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.

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.