The oxidative dehydrogenation of a coumarinyl scaffold with copper ion and metal ion detection in human liver cancer cells (HepG2)

Abstract

An unsymmetrical o-phenylenediamine derivative, L (7-hydroxy-4-methyl-8-(1-(phenyl- (pyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-2H-chromen-2-one), has been synthesized from (E)-N¹-(phenyl(pyridine-2-yl)methylene)benzene-1,2-diamine with 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde and characterized by X-ray, IR, ¹H NMR and ESI-MS spectral analyses. The X-ray structure shows L as a cyclic benzimidazole derivative, but it undergoes ring-opening upon reaction with transition metal ions. L is non-emissive in 9 : 1 (v/v) EtOH/H₂O (HEPES buffer, pH 7.4) but becomes highly fluorescent upon Zn²⁺ coordination, and the emissive Zn(II) complex undergoes transmetallation in the presence of Cu²⁺ ions specifically, followed by amine to imine oxidation, i.e. an oxidative dehydrogenation (OD) reaction –(2e + 2H⁺) occurs. The transmetallation of Zn²⁺ from the complex by Cu²⁺ (CuCl₂) separated the non-emissive X-ray diffractable crystal of [Cu(L′′)Cl] (L′′ = amine oxidized form of L). A square pyramidal [Cu(L′′)][ClO₄] complex was also isolated from the reaction of L with Cu(CH₃CN)₄(ClO₄) in the presence of air, and in this complex the amine is also oxidized to the imine. Here, copper ions in the presence of air play an important role in the OD reaction of L as determined by EPR and cyclic voltammetry studies. The ligand, L, is used for Zn²⁺ ion recovery from a municipally supplied water sample. A paper strip detection kit for Zn²⁺ and Cu²⁺ is designed using L. The ligand is also used for intracellular Zn²⁺ detection in a human liver cancer cell line (HepG2).