Synthesis Of Cr(?),Os(?) And Rare Earth Metal Complexes And Their Application In Tumor Therapy

Malignant tumor is harmful to human health.At present,the main methods of cancer treatment are surgical resection,chemotherapy and radiotherapy.Chemotherapy is still dominant.As a part of chemotherapeutic drugs,metal complexes play an important role in tumor treatment.In recent years,a large number of metal antineoplastic drugs have been synthesized through different metal elements and different valence states.High valence metal nitride has rich chemical reaction activity,such as activating C-H,C-N bond,and so on.Much attention has been paid to it as a new anti-tumor drug,showing good anti-tumor activity.In addition,rare earth metal complexes have attracted wide attention because of their potential applications in biological imaging,anticancer,anti-inflammation and antibacterial.In this paper,a series of Cr???nitrido complexes,Os???nitrido complexes and rare earth complexes were synthesized and their antitumor activities were studied in cells.The specific research of this paper is as follows:1.Study on the antitumor activity of chromium???nitrogen complexes.Chromium is a trace element needed by human.Trivalent chromium can treat diabetes,hexavalent chromium is highly toxic.The chromium???nitrogen complexes in the intermediate valence state may have good biological activity.According to the related literature,three kinds of chromium???nitrogen complexes were synthesized.In addition,they were characterized by ESI-MS,elemental analysis,FT-IR and UV-Vis.We also studied their anti-tumor activity by cyclic voltammetry,MTT experiment,cell absorption test,reactive oxygen species detection,cell cycle analysis and so on.The results show that,Cr???nitrogen complexes can promote the decomposition of H₂O₂,and increase the level of singlet oxygen in tumor cells.In addition,Cr???nitrogen complexes can also quickly cause mitochondrial damage in tumor cells,resulting in mitochondrial dysfunction.Lastly,the apoptosis factor is released to activate its downstream signal caspase family protein,and finally induce the apoptosis of tumor cells.Interestingly,Cr?N??Q?₂ inhibited cell migration and invasion.Therefore,Cr???nitrido complexes are expected to be developed as antitumor candidates.2.Synthesis of Osmium???nitrogen complexes and its Application as radiotherapy sensitizer.Osmium nitrogen complexes have excellent anti-tumor activity,but its poor water solubility and high toxicity limit its further use to a great extent.In order to improve the water solubility of osmium nitrogen complexes and reduce the toxicity of osmium nitrogen complexes,we designed and synthesized an osmium nitrogen complex with phenanthroline-2-ol as ligand by introducing hydroxyl groups into phenanthroline.The complexes were characterized by single crystal diffraction,ESI-MS,FT-IR and UV-Vis,and we also investigated the effect of osmium???nitrogen complex combined with radiotherapy on Hela cervical cancer cells.The results show that the lipid-water distribution coefficient of the complex was lowerthanOs?N??PhenH?Cl₃when the ligand was introduced into-OH,and the inhibitory effect in tumor cells was worse.In addition,the anti-tumor effect of the complex combined with X-Ray was greatly improved,and more ROSwas produced to damage mitochondria.Flow cytometry showed that Os?N??PhenOH?Cl₃ inhibited cell proliferation by inducing G2/M phase arrest.Western blotting results showed that,Os???nitrido complex combined with X-ray could significantly increase the phosphorylation level of ATM and ATR,and then activate the expression of Histone phosphorylation.3.Application of rare earth complexes combined with radiotherapy in tumor cells therapy.Rare earth metal complexes have potential applications in biological imaging,anticancer,anti-inflammation and antibacterial.We designed and synthesized three rare earth complexes of benzimidazolyl carboxylic acidand they were characterized by single crystal diffraction,powder diffraction,FT-IR,UV-Vis and elemental analysis.The antitumor activity of rare earth complexes combined with X-Ray was investigated.The results showed that rare earth metal complexes combined with X-Ray inhibited the proliferation of cervical cancer cells and induced G0/G1 phase arrest to achieve the effect on the cell cycle of cervical cancer cells.In addition,rare earth complexes combined with X-Ray increased the level of intracellular reactive oxygen species?ROS?and enhanced the sensitivity of Hela cells to radiotherapy.MR weighted imaging shows that rare earth gadolinium complexes can be used for T₁imaging.In summary,a series of Cr???nitrido complexes,Os???nitrido complexes and rare earth complexes were synthesized,and their antitumor activities and their effects on intracellular ROS levels were discussed.This provides a scientific basis for the further study of Cr???nitrido complexes,Os???nitrido complexes and rare earth complexes...