Study On The Structure And Properties Of Aromatic Oligoamide Foldamers With Disulfide Bonds

The biological functions of proteins are closely coupled to the their particular structures.The research on the relationship between protein structure and function will facilitate to explain the chemical nature of life phenomenon at the molecular level,and also boost the developments of other fields,such as biology and medicine.But the particular structures of proteins are determined by their polypeptide chains which usually contains large amounts of amino acids,and assembled in complex folding behavior,the relevant research is still a tremendous challenge.Therefore,chemists try to understand the folding behavior of proteins based on biomimetic structures which are relatively simple,hoping this researches would help us to learn more about the essence of protein structure.In proteins,disulfide bridges between residues play an important role in aspect of primary structure formation and stability of higher structure,which will be helpful for proteins to correct folding and to implement various functions.Meanwhile the formation/breakage of disulfide bond is also key to the function expression of proteins.Foldamer research is inspired by the folding of biological macromolecules.In this thesis,we try to research the influence on the structure and properties of the abiotic foldamers through introducing disulfide bonds into the sequences,and also attempt to utilize the dynamic covalent characteristics of disulfide bonds for dynamic contorlling the structures and functions of sequences.Following this,we designed and synthesized a series of aromatic oligoamide foldamers with terminal disulfide bridges,and their structures and properties were characterized and analyzed in detail.The design of the aromatic oligoamide sequence composed of a pyridine-based trimer and a fluoroquinoline-based tetramer,appending a thiol chain at its pyridine terminus.The antiparallel helix can be rearranged to parallel by disulfide connection of the sequence,which reorganizes the chiral inducers with closer proximity.NMR and circular dichroism spectroscopy demonstrate the chiral communication between the chiral inducers,which gives rise to full chirality control of the double helix.The formation/breakage of the disulfide bond can be governed by the oxidation-reduction cycle,thereby switching the structural arrangement and chiral bias enhancement.A high degree of preorganization afforded macrocyclic aromatic oligoamide foldmers with the connection of disulfide bridges has been designed.Single-crystal X-ray structures and NMR spectroscopy support the macrocyclic structure both in the solid state and in solution.The macrocyclic structure can be reversibly interconverted between α-helix and β-sheet configurations through rearrangement of intramolecular hydrogen bonds,and the reversibly process can be realized efficiently through alternating protonation and deprotonation.Further studies showed that the unique electronic character of the cavity in protonated configuration is capable of bindingπ-electron-rich guest molecules.A unique and robust artificial triple helix architecture based on disulfide bridges is presented.The aromatic oligoamide sequence composed of a pyridine-based trimer and a naphthyridine-based dimer,appending a thiol chain at its pyridine terminus.Single-crystal X-ray structure of the tertiary structure is successful obtained in chloroform-hexane binary solvents.This triple helix has the tendency to transform into parallel double helix and possesses sufficient affinity to tartaric acid guest molecule.It proves the potential application of disulfide bridges that could be a powerful tool to design elaborate tertiarylike abiotic architectures,and benefits to the structures and functions of foldamers.