| Since the clinical success of anticancer drugs cisplatin and related platinum complexes,developing biologically active metal complexes as potential therapeutic agents has become a central research theme in bioinorganic chemistry.Urease,a nickel-containing metalloenzyme,has marked negative impacts on plants and animals Therefore,it is important to control of the activity of urease through the use of inhibitors.With multidrug resistance of pathogenic species,Bacterial resistance is a major worldwide health problem.There is an urgent need to develop new antibacterials to overcome the problem of resistance.In the thesis,transition metal complexes and ligands based on 1,2,4-triazole,carboxyl functionalized quinoline and Schiff bases with pyridine and pyrazine as coordination sites have been synthesized and characterized by IR,elemental analysis,and X-ray diffraction single crystal analysis.And the antibacterial activity or urease inhibitory properties were investigated.The details of contents are as follow:1.Two dinuclear cobalt(Ⅱ)complexes,[Co2(L1)2(CH3OH)4].4(ClO4)2(1),and[Co2(L1)2(H2O)2(NO3)2]·2NO3(2),And two d10 complexes[Cd(L1)I2(H2O)](3)and[Ag2(L1)2]·2(CF3SO3)(4),(L1=4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole)have been obtained and characterized by IR,elemental analysis,and X-ray diffraction single crystal analysis.Complex 1 crystallizes in monoclinic space group C2/c.Co(Ⅱ)center coordinates with four nitrogen atoms(N1,N2,N3 and N6)and two ethanol molecules.Cell parameters:a=16.9082(7)(?),b=21.0229(1)(?),c=13.3146(6)(?),α=90.00°,β=90.87(2)°,γ=90.00°;Complex 2 crystallizes in triclinic space group P1.Each of the two Co(Ⅱ)centers binds one H2O and one NO3 coligands in the axial positions.Cell parameters:a=7.7390(1)(?),b=10.1564(1)(?),c=11.4124(2)(?),α=72.94(4)°,β=76.71(4)°,γ=87.21(4)°.The stabilization of complexes 1 and 2 crystal lattices is maintained by strong hydrogen bonds between counterions and host framework,which lead to various supramolecular architectures.Complex 3 is mononuclear and crystallizes in the Triclinic space group P-1.Cd(Ⅱ)center is five coordinated.Cell parameters:a=9.1383(9)(?),b=10.0300(1)(?),c=11.5590(4)A,α=98.829(3)°,β=109.141(3)°,γ=114.035(3)°.While complex 4 possesses a dinuclear structure with coordination number 4 for Ag(I)center and also crystallizes in the Triclinic space group P-1.Ag(Ⅰ)coordinates with four N-donors from two different L1.Cell parameters:a=7.9629(4)(?),b=9.5904(5)(?),c =11.9596(5)(?),a=70.0360(1)°,β=82.466(2),γ=72.535(2)°.The urease inhibitory properties of 1-4 and L1 were investigated,where the complexes 1-3 revealed strong urease inhibition activities with the IC50 value(half-inhibitory concentration)of 4.63,5.51 μM and 5.01 μM,respectively,which are superior to the positive control AHA(IC50=7.21 μM).Docking simulation of complex 2 has been performed with H.pylori urease(PDB code:1E9Y)to rationalize their binding models.2.Carboxyl functionalized 2-phenyl quinoline three derivatives,2-(4-bromophenyl)quinoline-4-carboxylic acid(L2).2-(4-fluorophenyl)quinoline-4-carboxylic acid(L3)and 2-(4-methoxyphenyl)quinoline-4-carboxylic acid(L4)were synthesized.Further coordination reactions of 2-(4-bromophenyl)quinoline-4-carboxylic acid(L2)with metal acetate afford dinuclear paddle-wheel like complexes,M2(L)4(CH3OH)4(M=Mn(Ⅱ),(5);M=Co(Ⅱ),(6);M=Zn(Ⅱ),(7);M=Cd(Ⅱ),(8).And the reaction of these ligands L3,L4 with Cd(CH3COO)2 afforded new cadmium complexes,[Cd2(L3)4(CH3OH)4]·1.5H2O(9)and[Cd2(L4)4(CH3OH)4](10),respectively.Complexes 5-10 are isostructual.They all crystallize in tetragonal space group I41/a.Two metalion centers bridged by four ligands.Each metal ion adopts a distorted octahedral geometry.Cell