Iron(III) Complexes of Vitamin B 6 Schiff Base with Boron‐Dipyrromethene Pendants for Lysosome‐Selective Photocytotoxicity

Abstract

Iron(III) complexes of a vitamin B6 Schiff base and NNN-donor ligands with pendant boron-dipyrromethene (BODIPY) moieties; namely, [Fe(L1–3)(L4,5)](NO3) (1–4), where L1 is benzyl-bis[(pyridin-2-yl)methyl]methanamine (bzdpa in 1), L2 is a noniodinated BODIPY-appended dipicolylamine ligand (in 2, 3), L3 is the diiodinated BODIPY analogue in 4, L4 is a vitamin B6 Schiff base, namely 3-hydroxy-5(hydroxymethyl)-4-{[(2-hydroxyphenyl)imino]methyl}-2-methylpyridine (in 1, 3, and 4), and L5 is 2-[(2-hydroxyphenylimino)-methyl]phenol (in 2) as a nonpyridoxal Schiff base, were prepared, characterized, and their cellular localization and cytotoxic activity in light and in the dark were studied. The diiodo–BODIPY complex 4 displays remarkable photoinduced cytotoxicity in visible light (400–700 nm), with IC50 values within 0.11–0.25 µm and about 200-fold lower dark toxicity. Complex 3, being fluorescent, was used for cellular imaging by confocal microscopy. Complex 4 shows supercoiled pUC19 DNA cleavage activity through the generation of singlet oxygen (1O2) as the reactive oxygen species (ROS). Selective uptake of the complexes is observed from competitive cellular incorporation assays in cancer and noncancer cells. The complexes also show no apparent toxicity up to 100 µm in the immortal human lung epithelial cells HPL1D in both light and the dark. Complex 3 shows preferential accumulation in lysosomes, giving a Pearson's correlation coefficient value of about 0.7.