Preparation And Property Manipulation Of Small Biomoecues-based Hybrid Supramolecular Systems

Supramolecular self-assembly is ubiquitous in nature,and the organization of various structures and the function of life are completed under the regulation of thermodynamics and dynamics.Inspired by nature,the simple and efficient construction of advanced functional materials through supramolecular self-assembly is critical to the development of society.The organic-inorganic hybrid supramolecular system can combine the excellent assembly ability of organic components and the unique optical,electrical and magnetic properties of inorganic components,and has important application value in the fields of energy,environment and biomedicine.In order to achieve simple structural regulation and efficient functional coordination,the selection of structural elements is particularly important.The biological small molecules having a wide range of sources,simple and clear structure,easy to process and modify,easy to assemble and study,biocompatible,biodegradable and low immunogencity,are highly promising building blocks.Thus,we have constructed supramolecular systems of biomolecule hybridized with polyoxometalate and metal ions.The structure of the assembly and physicochemical property were finely tuned by the synergism of electrostatic,coordination and other non-covalent interactions,and realized the application of photocatalysis,biosensing,and theranostics.The specific contents of this paper are as follows:Chapter ?.The basic concepts and important contents of supramolecular self-assembly are firstly described.Next,the research progress of polyoxometalate and metal ion hybrid supramolecular systems are introduced,including the regulation of structur and performance as well as multi-functional applications.Finally,based on the existing scientific problems,this paper proposes a strategy to use the minimally simple biological small molecule to control the hybrid functional system,and elaborates the basis and research content of this paper.Chapter ?.The assembly behavior and fluorescence properties of europium-containing polyoxymorate Na9[EuW10O36]·32H2O(EuW10)were controlled by using amino acids with minimal structure.Amino acids have an amino group,a carboxyl group,and a functional group provided by a polar branch.Its partial charge shielding effect makes it possible to provide proper electrostatic interaction with EuW10 to form vesicles,which is one of the few reports that polyoxometallates form vesicle structures in aqueous solution.The slight difference in the structure of the branches makes the electrostatic interaction different,and can flexibly regulate the enhancement and quenching of EuW10 fluorescence:basic amino acids including acids arginine(Arg),lysine(Lys)and histidine(His)can enhance the fluorescence of EuW10;non-polar amino acids including leucine(Leu),alanine(Ala)and phenylalanine(Phe)have no significant effect on the fluorescence of EuW10;acidic amino acid including glutamic acid(Glu)and aspartic acid(Asp)can quench the fluorescence of EuW10.Various characterizations were used to study the molecular mechanism also proved it.It was found that EuWio,as a polar head group,interacts with the positively charged residue of basic amino acids,the protonated amino group of acidic and non-polar amino acids,and the other parts of the amino acid,as a relatively hydrophobic structure,come together to form a bilayer.In addition,EuW10/Arg nano-vesicles can be used as biosensors to detect the neurotransmitter dopamine(DA)with low detection limit and high specificity.DA and EuWio have stronger hydrogen bond and electrostatic interactions,and the competitive combination with Arg is the working mechanism of the sensor.Chapter III.Based on the work in Chapter II,the DA/EuW10 micro-sized flower-like structure was constructed by the ionic self-assembly strategy(ISA).The characterization over time demonstrates nucleation growth based hierarchical self-assembly process,which mimics the bloom of natural flowers.By changing the ratio and concentration of the two components,flower-like structures with different morphologies were obtained.Electrostatic interactions and hydrogen bonding play a decisive role in the assembly process.Since the hydrogen bond between the amino group of DA and the oxygen atom of EuWio prevents the transition of the d1 electron,the fluorescence of the assembly is quenched.Interestingly,the structure-optimized micro-flowers were calcined at high temperature to remove organic components,and the resulting porous skeleton exhibited excellent photocatalytic degradation ability to the model molecules of the organic pollutants,methyl orange(MO)and rhodamine B(RhB).The calcined microporous framework increases the surface area and pore volume,exposing more active sites;at the same time,the absorption band is broaden,and the numbers of photogenerated electrons and holes are increased,leading to increased efficiency of the photocatalytic reaction.In particular,the catalyst can still maintain high activity after repeated degradation of the negative charge MO for 6 cycles,which indicates that they have potential application in wastewater treatment.Chapter IV.This chapter uses the amphiphilic amino acids(9-fluorenylmethoxycarbonyl-L-leucine,Fmoc-L-L)self-assembly of magnetic resonance imaging contrast agent(manganese ion,Mn2+)and photosensitive drug(chlorin e6,Ce6)to prepare a multi-component intelligent nanodrug.Coordination-driven assembly of Fmoc-L-L and Mn2+ resulted in a supramolecular network.Ce6 was encapsulated by ?-? stacking and hydrophobic interaction,and the drug loading rate was as high as 36 wt%.Due to the covalent bond property of the coordination bond and the synergic property of multi-covalent of the multi-component,the nanomedicine remains stable in vivo circulation and specifically responds to the microenvironment of the tumor tissue.The high concentration of glutathione(GSH)in tumor cells competes with Mn2+ can disassemble nanomedicine,releasing photodynamic drugs on the one hand;on the other hand,the GSH/Mn2+ complex can enhance the signal of magnetic resonance imaging and increase the retention time,while reduce intracellular GSH levels and improve the reductive microenvironment of tumor.Based on these ingenious designs and properties,the nanomedicine exhibits an efficient photodynamic therapeutic effect on tumors in vitro and in vivo.Chapter V.Size-switchable intelligent nanodrug can increase the accumulation amount and penetration depth at tumor tissue.On the basis of our previous work,simply changing the chelation site of manganese ions can regulate the pathway of light energy conversion.The synthesized molecular sensitizer has an exclusive photothermal effect independent of aggregation.Tumor microenvironment-responsive-nanodrug is obtained by the dipeptide-tuned self-assembly of the photothermal molecule,which completes self-delivery in the tumor tissue and achieves efficient photothermal therapy.Specifically,the molecular photothermal agent PM was synthesized by chelation of a paramagnetic metal ion Mn2+ into the pyrrole ring of photosensitizer pheophorbide a(Pheo a,P).First,the paramagnetic metal ion Mn2+ was chelated with the pyrrole ring of the photosensitive molecule pheophorbide a(Pheo a,P)to synthesize a molecular photothermographic agent PM.By comparing the photochemical properties of P and PM,including fluorescence,photodynamics,photothennal effect and photostability,PM was found to have a single photothermal conversion pathway and ideal photostability.The assembly of PM by amphiphilic small peptide(His-Phe)resulted in stable and dispersed nanoparticles with good colloidal stability and blood circulation stability.In the experiment simulating the hydrophobic microenvironment of tumors,the particle size of the nanomedicine is reduced to about 10 nm in 24 hours,and the photothermal effect and photoacoustic signal remain nearly unchanged with the enhancement of the magnetic resonance signal.In vitro cell experiments confirmed the cellular uptake and disassembly behavior of nanomedicines.In vivo,efficient photothermal therapy is achieved by the guidance of magnetic resonance and photoacoustic imaging.