Supramolecular Aggregation Of Folded Short Peptides Regulated By Halogen Bonding

Supramolecular chemistry is aimed to study the weak interactions between two or more molecules to form a complex and ordered structure with functions.Those weak interactions include hydrogen bond,hydrophobic interaction,π-π stacking,metal coordination,electrostatic interaction,etc.In recent years,as a new type of weak interaction,halogen bonding has drawed much attention as well.In this thesis,a series of folded short peptides based on N-amidourea or N-amidothiourea skeleton and chiral L/D-alanine resides were designed and synthesized,in which halogen atoms were introduced,via halogen bonding,to regulate the formation of supramoleciular aggregates and supramolecular chiral amplification in solution.In addition,halogen-bonded hetero-double helical structures were successfully created in the solid phase by employing bilateral folded short peptides that substituted with different halogens.This thesis consists of four chapters,including the followings:Chapter 1 is the preface.The development of supramolecular chemistry was first briefly introduced.The development,applications and research progress of halogen bond were next reviewed.Finally,the design strategies and research purpose of this thesis were described following the description of azapeptides,β-turn structure and chirality.In chapter 2,among these different halogen substituted "head-to-head" bilateral N-amideureas L,L/D,D-XUA(X = H,F,Cl,Br),the bromine substitution compounds L,L/D,D-BrUA could form supramolecular self-assembly structures at micro molar concentration in acetonitrile.The temperature-dependent CD results show that the supramolecular aggregates are thermal stable.The halogen anion titrations indicate that the weak interaction supporting those aggregates shall be of halogen bonding.Interestingly,driven by the hydrophobic interactions in nature,L,L/D,D-BrUA could assemble in aqueous TTAB solution.In chapter 3,a series of "tail-to-tail" N-amidoureas,i.e.,L,L/D,D-XAU(X = H,F,Cl,Br,I),were designed and synthesized.Among these compounds,the iodine,bromine and chlorin substituted ones L,L/D,D-XAU(X = Cl,Br,I)formed supramolecular aggregates at micro molar concentration in acetonitrile.Their critical aggregation concentrations are 0.28 μM,1.5 μM and 3.4 μM,respectively.According to temperature-depending CD spectra and solvent effect experiment,the stability sequence of their aggregates is in the order of L,L/D,D-IAU≈L,L/D,D-BrAU>L,L/D,D-CIAU.Compared with L,L/D,D-IAU,L,L/D,D-BrAU and L,L/D,D-CIAU show chiral amplification by the "majority-rules" experiments.By changing halogen atoms of the molecule,we succeed in constructing supramolecular aggregations with different properties,which presents important hints for the regulation of the stability of the supramolecular self-assembly system in solutionIn chapter 4,the hetero-double helical structures constructed by N-amidothiourea derivatives substituted by iodine and bromine were described.The results provide a new strategy for the design of supramolecular helix.The crossed C-I…S and C-Br…S halogen bonds link the helical β-turn fragments into two P-helical strands that are intertwined by the central covalent β-phenylenediamine linkage in L,L-IBrs to afford the β-double helix.