7 cancer cells, while being less toxic in dark (∼100 μM). The cell death was apoptotic in nature involving reactive oxygen species (ROS). Mechanistic data from pUC19 DNA photocleavage studies revealed photogenerated ROS as primarily 1O2 from the BODIPY moiety and ·OH radicals from the curcumin ligand.