Synthesis,Molecular Recognition And Self-Assembly Of Endo-Functionalized Amide Naphthotubes

Molecular recognition widely exists in living systems and is the basis of many biologucal functions.Artificial molecular recognition shows promising applications in gas adsorption separation,drug delivery,drug solubilization,and disease diagnosis.These applications are based on the stability and selectivity of artificial molecular recognition.The main tools for artificial molecular recognition are macrocyclic hosts,which can be roughly divided into two types:a)flexible macrocycles with polarity sites but without cavities,which are difficult to be used for recognition in gas phase or water;b)macrocycles with three-dimensional hydrophobic cavities which are difficult to distinguish guests of similar size but diffierent functional groups.These structural limitations narrows the application of macrocycles in the gas and water.By mimicking the binding pocket of bioreceptors,endo-functionalized cavity with polar groups in a hydrophobic cavity was proposed to be able to achieve high-affinity and selective molecular recognition in gas phase and water.Previously,a kind of macrocycles with endo-functionalized cavities—amide naphthotubes—were reported,and their recognition to hydrophilic molecules such as 1,4-dioxane in water has been preliminarily explored.However,the recognition mechanism and general applicability have not been thoroughly studied.Endo-functionalized amide naphthotubes posses hydrogen bonding sites in their deep hydrophobic cavities,which are ideal models to study molecular recognition of endo-functionalized cavities in gas phase and water.On this basis,this thesis reported the synthesis of a series of amide naphthotubes with sidechain modifications and a systematic study on their properties in molecular recognition in gas phase and gas separation,molecular recognition and controlled self-assembly in water.Firstly,a series of amide naphthotubes with different side-chains were synthesized,and their molecualr recognition in gas phase and gas-solid adsorption separation of benzene,cyclohexene and cyclohexane had been studied.The results showed that the amide naphthotubes with long side-chains could not achieve effective recognition and adsorption separation,because ester or butyl side-chains entered the cavities in the solid state.For the syn-isomer amide naphthotube with methyl side-chains,the recognition selectivity was poor,since the methyl group blocked the porch of the macrocycle.The anti-isomer amide naphthotube with methyl side-chains formed continuous channels in the solid state,which leaded to high recognition ability and adsorption selectivity,and the order was benzene>cyclohexene>cyclohexane.The selectivity for benzene relative to cyclohexene and cyclohexane was 91.3%and97.1%,respectively;selectivity for cyclohexene relative to cyclohexane was 92.8%;the selectivity for benzene was still 90.2%in the ternary mixture of benzene,cyclohexene and cyclohexane.It is found that the recognition selectivity is closely related to the NH··πinteraction between host and guest.At the same time,the system also has the characteristics of fast adsorption,large adsorption capacity,high selectivity,and recycling,indicating the promising in the industrial separation of benzene,cyclohexene and cyclohexane.Secondly,the molecular recognition of water-soluble amide naphthotubes with a series of polar molecules in water was studied by ¹H NMR,fluorescence titration,isothermal titration calorimetry,X-ray single crystal diffraction,molecular dynamics simulation and principal component analysis.The role of hydrophobic effect and hydrogen bonding of amide naphthotubes during the molecular recognition in water was revealed:the hydrophobic effect（by releasing high-energy water in the cavity）was the main driving force;shield hydrogen bonding was the key factor in determining the high selectivity between molecules with similar shape and size（only hydrophilic molecules with complementary hydrogen bonding sites can form stronger hydrogen bonds）.Thus,amide naphthotubes have high selectivity and affinity for guests with polar binding sites complementary to the hydrogen bonding group of the cavity and suitably sized hydrophobic groups.According to these rules,a“best fit”guest—2-phenyl-1,3-dioxolane was found,and the binding constant was as high as10⁶ M^-1.Finally,a series of side-chain mono-modified amide naphthotubes were synthesized and their properties of molecular recognition and controlled self-assembly in water were studied.The results showed that the introduction of alkynyl side-chain can partially affect the molecular recognition of amide naphthotubes,but the overall effect was small:for syn-isomers,the shielding of the alkynyl group makes the cavity more hydrophobic,which was beneficial to the recognition of small molecules;for anti-isomers,the alkynyl group caused steric hindrance and slightly reduced the binding constants of some guests.Moreover,a series of self-assembly monomers were synthesized by covalently connecting phenyloxazoline guest,β-cyclodextrin,and PEG side-chain with amide naphthotubes through the"click reaction"between alkyne groups and azide:hermaphroditic assembly monomers with amide naphthotube unit and guest unit,heterodimers of amide naphthotubes withβ-cyclodextrin and homodimers of amide naphthotubes.The results showed that the supramolecular polymers formed of self-assembly monomers could be further assembled to form larger structures in water.In addition,HCl,concentration and preparation method could affect the structure and morphology of the assembly.This study demonstrates the potential of amide naphthotubes in the controlled self-assembly in water.