Abstract
To characterize the thermosensitive coil–globule transition in atomistic detail, the conformational dynamics of linear polymer chains of acrylamide-based polymers have been investigated at multiple temperatures. Therefore, molecular dynamic simulations of 30mers of polyacrylamide (AAm), poly-N-methylacrylamide (NMAAm), poly-N-ethylacrylamide (NEAAm), and poly-N-isopropylacrylamide (NIPAAm) have been performed at temperatures ranging from 250 to 360 K for 2 μs. While two of the polymers are known to exhibit thermosensitivity (NEAAm, NIPAAm), no thermosensitivity is observed for AAm and NMAAm in aqueous solution. Our computer simulations consistently reproduce these properties. To understand the thermosensitivity of the respective polymers, the conformational ensembles at different temperatures have been separated according to the coil–globule transition. The coil and globule conformational ensembles were exhaustively analyzed in terms of hydrogen bonding with the solvent, the change of the solvent accessible surface, and enthalpic contributions. Surprisingly, independent of different thermosensitive properties of the four polymers, the surface affinity to water of coil conformations is higher than for globule conformations. Therefore, polymer–solvent interactions stabilize coil conformations at all temperatures. Nevertheless, the enthalpic contributions alone cannot explain the differences in thermosensitivity. This clearly implies that entropy is the distinctive factor for thermosensitivity. With increasing side chain length, the lifetime of the hydrogen bonds between the polymer surface and water is extended. Thus, we surmise that a longer side chain induces a larger entropic penalty due to immobilization of water molecules.
Highlights
Since their first discovery, thermosensitive polymers (TSPs) have been the subject of interest in many different fields of research.[1−4] Next to medical applications, such as tissue engineering, bioseparation, and drug delivery,[5−10] they have been proven to be highly valuable as programmable materials[11] and for gel actuators amongst other things
The above-mentioned macroscopic liquid-gel phase transition of TSPs has been linked to a microscopic conformational rearrangement, i.e., the coil−globule transition (CGT).[14−16] While the liquid−gel-phase transition can be measured by clear changes in the properties of the bulk fluid, such as the change of opacity, the conformational CGT can be reproduced in experiments in dilute solution, without necessarily exhibiting a phase transition of the liquid mixture.[15,17−20] Since detailed information about polymer conformations is extremely challenging to be obtained experimentally, this transition is solely defined by the change in the size distribution of the polymer chains in solution
To facilitate the comparison of C and G, we separated our conformational ensembles at different temperatures
Summary
Thermosensitive polymers (TSPs) have been the subject of interest in many different fields of research.[1−4] Next to medical applications, such as tissue engineering, bioseparation, and drug delivery,[5−10] they have been proven to be highly valuable as programmable materials[11] and for gel actuators amongst other things. Their development has advanced to the point that it is possible to use TSPs as a remote-controlled drug delivery platform in cancer therapy.[12] Crucial for the majority of the applications is the extraordinary phase behavior of these polymers. The extended conformational state is called coil (C), whereas the collapsed state is called globule (G).[13,21,22]
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