The strange case of PNIPAM: molecular answer of a thermosensitive synthetic macromolecule in water

Since it was first discovered, the phase behavior of poly(N-isopropylacrylamide), (PNIPAM), in aqueous solution has motivated over half century of research activity. Most recently, in the last decade, this polymer has been considered as a pivotal component to realize stimuli responsive soft microdevices, by translating the lower critical solution temperature behavior of the linear chain into the temperature induced volume phase transition, of PNIPAM based networks. In line with this, several investigations focusing on tuning the value of the lower critical solution temperature according to the requirements of specific applications have been published. A pivotal theoretical study postulated the correlation between the flat behavior of the phase separation line in the phase diagram of PNIPAM aqueous solution and the structure of the hydration shell, predicting also an upper critical solution temperature phase separation at low temperature. With reference to that work, and having the tools of the current molecular modeling methods, it is imperative that a thorough analysis of the markers of the cooperative hydration be undertaken, so as to explore the possible existence of an upper critical solution temperature, up until now never detected.

To this note, Dr. Letizia Tavagnacco who is currently postdoctoral research associate at the Institute for Complex Systems of the Italian National Research Council (CNR), Dr. Emanuela Zaccarelli, currently senior researcher at the Institute for Complex Systems of the Italian National Research Council (CNR), and Dr. Ester Chiessi, researcher at University of Rome Tor Vergata, studied the behavior of PNIPAM in water at temperatures below and above the lower critical solution temperature, including the undercooled regime, using atomistic molecular dynamics simulations. Specifically, they focused on investigating the molecular origin of the cooperativity of the celebrated PNIPAM transition and the evolution of the hydration pattern in the undercooled polymer solution. Their work is currently published in the research journal, Physical Chemistry Chemical Physics.

In brief, their research method commenced with the in-silico model fabrication, which entails a PNIPAM linear chain of 30 residues in explicit water at infinite dilution. The salient structural features of the polymer, such as tacticity and conformation, were accounted and simulations were carried in a time window of few hundreds of nanoseconds for 9 temperature conditions, namely from 243 to 323 K, every 10 K. Lastly, trajectory analysis was undertaken to extract structural and dynamical information.

The authors observed a correlation between polymer segmental dynamics and diffusion motion of bound water, that occur with the same activation energy. In addition, the simulation results showed that below the coil-to-globule transition temperature PNIPAM is surrounded by a network of hydrogen bonded water molecules and that the cooperativity arises from the structuring of water clusters in proximity to hydrophobic groups. The researchers also noted that the perturbation of the hydrogen bond pattern involving water and amide groups intervenes above the transition temperature, highlighting a differentiated thermal response of the hydration shell in the surrounding of hydrophobic and hydrophilic PNIPAM groups..

In summary, the study explored the temperature dependence of structure and dynamics of water in the surrounding of PNIPAM in the diluted aqueous solution of this polymer, from the supercooled regime to beyond the lower critical solution temperature. Exemplary care was taken in the realistic modeling of the polymer structure, according to the characteristics obtained in not stereo-selective syntheses. Altogether, the answers provided by the simulations do not provide evidence of the existence of an upper critical solution temperature, since hydration modality and water affinity at temperatures below the lower critical solution temperature do not show discontinuities.

PNIPAM – poly(N-isopropylacrylamide)