Amide nitrogen pyramidalization changes lactam amide spinning.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30692534.
- Also identified by DOI 10.1038/s41467-018-08249-9 and PMC identifier 6349922.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Although cis-trans lactam amide rotation is fundamentally important, it has been little studied, except for a report on peptide-based lactams. Here, we find a consistent relationship between the lactam amide cis/trans ratios and the rotation rates between the trans and cis lactam amides upon the lactam chain length of the stapling side-chain of two 7-azabicyclo[2.2.1]heptane bicyclic units, linked through a non-planar amide bond. That is, as the chain length increased, the rotational rate of trans to cis lactam amide was decreased, and consequently the trans ratio was increased. This chain length-dependency of the lactam amide isomerization and our simulation studies support the idea that the present lactam amides can spin through 360 degrees as in open-chain amides, due to the occurrence of nitrogen pyramidalization. The tilting direction of the pyramidal amide nitrogen atom of the bicyclic systems is synchronized with the direction of the semicircle-rotation of the amide.