A well-defined pyrrolidone based thermoresponsive polymer, poly [N-(2-methacryloyloxyethyl) pyrrolidone] (PNMP), was synthesized via reversible addition-fragmentation chain transfer radical polymerization or RAFT polymerization of N-(2-methacryloyloxyethyl) pyrrolidone monomer in methanol under a mild Visible light radiation at 30 °C. The average molecular weights and polydispersity indices of PNMP polymers were characterized by gel permeation chromatography (GPC) and static light scattering analysis. The kinetic studies indicated that this RAFT polymerization exhibited a well-controlled behavior. The living character of this RAFT polymerization was confirmed by the facile synthesis of a series of well-defined PNMP-based block copolymers via RAFT polymerization under this mild visible light radiation at 30 °C using the above-synthesized PNMP polymer as a macromolecular chain transfer agent. Temperature-variation 1 H NMR unambiguously revealed that the PNMP polymer with weight-average molecular weight (M w ) of 105.4 kg mol -1 and polydispersity index (M w /M n ) of 1.11 was molecularly dissolved in D 2 O at ambient temperature, e.g. 22 °C. Upon elevating the solution temperature, the dehydration process of this fully hydrated PNMP polymer was triggered at 46.1 °C, leading to a dramatic decrease of integral ratios of proton resonance signals of PNMP to that of D 2 O. Further elevating the solution temperature to 51.9 °C led to a sharp phase separation of PNMP polymer from aqueous solution. Laser light scattering analyses demonstrated that the cloud point of the PNMP polymer decreased with molecular weight in the M w range of 20.6-105.4 kg mol -1 . Moreover, this PNMP polymer exhibited a remarkably reversible thermoresponsive dehydration/hydration and phase transition behaviors in aqueous solution. Unlike what was observed in PNIPAM aqueous solution, no hysteresis phenomenon was observed in PNMP aqueous solution during one heating-and-cooling cycle.

A continuous supply of oxygen to tissues is vital to life and interruptions in its delivery are poorly tolerated. The treatment of low-blood oxygen tensions requires restoration of functional airways and lungs. Unfortunately, severe oxygen deprivation carries a high mortality rate and can make otherwise-survivable illnesses unsurvivable. Thus, an effective and rapid treatment for hypoxemia would be revolutionary. The i.v. injection of oxygen bubbles has recently emerged as a potential strategy to rapidly raise arterial oxygen tensions. In this report, we describe the fabrication of a polymerbased intravascular oxygen delivery agent. Polymer hollow microparticles (PHMs) are thin-walled, hollow polymer microcapsules with tunable nanoporous shells. We show that PHMs are easily charged with oxygen gas and that they release their oxygen payload only when exposed to desaturated blood. We demonstrate that oxygen release from PHMs is diffusion-controlled, that they deliver approximately five times more oxygen gas than human red blood cells (per gram), and that they are safe and effective when injected in vivo. Finally, we show that PHMs can be stored at room temperature under dry ambient conditions for at least 2 mo without any effect on particle size distribution or gas carrying capacity.hypoxemia | microparticle | oxygen | core-shell | colloids

This paper describes the molecular structure dependent thermoresponsive behaviors of pyrrolidone-based water-soluble polymers. A series of well-defined poly[N-(2-methacryloyloxyethyl)pyrrolidone] (PNMEP), poly[N-(3-acryloyloxypropyl)pyrrolidone] (PNAPP), and poly[N-(3-methacryloyloxypropyl)pyrrolidone] (PNMPP) were synthesized via visible light activating RAFT polymerization at 25 °C. Kinetic studies indicate a rapid and well-controlled behavior of this polymerization. Gel permeation chromatography (GPC) and 1H NMR analysis confirm their intact molecular structure, well-defined molecular weight, and narrow distribution. Laser light scattering and temperature-variable 1H NMR analyses demonstrate that the cloud point of a PNMEP sample at a degree of polymerization (DP) of 96 is 1.5 °C lower than that of PNAPP at a DP = 104. Additional backbone methyl groups in PNMPP lead to a dramatic cloud point lowering, e.g., cloud point of PNMPP at a DP = 100 is 37 °C lower than that of PNAPP at a DP = 104. This is contrary to what was observed in poly(N-isopropylacrylamide) (PNIPA) and its polymethacrylamide analogues. These pyrrolidone-based polymers show a dramatic solvent isotopic effect that is different from that of PNIPA; e.g., the cloud point of PNMEP at a DP = 237 is 8.5 °C lower in D2O than in H2O. Increasing polymer chain length or hydrophobicity may suppress this solvent isotopic effect. This phase transition is correlated to Hofmeister series but more sensitive than PNIPA. Na2CO3 dramatically lowers cloud point, while NaI significantly improves cloud point, up to full dissolution in H2O at 95 °C. The solvent isotopic effect in NaCl or Na2CO3 solution is the same as what observed in solution absent of salt. Upon heating D2O solution of PNMEP, the polymer first forms the hydrated irregular colloidal aggregates near the cloud point, the phase transition occurs at the fully hydrated state at cloud point, and further heating leads to the dehydration and separation from D2O. However, in NaCl solution, the dehydration of PNMEP occurs subsequently from apolar backbones, spacers, and finally pyrrolidone groups.

No abstract