Mitochondria-localizing BODIPY–copper(ii) conjugates for cellular imaging and photo-activated cytotoxicity forming singlet oxygen

Abstract

Copper(II) acetylacetonates of N,N,N-donor dipicolylamine (dpa) ligands, viz. [Cu(L1)(acac)]ClO4 (1), [Cu(L2)(acac)]ClO4 (2) and [Cu(L3)(acac)]ClO4 (3), where L1 is benzyldipicolylamine (bzdpa), L2 and L3 are non-iodinated and diiodinated BODIPY (borondipyrromethene) ligands and Hacac is acetylacetone, were synthesized and characterized and their photocytotoxicity was studied. The BODIPY complex 2, structurally characterized by X-ray crystallography, has copper(II) in a distorted square-pyramidal geometry (degree of trigonality, τ5 = 0.28). The one-electron paramagnetic and redox active copper(II) complexes displayed 1 : 1 electrolytic behaviour in polar organic solvents. The BODIPY complexes 2 and 3 showed respective visible bands at 498 and 539 nm in 5% DMSO–phosphate buffered saline (PBS). Complex 2 displayed an emission band at 511 nm in 5% DMSO–PBS (λex = 465 nm) with a fluorescence quantum yield (ΦF) value of 0.15. Cellular imaging using this complex showed significant mitochondrial localization in HeLa and MCF-7 cancer cells. Complex 3 with a diiodo-BODIPY moiety was non-emissive (ΦF = 0.01) but acted as an efficient photosensitizer with a singlet oxygen quantum yield value of 0.59 (ΦΔ). Complex 3 showed a remarkable PDT effect with apoptotic cell death due to singlet oxygen giving IC50 values within 0.04–0.06 μM in HeLa and MCF-7 cells using visible light (400–700 nm), while being less toxic in the dark.