# Transfer Free Energies and Partitioning of Small Molecules in Collapsed PNIPAM Polymers

## TL;DR

This study uses molecular dynamics simulations to analyze how small molecules partition into collapsed PNIPAM hydrogels, revealing how polarity and size influence solvation and transfer free energies, which are crucial for designing nanocarrier systems.

## Contribution

It provides a detailed molecular-level understanding of solute partitioning in collapsed PNIPAM, linking transfer free energies to adsorption on polymer chains and highlighting the effects of polarity and size.

## Key findings

- Transfer free energies favor nonpolar solutes and scale with surface area.
- Partitioning varies significantly with small changes in solute size.
- Polarity opposes transfer, especially for alkyl solutes.

## Abstract

A central quantity in the design of functional hydrogels used as nanocarrier systems, for instance for drug delivery or adaptive nanocatalysis, is the partition ratio, which quantifies the uptake of a molecular substance by the polymer matrix. By employing all-atom molecular dynamics simulations, we study the solvation and partitioning (with respect to bulk water) of small subnanometer-sized solutes in a dense matrix of collapsed Poly(N-isopropylacrylamide) (PNIPAM) polymers above the lower critical solution temperature (LCST) in aqueous solution. We examine the roles of the solute's polarity and its size on the solubility properties in the thermoresponsive polymer. We show that the transfer free energies of nonpolar solutes from bulk water into the polymer are favorable and scale in a good approximation with the solute's surface area. Even for small solute size variation, partitioning can vary over orders of magnitude. A polar nature of the solute, on the other hand, generally opposes the transfer, at least for alkyl solutes. Finally, we find a strong correlation between the transfer free energies in the gel and the adsorption free energies on a single extended polymer chain, which enables us to relate the partition ratios in the swollen and collapsed state of a PNIPAM gel.