Theoretical Insights into the Racemization Kinetics of Helical Foldamers: Extended Chain Inhibits Propagation of Helical Reversal from One End to Another

Helical foldamers have garnered significant attention recently with their unique chiral structures and diverse functionalities. However, their kinetic stability and racemization dynamics remain poorly understood. In this work, we introduced a novel model to describe the racemization of helical foldamers, deriving both general and approximated solutions to the kinetic equations. The general solution was in the double exponential form, while the approximated solution was in a single exponential form. The approximated solution clarified that the kinetic constant is in inverse proportion to the number of helical units (n). Analysis of the previously reported helical foldamers (o-phenylene oligomers and aromatic oligoamide) revealed that the two ends of the helical units are capped by the loose-end domains. The theory suggests that the larger n stabilizes the helical structure because the fraction of the helical domain relative to the loose domain increases, and the multiple inversion barriers in the helical domain prevent the helical reversal from traveling from one end to the other.