Accessing Improbable Foldamer Shapes with Strained Macrocycles

Abstract

The alkylation of some secondary amide functions with a dimethoxybenzyl (DMB) group in oligomers of 8amino-2-quinolinecarboxylic acid destabilizes the otherwise favored helical conformations, and allows for cyclization to take place. A cyclic hexamer and a cyclic heptamer were produced in this manner. After DMB removal, X-ray crystallography and NMR show that the macrocycles adopt strained conformations that would be improbable in noncyclic species.The high helix folding propensity of the main chain is partly expressed in these conformations, but it remains frustrated by macrocyclization. Despite being homomeric, the macrocycles possess inequivalent monomer units. Experimental and computational studies highlight specific fluxional pathways within these structures. Extensive simulated annealing molecular dynamics allow for the prediction of the conformations for larger macrocycles with up to sixteen monomers.

Metadynamics simulations on the key factors of handedness induction of quinoline oligoamide foldamers with a terminal chiral group

“…This is the main reason why 3a has better helical selection than 1a . Based on the above discussion, we conclude that the electronic delocalization effect influences the selection of helical handedness, and the delivery of chirality in the conjugated chains is easier than in the unconjugated system, which corresponds to some experimental results [12–15].…”

“…This is the main reason why 3a has better helical selection than 1a. Based on the above discussion, we conclude that the electronic delocalization effect influences the selection of helical handedness, and the delivery of chirality in the conjugated chains is easier than in the unconjugated system, which corresponds to some experimental results [12][13][14][15]. From the investigation of foldamers 1, 2, and 3, it is found that three-center hydrogen bonds between the terminal group and oligomers are found in both 2 and 3, but helical selection is better in 3 than in 2.…”

Hydrogen-bonded aromatic amide macrocycles: synthesis, properties and functions

“…18). 96 A series of noncyclic precursors 45a–d , 46a and 46b were produced and it was found that macrocyclization failed for those reactants containing a single DMB substituent or two consecutive DMB groups at the end. The remaining precursors could be lead to the corresponding macrocycles 47c , 47d , and 48b in moderate to good yields.…”

Hydrogen Bonded Foldamers with Axial Chirality: Chiroptical Properties and Applications

“…Recently, there have been extensive studies on the construction process and folding behavior of foldamer. [5][6][7][8] Diversified foldamers have been constructed by mimicking the folding behavior of biomolecules, with structural diversity and multiple functionalities. [9][10][11] The folded structures show dynamic property adaptive to the environments and guest molecules, greatly expanding applications in supramolecular chemistry and smart materials.…”