Intramolecular hydrogen bonding in ortho-substituted arylamide oligomers: a computational and experimental study of ortho-fluoro- and ortho-chloro-N-methylbenzamides.

ABSTRACT

As a part of our systematic study of foldamer structural elements, we analyze and quantify the conformational behavior of two model compounds based on a frequently used class of aromatic oligoamide building blocks. Combining computational and NMR approaches, we investigate ortho-fluoro- and ortho-chloro-N-methylbenzamide. Our results indicate that the -F substituent in an ortho position can be used to fine-tune the rigidity of the oligomer backbone. It provides a measurably attenuated but still considerably strong hydrogen bond (H-bond) to the peptide group proton when compared to the -OCH3 substituent in the same position. On the other hand, the ortho-Cl substituent does not impose significant restrictions on the flexibility of the backbone. Its effect on the final shape of an oligomer is likely governed by its size rather than by noncovalent intramolecular interactions. Furthermore, the effect of solvent on the conformational preferences of these building blocks has been quantified. The number of intramolecularly H-bonded conformations decreases significantly when going from nonprotic to protic environments. This study will facilitate rational design of novel arylamide foldamers.