parameters:5:a=22.0434(8)(?),b=22.0434(8)(?),c=12.4887(9)(?),α=β=γ=90.00°;6:a=21.9272(6)(?),b=21.9272(6)(?),c=12.4881(7)A,α=β=γ=90.00°;7:a=21.9395(5)(?),b=21.9395(5)(?),c=12.5238(6)(?),α=β=γ=90.00°;8:a=22.2704(4)(?),b=22.2704(4)(?),c=12.4016(5)(?),α=β=γ=90.00°;9:a=22.4253(4)(?),b=22.4253(4)(?),c=12.0499(4)(?),α=β=γ=90.00°:10:a=22.5144(3)(?),b=22.5144(3)(?),c=12.3995(5)(?),α=β=γ=90.00°.These complexes were characterized by infrared spectra,elemental analysis,and single-cyrstal X-ray diffraction.The antibacterial(Escherichia coli,Pseudomonas aeruginosa,Bacillus subtilis and Staphyhcoccus aureus)activities of these compounds have been studied.The results indicated that these complexes showed better antibacterial activities than the free ligand or metal salts alone.Among them,the Zn(Ⅱ)and Cd(Ⅱ)complexes(7 and 8)showed excellent antibacterial activity against Staphylococcus aureus(with corresponding IC50 of 0.57 μg/mL and 0.51 μg/mL).And the antibacterial level of complex 9 against B.subtilis and S.aurecs was close to the positive control streptomycin.3.Schiff base ligands,N’-(1-(pyrazin-2-yl)ethylidene)picoIinohydrazide(L5),N’-(1-(pyrazin-2-yl)ethylidene)nicotinohydrazide(L6)and N’-(1-(pyrazin-2-yl)ethylidene)isonicotinohydrazide(L7)were obtained using picolinohydrazide,nicotinohydrazide,isonicotinohydrazide and acetylpyrazine as the raw material.Further reaction of the ligand L5 with AgNO3,AgSO3CF3 and AgSbF6 aforded new three Ag(I)complexes,{Ag(L5)(NO3)}n(11).{[Ag(L5)]·SO3CF3·CHCl3}n(12),{[Ag(L5)]·SbF6·CHCl3}n(13).Complexes 11-13 crystallize in monoclinic space group P21.The pyrazine N-atoms(N2)connect the Ag(I)ions into one dimensional chain.And ligand L5 acts as tridentate chelators(11)or bidentate chelators(12,13).(Cell parameters:11:a=6.2200(4)(?),b=11.8822(7)(?),c=9.8175(6)(?),α=90.00°,β=97.581(2),γ=90.00°;12:a=7.8027(4)(?),b=13.7095(7)(?),c=20.7511(12)(?),a=90.00°,β=95.112(2),γ=90.00°;13:a=11.2866(13)(?),b=14.0121(16)(?),c=16.0329(15)(?),α=90.00°,β=127.229(6),γ=90.00°).Reactions of L6 with MnCl2,Mn(CH3COO)2,Cd(CH3COO)2 and CuCl2 afford four metal complexes,[Mn(L6)(Cl)2](14),[Mn(L6)2](15),{[Cd(L6)(CH3COO)]·2CHCl3}n(16),[Cu(L6)(CI)2](17).Reactions of L7 with CuCl2 obtained one metal complexes,[Cu(L7)(Cl)2](18).Complexes 14-17 are mononuclear structure.Complex 14 crystallizes in the monoclinic space group Cc.The central Mn ion coordinates with tridentate NNO pincer type ligand and two chloride ions.Cell parameters:a=14.1037(7)(?),b=7.4955(4)(?),c=14.5827(8)(?),α=90.00°,β=107.053(2)°,γ=90.00°.Complex 15 crystallizes in orthorhombic space group Aba2.15 possesses octahedral coordination sphere formed by two ligands chelating the Mn(Ⅱ)ion.Cell parameters:a=12.3790(7)(?),b=19.2445(13)(?),c=9.8987(6)(?) α=β=γ=90.00°.Complex 16 crystallizes in the Orthorhombic space group P212121.Complex 16 features a unique three-dimensional network with rectangular channels.Cell parameters:a=10.4215(4)(?),b=10.5323(4)(?),c=22.2477(10)(?),α=β=γ=90.00°.And Ligand L6 served as counter anion as in 15,16.Complex 17 has the similar structure with complex 18.They are mononuclear copper(Ⅱ)complexes,Complex 17 crystallizes in the Monoclinic space group P21/n.Complex 18 crystallizes in the Monoclinic space group Complex 17 crystallizes in the Monoclinic space group P21/n.Cell parameters:17:a=12.8197(11)(?),b=8,9507(8)(?),c=13.7803(12)(?),a=90.00°,β=105.477(3)°,γ=90.00°;18:a=10.9057(14)(?),b=16.185(2)(?),c=8.5774(11)(?),α=90.00°,β=90.727(4)°,γ=90.00°.These compounds have been characterized by IR,elemental analysis,and X-ray diffraction single crystal analysis.Complex 11-13 were 1D chain-like structures.Complexes 14-18 were mononuclear structure.The antibacterial activity of 11-18 and their interactions with serum albumin of 11-13 and L5 were investigated.The antibacterial activity results indicated that these complexes showed good antibacterial activities.The interaction of all the complexes with bovine serum albumins proteins(BSA)or human serum albumins proteins(HSA)revealed their good binding affinity to BSA and HSA with relatively high binding constants. |
