A new mixed-ligand Co(II) coordination polymer: treatment activity on ulcerative colitis by inhibiting the JAK2/STAT3 signaling pathway in the colonic epithelial cells

In the current study, a novel mixed-ligand coordination polymer, {[Co(L)(dpe)]·(ClO₄)} (<b>1</b>) (H₂LCl = 3-carboxy-1-(3-carboxybenzyl)pyridin-1-ium, dpe = (E)-1,2-di(pyridin-4-yl)ethene), was synthesized under hydrothermal conditions by a zwitterionic organic ligand and fully characterized by the single crystal X-ray diffraction, powder X-ray diffraction, elemental analysis along with the FT-IR. Furthermore, the treatment activity of the compound on the ulcerative colitis was evaluated and the related mechanism was explored. First, the level of the tumor necrosis factor (TNF)-α and superoxide dismutase (SOD) released by the colon tissue into the plasma was measured with enzyme-linked immunosorbent assay (ELISA) detection kit. In addition to this, the activation level of the JAK2/STAT3 signaling pathway in the colonic epithelial cells was also determined with western blot. With the help of molecular docking simulation, the potential interacting gestures between the complex and the protein have been revealed.

本研究中，研究人员以两性离子有机配体为原料，在水热条件下合成了一种新型混合配体配位聚合物{[Co(L)(dpe)]·(ClO₄)}（化合物1），其中H₂LCl=3-羧基-1-(3-羧基苄基)吡啶鎓，dpe=(E)-1,2-二(4-吡啶基)乙烯。随后通过单晶X射线衍射（single crystal X-ray diffraction）、粉末X射线衍射（powder X-ray diffraction）、元素分析以及傅里叶变换红外光谱（FT-IR）对该聚合物进行了全面表征。进一步，我们评估了该化合物对溃疡性结肠炎的治疗活性，并探究了其相关作用机制。首先，采用酶联免疫吸附测定（ELISA）试剂盒检测结肠组织释放入血浆的肿瘤坏死因子-α（TNF-α）与超氧化物歧化酶（SOD）水平；此外，通过蛋白质印迹（western blot）检测结肠上皮细胞内JAK2/STAT3信号通路的激活程度。借助分子对接模拟，本研究揭示了该配位聚合物与蛋白质之间的潜在相互作用模式。