Synthesis,Characterization And Biological Activities Of Transition Metal Complexes Derived From 2-hydroxy-1-naphthaldehyde Schiff Base Ligands

Based on the fact that Schiff base which itself has a certain biological activity is coordinated with metal ions to enhance the biological activity,in this paper,five different transition metal complexes containing[(E)-1-((1-(2-hydroxyethyl)-1H-pyrazol-5-ylimino)methyl)-naphthalen-2-ol)](L1)and[(E)-ethyl-5-((2-hydroxynaphthalen-1-yl)methyleneamino)-1-methyl-lH-pyrhzole-4-carboxylate](L2),namely[Co(L1)2(OAc)2](1-Co),[Ni(L1)2(OAc)2](2-Ni),[Zn(L1)2(CH30-H)2](3-Zn),[Zn(L1)2Cl2](4-Zn)and[Ni(L2)2](5-Ni)have been designed,synthesized and further structurally characterized by X-ray crystallography,ESI-MS,elemental analysis and IR,indicating that all the complexes are mononuclear,hexacoordinated octahedral configuration for 1-Co,2-Ni and 3-Zn,tetracoordinated tetrahedral configuration for 4-Zn,tetracoordinated Square planar for 5-Ni,respectively.The different coordination structures of these complexes may contribute to different biological activities.In the molecular level,the possible interaction mechanisms between the ligands and their metal complexes and biological macromolecules(BSA,DNA)were preliminarily investigated through electronic absorption,circular dichroism and fluorescence quenching.The electronic absorption spectroscopy experiments initially identified that they can be combined with BSA in different degrees.The circular dichroism demonstrated that the addition of ligands and their complexes reduced the content of a-helix structure,but it is still the main conformation in the BSA.At the same time,they also combined with the amino acid residues of BSA peptide chain to destroy the mesh hydrogen bonds backbone between them and change its secondary structure.In addition,the fluorescence spectra indicated that they could bind to BSA in the 1:1 ratio via hydrogen bonds or van der Waals force within a certain range of concentrations.On the other hand,the relational spectra results revealed both the ligands and their metal complexes were probably inserted into the double-stranded DNA base pairs in different degrees which depend on the coordination modes and center metal ions.Furthermore,the agarose gel electrophoresis experiments illustrated that there were no obvious intercalations between them and the plasmid DNA.In the cellular level,the in vitro cytotoxicities of the ligands,their metal complexes and metal salts were screened by MTT assay against eight different cell lines HepG2,MGC80-3,T-24,BEL-7404,NCI-H460,SK-OV-3,A549 and HL-7702.Furthermore,the effects of L1,L2,2-Ni,5-Ni on the cell cycle progression and early apoptosis of HepG2 and MGC80-3 were evaluated via Flow cytometry and preliminarily elaborated the possible death mechanisms of cancer cell.The results of experiments showed all of these compounds exhibited antitumor activity against all of these tested cell lines in different degrees.The cell cycle analysis identified that 2-Ni maybe arrested the cell cycle in S and G1/G2 phase of HepG2 and MGC80-3 and L2,5-Ni in G1 and G2 phase of MGC80-3,respectively.However,L1,L2 and 5-Ni had(?)maller effects on the cell cycle of HepG2.The cell early apoptosis results illustrated that the HepG2 and MGC80-3 treated with 2-Ni both respectively appeared remarkable early apoptotic phenomenons and 5-Ni only for MGC80-3 which were concentration-dependent while the ligands had smaller effects on the cell apoptosis.