Study On Vesicle Formation Through The Self-Assembly Of Oligo(Ethylene Glycol) Terminated Biphenol Small Molecule Ligands Modified Gold Nanoparticles

Gold nanovesicles（AuNVs）with unique plasmon resonance coupling characteristics are widely used in the drug encapsulation and delivery,disease diagnosis and treatment integration.The preparation of water stable and dispersible AuNVs is a hotspot in materials science and chemical biology.So far,AuNVs formed by the self-assembly of gold nanoparticles（AuNPs）based on amphiphilic block copolymers and their applications have been widely reported.But polymer blocks with long chain could potentially reduce the internal payload space of AuNVs,which limits their application in drug loading.The length of small organic molecules is shorter than that of polymers.Therefore,the AuNVs formed by the self-assembly of small molecules modified AuNPs could solve the above problems to a certain extent.My supervisor has long been engaged in the research of AuNVs based on the small organic molecules.The stability and dispersibility of AuNVs in water were achieved through the precise regulation of the hydrophobicity of small organic molecules.But the formation mechanism of AuNVs,especially the influence of the solvophobic properties of ligands on vesicle formation needs to be elucidated.The solvophobic properties of ligands are closely related to their solubility in solvents,and aromatic ring substituents have a significant effect on their solubility.So this theisis replaces the perfluorobiphenol fragments with bisphenol to obtain oligo（ethylene glycol）terminated bisphenol ligands.The ligand-modified AuNPs can efficiently self-assemble into AuNVs,and the formation mechanism of AuNVs is explored through the study of the solvophobic properties of the ligands,the main contents include:Chapter 1 systematically reviews the self-assembly of molecules,and AuNPs.The relevant research progress and the previous work of this topic are introduced.Chapter 2 introduces the design and synthesis of seven new small organic molecule ligands:（1）Four small biphenol ligands with oligoethylene glycol at the end.The structural characteristics is C11 alkyl chain ends containing thiol groups,biphenol in the middle,and diethylene glycol,triethylene glycol,tetraethylene glycol or pentaethylene glycol at the other end,namely Di BL,Tr BL,Te BL,Pe BL respectively;（2）Two kinds of biphenol small organic molecule ligands without OEG fragments are abbreviated to BL and Na BL;（3）Biphenyl ligand without hydroxyl group and oligo ethylene glycol fragment terminus is abbreviated to PPL.The structure of all the intermediates and target products are confirmed by FT-IR,HRMS,¹H NMR and ¹³C NMR.Chapter 3 uses the synthesized ligands to study the self-assembly with AuNPs under different conditions such as solvent,water content,ligand concentration and type,size and concentration of AuNPs on the formation of AuNVs by one-step protocol.The structure of the assemblies are characterized using UV-vis,TEM,SEM,and DLS.The formation mechanism of AuNVs is also discussed.The data reveals the solvents with small dielectric constant are in favor of the formation of AuNVs.While AuNVs can not be formed in solvents with large dielectric constants.The results showed that the size of AuNVs could be controlled by the water content in THF.The influence of ligands show that the balance of solvophilic/solvophobic effect is essential for the formation of AuNVs.The size of AuNVs can also be controlled by the unit number of ethylene glycol.With decreasing the unit number of ethylene glycol,the solvophobic properties of ligand molecules in THF increased,thus leading to the enhancement of the attraction between the ligands on the surface of AuNPs and the formation of smaller AuNVs.The effect of ligand concentration showed that Te BL and Au-10 NPs could self-assemble into AuNVs under the ligand concentrations of 2 m M and 0.5 m M.The calculated minimum ligand solution concentration for the fully covery of the ligands on the surface of 10 nm AuNPs under C_{Au-10 NPs}=2.85×10¹²is 12.4μM,and the lower ligand concentration such as 5μM and 5 n M were less than the minimum ligand concentration for the full coverage.Under these concentration,the surface of AuNPs should not be fully covered by the ligands.Thus,the solvophobic effect of the ligands is weak,resulting in the formation of vesicle-like structures with defects.Previous studies show that perfluorobiphenol ligands with oligoethylene glycol terminals cannot self-assemble with Au-30 NPs to form AuNVs,while the corresponding biphenol ligands in this thesis can form GNVs composed of Au-30 NPs.These data reveals that biphenol ligands provide stronger intermolecular attraction due to their strong solvophobic properties.With increasing the size of AuNPs,the size of AuNVs decreased.This may be attributed to the greater van der Waals attraction between large AuNPs,resulting in smaller-sized AuNVs.When N_{Au-10 NPs}=1.1×10¹²NPs/m L,the surface of the formed AuNVs showed local defects,which was attributed to the small number of Au-10 NPs at low Au-10 NPs concentration.The AuNPs were more closely arranged when the number of initial Au-10 NPs increased.Chapter 4 summarizes the research content of this thesis in general,envisages future research,and looks forward to the application prospects of this field.