Halogenation Effect Tunes The Nanofibers Chirality Of Supramolecular Hydrogel And Its Application In Cell Proliferation,Adhesion

In nature,chiral phenomena can be observed at molecular,supramolecular,nano-scale and macroscopic levels.Among these various levels,as the central structural motifs in living systems（e.g.,double helix in DNA,α-helix,β-sheet in proteins）,supramolecular helical systems arising from non-covalent interactions stacking of molecular units play a crucial role in a wide diversity of biochemical reactions（e.g.,gene replication,molecular recognition,ion transport,enzyme catalysis,and so on）.Inspired by the natural helical structure,scientists have constructed a number of artificial chiral helical structures with delicate structures using hydrogen bonding,π-πstacking,electrostatic interaction and other non-covalent interactions to control chirality from a few nanometers to the macroscopic scale.The electron density around the halogen nucleus is highly anisotropic,so halogens can act as both electron acceptors and electron donors.Non-covalent interactions involving halogen atoms also play an important role in biological systems.For instance,in natural chiral biomaromolecules,48 cases were found in Protein Data Bank（PBD）for high-resolution structures with halogen atoms.Investigation of halogen bonds in the occurrence and inversion behaviors of chirality at supramolecular scale is showing vital significance to biomimetics,biomedicine and chiroptical materials.This thesis consists of two parts:1.Fluorine atom and its positional substitution tunes the chirality of supramolecular hydrogel and the study of biological application.We selected C₂-symmetric phenylalanine derivatives as template compounds,and designed and synthesized six monofluorinated gel factors by introducing a fluorine atom into the ortho-site,meso-site and para-site respectively of the side chain amino acid benzene ring.The experimental results show that ortho-fluorosubstitution can preserve supramolecular chirality,while paratope and meso-fluorosubstitution can induce supramolecular chirality reversal.By a series of experimental characterization and theoretical calculation,it was found that the gel factors in the assembly process are affected by hydrogen bonding between amides,π-πstacking of central benzene ring,and fluorine hydrogen bonding.The fluorine atoms on the benzene ring of the side chain amino acid in the meso-site and para-site fluoro-substituted gel molecules formed the fluorine hydrogen bond interaction with the hydroxy hydrogen and methylene hydrogen in the side chain hydrophilic chain,and induced the intermolecular hydrogen bond between the inner amide and the outer amide C=O in the original template molecule to form the intermolecular hydrogen bond between the inner amide C=O and the outer amide.Finally,the chirality of supramolecule is reversed.Finally,we explored the effect of molecular（L/D）and supramolecular chirality（M/P）on cell adhesion growth according to the above designed and synthesized fluorinated hydrogel.The results showed that the positive effect of molecular chirality and high order supramolecular chirality on cell proliferation and adhesion was LM>DM>LP>DP.2.Halogen substitution tunes the chirality of supramolecular hydrogel.Based on the results of the first part of the experiment,different halogen atoms were introduced into the para-site of the side chain amino acid benzene ring.By replacing the amide bond outside the molecular structure with an ester group to reduce its hydrogen bond action site,non-halogen and four halogen atom substituted gel elements were synthesized.The inversion method showed that the gel was formed and had good gelatinization performance,indicating that the structure modification had improved the precipitation aggregation and poor gelatinization performance caused by the heavy atom effect of halogen atoms.The experimental results show that:Fluorinated,chlorinated and bromo-substituted supramolecular hydrogels all form the same left-hand spiral nanofibers as non-halogenated hydrogels,while iodo-substituted supramolecular hydrogels form the opposite right-hand spiral fibers.By a series of experiments,it was found that halogenated hydrogels and non-halogenated hydrogels were affected by hydrogen bonding between ester group and amide andπ-πstacking of central benzene ring during the assembly process.Finally,we explored the biocompatibility of supramolecular hydrogels with different halogen atoms,and the results showed that halogenated supramolecular hydrogels had good biocompatibility.