Pressure-Dependence of Poly(N‑isopropylacrylamide) Mesoglobule Formation in Aqueous Solution Bart-Jan Niebuur, † Kora-Lee Claude, † Simon Pinzek, † Coleman Cariker, ‡ Konstantinos N. Raftopoulos, †,§ Vitaliy Pipich, ∥ Marie-Sousai Appavou, ∥ Alfons Schulte,* ,‡ and Christine M. Papadakis* ,† † Physik-Department, Fachgebiet Physik weicher Materie, Technische Universitä t Mü nchen, James-Franck-Str. 1, 85748 Garching, Germany ‡ Department of Physics and College of Optics and Photonics, University of Central Florida, 2385 Central Florida Boulevard, Orlando, Florida 32816, United States ∥ Jü lich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Forschungszentrum Jü lich GmbH, Lichtenbergstr. 1, 85748 Garching, Germany * S Supporting Information ABSTRACT: Above their cloud point, aqueous solutions of the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM) form large mesoglobules. We have carried out very small-angle neutron scattering (VSANS with q = 0.21−2.3 × 10 −3 Å −1 ) and Raman spectroscopy experiments on a 3 wt % PNIPAM solution in D 2 O at atmospheric and elevated pressures (up to 113 MPa). Raman spectroscopy reveals that, at high pressure, the polymer is less dehydrated upon crossing the cloud point. VSANS shows that the mesoglobules are significantly larger and contain more D 2 O than at atmospheric pressure. We conclude that the size of the mesoglobules and thus their growth process are closely related to the hydration state of PNIPAM. W ater-soluble polymers, such as polyelectrolytes, biopol- ymers, and thermoresponsive polymers, may feature charged groups, hydrophilic groups and hydrophobic groups. The interplay between ionic interactions, H-bonds, and hydrophobic interactions governs their solubility, secondary structure, responsivity to changes of pH, ionic strength, or temperature and their aggregation behavior. At this, the hydrophobic interaction is of special importance as it displays interesting behavior when high pressure is applied. In proteins, for instance, it is the main driving force for stabilizing the native state at atmospheric pressure. 1 The clathrate-like structure of water formed around hydrophobic groups enhances the entropic contribution to the free energy, hindering the hydration of hydrophobic groups. In contrast, at high pressure, bulk water changes its state from an open tetrahedral structure to a more ordered hexagonal one, that is, ordered water around hydrophobic groups becomes more similar to bulk water. 2 A second effect of pressure concerns the compressibility of the hydration shell around a sequence of hydrophobic groups, which is significantly larger than the compressibility of bulk water and of hydration water around hydrophilic groups. With increasing pressure, exposure of the hydrophobic groups to an aqueous environment leads to the possibility to further compress water in the newly formed hydration layers, which, for instance, favors the denatured, unfolded state of proteins. 3−5 Nonionic thermoresponsive polymers featuring lower critical solution temperature (LCST) behavior in aqueous solution may serve as a simple model system to investigate the effect of pressure on the hydration behavior and its implications on the mesoscopic behavior at the phase boundary since they neither contain charged groups nor form secondary structures, but are restricted to the coil-to-globule transition with subsequent aggregation. 6 Fourier-transform infrared spectroscopic experiments showed that the thermoresponsive polymer poly(N-isopropy- lacrylamide) (PNIPAM) dehydrates when heated through the cloud point (CP) at atmospheric pressure. 7−9 However, it does not phase-separate macroscopically, but forms mesoglobules, typically in the size range of 50 nm to 1 μm with the size depending on the conditions. 10−18 In contrast, PNIPAM does not dehydrate at the CP when the phase separation is induced by increasing pressure at constant temperature. 7 The present study describes the previously unexplored structure of phase-separated aqueous PNIPAM solutions at high pressure. Using pressure as a tool to tune the degree of hydration, we aim to elucidate the relation between the hydration state and the mesoglobule size. This may further improve the understanding of the growth process of the mesoglobules and their composition, which is related to their Received: July 29, 2017 Accepted: October 6, 2017 Letter pubs.acs.org/macroletters © XXXX American Chemical Society 1180 DOI: 10.1021/acsmacrolett.7b00563 ACS Macro Lett. 2017, 6, 1180−1185