Design,Synthesis,Optical Properties And Cell Imaging Applications Of Several Nitrogen-Containing Heterocvclic Derivatives

Nitrogen-containing heterocycles are important components of organic heterocycles.They can be classified into aromatic or aliphatic heterocycles according to their aromaticity.They usually have good biological activities and widely distributed in natural products such as some Chinese herbal medicines,chlorophyll in plants,heme in animals,and base pairs in organisms.With the development of basic organic synthetic chemistry,the seeds of synthetic nitrogen-containing heterocyclic compounds are continuously dispersed to various fields of human production and life,and gradually take root,sprout and flourish.In recent years,aromatic nitrogen-containing heterocyclic compounds have been emerged in the fields of fluorescence imaging and labeling due to their excellent optical properties,good biological activity,low cytotoxicity and specific biological labeled ability.Many nitrogen heterocyclic derivatives with excellent properties have been designed as fluorescent probes for in vitro and in vpyrene derivatives with a large Stokes shift for nucleus staining.Chemical ivo detection,such as pH probes,biological thiol probes,reactive oxygen probes,etc.Some other nitrogen-containing heterocyclic derivatives have been used as organelle markers,such as mitochondria,endoplasmic reticulum and nucleic acid markers.Therefore,it is of great significance to design and synthesize derivatives of novel nitrogen-containing heterocyclic compounds by means of organic synthesis and apply them to fields such as fluorescence imaging and labeling.In this paper,several small molecular compounds containing nitrogen or nitrogen salt were designed and synthesized,and their optical properties were studied in detail on the premise of full characterization.In addition,their biological applications as lipid droplets and nucleic acid fluorescent probes were explored,the details are as follows:1.Two quinoline derivatives(1a,1b)containing quinolone-coumarin skeleton were synthesized by Friedlander synthesis method.1a and 1b had good photostability.The maximum fluorescence emission peaks of la and lb in various organic solvents were 469 to 509 nm and 1a-b showed high fluorescence quantum yield(0.79-0.96)in these solvents.In addition,optical tests showed that they exhibited strong and stable fluorescence in aqueous solutions with pH values from 6.0 to 9.0,which provided a premise for their cell application.Finally,cell experiments showed that la and lb can be used as lipid droplets fluorescent markers in living and fixed normal cells and cancer cells(1929 cells and HeLa cells),and can be used for polychromatic imaging analysis with some other commercial fluorescent markers..2.Heterocyclic derivatives containing azonia unit can bind to nucleic acids.In this work,five azonia unit-containing cyanine dyes(6a-e)were synthesized by the condensation reaction of pyridines[1,2-a]derivative(4)with different aldehydes(5a-e).All of them had excellent photo and good thermal stability.In addition to 6e,other probes could bind with nucleic acids and exhibited near "off-on" fluorescence enhancement phenomenon.Among all the six probes,6a showed the best performance and the increase of fluorescence intensity was the greatest before and after interaction with nucleic acids.The detection limits of 6a toward DNA or RNA were 2.29 ?M and 3.18 ?g·mL-1,respectively.Then,laser confocal of 6a showed that it could be used as a fluorescent probe for monitored mitochondrial nucleic acid.3.On the basis of the third chapter,three azonia unit heterocyclic derivatives(11a-c)were synthesized by changing the side chain of pyridine[1,2-a]pyrimidine(9a-c)and reacted their methyl groups with 7-diethylaminocoumarine-3-aldehyde(10).Due to the increase of conjugated structures of the compounds,their maximum emission peaks were located in the near infrared region(678-697 nm),and all of them showed obvious fluorescence enhancement after bound with nucleic acids.Under the influence of side groups,the fluorescence intensity of them showed different and regular increase multiples after interaction with nucleic acids,that was,when the side chain changed from electron-donating methyl group to electron-absorbing chlorine,the fluorescence intensity increased significantly reduced.In addition,cell imaging experiments showed that all of them could mark the nucleoli of fixed HeLa cancer cells and mainly bound to RNA.