二茂铁基咪唑并[1,2-a]吡啶化合物的合成及抗氧化性能

Synthesis and Antioxidant Properties of Ferrocenyl Imid-azo[1,2-a]pyridine Compounds

摘要:

以乙醇为溶剂，在加热条件下采用LaCl3催化2-氨基吡啶、二茂铁甲醛和异氰之间的Groebke-Blackburn-Bienaym?三组分反应（GBB-3CR）合成5个二茂铁基咪唑并[1,2-a]吡啶化合物。利用核磁共振氢谱（proton magnetic resonance，1H NMR）、核磁共振碳谱（carbon-13 magnetic resonance，13C NMR）和超高效液相色谱-电喷雾离子源质谱联用仪（ultra high performance liquid chromatograph electrospray ion source mass spectrometer，UHPLC-ESI-MS）对合成产物结构进行了表征，并通过抑制HO?和还原型谷胱甘肽自由基(glutathione，GS?)引发的DNA氧化反应体系对化合物的抗氧化活性进行了检测，采用淬灭2,2?-偶氮-双-(3-乙基苯并噻唑啉-6-磺酸)二铵盐自由基（2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical，ABTS?）和二苯苦味酰肼自由基（2,2’-diphenyl-1-picrylhydrazyl，DPPH?）体系探索了化合物还原自由基的能力，进而探究了取代基对二茂铁基咪唑并[1,2-a]吡啶抗化合物氧化性能的影响。结果表明：5个目标化合物不仅能够有效地抑制自由基引发的DNA氧化反应，也能捕获自由基，是一类潜在的抗氧化剂。其中，在抑制HO?引发的DNA氧化反应体系中，5个化合物相对空白TBARS吸光度百分数可达65.4%~93.7%；在抑制GS?引发的DNA氧化反应体系中，5个化合物相对空白TBARS吸光度百分数可达25.6%~62.5%；5个二茂铁基咪唑并[1,2-a]吡啶化合物均能够捕获ABTS?和DPPH?两种自由基；双二茂铁基化合物VI抑制自由基引发的DNA氧化反应活性和捕获自由基能力优于其它化合物。

Abstract:

Five ferrocenyl imidazo[1,2-a]pyridine compounds were synthesized by Groeb-ke-Blackburn-Bienaym? three-component-reaction (GBB-3CR) among 2-aminopyridine, ferro-cenecarboxaldehyde, and isocyanide with LaCl3 being catalyst in ethanol. The structure of the com-pounds were confirmed by proton magnetic resonance (1H NMR), carbon-13 magnetic resonance (13C NMR), and ultra high performance liquid chromatograph electrospray ion source mass spec-trometer (UHPLC-ESI-MS). Antioxidant abilities of the obtained compounds were evaluated by in-hibiting HO?- and Cu2 /glutathione (GSH)-induced oxidation of DNA. The radical-scavenging prop-erties of the obtained compounds were estimated by quenching 2,2?-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS?) and 2,2?-diphenyl- 1-picrylhydrazyl (DPPH?), and then the effects of substituents on the antioxidant properties of fer-rocenyl imidazo[1,2-a]pyridine compounds could be explored. The results showed that the TBARS percentages of five compounds were 65.4%~93.7% in inhibiting HO?- induced oxidation of DNA. The TBARS percentages of five compounds were 25.6%~62.5% in inhibiting GS?- induced oxidation of DNA. All five ferrocenyl imidazo[1,2-a]pyridine compounds could scavenge ABTS? and DPPH?. The compounds VI containing two ferrocenyls exhibits higher activity than other compounds in quenching radicals and inhibiting radicals induced oxidation of DNA.