Poly(N-isopropylacrylamide) (variously abbreviated PNIPA, PNIPAM, PNIPAAm, NIPA, PNIPAA or PNIPAm) is a temperature-responsive polymer that was first synthesized in the 1950s. It can be synthesized from N-isopropylacrylamide which is commercially available. It is synthesized via free-radical polymerization and is readily functionalized making it useful in a variety of applications. PNIPA dissolves in water, however, when these solutions are heated in above their cloud point temperature, they undergo a reversible lower critical solution temperature (LCST) phase transition from a soluble hydrated state to an insoluble dehydrated state. Although it is widely believed that this phase transition occurs at 32 °C (90 °F), the actual temperatures may differ 5 to 10 °C (or even more) depending on the polymer concentration, molar mass of polymer chains, polymer dispersity as well as terminal moieties. Furthermore, other molecules in the polymer solution, such as salts or proteins, can alter the cloud point temperature. Since PNIPA expels its liquid contents at a temperature near that of the human body, PNIPA copolymers have been investigated by many researchers for possible applications in tissue engineering and controlled drug delivery.
History The synthesis of poly(N-isopropylacrylamide) began with the synthesis of the acrylamide monomer by Sprecht in 1956. In 1957, Shearer patented the first application for what would be later identified as PNIPA for the use as a rodent repellent. Early work was piqued by theoretical curiosity of the material properties of PNIPA. The first report of PNIPA came in 1968, which elucidated the unique thermal behavior in aqueous solutions. The 1980s marked an explosion in interest in PNIPAs with the realization of potential applications due to its unique thermal behavior in aqueous solutions.
Chemical and Physical Properties PNIPA is one of the most studied thermosensitive hydrogel. In dilute solution, it undergoes a coil-to-globule transition. PNIPA possesses an inverse solubility upon heating. It changes hydrophilicity and hydrophobicity abruptly at its LCST. At lower temperatures PNIPA orders itself in solution in order to hydrogen bond with the already arranged water molecules. The water molecules must reorient around the nonpolar regions of PNIPA which results in a decreased entropy. At lower temperatures, such as room temperature, the negative enthalpy term ( Δ H {\displaystyle \Delta H} ) from hydrogen bonding effects dominates the Gibbs free energy,
Δ G = Δ H − T Δ S {\displaystyle \Delta G=\Delta H-T\Delta S\,}
causing the PNIPA to absorb water and dissolve in solution. At higher temperatures, the entropy term ( Δ S {\displaystyle \Delta S} ) dominates, causing the PNIPA to release water and phase separate which can be seen in the following demonstration.
Synthesis of Heat and pH Sensitive PNIPA Homopolymerization
The process of free radical polymerization of a single type of monomer, in this case, N-isopropylacrylamide, to form the polymer is known as a homopolymerization. The radical initiator azobisisobutyronitrile (AIBN) is commonly used in radical polymerizations.
Copolymerization
A free-radical polymerization of two different monomer results in a copolymerization. An advantage to a copolymerization includes fine tuning of the LCST.
Terpolymerization
A free-radical polymerization of three different monomer is known as a terpolymerization. Advantages to a terpolymerization may include enhancing multiple properties of the polymer including thermosensitivity, pH sensitivity or fine tuning of the LCST.
Cross-linked Hydrogel
The reaction scheme below is a terpolymerization to form a cross-linked hydrogel. The reactant ammonium persulfate (APS) is used in polymer chemistry as a strong oxidizing agent that is often used along with tetramethylethylenediamine (TMEDA) to catalyze the polymerization when making polyacrylamide gels.
Synthesis of Chain-End Functionalized PNIPA PNIPA can be functionalized using chain transfer agents using a free radical polymerization. The three schemes below demonstrate functionalization using chain transfer agents (CTA), where one end of the polymer is the radical initiator and the other is a functionalized group. Functionalization of the polymer chain-end allows for the polymer to be used in many diverse settings and applications. Advantages to a functionalizing the chain-end may include enhancing multiple properties of the polymer including thermosensitivity, pH sensitivity or fine tuning of the LCST. (1) (2) (3)
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