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

Abstract

The behavior of thermoresponsive polymer poly(Nisopropylacrylamide) (PNiPAM), an essential building block in the design of smart soft materials, in aqueous solutions has attracted much interest, which contrasts with our knowledge of Nisopropylacrylamide (NiPAM) monomer. Strikingly, the physicochemical 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 joint study, we have probed the thermodynamic behavior of aqueous NiPAM by experimental methods, molecular dynamics (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 a novel NiPAM force field, which not only reproduces KB integrals (G ij ) and adequately captures macroscopic thermodynamic quantities but also provides more accurate structural insight than the original force fields. We revealed in the vicinity of NiPAM the competing effect of amide hydration with interaction between nonpolar regions. This microscopic picture is reflected in the experimentally observed NiPAM−NiPAM association, which is present from highly dilute conditions up to the solubility limit and is evidenced by G 22 . From intermediate concentrations, it is accompanied by the existence of apparent dense-water regions, as indicated by positive G 11 values. The here-employed KB-based framework provided a mutually consistent thermodynamic and microscopic insight into the 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.

Thermosensitive Hydration of Four Acrylamide-Based Polymers in Coil and Globule Conformations

“…This may lead to shifted thermosensitive behavior, as already reported by the referenced studies. 72 , 73 We furthermore believe, that the strength of the polymer–polymer and polymer–solvent bonds may be influenced by sterical hindrance, i.e., binding partners with high affinity may not get into close contact for geometrical reasons. This would not be contradicted by the known effect of the tacticity on the thermosensitivity.…”

Thermo-Responsive Hydrogels: From Recent Progress to Biomedical Applications

“…Paulo et al found that the collapse of PNIPAM chain at high temperatures is related to the reduced coordination of both amide group and isopropyl group with water, and is observed together with an increase in the monomer–monomer hydrogen bond [ 35 ]. The thermodynamics of NIPAM monomer was investigated by Heyda et al [ 36 ], which could allow for better control of PNIPAM phase behavior. Nellas and coworkers performed a molecular dynamics simulation of pentamer PNIPAM [ 37 ], and they suggest a clathrate-like behavior in the coordinate shell might be responsible for the LCST behavior of PNIPAM.…”

Cononsolvency of thermoresponsive polymers: where we are now and where we are going

“…These should be sufficiently accurate to reproduce experimental data, such as the enthalpy of the coil–globule transition, which depends on the strength of the hydrogen bonds between polymer and water. While this accuracy has been achieved for PNIPAM, 66,86 no further studies have been reported to our knowledge that validate force fields for responsive polymer systems based on different chemical constituents. Therefore, experiments and simulations should go hand in hand to investigate effects related to cononsolvency beyond the application to PNIPAM.…”