The Synthesis Of 1,2,3-Triazoles With Rhodamine B,Chromogenic Reactions,and The Interactions With Globular Proteins

1,2,3-Triazole based compounds have attracted much attention because of their unique physical and chemical properties.They can conjugate or combine with other substituents and form types of derivatives.They also exhibit excellent biological activity.Thus,they have broad application prospects in organic chemistry,organic chemistry,pharmaceutical chemistry,materials chemistry and other fields.It is exactly a very practical application to design and synthetize a compound containing 1,2,3-triazole as a metal ion probe.It is well known that the lack or overdose of metal ions will lead to the physiologic disturbance of organisms.The explorations for a rapid and effective method to detect metal ions are extremely important.The fluorescence analysis method is simple to operate with low detection limit.The corresponding device is easy to handle without complex multi-level sample preparation.Rhodamine-based compounds have the advantages of high quantum yield,large molar extinction coefficient and long emission wavelength,which are widely used in the fluorescence and chromogenic recognization of metal ions.To explore the color recognition to metal ions of 1,2,3-triazole based compounds is helpful in establishing new methods to detect metal ions.In addition,considering that the 1,2,3-triazoles may be further exploited and used as new drugs,it is necessary to study their interactions with biological macromolecules.Since the functions of the drugs in the body are the results of their interactions with important macromolecules in the organism.Protein is an important research object in life science and one of the most important transport carriers of drugs.The binding of protein to drugs has a great influence not only upon the distribution of the drugs in the body but also upon their patterns of metabolism and excretion.Therefore,the studies on the interaction between drugs and proteins has become one of the most important subjects in the field of life science,chemistry and clinical medicine.This dissertation is divided into two parts.The first part is the study on the synthesis of 1,2,3-trizoles with Rhodamine B through a serious of reactions.These compounds include ethyl 2,5-diphenyl-2H-1,2,3-triazole-4-carboxylate(S1),ethyl 5-phenyl-2-(3-(trifluoromethyl)phenyl)-2H-1,2,3-triazole-4-carboxylate(S2),ethyl 5-phenyl-2-(o-tolyl)-2H-1,2,3-triazole-4-carboxylate(S3),ethyl 2-(4-methoxyphenyl)-5-phenyl-2H-1,2,3-triazole-4-carboxylate(S4),ethyl 2-phenyl-5-(trifluoromethyl)-2H-1,2,3-triazole-4-carboxylate(S5),ethyl 5-phenyl-2-(ptolyl)-2H-1,2,3-triazole-4-carboxylate(S6),5-methyl-2-phenyl-2H-1,2,3-triazole-4-carboxylic acid(S7)and 5-methyl-1-phenyl-1H-1,2,3-triazole-4-carboxylic acid(S8).The corresponding products were characterized by NMR and HRESIMS methods.The chromogenic reaction of the compounds with 15 kinds of metal ions were investigated by UV absorption spectra and fluorescence spectra.The results showed that all of them displayed more sensitive to Hg2+ ion than other metal ions in N,N-Dimethylformamide(DMF)-water(pH7.4)under given conditions with an fluorescent enhancement and a rapid chemical reaction.In the second part of the thesis,three kinds of 1,2,3-triazole compounds(S1,S3,S6)were selected to investigate the interactions with three model proteins including human serum albumin(HSA),human immunoglobulin(HIgG)and bovine hemoglobin(BHb)by using the fluorescence spectra,UV spectra and molecular docking.The results showed that the three kinds of compounds could enhance the fluorescence of three proteins with a red shift,which indicating that the addition of the compound changed the microenvironment of the amino acid and made them more hydrophilic.The binding constants under different temperatures were obtained according to the experimental data of fluorescence spectrum.The intermolecular force model were determined according to the thermodynamic parameters and the results were further confirmed by molecular docking.The synchronous fluorescence spectra and the three dimensional fluorescence spectra were used to investigate the influence of the compounds on the secondary structure and the change of the amino acids microenvironments of three kinds of proteins.These are the first spectroscopic and bioactivity results on 1,2,3-triazoles at the molecular level,which can illustrate the nature of 1,2,3-triazoles information in vitro and in vivo.