Thermodynamics of N-Isopropylacrylamide in Water: Insight from Experiments, Simulations and Kirkwood-Buff Analysis Teamwork.

The behavior of thermoresponsive polymer poly(N-isopropylacrylamide) (PNiPAM), an essential building block in design of smart soft materials, in aqueous solutions attracted a lot of interest, which contrasts with our knowledge of N-isopropylacrylamide (NiPAM) monomer. Strikingly, the physico-chemical properties of aqueous NiPAM are similarly rich, and their understanding is far from being complete. This stems from the lack of accurate thermodynamic data and quantitative model for atomistic simulations. In this joined study, we have probed the thermodynamic behavior of aqueous NiPAM by experimental methods, MD simulations, and Kirkwood-Buff (KB) analysis at ambient conditions. From the partial molar volumes and simultaneously correlated osmotic coefficients, with excess partial molar enthalpies of NiPAM in water the concentration and temperature dependence of KB-integrals was determined. For the purpose of this work, we have developed and employed novel NiPAM force-field, which reproduces not only KB-integrals (Gij) and adequately captures macroscopic thermodynamic quantities, but also provides more accurate structural insight than the original force-fields. We revealed in NiPAM vicinity the competing effect of amide hydration with interaction between nonpolar regions. This microscopic picture is reflected in experimentally observed NiPAM-NiPAM association, which is present from dilute conditions up to the solubility limit and is evidenced by G22. From intermediate concentrations it is accompanied by existence of apparent dense-water regions as indicated by positive G11 values. Here employed KB-based framework provided mutually consistent thermodynamic and microscopic insight in NiPAM solution, and may be further extended for ion-specific effects. Moreover, our findings contribute to the understanding of thermodynamic grounds behind PNiPAM collapse transition.