Controllable Association,Assembly And Function Of Cucurbiturils Host-Guest Chemistry

Since the discovery of crown ether by C.J.Pederson in 1967,the breadth and depth of research on host-guest chemistry has been significantly developed in many aspects.It moves forward from static to dynamic research,from microscopic to macroscopic level,and from structural architectures to functional assemblies.Along a line of?association--assembly--function?,this thesis concerns controllable association,controllable assembly and controllable function.Three main achievements are summarized as follows.?1?Controllable association:to answer a basic question about how to precisely control binding cooperativity,cucurbit[8]uril-mediated ternary host-guest complexation was selected as our research objective.We designed and synthesized a series of guest molecules with different hydrophilic and hydrophobic side groups for balancing classical and non-classical hydrophobic effect behind this association.In this way,we realize precise control over binding cooperativity behind this ternary host-guest complexation,of which the cooperative parameter can be well tuned from 10^-3 to 10².The basic logic of controlling cooperativity is to manipulate non-covalent interactions by tuning molecular structures for balancing entropy and enthalpy in an elegant way.This work may provide a general strategy for tailoring controllable associations.?2?Controllable assembly:to solve a scientific question about how to realize control over supramolecular polymerization,we introduced a controllable self-sorting system among a non-covalent driving force for polymerization and a non-covalent lever to control the rigidity of monomers.Through self-sorting,the ring-chain equilibrium behind supramolecular polymerization can be well controlled by gradually controlling the rigidity of monomers.In this way,a new method for controllable supr amolecular polymerization is developed,of which the molecular weight of supramolecular polymer can be well tuned from 10 kDa to 97 kDa.Similar methodologies can be extended to other host-guest chemistry or reversible chemistry for fabricating supramolecular polymers with tailor-made structures and topologies.?3?Controllable function:to tackle a practical problem about how to improve chemotherapeutic drugs,we presented a new concept of supramolecular chemotherapy.As a proof of concept,we utilized ho st-guest complexation between cucurbit[7]uril and dimethyl viologen for decreasing its cytotoxicity to normal cells.And with the aid of a tumor cancer biomarker,spermine,dimethyl viologen can be competitively replaced from host cavity,thus sucessfully recovering its anticaner biaoactivty.Furthermore,we extended supramolecular chemotherapy to oxaliplatin,which is a chemotherapeutic drug for colorectal cancer.We empolyed cucurbit[7]uril to encapsulate oxaliplatin for reducing tis cytotoxicity to normal cells,and controlled release of oxaliplatin can be also achieved through competitive replacement by spermine.More importantly,the release of oxaliplatin and consumption of spermine can further result in the enhanced anticancer bioactivity.In this way,we finally established this new concept of supramolecular chemotherapy.Supramolecular chemotherapy could be extended to various supramolecular hosts and traditional chemotherapeutic drugs,thus opening a new horizon for the realm of chemotherapy.