Greasy Cations Bind to Neutral Macromolecules in Aqueous Solution

Ions influence the solution properties of macromolecules. Although much is known about anions, cationic effects are considered mostly in terms of weak interactions or exclusion from neutral interfaces. Herein, we have systematically studied the effect of quaternary tetraalkylammonium cations (NH₄⁺, NMe₄⁺, NEt₄⁺, NPr₄⁺, NBu₄⁺) on the phase transition of poly(N-isopropylacrylamide) (PNIPAM) in aqueous solution. Solubility measurements were coupled to ¹H NMR and ATR-FTIR spectroscopic measurements. The solubility and NMR measurements revealed a direct binding between the greasiest cations and the isopropyl group of the macromolecule, evidenced from the nonlinear, Langmuir-type chemical shift response only at the isopropyl NMR signals with increasing salt concentrations. The ATR-FTIR measurements focusing on the amide oxygen showed that it is not the main direct-binding site. Additionally, the salting-out effects of the greasier cations correlate with their hydration entropies. These results demonstrate that the most weakly hydrated cations can bind to macromolecules as strongly as the weakly hydrated Hofmeister anions.