Description
Poly(2-oxazoline)s (POx) are an interesting class of biocompatible polyamides whose physical and chemical properties can easily be tuned. These polymers are readily synthesized via cationic ring-opening polymerization (CROP) of various monomers, yielding polymers with distinct properties. The characteristics of the resulting pseudo-polypeptides can be altered even further by chemical functionalization of the residue side chains. Because of their versatility and biocompatibility, poly(2-oxazoline)s are candidate drug-delivery systems, providing a viable alternative to the gold standard in this field, polyethylene glycol (PEG). Their polymerization is still a bottleneck, however, and more computational efforts should be directed toward it.
The CROP rate is highly dependent on the monomer side chain and this effect has been successfully modeled by static ab initio calculations. Since the effects at play are localized, model systems typically only include the last residue of the living polymer chain and the attacking monomer. However, our recent study of monomers with flexible, polar side chains, e.g. 2-methoxycarboxy-2-oxazoline (MestOx), has shown that nearby residues in the polymer chain are able to stabilize the CROP transition state (unpublished results). The size of the conformational space which has to be sampled to understand these interactions warrants a molecular dynamics (MD) approach.
In vivo, POx chains are involved in a complex equilibrium between hydration, intra- and intermolecular aggregation. The influence of different monomers on these phenomena is poorly understood, although they are the basis of clinically relevant supermolecular effects like micellation. Again, MD is the computational method of choice, since these effects are inherently dynamic.
