Stabilizing effect of TMAO on globular PNIPAM states: preferential attraction induces preferential hydration

We study the effect of the organic co-solute trimethylamine N-oxide (TMAO) on the volume phase transition of microgel particles made from poly(N-isopropylacrylamide) (PNIPAM) using dynamic light scattering (DLS) and all-atom molecular dynamics (MD) simulations. The DLS measurements reveal a continuous TMAO-induced shrinking process from a coil to a globular state of PNIPAM microgel particles. Analyzing the DLS data by the phenomenological Flory-Rehner theory verifies the stabilization of the globular state of the particles in the presence of TMAO. Complementary atomistic MD simulations highlight a pronounced accumulation of TMAO molecules around PNIPAM chains. We observe a significant preferential attraction between TMAO and the globular state of PNIPAM, which is additionally stabilized by a larger number of hydrating water molecules compared to pure aqueous solutions. Further DLS measurements were also conducted on PNIPAM suspensions with the co-solute urea added. The observed differences compared with the results obtained for TMAO support the proposed mechanism.