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 (O 2 −• , H 2 O 2 , and • OH) and metal (Cu + ) stress conditions. Furthermore, its association with Cu 2+ generates [Cu(HL)Cl 2 ] (1) and [Cu(HL) 2 ](ClO 4 ) 2 (2) complexes that also exhibit antioxidant properties. Potentiometric titration data show that HL can coordinate to Cu 2+ in 1:1 and 1:2 Cu 2+ :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 H 2 O 2 (k obs = 2.32 × 10 7 M −1 s −1 ), efficiently dismutases the superoxide anion (k cat = 3.08 × 10 7 M −1 s −1 ), and scavenges the hydroxyl radical (RSA 50 = 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)Cl 2 ] with H 2 O 2 and O 2•− , respectively. Furthermore, both 1 and 2 also reduce the oxidative stress of neuronal glioma C6 cells exposed to different ROS, including O 2•− and • OH.