Tannic Acid-Cu^? Enhanced Antibacterial Activity Of Curcumin And Mechanism Study Of Hydrogen Bond Organocatalysis Of Azoles In Transamidation Reaction

In the first chapter of this thesis,metal-phenolic networks of tannic acid-Cu^? drug system enhanced antibacterial activity of curcumin nanoparticle against staphylococcus aureus was discussed.Recently,the rising bacterial infection severely threatens human health and has already become a worldwide issue.Safe,green and efficient antibiotics are urgently needed.Curcumin is well known as a natural and green food additive,and has effective biological and pharmaceutical activity.As a green and non-toxic nature medicine,it has promising application in anti-cancerous and anti-inflammatory area,it's also an antibacterial.Although the curcumin is found to own the good therapic efficiency and safety,it has not been approved to be a therapeutic drug in the market,which is due to the low bioavailability and poor solubility.To overcome its hydrophobic disadvantage,here,tannic acid and metal coordination were used to coat curcumin nanoparticles?NPs?for the antibacterial application.On one hand,the coating method produced a high drug loading efficiency.On the other hand,the involvement of metal ions enhanced the bacterial inhibition efficiency compared to curcumin and metal ions alone.The MIC of Cur@TA-Cu^? for Staphylococcus aureus could be determined at about 20 ?g/m L?curcumin concentration?,which was 7.5 times lower than that by using curcumin only.As the CuII mass content was 4.7% in the complex,the MIC as the concentration of CuII could be calculated as 1.5 ?g/m L,which was about 260 times lower than that of CuII alone.In addition,the coordination strength between tannic acid and metal ions is depended on the p H of solution,the nanoparticles prepared in this paper are expected to be used for antibacterial biofilms.Thus,our research provides a natural and green antibiotics system to effectively prevent Staphylococcus aureus infections,and has potential to be widely produced in industry due to the naturally derived raw materials.In the second part of this thesis,mechanism study of hydrogen bond organocatalysis of azoles in transamidation reaction was discussed.In this part,density functional theory of M062X/6-31+G?d?is used to study the reaction mechanisms in transamidation of carboxamides with methylamines catalyzed by imidazole,pyrazole and benzotriazole.In the transamidation reaction,the azoles activate the substrate carboxamide through dihydrogen bonds with carbonyl oxygen and one hydrogen of amino group,which favors the subsequent nucleophilic attack of methylamine with carboxamide.Our theoretical results show that the enthalpy barriers are 123.9 k J·mol-1 and 92.3 k J·mol-1 for imidazole and pyrazole,respectively,while it decreases to 88.3 k J·mol-1 for benzotriazole.Clearly,the benzotriazole favors most for the transamidation.The solvent effect of toluene and water simulated by SMD?Solvation Model Density?for the transamidation reaction catalyzed by benzotriazole elevated the enthalpy barriers significantly,which coincides well with the experimental result.Our theoretical study would be useful for further understanding and future experimental investigation on such transamidation reaction.