Study On The Synthesis Of Polypyridyl Iridium(Ⅲ) Complexes And Their Activities Against Candida Albicans

In recent years,with the increase of immunodeficiency patients,organ transplant recipients and cancer patients,the incidence of deep fungal infections has increased year by year,and the incidence and mortality of fungal infections have increased progressively year after year,which seriously threatens human health.The main pathogenic fungi are Cryptococcus,Candida,Aspergillus,Trichophyton,etc.But among Candida,candida albicans is the main type of bacterias which can cause deep infections.With a high mortality rate Candida albicans is the most clinically isolated fungus,Candida albicans infection has become a difficult clinically problem.However,with the large-scale use of antifungal drugs,the growing resistance problem of Candida albicans,and the emergence of drug-resistant strains haves made the development of new anti-candida albicans drugs very urgent.The discovery of platinum anticancer drugs has greatly promoted the development of metal drugs.Platinum-based metal complexes as a typical representative of metal drugs these complexes have unique bonding methods,good light stability,wide diversity and electrochemical properties.The change in the valence state of the metal ion at the center of the molecular structure,and the diversity of ligands that bind the metal ion,these two characteristics provide great structural diversity for the development of metal drugs.Iridium(Ⅲ)complex can be changed from kinetically unstable to substituted inert,because of its special physical and chemical properties.In addition,compared with platinum drugs,iridium(Ⅲ)complexes also have rich photophysical and photochemical properties for easy detection.At present,the main application of the metal iridium(Ⅲ)complexs are mainly used in catalysts in chemical industry,photoelectric sensors in organic electroluminescence(OLED)electronic equipment,etc.and the application in biology is still in infancy.Polypyridyl ligands with metal iridium easily form a variety of electronic transition states,making iridium complexes have rich photophysical and photochemical properties.In this study,2-phenylpyridine,2-(p-tolyl)pyridine,1-phenylisoquinoline,2-phenylquinoline,2-(2,4-difluorophenyl)pyridine were selected as backbone ligands for five synthesis iridium dimers,and then 1,10-phenanthroline-5,6-dione,1,10-phenanthrolin-5-amine,dipyrido[3,2-a:2’,3’-c]phenazine(dppz)were used as the binding ligand to synthesize 15 polypyridyl iridium(Ⅲ)complexes,and the structure of these complexes was characterized.Through in vitro antibacterial experiments,the minimum inhibitory concentration(MIC)and minimum fungicidal concentration(MFC)of these complexes against Candida albicans were determined,and complexes with anti-Candida albicans activity were selected from them.Drug susceptibility experiments found that the polypyridyl iridium(Ⅲ)complex with ligand dppz showed good anti-Candida albicans activity,among those complexes,Ir15 had the best anti-Candida albicans activity in vitro,and its MIC=1μg/mL,MFC=2μg/mL,which is equivalent to the positive control fluconazole’s.Because of Ir15 has the best anti-Candida albicans activity in vitro,this article only studies the anti-Candida albicans activity of Ir15 in vivo.Because Ir15 is insoluble in water,therefore it is not suitable for studies in vivo as an injection.In this paper,long-circular Ir15 liposomes were prepared and characterized by thin film hydration,with a particle size of 119.77±1.78 nm and a Zeta potential of-3.1±0.28 m V,the entrapment efficiency is 82.73±2.3%.Finally,a systemic Candida albicans infection mouse model was established by tail vein injection Candida albicans,which was treated with the administration of Ir15 liposomes through tail vein injection to verify the anti-Candida albicans activity of Ir15 in vivo.The results show that Ir15 also has good anti-Candida albicans activity in vivo.When the dose was 10 mg/kg,it could reduce the load of Candida albicans in the kidneys of model mice from 10~7 CFU/g to 10~4 CFU/g.In summary,in this research work,we synthesized a total of 15 octahedral polypyridyl iridium(Ⅲ)complexes,and got a iridium(Ⅲ)complexes Ir15 with good Anti-Candida albicans activity by drug sensitivity experiments.We using pharmaceutical technology to preparation Ir15 long-circulating liposome and its anti-candida albicans efficacy was preliminary evaluated.This study proves that the iridium complex with a specific chemical structure has good activity against Candida albicans and has the potential to be a medicine.At the same time,this article also provides some experiences for other metal complexes’s structural modification and structure-activity relationship and gives some new clues for the development of new antifungal drugs.