# Synergistic Density Functional Theory and Molecular Dynamics Approach to Elucidate PNIPAM–Water Interaction Mechanisms

## TL;DR

This study uses advanced simulations to understand how water interacts with a temperature-sensitive polymer, revealing key molecular interactions and structural changes.

## Contribution

The work introduces a combined DFT, QTAIM, and MD approach to systematically quantify hydration dynamics and pseudo-saturation thresholds in PNIPAM.

## Key findings

- DFT identifies enhanced water binding in the linker zone of PNIPAM.
- Hydrogen bonding and steric hindrance are critical for hydration dynamics.
- Temperature changes alter hydration behavior, increasing hydrophobicity above the LCST.

## Abstract

This study employs Density Functional Theory (DFT) and Molecular Dynamics (MD) simulations to investigate interactions between water molecules and Poly(N-isopropylacrylamide) (PNIPAM). DFT reveals preferential water binding sites, with enhanced binding energy observed in the linker zone. Quantum Theory of Atoms in Molecules (QTAIM) and electron localization function (ELF) analyses highlight the roles of hydrogen bonding and steric hindrance. MD simulations unveil temperature-dependent hydration dynamics, with structural transitions marked by changes in the radius of gyration (Rg) and the radial distribution function (RDF), aligning with DFT findings. Our work goes beyond prior studies by combining a DFT, QTAIM and MD simulations approach across different PNIPAM monomer-to-30mer structures. It introduces a systematic quantification of pseudo-saturation thresholds and explores water clustering dynamics with structural specificity, which have not been previously reported in the literature. These novel insights establish a more complete molecular-level picture of PNIPAM hydration behavior and temperature responsiveness, emphasizing the importance of amide hydrogen and carbonyl oxygen sites in hydrogen bonding, which weakens above the lower critical solution temperature (LCST), resulting in increased hydrophobicity and paving the way for understanding water sorption mechanisms, offering guidance for future applications such as dehumidification and atmospheric water harvesting.