Cooperation of Intermolecular Forces in Model Peptide-Poloxamer Fragment Binding

A quantum chemical study of the interactions between N-methylacetamide (NMA), which serves as a peptide model, and poloxamer building blocks made up of polyethylene oxide (PEO) and polypropylene oxide (PPO) dimers shows a range of noncovalent interactions. Eight stable NMA···PEO complexes were found, with interaction energies between 2.24 and 6.73 kcal/mol. NMA···PPO complexes show slightly stronger interactions, reaching up to 7.39 kcal/mol. Besides NH···O and CH···O hydrogen bonding, several complexes also exhibit notable nonclassical C═O···O interactions. These are stabilized by bidirectional charge transfer (CT) that includes C═O π → O-C σ* and O(lp) → C═O π* donations. Such interactions improve binding strengths to levels similar to those of typical hydrogen bonds. The findings highlight that hydrogen bonding and CT work together in peptide-poloxamer interactions.