| Over the past three decades,supramolecular chemistry has been widely used in the fields of self-assembly,molecular devices,molecular machines,nanomaterials and so on,but the intermolecular force is too limited to limit its application.As a strategy to construct supramolecular assembly,the dynamic covalent bond is widely used in the field of intelligent regulation and biomimetic materials because of its thermodynamically reversible and strong intermolecular interaction.Hydrazone is a common type of covalent bond produced by the reaction of hydrazine and ketone or aldehyde.The hydrazone bonds formed by the hydrazide groups are strongly motivated,mainly because the acyl groups have strong ability to absorb electrons and thus weaken the stability of carbon and nitrogen double bonds.Weak acid or aniline(nucleophile)catalyzes the rapid formation of hydrazone bonds and controls the morphology of the assembly.As a common form of supramolecular assembly,the internal hollow core-shell structure of vesicles has been fully studied.It is self-assembled by the amphiphilic molecules with critical buildup parameters between 0.5 and 1 in the solvent.Size of nanosized or micronous vesicles has its specific application areas.Nano-vesicles are used to cover functional molecules such as transport-release drugs,which require the assembly of vesicles and assembly and assembly control.The structural changes of the assembly are derived from structural changes in the building elements,and the elements respond to stimuli such as light,electricity,redox,p H and other external environments.The report of non-liposome vesicles to nanometer-based,micron-level is still relatively rare,in order to achieve this size,its building elements to macromolecules as common.Large vesicles are similar in morphology and size to cells,and are often used as cell models to simulate cell behavior.As one of the important behaviors of cells,membrane fusion plays a key role in the intercellular exchange of substances and information as well as the generation of new cells.At present,the mechanism of membrane fusion is still controversial,so it is rare to attract a variety of liposome models to simulate them,but the membrane fusion model with non-liposomal vesicles is still rare.In this paper,amphiphilic molecules were synthesized by the use of acylhydrazide-containing molecules and aldehyde-containing molecules in weak acid catalysis to form amphiphilic molecules,which self-assemble to form vesicle structures.The nano-drug delivery system and the micrometer cell fusion model with p H response were further constructed,and the following results were obtained:1.Construction of nano-capsules based on hydrazone-based H-type amphiphilic small moleculesTwo small molecules of acylhydrazine and bi PEG-benzaldehyde were designed and synthesized,both of which reacted rapidly in weakly acidic phosphate buffer to form amphiphilic with hydrazone Molecules,which are self-assembled into aqueous small vesicles in aqueous solution.When the p H of the conditioning solution drops below 5,the hydrazide is easily protonated to produce the primary amine salt,which promotes the hydrolysis of the hydrazone to accelerate the final formation of two hydrophilic substances,which leads to the assembly of the capsules;To more than 5,reversible reaction to facilitate the formation of hydrazone in the direction of movement,vesicle structure has been restored.Based on this,we encapsulate the fluorescent probe,rhodamine B,into the hollow vesicles,and release the fluorescent probe through its controlled solution to successfully construct a p H-responsive nanocapsule for coating and releasing the drug.2.Cell fusion model established by using hydrazone pillar[5]areneSimulated cells need to be constructed in micron-sized vesicles,and at similar levels of hydrophobicity,the vesicle size is controlled to a micron level by designing larger constituent elements.Considering the permeability of the cell membrane,it is an ideal design to construct the element with a large ring as a skeleton.Using a macrocyclic molecule,a hydrazone pillar[5]arene,similar to the phenoxy hydrazide structure,is catalyzed with bi PEG-benzaldehyde in phosphate buffered saline in the weak acid environment The reaction forms an amphiphilic pillar[5]arene containing hydrazone bond.The ten-site capping resulted in a larger molecular volume of the hydrazone-pillar[5]arene,which in the aqueous solution was self-assembled to form a multi-layered large vesicle of micron size.With the molecular assembling,ultrasound has the energy to break the hydrogen bonds of the polyethylene glycol chain,causing the vesicles to create gaps.The concentration of large vesicles at the appropriate concentration will accumulate,especially in the process of evaporation of aqueous solution will be a lot of contact,coupled with the removal of ultrasound after the hydrogen bond recovery,resulting in two vesicles in the gap at the fusion to form a larger vesicle.Depends on the outer wall of the vesicle outside the reversible hydrolysis of the formation of benzaldehyde liquid slow evaporation,the process of vasoconstriction of the more hysteresis.So that we can easily use the optical microscope in situ observation of the whole process of vesicle fusion.This new type of cell fusion model based on dynamic covalent bonds enhances our understanding of membrane fusion. |
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