Cation−π Interactions Accelerate the Living Cationic Ring-Opening Polymerization of Unsaturated 2-Alkyl-2-oxazolines

Abstract

Cation−dipole interactions were previously shown to have a rate-enhancing effect on the cationic ring-opening polymerization (CROP) of 2-oxazolines bearing a side-chain ester functionality. In line with this, a similar rate enhancementvia intermolecular cation−π interactionswas anticipated to occur when π-bonds are introduced into the 2-oxazoline side-chains. Moreover, the incorporation of π-bonds allows for facile postfunctionalization of the resulting poly(2-oxazoline)s with double and triple bonds in the side-chains via various click reactions. Herein, a combined molecular modeling and experimental approach was used to study the CROP reaction rates of 2oxazolines with side-chains having varying degrees of unsaturation and side-chain length. The presence of cation−π interactions and the influence of the degree of unsaturation were initially confirmed by means of regular molecular dynamics simulations on pentameric systems. Furthermore, a combination of enhanced molecular dynamics simulations, static calculations, and a thorough analysis of the noncovalent interactions was performed to unravel to what extent cation−π interactions alter the reaction kinetics. Additionally, the observed trends were confirmed also in the presence of acetonitrile as solvent, in which experimentally the polymerization is performed. Most intriguingly, we found only a limited effect on the intrinsic reaction kinetics of the CROP and a preorganization effect in the reactive complex region. The latter effect was established by the unsaturated side-chains and the cationic center through a complex interplay between cation−π, π−π, π−induced dipole, and cation−dipole interactions. These findings led us to propose a two-step mechanism comprised of an equilibration step and a CROP reaction step. The influence of the degree of unsaturation, through a preorganization effect, on the equilibration step was determined with the following trend for the polymerization rates: n-ButylOx < ButenOx < ButynOx ≥ PentynOx. The trend was experimentally confirmed by determining the polymerization rate constants.

Fluorine-Containing Block and Gradient Copoly(2-oxazoline)s Based on 2-(3,3,3-Trifluoropropyl)-2-oxazoline: A Quest for the Optimal Self-Assembled Structure for 19F Imaging

“…This phenomenon may be attributed to the fluorine–cation interaction in the 2-oxazolinium end group, as well as potential stabilization of the prereactive complex of the incoming monomer (Figure ). A similar acceleration effect was reported for the CROP of 2-oxazolines with ester side chains and double and triple bonds in the side chains. − These electron-rich side chains accelerate the CROP of both the homopolymerization and copolymerization of these monomers. However, for copolymerization, the attack of both monomers present is accelerated, and this is most pronounced for the most nucleophilic monomer, in this case, MeOx or n PropOx rather than CF 3 EtOx.…”

Modeling Exchange Reactions in Covalent Adaptable Networks with Machine Learning Force Fields

“…The amine-imine exchange reactions involve transition states that are infrequently accessed; thus, transition states can only be accessed using enhanced sampling methods. Besides the unbiased sampling using standard MD, we also collected the reference data set using enhanced sampling in the exploration step, thus we can explore high-energy configurations far from geometries of metastable states and improve the accuracy of fitted potential energy surface throughout the relevant reaction space. , Metadynamics is an enhanced sampling technique based on appropriate collective variables (CVs) that describe the slow degrees of freedom, , and has been used in MD studies of polymers such as dynamics of supramolecular polymers, , molecular relaxation mechanisms, ion solvation environments in polymer electrolytes, , and cationic ring-opening polymerization . In metadynamics simulations, a history-dependent bias potential defined as a sum of Gaussian functions is added to the space of CVs.…”

“…44,45 Metadynamics is an enhanced sampling technique based on appropriate collective variables (CVs) that describe the slow degrees of freedom, 28,46 and has been used in MD studies of polymers such as dynamics of supramolecular polymers, 47,48 molecular relaxation mechanisms, 49 ion solvation environments in polymer electrolytes, 50,51 and cationic ring-opening polymerization. 52 In metadynamics simulations, a history-dependent bias potential defined as a sum of Gaussian functions is added to the space of CVs. Chemical processes in aqueous systems can be characterized by relatively complex mechanisms, which may involve several water molecules; thus, the design of CVs that fully capture the influence of water molecules is essential.…”

Mechanistic Characterization of Zeolite-Catalyzed Aromatic Electrophilic Substitution at Realistic Operating Conditions

“…As recently shown by some of us, 53 , 57 the information derived from an US simulation can be combined to classical transition state theory (TST) to remove the dependency on the chosen CV and retrieve reliable kinetic constant for the reaction of interest. In this framework, the reaction kinetic constant can be written as in which β = 1/ k B T and CV ⧧ is the value of the collective variable corresponding to the reaction transition state.…”