A Multipurpose Metallophore and Its Copper Complexes with Diverse Catalytic Antioxidant Properties to Deal with Metal and Oxidative Stress Disorders: A Combined Experimental, Theoretical, and In Vitro Study.

Abstract

We report the discovery that the molecule 1-(pyridin-2-ylmethylamino)propan-2-ol (HL) can reduce oxidative stress in neuronal C6 glioma cells exposed to reactive oxygen species (O₂^-•, H₂O₂, and ^•OH) and metal (Cu⁺) stress conditions. Furthermore, its association with Cu²⁺ generates [Cu(HL)Cl₂] (1) and [Cu(HL)₂](ClO₄)₂ (2) complexes that also exhibit antioxidant properties. Potentiometric titration data show that HL can coordinate to Cu²⁺ in 1:1 and 1:2 Cu²⁺:ligand ratios, which was confirmed by monocrystal X-ray studies. The subsequent ultraviolet-visible, electrospray ionization mass spectrometry, and electron paramagnetic resonance experiments show that they can decompose a variety of reactive oxygen species (ROS). Kinetic studies revealed that 1 and 2 mimic the superoxide dismutase and catalase activities. Complex 1 promotes the fastest decomposition of H₂O₂ (k_obs = 2.32 × 10⁷ M^-1 s^-1), efficiently dismutases the superoxide anion (k_cat = 3.08 × 10⁷ M^-1 s^-1), and scavenges the hydroxyl radical (RSA₅₀ = 25.7 × 10^-6 M). Density functional theory calculations support the formation of dinuclear Cu-peroxide and mononuclear Cu-superoxide species in the reactions of [Cu(HL)Cl₂] with H₂O₂ and O₂^•-, respectively. Furthermore, both 1 and 2 also reduce the oxidative stress of neuronal glioma C6 cells exposed to different ROS, including O₂^•- and ^•OH.