Hydrogen bonding in ortho-substituted arylamides: the influence of protic solvents.
We combine molecular modeling and NMR methods to better understand intramolecular hydrogen bonding (H-bonding) in a frequently used arylamide foldamer building block, ortho-methoxy-N-methylbenzamide. Our results show that solvents have a profound influence on the cumulative number and stabilizing effects of intramolecular H-bonds, and thus conformational preferences, of foldamers based on this compound. While intramolecular H-bonds are conserved in aprotic environments, they are significantly disrupted in protic solvents. Furthermore, these solvent effects can be accurately quantified using the computational approach presented here. The results could have significant implications in foldamer design, particularly for applications in aqueous environments.
Liu
Zhiwei
Z
Department of Chemistry & Biochemistry and Center for Drug Design and Delivery, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, Pennsylvania 19104-4495, USA.
Remsing
Richard C
RC
Liu
Dahui
D
Moyna
Guillermo
G
Pophristic
Vojislava
V
D000577:Amides / Q000737:chemistry*; D002725:Chloroform / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D011522:Protons; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000577:Amides; D011522:Protons; D012997:Solvents; D014867:Water; D002725:Chloroform; D000432:Methanol