Chiral Adaptive Recognition Of Biomolecules By Tetraphenylethene-Based Cages

The development of chemical research has experienced the extension from molecular chemistry to supramolecular chemistry,and further extended to dynamic chemistry and adaptive chemistry,which is similar to the survival mode of the fittest in biological evolution and always develops in the direction of adapting to the environment.Host-guest chemistry based on molecular recognition is the basis and important branch of supramolecular chemistry and has been widely studied for its dynamic controllability and design diversity.The research on host-guest recognition in aqueous phase has opened a new way for the development of new biocompatible materials.Chirality,as a basic property of nature,makes biological evolution more inclined to develop in a way of chirality.The integration of chirality into supramolecular biomimetic research can provide new possibilities for understanding complex physiological processes.In this paper,a new recognition mechanism,Chiral Adaptive Recognition（CAR）,is proposed by combining host-guest chemical recognition and dynamic conformational chirality.In this new system,chiral guests induce selective conformational chirality of achiral hosts through efficient steric chirality transfer and form chiral host-guest complexes.We use tetraphenylethene-based octacationic cage to recognize different biomolecules（e.g.,nucleotides,amino acids,peptides and proteins）in aqueous phase,which verifies the universality and superiority of CAR mechanism,and has potential application value for the monitoring of biomolecular transformation process.The specific research contents are as follows:1.the synthetic route of cationic tetraphenylethene-based cage（1）was optimized,and it was proved that there are three conformational isomers of 1（i.e.,a mesomeric PM-1 and a pair of racemic MM-1 and PP-1）by their X-ray structures in the crystalline state.The selective expression of this dynamic conformation is the basis for the realization of CAR mechanism.the adaption-chiral recognition of amino acids,peptides and proteins by the cage is further studied.We first selected glycine,19 pairs of D/L-amino acids,44 L-dipeptides and 3 D-dipeptides for CAR study of the cage.The results showed that D/L-type dipeptides induce the mirror-symmetrical CD and CPL signals of the cage:D-dipeptides induce the adaptive conformation chirality of MM-1 with positive circular dichroism（CD）and circular polarized luminescence（CPL）signals and L-dipeptides induce the adaptive conformation chirality of PP-1 with negative CD and CPL signals,which can be applied to determine enantiomeric purity and absolute configurations of the dipeptide enantiomers.At the same time,we found that the cage can form 1:2 host-guest complexes with aromatic-aromatic dipeptides with high binding affinity(up to 10¹⁴ M^-2)and sequence selectivity（up to 10⁵ times）over other aliphatic-aromatic dipeptides.Based on this,we further selected two series of tetrapeptides with Trp Trp or Phe Phe residues at the N-terminal,middle,and C-terminal positions,respectively,to study the position effect of aromatic residue on the CAR responses by the cage.In addition,two polypeptides（e.g.,amyloidβ-peptide1-20 and somatostatin）and one protein（e.g.,human insulin）could also exhibit CAR after interacting with the cage.In short,it shows the universality of CAR mechanism,and the research in this chapter can provide a reference for the evaluation and localization of complex and diverse sequences in organisms.2.In chapter 3,it is proved that the hydrophobic cavity of the cage can efficiently stabilize the hydrogen-bonded dimerization of homogeneous or heterogeneous deoxyribose base pairs in aqueous solution.And according to the CAR response mechanism,the encapsulation of chiral base pairs can induce PP-adaptive chiral rotational conformation of the achiral cage,which can be used to determine the base sequences of DNA.3.Based on the research in chapter 3,10 ribonucleotides were selected for the CAR study of the cage.Combined with the four kinds of deoxyribonucleotides in chapter 3,we compared the response differences of nucleotides with different base,ribose and phosphate numbers to the CAR mechanism of the cage,which has a certain reference value for distinguishing deoxyribonucleotides from ribonucleotides and purine and pyrimidine nucleotides.At the same time,it also explains the reliability of CAR mechanism again.4.Studies in chapters 2,3 and 4 confirmed the CAR properties of the cage for different biomolecules.In chapter 5,we selected three pairs of oxidation-reduced biomolecules（coenzymeⅠ,coenzymeⅡand glutathione）for the CAR study of the cage.And it is expected to monitor the biotransformation process of oxidized and reduced molecules based on their different responses to the cage.The study proved that biomolecules in two states showed different CAR responses after interacting with the cage,which can be used for the preliminary monitoring of molecular transformation process,laying a foundation for our further research.