Study Of Functional Supramolecular Assembly Materials Based On Macrocycles

Supramolecular chemistry is the chemistry of molecular aggregates based on noncovalent bond interactions.Macrocyclic host compounds are important research topics in supramolecular chemistry.The coming of any new generation of macrocycles can not only greatly enrich the research content of supramolecular chemistry but also accelerate the development of supramolecular chemistry.Macrocyclic hosts,such as crown ethers,cyclodextrins,calixarenes,cucurbiturils,pillararenes,biphenarenes and metallacycles,play an extremely important role in constructing functional supramolecular assembly materials.Up to now,functional supramolecular assembly systems based on macrocyclic hosts have been widely used in the fields of supramolecular amphiphiles,macrocyclic amphiphiles,supramolecular polymers,drug delivery systems and adsorptive separation processes.Our research focus on the structures,properties and applications of functional supramolecular assemblies.The main content of the dissertation includes the following seven parts:In the first part,we developed a new supramolecular luminogen through the host-guest interaction between a monofunctionalized pillar[5]arene 2.1 and a tetraphenylethene derivative 2.2.Upon formation of the host-guest complex,the fluorescent emission of the TPE-based fluorogen was enhanced effectively,because the intramolecular rotation of the aromatic rings of the TPE group was restricted and the nonradiative decay channels were blocked effectively by forming a[2]pseudorotaxane-type structure.Through the reprecipitation technique,NPs with an average diameter of about 43 nm were obtained,which could be utilized as an imaging agent to light up the cells.These results demonstrate that the combination of the AIE effect with supramolecular chemistry has enormous potential applications in biologically relevant fields,such as biosensors,drug and gene delivery systems,protein-protein interactions and cell imaging.In the second part,a cationic water soluble pillar[6]arene(CWP6)selectively interacted with ATP to form a stable 1:1 inclusion complex CWP6=DATP mainly driven by entropy change.As a result,the hydrolysis of ATP was efficiently inhibited in the presence of alkaline phosphatase due to the existence of a hydrophobic cavity of CWP6.A folic acid ended diblock polymer FA-PEG-b-PAA was employed to PEGylate the cationic pillar[6]arene CWP6 to obtain PIC micelles in buffer,endowing them with specific targeting ability to deliver CWP6 to folate receptor over-expressing cancer cells.The ATP-dependent efflux pump was blocked by cutting off the energy source from ATP hydrolysis due to the formation of the host-guest inclusion complex.Furthermore,MTT assay demonstrated that the efficacy of the anticancer drug DOX HCl was improved effectively in the presence of PIC micelles.The present results pave a way to develop novel therapeutic agents,implying that supramolecular chemistry may be engineered into promising vehicles to overcome multidrug resistance in cancer therapy.More detailed biologic investigations need to be carried out to figure out the deeper-level mechanism of the MDR treatment.In the third part,we synthesized the first anionic water-soluble biphen[3]arene(WB3)and investigated its pH-controlled complexation with l-cetyiethylammonium chloride(4.1)in water.We demonstrated that model compound 1-bishexylamine chloride(4.2),as an axis,was threaded through the cavity of the cyclic host WB3 to form a 1:1 inclusion complex with the association constant of(2.57±0.80)× 104 M-1 mainly driven by electrostatic and hydrophobic interactions.Furthermore,we used this novel recognition motif to construct a supra-amphiphile based on WB3 and amphiphilic 4.1 in water.By adjusting the solution pH,the transformations between micelles formed by 4.1 and vesicles based on WB3(?)D4.1 were realized.This novel recognition motif based on the anionic water-soluble biphen[3]arene in aqueous media will be helpful for the fabrication of functional architectures and definitely bring about many promising applications,such as supramolecular polymers,sensors,nanoelectronics,drug delivery and controlled release.In the fourth part,we have successfully prepared the first cationic water-soluble biphen[3]arene CWB3 bearing three trimethylammonium moieties on both sides.The presence of six positive charges makes it possible to act as an anion receptor.Mainly driven by hydrophobic and electrostatic interactions,this cationic water-soluble bipl:en[3]arene could bind sodium l-hexaneSsulfonate to form a host-guest complex with the association constant of(1.56 ± 0.07)× 103 M-1.In addition,we used this novel recognition motif to construct a supra-amphiphile by using CWB3 and amphiphilic 5.2 as the building blocks,which was further used to change the aggregation of the amphiphilic guest in water.In contrast to the small sphere micelles formed by amphiphilic molecule 5.2,the host-guest complex between CWB3 and 5.2 self-assembled into regular nanoparticles in water.This new recognition motif based on the cationic water-soluble biphen[3]arene absolutely will be helpful for the fabrication of biphenarenes-based functional architectures and definitely bring about many prospective substantial applications,such as chemo-sensors,molecular machines,supramolecular polymers,drug delivery systems and controlled release.In the fifth part,we reported a new macrocyclic receptor,[2]calix[1]biphenyl-type hybrid[3]arene(2C1BH3A).It is made of two 1,3,5-trimethoxybenzene units and one 4,4'-biphenol diethyl ether unit linked by methylene bridges.The macrocyclic product offers a simple and effective method to synthesize supramolecular scaffolds with different types of building units by a hybrid approach.We can forecast that the integration of other types of building units,such as phenol,hydroquinone,biphenol,dinaphthalene,or the introduction of diverse functional groups,such as alkoxy,propargyl,ester,amino,will endow the resultant synthetic macrocycles with rich topologic structures and prosperous host-guest properties.Furthermore,their functionalized derivatives can be made by modifying selectively,making them promising candidates for applications in the construction of chemosensors,transmembrane channels,supramolecular polymers,liquid crystals and drug delivery systems.Currently,relevant efforts are underway in our laboratory.In the six part,we reported the first examples of highly emissive Pt(?)supramolecular triangles bearing a pyridine-functionalized BODIPY ligand via coordination-driven self-assembly for theranostic studies.The formation of two triangular metallacycles was fully characterized by multinuclear NMR(1H and 31P),ESI-MS,2D DOSY,UV-vis spectroscopy,and fluorescence spectroscopy.These triangles possessed promising potential applications in cancer theranostics,in which the platinum acceptors were toxic chemotherapeutics and the BODIPY donor was imaging probe and photosensitizer.In vitro studies demonstrated that the formation of metallacycles improved their anticancer efficacy,and the combination of PDT and chemotherapy showed excellent synergistic effect.More importantly,these SCCs exhibited superior anticancer outcomes agaist drug resistant A2780cis cells integrating two different therapeutic modalities into the supramolecular platforms.The self-assembled BODIPY-platinum supramolecular triangles provides a promising platform for fluorescence imaging-guided cancer therapy.In the seventh part,we demonstrated that the host-guest complexation between H and G remarkably decreased the detection limit for CN-as compared with that of the guest alone.From H and G,a[2]pseudorotaxane driven by hydrogen bonding and face-to-face;?-stacking interactions formed.Interestingly,this host-guest complexation was responsive to CN-.Moreover,the cyanide-responsive[2]pseudorotaxane was developed iinto supramolecular materials for the visual detection of cyanide anion,especially the detection of cellular cyanide excretion with a detection limit of 0.2 pM/cell.This cyanide-responsive binding property is a novel feature of the host-guest properties of bis(p-phenylene)-34-crown-10.More importantly,this cyanide-responsive host-guest complex holds promising potentials in biomedical applications such as disease-specific biomarker detection and early-stage precise diagnosis.