Folding-Induced Folding: The Assembly of Aromatic Amide and 1,2,3-Triazole Hybrid Helices

• Published in: Chemistry : a European journal Vol. 20; no. 5; pp. 1418 - 1426
• Main Authors: Wu, Chun-Fang, Li, Zhi-Ming, Xu, Xiao-Na, Zhao, Zhi-Xiong, Zhao, Xin, Wang, Ren-Xiao, Li, Zhan-Ting
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 27.01.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Amides - chemistry; Chemistry; Circular Dichroism; foldamers; helices; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Molecular Conformation; Spectrum analysis; stacking; triazoles; Triazoles - chemistry; triazoles; hydrogen bonding; helices; foldamers; stacking
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201304161

Folding‐induced folding for the construction of artificial hybrid helices from two different kinds of aromatic sequences is described. Linear compounds 1 a, 1 b, and 2, containing one aromatic amide trimer or pentamer and one or two aromatic 1,2,3‐triazole tetramers, have been designed and synthesized. The trimeric and pentameric amide segments are driven by intramolecluar NH⋅⋅⋅F hydrogen bonding to adopt a folded or helical conformation, whereas the triazole segment is intrinsically disordered. In organic solvents of low polarity, the amide foldamer segment induces the attached triazole segment(s) to fold through intramolecular stacking, leading to the formation of hybrid helices. The helical conformation of these hybrid sequences has been confirmed by 1H and 19F NMR spectroscopy, UV/Vis spectroscopy, circular dichroism (CD) experiments, and theoretical calculations. It was found that the amide pentamer exhibits a stronger ability to induce the folding of the attached triazole segment(s) compared with that of the shorter trimer. Enantiomers (R)‐3 and (S)‐3, which contain an R‐ or S‐(1‐naphthyl)ethylamino group at the end of a tetraamide segment, have also been synthesized. CD experiments showed that introduction of a chiral group caused the whole framework to produce a strong helicity bias. Density‐functional‐theory calculations on (S)‐3 suggested that this compound exists as a right‐handed (P) helix. Forced to fold: When one or two intrinsically disordered aromatic 1,2,3‐triazole oligomers are attached to a hydrogen‐bonding‐driven aromatic amide foldamer, the triazole segments can be encouraged to fold. This folding is due to intramolecular stacking and results in the formation of new longer hybrid helices (see figure).