Development Of Folded Short Peptides And Supramolecular Self-Assembly

Chirality is the basic feature of living substances in Nature.During the investigation of the origin and evolution of life,chiral molecules have been studied for several decades.Especially since 1980,with the booming of life science and functional materials,the research based on chiral molecules has become hotspots in chemistry field,in which the biomimetic peptides have opened a broad view for the study of chiral materials.Furthermore,the chirality transfer and conformation control of peptidomimetics provide important ways for the novel functional materials.The a-amino acids,basic element of biomolecules on the earth,are mostly of L-configuration,proteins and DNA are characterized as right-handed structures,as well as conch threads.Inspired by the natural helical structures,building supramolecular helices based on intermolecular weak interactions become a necessity for the development of chirality.Recently,halogen bonding has become a novel intermolecular weak interaction,yet building supramolecular helices that features are driven by halogen bonding in solution remain a challenge.In this Thesis,a series of dipeptide based amidothioureas and two-or three-sidedhalogenated derivatives are designed and synthesized by using N-amidothioureas that contain a ?-turn structure as the structural skeleton and introducing amino acid residues.These amidothioureas are successfully applied in the research of conformation control,chirality transfer,supramolecular helix and chiral amplification.This Thesis consists of four chapters.Chapter 1 is the preface.Firstly,peptidomimetics,turn structures,chiralitytransfer and conformation control are reviewed.Secondly,an overview of the halogen bonding and the progress of supramolecular self-assembly are described.Finally,the design and research objective of this Thesis are proposed.In chapter 2,N-amidothioureas GF-z and AibF-z based on dipeptide Gly-Pheand Aib-Phe are designed and synthesized.They are modified by different achiral amino acid residues Gly or Aib at N-terminus together with CD reporter(benzylthiourea chromophore)and nuclear magnetic resonance probe(-CH2)at C-terminus,which are used to monitor conformational characteristics and intramolecular chirality transfer of GF-z and AibF-z in both aqueous and organic solutions.GF-z forms a stable ?-turn in acetonitrile,while AibF-z of more rigid structure with both ?-turn and ?-turn.In aqueous solutions,the overall conformations also differ significantly between them that different-NH protons participate in intramolecular hydrogen bonding networks with ten-membered trings in GF-z and AibF-z respectively.In addition,the intramolecular chirality transfer efficiency of AibF-z is significantly better than that of GF-z in either acetonitrile or aqueous solution.Surprisingly,both GF-z and AibF-z can form stable ?-turn structure in aqueous solution,which provides an important strategy for building the folded structure of short peptides in aqueous solution.In chapter 3,we develop a series of two-sided halogenated derivatives LL-/DD-NAX(X = H,F,Cl,Br,I),which contain potential halogen bonding donor(halogen substituent)and take naphthalene dicarboxylic acid as internal linker.In these molecules,iodine,bromine,and chlorine substituted derivati-ves can form supramolecular helices in highly dilute solutions of micromolar concentration in acetonitrile,with critical aggregation concentration of approximately 2 ?M,6 ?M and 5 ?M respectively.Furthermore,X-ray crystal structure of LL-NAI indicates that a supramolecular helix exists that is driven by intermolecularC-I…S halogen bonding.Meanwhile,temperature-dependent CD of LL-NAI shows that the supramolecular helix of this iodine-substituted derivative is highly thermal stable.Interestingly,these experimental results present important hints for the study of supramolecular helix based on halogen bonding in solution.In chapter 4,supramolecular self-assembling of a series of BTA derivatives containing a ?-turn structure in each of the three branches have been studied.By introducing different halogen substituents to each end of the three branches,a novel supramolecular self-assembly based on BTA is successfully constructed,with spherical morphology and a significant chiral amplification.