A Thermodynamic Study of the Interactions between Acetamide Derivatives and PCA-PEG-PCA Copolymers: ONIOM Calculations

To improve drug selectivity toward target cells, one interesting approach for drug delivery is to use polymer nanoparticles. A twolayered ONIOM Becke3-LYP: UFF calculation was carried out to study the structural and thermodynamic properties of the interaction between acetamide derivatives and the PCA-PEG-PCA copolymers. The Interaction enthalpies and the Gibbs free energies between acetamide derivatives as anti-HIV and polymeric nanoparticles in the gas and solution phases were calculated. The structure as well as the thermodynamics of optimized complexes was discussed from the biological point of view. In the gas phase, substitutes of phenyl, flurophenyl, 4-acetyl-2-bromophenyl, and 3-methyl-acetate-thiophen-2-yl had the highest energies, and in the water phase, the enthalpies and Gibbs free energies of the interaction for most compounds were almost identical. In the both phases the interaction is relatively weak and copolymers can be used for drug delivery.