Supramolecular Helix Consisting Of Folded Peptidomimetics Driven By Intermolecular Halogen Bonding Or Anion Binding

The imaginations of scientists are often captured by wonderful phenomena in nature.For example,the ubiquitous spiral structures,especially the DNA double helices and protein a-helix in life system enlighten the exploitation and development of biomimetic helical structures.Supramolecular helix bearing dynamic property is quick similar to helical biological macromolecules in nature,thus serving as one kind of important biomimetic helices.In general,supramolecular helix is driven by non-covalent interactions,including hydrogen bonding,electrostatic,?-? stacking,hydrophobicity and metal coordination,in which hydrogen bonding is the most popular.Recently,as an analogue of hydrogen bonding,halogen bonding has attracted extensive attentions as one new type of intermolecular weak interaction.However,supramolecular helix driven by halogen bonding remains to be explored,especially in the solution phase that has not been reported.Peptide that built from amino acids through amide bond(peptide bond)is one indispensable basic substance of life.Supramolecular helix based on peptide or peptidomimetic not only can simulate the helical or folded structure of natural peptide,but also feature excellent biodegradable and biocompatibility,thus being focused and showing potential applications in pharmaceutical chemistry.Short peptide-based N-amidothiourea developed in our lab is one kind of folded peptidomimetic due to the preferred ?-turn conformation,which can serve as feasible building block for supramolecular helix.In this dissertation,peptide-based N-amidothioureas bearing ?-turn structures have been applied to build supramolecular helix through intermolecular halogen bonding or anion induction.The dissertation consists of four chapters.In Chapter 1,supramolecular and halogen bonding are introduced briefly at first,then research progress of hydrogen bonding driven supramolecular helix,halogen bonding and N-amidothioureas are reviewed.Lastly,the design thoughts and research contents of this dissertation are presented.In chapter 2 we propose a strategy for building supramolecular helix driven by halogen bonding,that is using helical building blocks.The halogen bonding interactions afford head-to-tail linkages to propagate the helicity of the helical fragments that leading to the formation of supramolecular helix.In our proof-to-principle experiment,we demonstrate for the first time the single-stranded supramolecular helix in solution phase at micromolar concentration,driven by intermolecular C-I…? halogen bonding.This was realized by designing a bilateral alanine based N-amidothioureas AI that bear two ?-turn structures as the helical fragments,with two iodophenyl groups equipped at two terminals of the compound as the donor and/or acceptor of the C-I…? halogen bonding,while attempting to avoid other inter-helix interactions except this "head-to-tail" intra-helix halogen bonding.This single-stranded supramolecular helix was verified by crystal structures,spectral analysis,NMR data and DFT calculations,and exhibits a chiral amplification according to "majority rules".These findings open a new avenue towards the rational design of building blocks to create functional supramolecular helices driven by halogen bonding.Chapter 3 develops supramolecular helical polymers in water by phenylalanine based bilateral N-amidothioureas FX that bearing ?-turns.The driving forces for the helical structures are hydrogen and halogen bonding,?-? stacking and hydrophobic interactions.Notably,the stability of these supramolecular helices can be regulated by the halogen substituents through halogen bonding.Especially,supramolecular helical polymers from the iodine substituted N-amidothioureas FI arc quick stable that insensitive to temperature and feature chiral self-sorting of the enantiomers in water,forming left and right-handed helical polymers.Hence halogen bonding-assisted supramolecular helical polymers in water are prepared from folded peptidomimetics,which can mimic the helical structures of peptides and proteins and are instructive for the investigation of halogen bonding in water.Chapter 4 presents helical oligomers of bilateral alanine based N-amidothioureas AX bearing folded ?-turn structures that induced by bilateral anions.Two processes were evaluated for the binding of AX with isophthalic acid anions(IPA2-),featuring 2:1 and 1:2 binding model of host to guest.Importantly,the 2:1 complex exhibits helical property caused by the unspoiled P-turn structures and the exciton couplings induced by the linkage of IPA2-.However,only 1:2 binding model was showed for AX with terephthalic acid anions(TPA2-),indicating the importance of linkage.Here the formation of supramolecular helical oligomers promotes the 2:1 complex of AX with IPA2-,which is instructive for the construction of supramolecular helix from two components.