Studies On Supramolecular Self-Assembling And Bioactivity Of The Pseudorotaxanes Composed Of Cucurbit[6]uril And The Guest Molecules With Imidazolyl Groups

Cucurbit[n]uril (n=4-12) is a novel class of macrocyclic molecules with highly symmetrical drums in the development of supramolecular chemistry after the cyclodextrin, crown ethers and calixarenes. Cucurbit[6]uril, abbreviated as CB [6], is the incontrovertible representive in the the family of Cucurbit[n]uril. CB[6] is a macrocyclic molecule composed of the six glycoluril units linked by the twelve methylene bridges, and has an internal hydrophobic cavity and the two ports formed by the carbonyl oxygen atoms. Its structural characteristics makes it distinguished from other supramolecular macrocyclic molecules, bond with the organic cations or molecules through interactions of hydrophobic, hydrogen binding and ion-dipole bonding, etc.,, and coordinate with many metal ions to form complexes. With the rise of supramolecular chemistry, cucurbituril chemistry has become a conspicuous flower in the science garden of supramolecular chemistry, exhibiting huge potential applications both widely and inetrestingly in supramolecular catalysis, supramolecular self-assembly, molecular recognition, ion channels, molecular biology, nano-technology, supramolecular drug, supramolecular material and other fields. Many works on cucurbit[6]uril have been published, including the recognition of cucurbit[6]uril towards the aliphatic amines ions, pyridylmethyl-ended alklyammonium ions and other guest molecules, the formations of pseudorotaxanes, rotaxanes, pseudopolyrotaxanes, polyrotaxanes, molecular machines, molecular necklaces, etc. from cucurbit[6]uril. However, guest molecules with the imidazole groups have not appeared so far.In this thesis, all studies focused on the cucurbit[6]uril as a host molecule and the imidazolyl-ended fat alkanes as the guest molecules. In aqueous solution, a series of new pseudorotaxanes were prepared and characterized, and their biological activity were investigated. The studies are as following:1. We synthesized a series of guest molecules containing imidazole groups, including 1,3-diimidazolyl propane (BIMP3), 1,4-diimidazolyl butane (BIMB), 1,5-diimidazolyl pentane (BIMP5), 1,6-diimidazolyl hexane (BIMH), N,N'-bis (4-methylimidazole)-1,6-hexanediamine (BMIMHA). Their structures were characterized by the elemental analysis (EA), ¹H,¹³C NMR spectra, mass spectrometry(MS) and so on.2. Some new pseudorotaxanes including CB[6]/BIMP3, CB[6]/BIMB. CB[6]/BIMP5, CB[6]/BIMH, CB[6]/BMIMHA were prepared in aq. solution. The complexes were characterized by means of the EA, IR, NMR, electrospray ionization mass spectrometry (ESI- MS), X-ray crystallography. All the work set a good foundation to prepare and explore the novel supramolecular complexes, including molecular necklaces, metal-coordiated polyrotaxanes, and so on. All these pseudorotaxanes were also studied in the solution by NMR methods and the shift data of proton signals of the guest molecules due to the effections of cucurbit[6]uril were discussed.3. The CB[6]/BIMH pseudorotaxanes with the different inorganic anions were prepared and investigated the influence of different inorganic anions on self-assembly though the X-ray diffraction crystallography to probe the solid-state properties of these supermolecules. We found new pseudopolyrotaxanes stacked via theÏ€...Ï€non-covalent interactions. On the other hand, the electrospray ionization mass spectrometry revealed that this type of pseudorotaxanes can exist stably as single-charged and double-charged species both in solution and gas-phase. Transmission electron microscopy (TEM) revealed the formation of nanowires and nanotubes with diameters of 25-40 nm.4. The biological activity of the CB[6]/BIMH pseudototaxanes were studied by monitoring the cleavage reaction on plasmid DNA with agarose gel electrophoresis. The CB[6]/BIMH [2]pseudorotaxane exhibited efficient cleavage to double-stranded pBR322 DNA in quasi-physiological conditions. The cleavage mechanism were studied by fluorescence spectra, DNA thermal denaturation experiments, crystal structure, High Resolution Mass Spectrum (HRMS) structural analysis, Molecular Modeling and the hydrolysis of bis(2,4-dinitrophenyl)- phosphate (BDNPP) as a model compound of DNA. The results showed that the scission was taken place via hydrolysis mechanism, with good cooperation between the host (CB [6] and the guest (BIMH) molecules. In this mechanism, the protonated imidazole might bind DNA via the electrostatic hydrogen bonding and the oxygen atoms from CB[6] glycoluril carbonyl activated a water molecule which attacked the phosphorus atoms on DNA. This is the first case to report an artificial nuclease assembled from two non-bioactivity small molecules based on the supramolecular assembly with satisfaction behavior. It is noticeable that we have developed some new complexes as metal-free nucleic acid cleavage reagents with great potential applications in biomedicine.