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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
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2024-07-30 , DOI: 10.1021/acs.inorgchem.4c00232
Lucas B Menezes 1 , Raquel M S N Sampaio 2 , Lino Meurer 1 , Bruno Szpoganicz 1 , Rodrigo Cervo 3 , Roberta Cargnelutti 3 , Lukun Wang 4 , Jiawen Yang 4 , Rajeev Prabhakar 4 , Christiane Fernandes 1 , Adolfo Horn 1
Affiliation  

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 (kobs = 2.32 × 107 M–1 s–1), efficiently dismutases the superoxide anion (kcat = 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.

中文翻译:


一种多用途金属团及其具有多种催化抗氧化特性的铜配合物,可处理金属和氧化应激障碍:实验、理论和体外综合研究



我们报告发现分子 1-(pyridin-2-ylmethylamino)propan-2-ol (HL) 可以减少暴露于活性氧(O 2 –• 、H 2 O 2 OH) 和金属(Cu + ) 应力条件。此外,它与 Cu 2+结合生成 [Cu(HL)Cl 2 ] ( 1 ) 和 [Cu(HL) 2 ](ClO 4 ) 2 ( 2 ) 络合物,也具有抗氧化性能。电位滴定数据表明,HL 可以以 1:1 和 1:2 Cu 2+ :配体比例与 Cu 2+配位,这已通过单晶 X 射线研究得到证实。随后的紫外可见光、电喷雾电离质谱和电子顺磁共振实验表明它们可以分解多种活性氧(ROS)。动力学研究表明, 12模拟了超氧化物歧化酶和过氧化氢酶的活性。配合物1促进 H 2 O 2最快分解 ( k obs = 2.32 × 10 7 M –1 s –1 ),有效歧化超氧阴离子 ( k cat = 3.08 × 10 7 M –1 s –1 ),并清除羟基自由基 (RSA 50 = 25.7 × 10 –6 M)。 密度泛函理论计算支持在[Cu(HL)Cl 2 ]与H 2 O 2和O 2 •–的反应中分别形成双核过氧化铜和单核超氧化铜物质。此外, 12还可以减少暴露于不同ROS(包括O 2 •– OH)的神经胶质瘤C6细胞的氧化应激。
更新日期:2024-07-30
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