Sulfur-Controlled Modulation of Peptoid Atropisomeric Foldamers

Area of Science:

• Organic Chemistry
• Supramolecular Chemistry
• Stereochemistry

Background:

• Peptoid foldamers are valuable synthetic macromolecules with tunable structures.
• Chiral N-aryl peptoids with restricted rotation around the C-N bond exhibit atropisomerism.
• Controlling rotational barriers is crucial for designing specific foldamer architectures.

Purpose of the Study:

• To investigate the steric and electronic effects of ortho-heteroatoms (O/S) on the C-N rotational barrier in N-aryl peptoids.
• To elucidate the chiral attributes and conformational properties of sulfur-containing peptoid atropisomers.
• To explore sulfur-controlled modulation of atropisomeric foldamer structures.

Main Methods:

• Dynamic High-Performance Liquid Chromatography (HPLC) to determine rotational energy barriers.
• Single-crystal X-ray crystallography to analyze local conformational ordering.
• Computational studies (e.g., DFT) to identify noncovalent interactions and conformational preferences.

Main Results:

• Simultaneous installation of a C-N chiral axis and sulfur-containing stereogenic elements in peptoid foldamers.
• Demonstrated that variations in sulfur oxidation states significantly influence the rotational energy barrier.
• Elucidated local conformational ordering and identified key noncovalent interactions governing atropisomer stability.

Conclusions:

• Sulfur heteroatoms, particularly their oxidation states, play a critical role in modulating the rotational barrier of the C-N bond in N-aryl peptoids.
• This study provides a method for designing and controlling the chirality and conformational properties of peptoid atropisomeric foldamers.
• The findings offer insights into the structure-property relationships of sulfur-containing foldamers for potential applications in molecular recognition and materials science.