Chuang Li

Peptide Mimics by Linear Arylamides: A Structural and Functional Diversity Test

Hydrogen-bonded oligoamide foldamers represent a large family of peptide mimics. Pioneered by Gellman and Seebach (Appella , J. Am. Chem. Soc. 1996, 118, 13071- 13072; Seebach , Helv. Chim. Acta 1996, 79, 913- 941), aliphatic amino acid-based mimic structures have been extensively studied. Results of these studies have found many useful applications in areas including chemical biology and drug design. This Account describes our efforts in creating arylamide-based foldamers whose compact conformations are stabilized by hydrogen bonding. The aim of our study was to test whether this class of mimic structures is sufficiently rigid to lead to new interesting functions. It was envisioned that, if our approach was workable, it might be developed into a new family of useful soft frameworks for studies toward molecular recognition, self-assembly, and materials science. Three classes of mimic structures, that is, folded or helical, zigzag, and straight oligomers, have been constructed by simply changing the positions of the substituents at the benzene rings in the backbones. Both amide and hydrazide units have been employed to construct the frameworks. In most cases, O...H-N hydrogen bonding was chosen to stabilize the compact conformations. Notably, for the first time the F...H-N hydrogen-bonding pattern has been used to tune the size of the cavity. To test their usefulness, these frameworks have been extensively modified and functionalized. (1)H NMR, UV-vis, fluorescence, circular dichroism, and X-ray diffraction techniques have all been employed to establish the compact structures and their interactions with guest molecules. The properties or functions of the mimic structures have been studied in seven aspects. (1) Acyclic molecular receptors: The amide foldamers can bind amine cations, while the hydrazide foldamers can complex saccharides. (2) Acceleration of anisole hydrolysis: Several folded oligomers are able to bind alkali metal cations and consequently promote the hydrolysis of the nitro-substituted anisole by alkali hydroxides. (3) Facilitation of macrocyclization: The straight and zigzag backbones can be readily functionalized, from which two classes of macrocycles have been prepared. (4) Homoduplex assembly: Zigzag oligomers that are appended with amide units at one side can form stable homoduplexes through the cooperative self-binding of the amide units. (5) Assembly of molecular tweezers: Discrete binding moieties are introduced at the ends of the oligomers, which can bind structurally matched guests. (6) Assembly of nano networks: F...H-N hydrogen-bonded foldamers can stack with fullerenes; thus a mixture of fullerenes with a trifoldamer generates honeycomb-styled nanoarchitectures. (7) Assembly of dynamic [2]catenanes: A preorganized porphyrin tweezer has been synthesized, from which dynamic three-component [2]catenanes have been assembled in high yields. Our results demonstrate that hydrogen-bonding-driven arylamide oligomers are a class of structurally unique mimic structures. The folded oligomers themselves can be used as synthetic receptors for binding different guest molecules, while incorporation of different segments into one system can produce many desired shapes. In addition, all of the rigid frameworks can be readily functionalized at specific sites. We believe that our results have helped to open the door for some new chemistry in molecular recognition, self-assembly, and other related areas.

Hydrogen-bonded aryl amide macrocycles: synthesis, single-crystal structures, and stacking interactions with fullerenes and coronene.

Six hydrogen-bonded shape-persistent aryl amide macrocycles have been prepared by using one-step and (for some) step-by-step approaches. From the one-step reactions, 3 + 3, 2 + 2, or even 1 + 1 macrocycles were obtained in modest to good yields. The reaction selectivity was highly dependent on the structures of the precursors. The X-ray structural analysis of two methoxyl-bearing macrocycles revealed intramolecular hydrogen bonding and weak intermolecular stacking interaction; no column-styled stacking structures were observed. The 1H (DOSY) NMR, UV-vis, and fluorescent experiments indicated that the new rigidified macrocycles complex fullerenes or coronene in chloroform through intermolecular pi-stacking interaction. The association constants of the corresponding 1:1 complexes have been determined if the stacking was able to cause important fluorescent quenching of the macrocycles or coronene.

Hydrogen bonding-mediated oligobenzamide foldamer receptors that efficiently bind a triol and saccharides in chloroform

The self-assembly of two novel intramolecular hydrogen bonding-driven foldamers is described. Two linear symmetric aromatic amide oligomers, 1 and 2, which are incorporated with benzene subunits, have been prepared by continuous amide-coupling reactions. The existence of three-centred hydrogen bonds in the oligomers and consequently the folding conformation of the oligomers in solution have been characterized by 1H NMR experiments and by comparing them with the reported solid state structure of the identical structural skeleton. Molecular modeling reveals a rigid crescent conformation for 1 with a cavity of ca. 0.9 nm in diameter and a helical conformation for 2 with a cavity of ca. 0.8 nm in diameter. Due to the existence of intramolecular hydrogen bonding, all the CO groups in both oligomers are located inwardly. The binding of 1 and 2 towards a trihydroxyl guest and four saccharide derivatives have been investigated with 1H NMR, fluorescence, and circular dichroism spectroscopy. The association constants of the corresponding 1 ∶ 1 complexes have been determined by fluorescence titration experiments.