This review focuses on polymers with upper critical solution temperature (UCST) in water or electrolyte solution and provides a detailed survey of the yet few existing examples. A guide for synthetic chemists for the design of novel UCST polymers is presented and possible handles to tune the phase transition temperature, sharpness of transition, hysteresis, and effectiveness of phase separation are discussed. This review tries to answer the question why polymers with UCST remained largely underrepresented in academic as well as applied research and what requirements have to be fulfilled to make these polymers suitable for the development of smart materials with a positive thermoresponse.

We present a powerful universal and versatile approach for the synthesis of polymers that show a UCST in water. Up to now only a few polymers were known that show an upper critical solution temperature (UCST) in water. This study establishes general requirements to obtain polymers with a UCST in water as well as electrolyte solution. It is demonstrated that old homo- and copolymer systems like poly(methacrylamide) and poly(acrylamide-co-acrylonitrile) can exhibit a UCST in water and how polymers with a tunable UCST can be synthesized by copolymerization of acrylamide and acrylonitrile, monomers that are industrially produced on large scales. Controlled increase of the UCST by copolymerization of acryamide with varying amounts of acrylonitrile was shown, and it could be varied between 6 and 60 °C. The hysteresis between the cloud point upon cooling and heating was very small with only 1–2 °C in most cases. The cloud points in pure water were similar to the cloud points measured in phosphate buffered saline. Also, it is possible to prepare highly concentrated thermoresponsive polymer solutions without gel formation.

Polymers showing an upper critical solution temperature (UCST) in water are rare. Recently, the nonionic homopolymer poly(N-acryloyl glycinamide) (poly(NAGA)) has been shown to exhibit a sharp upper critical solution temperature in pure water as well as in electrolyte solution. Although poly(NAGA) is known for decades the UCST behavior had not been reported. The first controlled radical polymerization of poly(NAGA) by the RAFT (reversible addition–fragmentation transfer) process was also achieved recently, but no UCST was observed. The present study shows that traces of ionic groups in the polymer prevent phase separation. Failure to notice the UCST in the past was because ionic groups have been introduced unintentionally by either acrylate impurities in the monomer, hydrolysis of the polymer side chains, and/or usage of ionic initiators or chain transfer agents. A synthetic procedure for high purity NAGA monomer free of ionic impurities is reported. It is also shown how to obtain stable aqueous solutions of nonionic poly(NAGA) so that the UCST behavior can be exploited in pure water as well as in a physiological milieu. Further, ultrasensitive differential scanning calorimetry and light scattering were used to get insights into the phase separation mechanism. We believe that this knowledge is transferable to other systems and will greatly accelerate research in the field of macromolecules that feature thermally reversible hydrogen bonding.

Polymers showing an upper critical solution temperature (UCST) in aqueous solution were not rare, but the UCST was rarely observed under practically relevant conditions. Recently, much progress has been made in the synthesis of polymer systems that display UCST behavior under mild and physiologic conditions. Current developments focus on polymers that rely on hydrogen bonding. This viewpoint explains the historical context, presents the major properties, and concludes with a discussion of the most recent examples.

A well‐studied example of a thermoresponsive polymer is PNiPAAm, which exhibits a sharp coil‐to‐globule transition in water at its LCST. A study relating to the missing counterpart of LCST polymers is presented: N‐acryloylglycinamide (NAGA) homopolymer and copolymers from NAGA and N‐acetylacrylamide (NAcAAm) that show a sharp UCST (where the sharpness depends on the composition). The polymers were synthesized by free‐radical copolymerization and the copolymerization parameters were determined by the method of Kelen‐Tüdös. The UCST was investigated by turbidimetry, regarding the influence of the copolymer composition, the polymer concentration and the addition of electrolytes. magnified image