Synthese And Mechanism Investigations On Aromatic Rhodium(Ⅲ)and Ruthenium(Ⅱ)complexes As Antitumor And Aβ Aggregation Inhibition Agents

Cancer is increasingly threatening people’s physical and mental health.Although platinum-based metal complexes have achieved good results in anti-tumor therapy,their use has been limited due to serious toxic and side effects.In recent years,rhodium complexes have become the focus of current anti-cancer drug research due to their significant anti-tumor activity.Mitochondria is the energy center of the cell and the source of cell metabolism.The mitochondrial DNA（mt DNA）contained in it is its unique genetic replication system.The protease encoded by mt DNA plays a huge role in maintaining the stability of the respiratory chain.Based on this,the design of drugs that target mitochondria and disrupt the structure of the mt DNA of the thread has great research significance in anti-tumor therapy.Alzheimer’s Disease is a common neurodegenerative disease.The pathological factor is that the brain’s amyloid peptide（β-amyloid）gradually accumulates in cells,causing cell damage and disrupting nerve impulse transmission.Therefore,inhibition of Aβpeptide aggregation is the main direction of the development of anti-AD drugs.The polypyridyl ruthenium metal complex can not only bind to Aβ,but also contain ligands that can chelate Cu²⁺,so it can inhibit Cu²⁺-induced aggregation of Aβpeptide,which is more innovative in inhibiting Aβprotein aggregation.Based on the above research background,we synthesized a series of aromatic hydrocarbon rhodium complexes and polypyridine ruthenium complexes,systematically studied the anticancer mechanism of rhodium complexes and the effect of ruthenium complexes in inhibiting Aβaggregation.This thesis is divided into three chapters.Chapter 1:Introduce the research progress of Ru（II）,Ir（III）and Rh（III）complexes in anti-cancer and the main drugs and methods for inducing DNA condensation.At the same time,the drugs that inhibit Aβaggregation are introduced,and the research on metal complexes in inhibiting Aβaggregation is mainly introduced.Chapter 2:This chapter designs and synthesizes the aromatic rhodium complexes Rh1-Rh4 with 1-4 benzene rings,the auxiliary ligands are pip,nip,aip and pyip.Rh1-Rh4 can induce DNA condensation and localize to mitochondria.Rh3 was selected for subsequent cell experiments,confirming that Rh3 can target mitochondria,increase ROS levels,cause mitochondrial damage,release cytochrome C into the cytoplasm,and promote cell apoptosis.In addition,Rh3 also up-regulated the expression of tumor suppressor gene P53,and induced bcl-2/bax homodimerization.Chapter 3:This chapter designs and synthesizes 8 polypyridine ruthenium complexes containing bidentate or tridentate ligands,of which Ru1,Ru4,Ru5,Ru8can chelate Cu²⁺.These ruthenium complexes have good biocompatibility and can inhibit Aβpeptide aggregation and Cu²⁺-induced aggregation.At the same time,the ruthenium complex can reduce the cytotoxicity caused by Aβpeptide aggregation and improve the survival rate of cells.Then,Ru1 was used for subsequent experiments.The morphology of Aβwas observed by TEM and AFM,which further verified that the ruthenium complex can inhibit the aggregation of Aβ.In cell experiments,Ru1inhibited reactive oxygen species（ROS）and damage to mitochondria due to Aβaggregation,maintaining normal levels of mitochondrial membrane potential.