Cumulative Submillisecond All-Atom Simulations of the Temperature-Induced Coil-to-Globule Transition of Poly(N‑vinylcaprolactam) in Aqueous Solution

• Published in: Macromolecules Vol. 53; no. 22; pp. 9793 - 9810
• Main Authors: Dittrich, Jonas, Kather, Michael, Holzberger, Anna, Pich, Andrij, Gohlke, Holger
• Format: Journal Article
• Language: English
• Published: American Chemical Society 24.11.2020
• ISSN: 0024-9297; 1520-5835
• DOI: 10.1021/acs.macromol.0c01896

Poly­(N-vinylcaprolactam) (PNVCL) polymers are stimuli-responsive and change their conformation in aqueous solutions upon changes in salt concentration, concentration of organic solvents, or temperature, making these molecules highly interesting for tailored release of drugs or fabrication of sensors or actuators. At lower critical solution temperature (LCST), PNVCL chains undergo a transition from a coil to a globule and become insoluble. In contrast to other polymers, however, PNVCL has received much less attention as to elucidating driving forces of its coil-to-globule transition at an atomistic level. Here, we show by a combined computational and experimental study that upon temperature increase, PNVCL chains dissolved in water experience an increase of intramolecular interactions between C3 and C4 of the caprolactam ring. Therefore, more favorable cavity formation energies and the increase of intramolecular interactions outweigh the loss in polar and hydrophobic solvation, and the loss of configurational entropy in the coil-to-globule transition and, thus, may be considered driving forces of the polymer’s collapse at LCST. These results are based on molecular dynamics simulations of in total 600 μs length and transition (free) energy computations that have been validated internally and against experimental data. We systematically tested the influence of the polymer’s length, concentration, tacticity, of the thermodynamic ensemble, and of the water model. Tacticity was found to be most influential, with atactic polymers showing the strongest tendency to collapse. The presented approach should be applicable to scrutinize at the atomistic level the impact of, for example, ion and polymer dispersity on the coil-to-globule transition of PNVCL, and the LCST behavior of other polymers.