Design,Synthesis,and Biological Evaluation Of Complexes Based On Schiff Bases

In recent years,the studies on the coordination compounds with Schiff-base as ligands have attracted our great attentions for their potential applications in biological activities such as urease inhibitory,antibacterial and antitumor.In this paper,a series of Schiff-base ligands and their metal complexes were designed and synthesized,Crystal structures have been characterized by X-ray diffraction,IR and elemental analysis.Meanwhile,the related biological activities of the compounds have been studied.1.Three mononuclear Cu（II）complexes Cu（HL1’）Cl2（1）,Cu（HL2’）Cl2（2）,and Cu（L3）SCN（3）havebeensynthesized.[HL1=N’-（1-（pyrazin-2-yl）ethylidene）isonicotinohydrazide,HL2=N’-（1-（pyrazin-2-yl）ethylidene）-2-（pyridin-3-yl）acetohydrazide,HL3=N’-（pyridin-2-ylmethylene）picolinohydrazide].The crystal structures of these new compounds were characterized by X-ray diffraction,IR and elemental analyses.In the complexes 1-3,Cu（II）center is five coordinated.Their urease inhibitory evaluation was tested in vitro against jack bean urease.The results showed that these Cu（II）complexes display effective urease inhibitory activity with IC₅₀values 5.39μM for 1,2.02μM for 2,and 5.21μM for 3,which are all superior to the positive reference AHA.Enzyme kinetics studies were undertaken to estimate the inhibition mechanism of the copper complexes.The results showed complexes 1 and 3 are mixed type inhibitors,while 2 is uncompetitive type of inhibition.Molecular docking simulations have been performed to rationalize their binding models.In addition,these complexes also exhibited tight binding affinity to the SAs,which are indicative of the potential of binding to SA,getting transferred,and release upon arrival at their targets.So complexes 1-3 might be considered for the use as potential urease inhibitors.2.N′-（1-（pyrazin-2-yl）ethylidene）isonicotinohydrazide（HL1）as the ligand has been prepared.Reaction with Zn（NO₃）₂?6H₂O,Cu（NO₃）₂?3H₂O and Ag NO₃afford three complexes,[Zn（HL1’）₂]·2NO₃·3H₂O（4）,{[Cu₂（L1）₂（NO₃）（H₂O）₂]·NO₃}_n（5）,{[Ag₂（L1）₂]·3H₂O}_n（6）.These complexes have been structurally characterized by elemental analysis,IR spectroscopy and X-ray diffraction.In 4,HL1 acts as neutral tridentate ligand,whereas in 5 and 6,HL1 acts as deprotonated four-dentate ligand.The hydrogen bonding interactions result in various supramolecular polymeric structure,2-D layer for 4,3-D network for 5 and 6,respectively.The antibacterial activity of these complexes have been investigated,the result indicated that complex 6 showed good antibacterial activities.3.HL4,HL5 and HL6 were obtained using hydrazinecarbothioamide,N-methylhydrazinecarbothioamide,N-（3-（trifluoromethyl）phenyl）hydrazinecarbothioamide and 2-acetylpyrazine as the raw material.Further reaction of the ligand HL4 with Zn（NO₃）₂?6H₂O afforded complexes Zn（L4）₂（7）.Reactions of HL5 with Cd（NO₃）₂·4H₂O afforded complexes Cd（L5）₂（8）.Reactions of HL6 with Co（NO₃）₂?6H₂O,Zn（NO₃）₂?6H₂O afforded complexes Co（L6）₂（9）,Zn（L6）₂（10）.Crystal structures of these new compounds were characterized by X-ray diffraction,IR and elemental analyses.On the self-assemble process,all ligands featured thiol tautomerism and are anionic form of ligands.During the assembly of supramolecular architectures,the hydrogen-bonding interactions play an important role,leading to 2-D layer for 7 and 8,dinuclear structure for 9 and 10.The antibacterial activity of these complexes have been investigated,the result indicated that complex 8,9 and 10 showed more effective antibacterial activities than their ligands,especially complex 8 exhibits significant antibacterial effect.