Targeted photodynamic therapy in visible light using BODIPY-appended copper(ii) complexes of a vitamin B6 Schiff base

Abstract

Copper(II) complexes [Cu(L¹/L²/L³)(A)] (1–3), where H₂A·HCl is a vitamin B₆ Schiff base, viz. 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-1-ium chloride, L¹ and L² are 2-(2-pyridyl)benzimidazole based borondipyrromethene (BODIPY) ligands and L³ is 2-(2-pyridyl)benzimidazole, were prepared, characterized and their visible light-induced anti-cancer activity was studied. Complex 3, characterized by X-ray crystallography, exhibits a distorted square-pyramidal geometry for copper (τ = 0.33). Complexes 1 and 2 showed absorption bands at 500 and 535 nm, respectively, in 20% DMSO/Dulbecco's phosphate buffered saline (DPBS) medium. Complex 1 exhibited emission at ∼510 nm (λ_exc = 480 nm) (Φ_F = 0.1) in 20% DMSO/DPBS, while the non-emissive diiodo-BODIPY complex 2 is an efficient photosensitizer. The green fluorescent complex 1 enabled us to study its cellular uptake and localization. It showed selective uptake in proliferating cancer cells and significant mitochondrial localization (Pearson's coefficient = 0.7). Complex 2 showed excellent photocytotoxicity (400–700 nm, 10 J cm⁻²) in HeLa, MCF-7 and HepG2 cancer cells with IC₅₀ values within 0.4–0.6 μM, while remaining less toxic in the dark and in non-cancerous HPL1D cells (photocytotoxic index ∼50). Complex 2, remarkable in targeting cancer cells over non-cancerous cells, showed photoinduced generation of singlet oxygen, causing apoptotic cell death, thus satisfying the major requirements of targeted photodynamic therapy.