Synthesis Of Salicylaldehyde Schiff Base Metal Complexes And Their Interactions With BSA

Malignant tumor is one of the three diseases with the highest mortality rate in the world today and is extremely harmful.The research field of metal complexes with anticancer activity is developing rapidly,and the development of new high-efficiency and low-toxicity anti-cancer drugs is the focus of scientists’research at present.The salicylaldehyde Schiff base metal complexes have good anticancer activity,and these complexes undoubtedly provide a good idea and a model for the development of new biologically active complexes.Protein-drug interactions may control the absorption,transport,distribution and metabolism of drugs.In this article,a series of salicylaldehyde Schiff base ligands and their Ni（II）,Mg（II）,Zn（II）and so on metal complexes were synthesized,and the interaction of some of the complexes with bovine serum albumin（BSA）was investigated to provide a feasible way to design and develop novel,efficient,low-toxic anticancer drugs.In this article,a series of ligands were synthesized from salicylaldehyde,2-pyridinecarboxaldehyde and diethylenetriamine,triethylenetetraamine and ethylenediamine by changing the ratio of raw materials:N⁴,N⁷-Ethylene-N¹,N¹⁰-bis（2-hydroxybenzylidene）triethylenetetramine（HL₁）,trisalicylaldehyde triethyltetraamine（HL₂）,disalicylaldehyde diethyltriamine（HL₃）,and ethylenediamine-2-pyridinecarboxaldehyde（HL₄）.Then the ligands interacted with metal ions,a series of novel metal complexes were synthesized,and the structures of their ligands and complexes were characterized by using infrared spectroscopy,ultraviolet spectroscopy,and nuclear magnetic resonance.The single crystal of HL₁ligand,HL₂ligand,N⁴,N⁷-Ethylene-N¹,N¹⁰-bis（2-hydroxybenzylidene）triethylenetetramine nickel complex HL₁-Ni（II）,the trisalicylaldehyde triethyltetramine magnesium complex HL₂-Mg（II）and the trisalicylaldehyde triethyltetramine zinc complex HL₂-Zn（II）were successfully cultured by solution volatilization method.The crystal structures of the HL₁and HL₂ligands,the HL₁-Ni（II）and HL₂-Mg（II）complexes were determined as monoclinic P2（1）/c space group using X-ray single crystal diffraction,and the crystal structure of the HL₂-Zn（II）complex was an orthorhombic crystal system with P2（1）2（1）2（1）2（1）space group.The changes of protein geometry,size and hydrophobicity are helpful to evaluate the binding of metal complexes to BSA.The interactions of Schiff base metal complexes HL₁-Ni（II）,HL₂-Mg（II）and HL₂-Zn（II）with bovine serum albumin were investigated using UV spectroscopy,fluorescence spectroscopy and circular dichroism.The fluorescence quenching type of their metal complex-BSA system was determined by fitting the fluorescence spectral curve with the Stern-Volmer equation;the binding distances,binding constants and binding sites of the interactions of HL₁-Ni（II）,HL₂-Mg（II）and HL₂-Zn（II）with BSA were calculated,and the number of binding sites of the complexes with BSA were measured to be about 1.The thermodynamic parameters（ΔG,ΔH andΔS）of the[HL₁-Ni（II）]-BSA,[HL₂-Mg（II）]-BSA and[HL₂-Zn（II）]-BSA systems were measured by fluorescence spectroscopy to analyze their interaction forces,the results showed that the HL₁-Ni（II）was bound to BSA by van der Waals forces or hydrogen bonding forces,the forces between HL₂-Mg（II）and BSA were electrostatic gravitational force,the forces between HL₂-Zn（II）and BSA were van der Waals forces or hydrogen bonding forces.From the resonance scattering spectra,it can be inferred that all three metal complexes form new complexes with BSA and the molecular particle size may be larger than that of BSA.The microenvironments of tyrosine（Tyr）and tryptophan（Trp）residues in the BSA-metal complex systems were determined by simultaneous fluorescence spectroscopy,and showed an increase in hydrophilicity,a transition from a hydrophobic to a polar environment in the BSA lumen,and an extension of the peptide chain,resulting in a change in the conformation of the protein.The secondary structure of BSA in the BSA-metal complex systems was determined by circular dichroism,and the secondary structure of BSA wasα-helical structures.