Poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers that respond sharply to temperature and pH

Biomacromolecules. 2006 May;7(5):1381-5. doi: 10.1021/bm0507812.


Temperature- and pH-sensitive random copolymers of N-isopropylacrylamide (NIPAAm) and propylacrylic acid (PAA) were prepared using the reversible addition fragmentation chain transfer (RAFT) polymerization method. The lower critical solution temperatures (LCSTs) (or phase separation temperatures) of the NIPAAm-co-PAA copolymer solutions were measured by the cloud-point method. At slightly acidic conditions, the LCST decreased with increase in PAA content, which suggests that the hydrophobic propyl group of PAA has a greater influence on the LCST than the polar carboxylic acid group at those conditions. An increase of pH led to a significant increase in LCST of the copolymers due to the ionization of the -COOH group. The LCSTs were studied as a function of copolymer composition over the pH range from 5.0 to 7.0. Because the pK(a) of the polymers can be tuned to fall close to neutral pH, these polymer compositions can be designed to have phase transitions triggered near physiological pH or at slightly acidic pH values that fall within acidic gradients found in biology. The NIPAAm-co-PAA copolymers thus display tunable properties that could make them useful in a variety of molecular switching and drug delivery applications where responses to small pH changes are relevant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides*
  • Biocompatible Materials*
  • Hydrogen-Ion Concentration
  • Macromolecular Substances
  • Magnetic Resonance Spectroscopy
  • Molecular Weight
  • Solutions
  • Thermodynamics


  • Acrylamides
  • Biocompatible Materials
  • Macromolecular Substances
  • Solutions
  • poly(N-isopropylacrylamide-co-propylacrylic acid)