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

Abstract

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.

Loading and Co-Solvent-Triggered Release of Okanin into/from Functional Microgels for Potential Plant Protection

“…To evaluate the influence of the chosen water model, we performed simulations of a crosslinked pVCL model with an inter-crosslink chain length of 20 in OPC 50 water (Table S11), resulting in a cumulative simulation time of 75 µs. In agreement with previous studies, 49 the collapse of the syndiotactic pVCL is well-defined using TIP3P water (Figure S8 and Figure S9), whereas the collapse is less pronounced in OPC water (Figure S10).…”

“…For each tacticity, ten replicas were simulated for 500 ns at 293 K, 313 K, and 343 K in the TIP3P 48 water model, resulting in a cumulative simulation time of 150 µs (Table S10). In line with previous experiments 49 , we found a dependency of the phase transition of the pVCL model on the polymer's tacticity. Atactic and isotactic pVCL models collapse irrespective of the temperature and intercrosslink chain length (Figure S8 and Figure S9).…”

“…The generation of the parameters for the pVCL repeating unit was described in detail in our previous work. 49 For computing atomic charges, we followed the Restrained Electrostatic Potential (RESP) procedure. 51 The electrostatic potential (ESP) was calculated at the HF/6-31G* level using Gaussian09.…”

Implementation of the Freely Jointed Chain Model to Assess Kinetics and Thermodynamics of Thermosensitive Coil–Globule Transition by Markov States

“…In particular, we expect the thermodynamics of solvation to be crucial for the energetic balance (see below). Because the choice of the water model is known to influence the effective force field temperature in simulations, it is not surprising that a shift in the transition temperature of processes, such as the CGT, ,, but also of protein folding may be observed. Several attempts have been made to optimize a force field to correctly reproduce the experimental LCST behavior of this system. , However, we decided to use the OPLS-AA force field, because, in contrast to NIPAAM-specific force fields, it has been validated to qualitatively reproduce the thermosensitive character of a series of different polymers …”

Less-Ordered Hydration Shell around Poly(N,N-diethylacrylamide) Is Insensitive to the Clouding Transition

“…The impact of hydration-shell structure and its transformation on the self-conformational change and multimolecular assembly of solutes in water is of great interest in fundamental sciences and applications. − The molecular mechanism on the coil–globule transition of thermoresponsive water-soluble polymers has been discussed from the viewpoint of the order-to-disorder transformation of the hydration shell in numerous studies. − …”