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

Copper(ii) acetylacetonates of N,N,N-donor dipicolylamine (dpa) ligands, viz. [Cu(L-1)(acac)]ClO4 (1), [Cu(L-2)(acac)]ClO4 (2) and [Cu(L-3)(acac)]ClO4 (3), where L-1 is benzyldipicolylamine (bzdpa), L-2 and L-3 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, (5) = 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 ((ex) = 465 nm) with a fluorescence quantum yield (phi(F)) 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 (phi(F) = 0.01) but acted as an efficient photosensitizer with a singlet oxygen quantum yield value of 0.59 (phi). Complex 3 showed a remarkable PDT effect with apoptotic cell death due to singlet oxygen giving IC50 values within 0.04-0.06 M in HeLa and MCF-7 cells using visible light (400-700 nm), while being less toxic in the dark.