Schiff碱Cu(Ⅱ)配合物的合成,表征,及其抑制脲酶活性的机理研究

为了得到一种新型脲酶抑制剂,以5-氯水杨醛和2-氨甲基哌啶合成Schiff碱配体,再与硝酸铜反应合成了一种Schiff碱Cu(Ⅱ)配合物。分别采用元素分析,单晶衍射、红外光谱测试技术对其进行表征,采用热重分析法探讨其对热稳定性,采用酚红法测定该配合物抑制脲酶活性的大小,采用Lineweaver-Burk模型研究其抑制脲酶的动力学机理,通过分子对接技术探讨配合物与脲酶的作用方式,并对其抑制机理进行分析。结果表明,目标配合物属于单斜晶系,P2₁/n空间群,四方形结构,它通过氢键、疏水键与脲酶形成稳定的结合模式;抑制脲酶活性的机制属于竞争性和非竞争性混合型抑制机制,其竞争性抑制作用大于非竞争性抑制作用。配合物对刀豆脲酶的IC₅₀为10.03μmol·L^-1,远低于常规脲酶抑制剂(45.06μmol·L^-1),从理论上解释了体外抑制脲酶活性的实验结果。

Synthesis,characterization and mechanism of urease inhibition of Cu(Ⅱ)complex of Schiff base

Schiff base ligand synthesized from 5-chloro salicylic aldehyde and 2-aminomethylpiperidine was reacted with copper nitrate to form a Schiff Base Cu(Ⅱ)complex type urease inhibitor.The final complex was characterized by elemental analysis,single crystal X-ray diffraction and infrared spectroscopy.The thermal stability of the complex was investigated by thermogravimetry whereas its urease inhibition activity was determined by phenol red method.The kinetic mechanism behind the inhibition was studied by Lineweaver-Burk model.Further,molecular docking technique was used to investigate the complex’s mode of action and its inhibitory mechanism.The analysis revealed that the target complex belonged to monoclinic system,P2₁/n space group with square structure.It formed a stable binding structure with urease through hydrogen and hydrophobic bondings.The mechanism of urease inhibition was identified as mixed competitive and non-competitive inhibitory mechanism with the domination of the competitive inhibitory effect.The IC₅₀ of the complex was 10.03μmol·L^-1,which was much lower than that of the conventional urease inhibitor(45.06μmol·L^-1).The experimental results of inhibiting urease activity in vitro were explained theoretically.