Mitochondria localizing high-spin iron complexes of curcumin for photo-induced drug release

Abstract

High-spin iron complexes [FeII(L1)(cur)]Cl (1), [FeIII(L2)(cur)]Cl (2) and [FeIII(L3)(cur)] (3), where L1 is tris(2-pyridylmethyl)amine, HL2 is N,N-bis(2-pyridylmethyl)-N-(2-hydroxybenzyl)amine and H2L3 is N,N-dimethyl-N’,N’-bis(4,6-ditertiarybutyl-2-hydroxybenzyl)ethylenediamine and Hcur is curcumin, were synthesized, characterized and their redox-mediated and/or visible light induced release of curcumin, photo-induced DNA cleavage and anticancer activity studied. The molecular structures of 1–3 were optimized from DFT (density functional theory) calculations. The t2g3eg2-iron(III) complexes showed a curcumin based electronic spectral band at ∼ 425 nm in 1:1 DMF/DPBS (Dulbecco's phosphate-buffered saline) and displayed the Fe(III)-Fe(II) redox couple near −0.36 V vs. SCE (saturated calomel electrode) in DMF-0.1 M TBAP (tetrabutylammonium perchlorate). The complexes are avid binders to calf thymus DNA. Complex 1 showed photo-cleavage of pUC19 DNA in visible light of 446 nm forming OH radicals as the reactive oxygen species. The complexes as curcumin carrier showed photo-cytotoxicity in different cell lines on visible light activation. Imaging study showed their subcellular mitochondrial localization.