BODIPY-linked cis-dichlorido zinc(ii) conjugates: the strategic design of organelle-specific next-generation theranostic photosensitizers

Dipicolylamine (dpa) based cis-dichlorido zinc(ii) complexes [Zn(L1-3)Cl-2] (1-3), where L-2 and L-3 are non-iodo and di-iodo BODIPY-appended dpa in 2 and 3, and L-1 is dpa in control complex 1, were prepared and characterized and their photocytotoxicity was studied. Complexes 2 and 3 were developed as potential substitutes for zinc(ii)-porphyrins/phthalocyanines that are photodynamic therapeutic agents with moderate activity owing to their inherent hydrophobicity and aggregation-induced deactivation mechanism. In our approach, we strategically designed hybrid inorganic-organic zinc-BODIPY conjugates as theranostic photosensitizers. The structurally characterized diamagnetic Zn(ii) cis-dichlorido complexes mimic cisplatin and serve as new-generation photosensitizers with enhanced aqueous solubility and mito-DNA targeting propensity while imparting significant physiological stability to the heavy atom tethered BODIPY ligand, L-3. The BODIPY complexes showed a visible band near 500 nm (epsilon similar to 34 000-44 000 dm(3) mol(-1) cm(-1)) and an emission band at 507 nm for 2 in 1% DMSO-Dulbecco's phosphate buffered saline. The labile chlorido ligands (Lambda(M) similar to 200 S m(2) mol(-1) in 9 : 1 H2O-DMSO) generated positively charged complexes inside the cellular medium enabling them to cross the mitochondrial membrane for this organelle-selective localization and singlet oxygen-mediated apoptotic photocytotoxicity at nanomolar concentrations for 3 in HeLa and MCF-7 cells in light (400-700 nm), while being less active in the dark.