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Accessing Improbable Foldamer Shapes with Strained Macrocycles
Author(s) -
Urushibara Ko,
Ferrand Yann,
Liu Zhiwei,
Katagiri Kosuke,
Kawahata Masatoshi,
Morvan Estelle,
D'Elia Ryan,
Pophristic Vojislava,
Tanatani Aya,
Huc Ivan
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101201
Subject(s) - random hexamer , chemistry , foldamer , monomer , homomeric , folding (dsp implementation) , amide , molecular dynamics , crystallography , stereochemistry , computational chemistry , polymer , organic chemistry , biochemistry , protein subunit , electrical engineering , gene , engineering
The alkylation of some secondary amide functions with a dimethoxybenzyl (DMB) group in oligomers of 8‐amino‐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.