a b s t r a c tDiblock copolymers of 4-vinylpyridine (4VP) and oligoethyleneglycol methyl ether methacrylate (OEGMA) were synthesized for the first time using RAFT polymerization technique as potential drug delivery systems. Effects of the number of ethylene glycol units in OEGMA, chain length of hydrophobic P4VP block, pH, concentration and temperature on the solution behavior of the copolymers were investigated comprehensively. Copolymer chains formed micelles at pH values higher than 5 whereas unimeric polymers were observed to exist below pH 5, owing to the repulsion between positively charged P4VP blocks. The size of the micelles was dependent on the relative length of blocks, P4VP and POEGMA. Thermo-responsive properties of copolymers were investigated depending on the pH and length of P4VP block. The increase in the length of P4VP block decreased the LCST substantially at pH 7. At pH 3, LCST of copolymers shifted to higher temperatures due to the increased interaction of copolymers with water through positively charged P4VP block.

The solubility and lower critical solution temperature (LCST) behaviour of poly(oligo(ethylene glycol)methyl ether methacrylate) (POEGMA300) in water were comprehensively investigated by all-atom molecular dynamics (MD) simulations for 5-, 20-, 50- and 75-mer homopolymers. According to various structural and dynamic properties, the water-solubility of POEGMA300 below the LCST is mainly provided by hydrophobic hydration around the side chain carbon atoms, which is achieved by cage-like water formations. The LCST phase transition occurs when these cage-like structures are disrupted by increasing the temperature above the LCST. During this process, significant amounts of water molecules are released and the local water-ordering is reduced. Moreover, the number of hydrogen bonds and hydrogen bond lifetime results indicate that the hydrogen bonding between polymers and water molecules has relatively little effect on the phase transition. Also, the diffusion rates of 50- and 75-mer POEGMA300 decrease with increasing temperature, which may be due to the breakage of cage-like water structures when the polymer exceeds a certain chain length. Our atomistic level findings will enhance the understanding of the LCST phase transition of OEGMA based homopolymers and will be helpful to design homo- and co-polymers of OEGMAs with required properties.

Fully atomistic molecular dynamics simulations of poly(2-[2-methoxyethoxy]ethyl methacrylate) (PMEO 2 MA) in water at temperatures below and above its lower critical solution temperature (LCST) were performed to improve the understanding of its LCST behavior. Atomic trajectories were used to calculate various structural and dynamic properties. Simulation results show that PMEO 2 MA undergo a distinct coil-to-globule transition above LCST. Detailed analyses of the number of first hydration shell water molecules around various atomic regions are revealed that the water solubility of PMEO 2 MA below LCST is mainly provided by the hydrophobic hydration around the side chain carbon atoms. This is achieved by the cage-like water network formations which are disrupted when the temperature is increased above LCST, accompanied by significant amount of water molecule release and local water-ordering reduction, which leads to the LCST phase transition. Furthermore, other analyses such as the number of hydrogen bonds and hydrogen bond lifetimes suggest that intermolecular hydrogen bondings between polymer and water molecules have little effect on the phase transition. Our results will contribute to a better understanding on the LCST phase transition of oligo(ethylene glycol) methyl ether methacrylate (OEGMA)based homopolymers at atomistic level that will be useful when designing homo-and co-polymers of OEGMAs with desired properties.

The atomistic origin underlying the lower critical solution temperature (LCST) behavior of thermoresponsive copolymers in water is still elusive. Here, we report all-atom molecular dynamics simulations of block copolymers of 2-(2-methoxyethoxy)ethyl methacrylate (MEO 2 MA) and oligo(ethylene glycol) methyl ether methacrylate (OEGMA 300 ) in water at various block ratios and at temperatures below and above the LCST values of each homopolymer block. Our single chain simulations showed that hydration water molecules accumulate particularly near the side chain carbon atoms by forming ordered cage-like structures via extensive hydrogen bonding between them. These water cage formations surround the entire surface of PMEO 2 MA-b-POEGMA 300 and enable the copolymer to remain in water below the LCST. As the temperature increases, each block exhibits a separate coil-to-globule transition above its own LCST. A detailed analysis of the interactions between polymer−water and water−water revealed that this phase transition is mainly driven by the reduced local water ordering by the disruption of the water cages when the temperature is increased above the LCST. We found that the transition occurs differently in the copolymer than the POEGMA homopolymers due to the interaction of the blocks, especially around the joint of the blocks. Accordingly, the phase transition of a block acts as an additional disruptive effect on the other block's water cage structure, which reduces the LCST values of PMEO 2 MA and POEGMA 300 in the copolymer, compared to their individual single chain homopolymers.