A molecular dynamics perspective on the cyclization efficiency for poly(2-oxazoline)s and poly(2-oxazine)s

The synthesis of cyclic polymers has made tremendous progress over the last decade. However, upscaling remains a challenge. To achieve acceptable cyclization yields, time, and labour intensive screening of experimental reaction parameters, such as catalyst concentration, solvent volume, or polymer concentration is the current status quo. The influence of the polymer structure on the cyclization process is usually overlooked. Recently, we compared heterotelechelic poly(2-oxazoline)s and poly(2-oxazine)s and demonstrated that an additional CH₂ group in the polymer backbone significantly affects cyclization efficiency. In this study, we explored this surprising result using molecular dynamics simulations comparing poly(2-n-propyl-2-oxazoline) and poly(2-n-propyl-2-oxazine) in dichloromethane. Through analysis of polymer conformations, radii of gyration, radial distribution functions and monitoring of termini distances, we could demonstrate that the oxazine polymer is more solvated and has significantly increased backbone flexibility compared to the oxazoline. These properties lead to more frequent and closer contacts between the polymer termini. It is hypothesized that this provides favourable conditions for intra-molecular cyclization. Our results highlight the importance of the polymer structure in cyclization reactions and the utility of polymer molecular dynamics simulations for these systems.