Structure, Antioxidiative And Interaction With Biomacromolecule Of Complexes With Ofloxacin Acylhydrazone

The essential biological materials——protein and nucleic acid, have been playing vital roles in all kinds of biological phenomena. Exploring the interaction mechanisms on these biomacromolecules with small molecules, especially for those drug molecules, at the molecular level is of current interest in many research areas such as biology, clinical medicine chemistry, and so on. In this paper, we have reported the synthesis, characterization of five ofloxacin acylhydrazones and their metal complexes. The complexes are more soluble compare with the corresponding ligand, which may result in new biological activities, so some of them were evaluated for DNA and BSA binding properties and antioxidant activities. A series of significant conclusions have achieved from the results. The dissertation includes following five chapters:In chapter one, the research progress in the interactions of DNA and BSA with small molecules, as well as the interaction mode, influence factors, research methods are reviewed. The important theoretical and practical significance of the research work in the drug screening and biochemistry are also discussed herein. Moreover, the aim and significance of this thesis have been outline.In chapter two, three ofloxacin acylhydrazones with different number and location of hydroxyl substituting groups (H2L1, H2L2 and H3L3) and their metal complexes ML1-3(M=Pr(Ⅲ), Nd(Ⅲ), Sm(Ⅲ)) have been synthesized and characterized. The crystals structures of PrL1 and NdL1 characterized by single crystal X-ray diffraction showed that the complexes have a similar molecular structure. The interactions of above compounds with DNA were investigated by spectrophotometric methods and viscosity measurement, which suggested that the complexes bind with DNA in intercalation mode and the different position and number of substituting groups lead in different DNA binding affinity of the complexes. Experiments with pBR322 DNA show that the free ligand does not show any DNA-cleaving abilities and the complexes display chemical nuclease activity. Antioxidant tests in vitro show some complexes possess significant antioxidant activity against superoxide and hydroxyl radicals and the different number of substituting groups leads in different antioxidant activity of the complexes.In chapter three, the interactions of H2L1, H2L2, H3L3 and their metal complexes ML1-3 with BSA have been studied using UV-visible, fluorescence spectroscopic and CD methods. The results suggested that the quenching mechanism of BSA fluorescence by complexes was proved to be a static quenching and the numbers of binding sites were about 1. The binding constants and types of interaction forces between BSA and compounds were obtained. The average binding distance between complexes and BSA has been determined on the basis of the Forster'theory. The CD data well supports the idea that the complexes had some effect on BSA'structure. The different position and number of hydroxyl substituting groups lead in different BSA binding affinity of the complexes.In chapter four, two ofloxacin derivatives with different five-heterocyclic (HL4 and HL5) and their metal complexes (ML4(M=La(Ⅲ), Nd(Ⅲ, Er(Ⅲ)) and ML5(M=La(Ⅲ), Pr(Ⅲ), Sm(Ⅲ))) have been synthesized and characterized. ML4 and ML5 have a similar molecular structure. The interactions of complexes with DNA were investigated by spectrophotometric methods and viscosity measurement, which suggested that the complexes bind with DNA in groove mode. The data of the binding constants and quenching constants present the order of K (HL4)< K (LaL4)< K (NdL4)