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(-center dot), H2O2, and( center dot)OH) and metal (Cu+) stress conditions. Furthermore, its association with Cu2+ generates [Cu(HL)Cl-2] (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 x 10(7) M-1 s(-1)), efficiently dismutases the superoxide anion (k(cat) = 3.08 x 10(7) M-1 s(-1)), and scavenges the hydroxyl radical (RSA(50) = 25.7 x 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 H2O2 and O-2(center dot-), respectively. Furthermore, both 1 and 2 also reduce the oxidative stress of neuronal glioma C6 cells exposed to different ROS, including O-2(center dot-) and (OH)-O-center dot.