Preparation Of Metal Complexes Of Diazine Derivatives And Chemical Biological Properties

Diazine is a six-membered heterocyclic ring system containing two nitrogen atoms.Depending on the relative position of the two nitrogen atoms in the ring,they are pyridazine,pyrimidine,and pyrazine.Diazine derivatives have potent biological activity and have important research value in medical biology.Metal complexes are new polymer materials with a variety of biomedical applications,with the advantages of biodegradability,high loading capacity and easy surface modification,and have great potential in the fields of material science,biology and drug delivery.Therefore,to study the preparation and chemical biological properties of diazine derivatives and their metal complexes,and to explore their interactions with biological macromolecules.It is of great significance to explore the application of diazine metal complexes in anti-tumor drugs,molecular biology,bioengineering technology and other related fields.In this paper,5 compounds were synthesized and 12 metal complexes were prepared,including 2 new compounds（compounds 51,58）and 6 new metal complexes（complexes 1,2,5,6,11,12）.The antibacterial and antitumor activities of metal complexes were explored,and the chemical and biological properties were also studied.It was found that some metal complexes can effectively inhibit Brucella and cut plasmid DNA effectively.This experimental work will provide new ideas for the development and utilization of diazine compounds.Part I:Four metal complexes were synthesized by hydrothermal method:6-hydroxy-2-phenyl-pyrimidine-4-carboxylic acid（Hpca）bridged Cd（II）complex Cd₄C₁₃₆N₂₄O₂₄H₈₈·（H₂O）₇（complex 1）,6-Hydroxy-2-phenyl-pyrimidine-4-carboxylic acid（Hpca）bridged Cu（II）complex C₂₃H₁₅Cl Cu N₄O₃（complex 2）,1,10-phenanthroline bridged Cd complex C₂₀H₁₁Cd N₃O₆（compound 3）,1,10-phenanthroline bridged Cu complex 1,10-phenanthroline bridged Cd complex C₂₄H₁₈Cl Cu N₅O₄（complex 4）.The four metal complexes were characterized by single crystal X-ray diffraction,（IR）,solid-state fluorescence and thermogravimetric analysis（TGA）.Among them,complex 1 and complex 2 are new structures.The study found that the complex 1 got green fluorescence at 525nm,and the complex 2 got purple fluorescence at 370nm,and the two new metal complexes had good thermal stability.At the same time,the antibacterial and anti-tumor activities of two main ligands（1,10-phenanthroline,Hpca）and metal complexes 1,2,and 4were tested.The experiment showed that metal complexes 1,2 have inhibitory effects on Acinetobacter baumannii.The activity of Acinetobacter mannanensis,the main ligand hpca and complex 4 have inhibitory effects on human melanoma tumor cells（A375 cells）.PartⅡ:Based on 7,16-diaza-18 crown 6（ACE1）,two novel diazine compounds were synthesized by introducing 5-bromo-2-（bromomethyl）pyrimidine and carboxylic acid functional groups,and four complexes were prepared（Complexes 5（ACE1-BBP-Cu）,6（ACE1-BBP-Zn）,7（ACE1-COOH-Cu）and 8（ACE1-COOH-Zn））.The above compounds were characterized by nuclear magnetic（NMR）and mass spectrometry（MS）.The effect of metal complexes on the catalytic cleavage of p UC19 plasmid DNA was studied.The experimental results show that all the four metal complexes have good nuclease catalytic activity,and the catalytic activity of diazine metal complexes is better.The optimal reaction conditions for metal complex 5（ACE1-BBP-Cu）are:c=9.2×10^-4mol/L,T=8h,p H=7.5;the best reaction conditions for metal complex 6（ACE1-BBP-Zn）The reaction conditions are:c=9.2×10^-4mol/L,T=4h,p H=7.5;the optimal reaction conditions for metal complex 7（ACE1-COOH-Cu）:c=9.2×10^-4mol/L,p H=7.5;The optimal reaction conditions of metal complex 8（ACE1-COOH-Zn）are:c=4.6×10^-4mol/L,p H=7.Part III:Based on monoaza-18 crown 6（ACE2）,two novel diazine compounds were synthesized by introducing 5-bromo-2-（bromomethyl）pyrimidine and carboxylic acid functional groups,and four complexes were prepared（Complexes 9（La-ACE2）,10（Ce-ACE2）,11（La-ACE2-BBP）and 12（Ce-ACE2-BBP））.The above compounds were characterized by nuclear magnetic（NMR）and mass spectrometry（MS）.In this paper,by studying the activity of four synthetic aza crown ether metal complexes to catalyze DNA,gel electrophoresis was used to test the effect of the synthesized metal complexes to catalyze the hydrolysis of p UC19 plasmid DNA.The experimental results show that all the four metal complexes have good nuclease catalytic activity,and the catalytic activity of diazine metal complexes is better.The optimal reaction conditions for metal complex 9（ACE2-La）are:c=6.9×10^-4mol/L mol/L,T=10h,p H=7.5;the best reaction conditions for metal complex 10（Ce-ACE2）The reaction conditions are:c=9.2×10^-4mol/L,T=10h,p H=8;the optimal reaction conditions for metal complex 11（La-ACE2-BBP）:c=9.2×10^-4mol/L,T=12h,p H=6;The optimal reaction conditions of metal complex 12（Ce-ACE2-BBP）are:c=6.9×10^-4mol/L,T=10h,p H=6.In this paper,the antibacterial and antitumor activities of metal complexes and their catalytic cleavage of plasmid DNA（p UC19）as artificial nucleases were studied.This study provides a strong basis for the study of azine metal complexes as artificial nucleases in biomedicine and biochemistry.The research and development of drugs for the treatment of genetic diseases,the application of enzymes,and the degradation of toxic substances have important academic significance and application value.