Iron(III) Complexes of a Pyridoxal Schiff Base for Enhanced Cellular Uptake with Selectivity and Remarkable Photocytotoxicity

Iron­(III) complexes of pyridoxal (vitamin B6, VB6) or salicylaldehyde Schiff bases and modified dipicolylamines, namely, [Fe­(B)­(L)]­(NO3) (1–5), where B is phenyl-N,N-bis­((pyridin-2-yl)­methyl)­methanamine (phbpa in 1), (anthracen-9-yl)-N,N-bis­((pyridin-2-yl)­methyl)­methanamine (anbpa in 2, 4) and (pyren-1-yl)-N,N-bis­((pyridin-2-yl)­methyl)­methanamine (pybpa in 3, 5) (H2L1 is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)­imino)­methyl)-2-methylpyridine (1–3) and H2L2 is 2-[(2-hydroxyphenyl-imino)­methyl]­phenol), were prepared and their uptake in cancer cells and photocytotoxicity were studied. Complexes 4 and 5, having a non-pyridoxal Schiff base, were prepared to probe the role of the pyridoxal group in tumor targeting and cellular uptake. The PF6 salt (1a) of complex 1 is structurally characterized. The complexes have a distorted six-coordinate FeN4O2 core where the metal is in the +3 oxidation state with five unpaired electrons. The complexes display a ligand to metal charge transfer band near 520 and 420 nm from phenolate to the iron­(III) center. The photophysical properties of the complexes are explained from the time dependent density functional theory calculations. The redox active complexes show a quasi-reversible Fe­(III)/Fe­(II) response near −0.3 V vs saturated calomel electrode. Complexes 2 and 3 exhibit remarkable photocytotoxicity in various cancer cells with IC50 values ranging from 0.4 to 5 μM with 10-fold lower dark toxicity. The cell death proceeded by the apoptotic pathway due to generation of reactive oxygen species upon light exposure. The nonvitamin complexes 4 and 5 display 3-fold lower photocytotoxicity compared to their VB6 analogues, possibly due to preferential and faster uptake of the vitamin complexes in the cancer cells. Complexes 2 and 3 show significant uptake in the endoplasmic reticulum, while complexes 4 and 5 are distributed throughout the cells without any specific localization pattern.