The Synthesis And Study Of Suprmolecular Self-assembling Behavior Of Lipodipeptides

For the past a few decades,with the further investigation of supramolecular chemistry,supramolecular self-assembly of peptides and peptide derivatives have attracted much attention.Lipopeptide,also known as peptide amphiphiles(PAs),are a kind of peptide derivatives which have one or several alkyl chains attached to the peptide sequence.Usually,this kind of peptide derivatives is able to self-assemble in aqueous solution under appropriate pH condition spontaneously.Considering peptide sequences themselves are consisted of amino acids,moreover,one of the natural properties of most amino acids is chirality,so it is of great pragmatic significance to probe into the chirality control mechanism of lipopeptide self-assembling process.Herein,the study described in this paper which based on the previous work of our group is demonstrated as follows:First.A series of(24 in total)heterogeneous lipodipeptides consisted of different amino acids(lipodipeptide)with aromatic side groups were designed and synthesized.What we intended was to investigate(1)the detailed influence of different stereochemical sequence on the way of molecular arrangement in the self-assembling process of heterogeneous lipodipeptide,(2)whether the ?-?stacking among phenyl groups of aromatic side chains could influence the stacking chirality of functional groups or the morphological chiality of lipodipeptides self-assemblies.Second.A group of(8 in total)lipodipeptides based on valine were designed and synthesized.The purpose was to probe into the possible chirality transformation of self-assemblies nanostructures in the case of co-assembling with different additives as well as expanded the study of lipodipeptides self-assembling process from aqueous systems to organic solvent.Third.A group of(6 in total)lipotripeptides based on alanine were designed and synthesized.The primary object was to make clear the chirality control phenomenon in the self-assembling process of alanine lipotripeptides.By taking advantage of spectroscopic study including circular dichroism spectra,solution and gel state Fourier transform infrared spectra,1H nuclear magnetic resonance spectra and X-ray diffraction spectra,we managed to analyze the chiral molecular packing,the supramolecular weak interactions which drove the self-assembling process,intermolecular hydrogen bonding sites,the different contribution of intermolecular hydrogen bonding at different position and the organization of lipodipeptides molecules within the self-assemblies.Our research demonstrated that,First,The study of the self-assembling behavior of heterogeneous lipodipeptides in aqueous solution revealed that:(1)The different sterochemical sequence of lipodipeptides could eventually lead the lipodipeptides molecules to arrange into parallel or antiparallel way within their self-assemblies.For instance,in the case of Group 7.four lipodipeptides based on the Phe-Ala sequence,molecules packed parallelly in the self-assemblies of homochiral lipodipeptides.In contrast,molecules arranged into antiparallel way in the self-assemblies of heterochiral lipodipeptides.(2)There would not be effective ?-? stacking among phenyl groups as the consequence of those aromatic side groups on the backbone of lipodipeptides possessing too large steric hindrance.This phenomenon could be found with regard to Group 5,four lipodipeptides based on the Phe-Phg sequence.Because of the steric hindrance of phenyl side group of phenylglycine at the C-terminal was too large,the phenyl groups of neither phenylalanine nor phenylglycine failed to form effective ?-? stacking in the self-assembling process.(3)The ?-? stacking among phenyl groups could also determined the chirality of self-assemblies nanostructure or the packing of functional groups.The chiral stacking of phenyl groups of phenylalanine controlled the chirality of functional groups packing and self-assemblies nanostructure in Group 6 and 7.Second.The study of self assembling behavior of lipodipeptides based on valines indicated that:(1)Solvent evaporation could induce lipodivalines self-assembled into large sum of entangled twisted nanoribbons in methanol.(2)It was found that after introduced o-or m-toluidine into the solution of lipodivalines in methanol,toluidine and lipodivaline derivatives would undergo co-assembling process spontaneously.The chirality of nanostructures of co-assemblies turned out to be just opposite to the original chirality of nanostructures of lipodivalines.However,the addition of p-toluidine failed to make any difference.The chirality reversion possibly due to the interference of amino and phenyl group of toluidine during the self-assembling process as well as the molecular steric hindrance.(3)The chiral stacking of functional groups in the self-assembling process of lipodivalines well exhibited the "C-terminal determination" rule.Third.The preliminary study of self-assembling process of lipotrialanines in aqueous solution indicated that the chirality of the alanine at the middle of the tripeptide sequence determined the stacking chirality of functional groups.