Cooperation of Intermolecular Forces in Model Peptide-Poloxamer Fragment Binding.

Area of Science:

• Computational chemistry
• Materials science
• Biophysics

Background:

• Poloxamers are widely used polymers with applications in drug delivery and biomaterials.
• Understanding peptide-polymer interactions is crucial for designing advanced biomaterials and effective drug delivery systems.

Purpose of the Study:

• To investigate the noncovalent interactions between N-methylacetamide (NMA), a peptide model, and poloxamer (polyethylene oxide/polypropylene oxide) building blocks.
• To elucidate the nature and strength of these interactions using quantum chemical calculations.

Main Methods:

• Quantum chemical calculations were employed to model interactions.
• Analysis of stable complexes, interaction energies, and types of noncovalent bonds (hydrogen bonding, C═O···O interactions).
• Examination of charge transfer (CT) mechanisms contributing to binding.

Main Results:

• Identified eight stable NMA···polyethylene oxide (PEO) complexes with interaction energies from 2.24 to 6.73 kcal/mol.
• Observed stronger interactions for NMA···polypropylene oxide (PPO) complexes, up to 7.39 kcal/mol.
• Discovered nonclassical C═O···O interactions stabilized by bidirectional charge transfer (CT), enhancing binding strength.

Conclusions:

• Peptide-poloxamer interactions are governed by a combination of hydrogen bonding and charge transfer.
• Nonclassical C═O···O interactions play a significant role, comparable to traditional hydrogen bonds.
• These findings provide insights into the molecular basis of peptide-poloxamer association.