| 1,3,5-triazine has structural symmetry and strong electron affinity.The presence of N heteroatom on the triazine ring makes it possible to form hydrogen bonds with hydroxyl groups,amino groups,carboxyl groups,etc.,or form a non-covalent bond by coordination with metal ions.Thus,compounds with the core of 1,3,5-triazine have excellent stability and high biological activity.Therefore,1,3,5-triazine derivatives have been widely used in many areas such as synthetic chemistry,antibacterial and antitumor drugs,fluorescent probes,organic photoelectric materials,organic framework materials,ultraviolet absorbers and nitrogen-containing high energy materials.This thesis aims to discuss the design and the synthesize of organic small molecules based on 1,3,5-triazine,and explore their potential applications in fast coupling reaction,intracellular delivery of proteins and antibacterial drugs.The following parts are reported in this thesis:(1)Click reaction between 2-azido-4,6-dimethoxy-1,3,5-triazine and reactive methylene compounds could be directed by the solvent.1,2,3-triazolyl-1,3,5-triazine was formed in H2O/DMSO mixed solution.The reaction had various advantages such as fast reaction rate,good functional group compatibility,mild reaction condition,high regioselectivity,excellent yield,simple separation and purification operation,and good atomic economy.Therefore,it meets the standards of the click reaction.Interestingly,when using ?-methylene nitrile compounds as the substrate,Dimroth rearrangement products were produced.The reactivity of azido-1,3,5-triazine is related to the substituents on the triazine ring:when 1,3,5-triazine is substituted by amino or thiol groups,these substitution groups change the electron density of the 1,3,5-triazine ring,which tunes the activity of the azido-1,3,5-triazines with:alkoxy>thiol>amino substitution.We also provided a reasonable reaction mechanism,which was further evidenced by DFT calculations.Therefore,we offer a novel method for the synthesis of novel 1,2,3-triazole derivatives.(2)Triazine-based organic molecule TG6 was designed and synthesized.Electrostatic interaction between guanidinium of TG6 molecule and negatively charged carboxyl groups,sulfonic acid groups or phosphoric acid groups on the cell membrane surface and hydrophobic interaction between alkyl side chains of TG6 and hydrophobic cell membranes promote TG6 molecules efficient and rapid penetration of the cell membrane.TG6 molecule is a serum-stable and low-toxic molecular transporter.Also,the synthesis route of TG6 molecule is short and the reaction conditions are mild.TG6 molecule can couple with protein such as fluorescein isothiocyanate-labelled bovine serum albumin(BSA-FITC)and horseradish peroxidase(HRP)by the condensation reaction between carboxyl groups and amino groups.Three-dimensional structure of the protein and original biological activity are well preserved.In particular,the TG6-BSA-FITC and TG6-HRP conjugates could efficiently internalize into the cytosol and perform the corresponding biological functions.Therefore,we provide a convenient strategy for intracellular delivery of bioactive proteins.(3)A series of amphiphilic flexible organic small molecules based on 1,3,5-triazine were designed and synthesized.The hydrophilicity of these triazine compounds was regulated by changing the length of alkyl side chains.The synthesis processes of these triazine molecules are simple,the raw materials are cheap and commercially available,and the reaction conditions are mild.The structure-activity relationship was studied from the choice of the flexible linker,the length of the hydrophobic chain,and the number of triazine rings.D6E1N3 compound which displays the best antibacterial activity was screened out by bacteriostatic experiments.The result shows that D6E1N3 compound has high antibacterial activity,low toxicity,low hemolytic activity,good water solubility,and stability.D6E1N3 compound also possesses faster sterilization rate against methicillin-resistant staphylococcus aureus(MRSA),effectively inhibits biofilm formation of MRSA,and would not produce drug resistance.Therefore,we provide a new method to design new antibacterial drugs. |
PDF Full Text Request