Metal Complexes Of Marbofloxacin:Synthesis,Structural Characterization,Antibacterial Activity And Acute Toxicity In Mice Model

In this dissertation,a fluoroquinolone-type veterinary drug,marbofloxacin,was selected as bioactive ligand to afford a series of coordinated complexes,in which the central cations were chosen to be Mg? and several transition metal ions(Mn??Co??Ni??Cu??Zn?).These six metal complexes of marbofloxacin were synthesized via solution method,whose structures were characterized by IR,ESI-MS,and single crystal X-ray diffraction analysis.Their in vitro antibacterial activities were also determined by the bacteriostatic tests.Furthermore,the acute toxicity of the marbofloxacin and its metal complexes by acute toxicity test were completed on mice model.This research provides scientific data and preliminary research basis to develop new type of metal-based veterinary drugs of marbofloxacin.The detailed parts are as following:Six metal complexes with the marbofloxacin(H-L)were synthesized by solution method,which were:[Mg(L)₂(H₂O)₂](1)?[Mn(L)₂(H-L)](2)?[Co(L)₂(H₂0)₂](3)?[Ni(L)₂(H₂0)₂](4)?[Cu(L)₂](5)?[Zn(L)₂(H₂O)](6).All these six metal complexes have been structurally characterized by IR,ESI-MS and single crystal X-ray diffraction analysis.As to the crystal structures of these complexes,they all crystallized in the mononuclear structure.Each of complexes 1,3 and 4 adopted a six-coordinated octahedral geometry,in which two marbofloxacin ligands bidentated to the center metal ion via the deprotonated 3-carboxyl hydroxyl O atom and the 4-carbonyl O atom,respectively,to occupy the equatorial plane,and two H2O molecules occupied the axial positions of the octahedron.For complex2,three marbofloxacin ligands bidentated to the central Mn(?)in the same mode to form a six-coordinated octahedral geometry,in which any one of the three was protonated on its peperazine N atom,so that the whole complex remained neutral.In complex 5,the central Cu(?)was four-coordinated by two marbofloxacin ligands in the same mode to form a square planar geometry.As to the complex 1,it adopted a five-coordinated tetragonal pyramid geometry,in which two marbofloxacin ligands bidentated to the center metal ion via the deprotonated 3-carboxyl hydroxyl O atom and the 4-carbonyl O atom,respectively,and one H2O occupied the axial position.Furthermore,the copper(?)complex 5 was selected as representative to study its solution chemistry by potentiometric titration method.The results indicated that marbofloxacin could stably coordinate to Cu(?)in aqeous solution and exist in the cationic species in complexation.its coordination stability constant of approximately 3.44�107,It strongly suggested that this kind of complex would not dissociate in aqueous solution.The antibacterial activity of these complexes comparing with marbofloxacin on seven bacterias(Staphylococcus aureus?Micrococcaceae?E.coli?P.aeruginosa?typhoidal salmonellosis?proteus species?Bacillus subtilis)was examined by in vitro antibacteriostatic tests.The results of the experiments indicated that The E.coli is the most sensitive for these complexs,while the P.aeruginosa is the lowest sensitive for them.Targeting the same bacterial strain,the inhibition acitivity of the complexes was comparable with the marbofloxacin ligand,although small differentiation existed.The acute toxicity of these complexes was also tested by the acute toxicity tests,which indicated that the LD50 value of marbofloxacin is 1294mg/Kg,while the LD50 values of the six complexes ranged from 5000?15000mg/Kg.According to the grading standards for toxicity,all the six complexes belong to grade 2 on toxicity,as practically non-toxic compounds.It suggestes the coordination of marbofloxacin to the appropriate metal ion may reduce its toxicity from the molecular level.This research exhibited important practical value and scientific significance.