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

Abstract

Dipicolylamine (dpa) based cis-dichlorido zinc(II) complexes [Zn(L^1–3)Cl₂] (1–3), where L² and L³ are non-iodo and di-iodo BODIPY-appended dpa in 2 and 3, and L¹ 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, L³. The BODIPY complexes showed a visible band near 500 nm (ε ∼ 34 000–44 000 dm³ 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 (Λ_M ∼ 200 S m² 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.