Full Citation: Fluorescence Analysis of Thermoresponsive Polymers. A.G. Ryder and C. Morris, Reviews in Fluorescence 2015 ,
Annual Volumes, Vol. 8, pp. 97-126, (2015). ISBN: 978-3-319-24607-9 (Hardcover), 978-3-319-24609-3 (ebook) Springer.
Page 6 of 31
Of the family of poly(N-substituted acrylamides), PNIPAm (Figure 3) is probably the most widely
known and studied. PNIPAm is a chemical isomer of poly-leucine, in that it has the polar peptide
group in its side chain rather than in the hydrocarbon backbone [45]. In aqueous solution, PNIPAm
has a LCST of 32C; at this temperature it undergoes a sharp and reversible coil-to-globule phase
transition from a hydrophilic to a more hydrophobic state, forcing water from the matrix
[3,7,14,16,27,46-48]. This phenomenon occurs due to the domination of entropic over enthalpic
effects as the temperature increases above the LCST [30,42]. Below the LCST, PNIPAm chains exist
in an extended coil conformation, and solvation is driven by the enthalpic gain from intermolecular
hydrogen bonding between the PNIPAm chains and water molecules [16,49]. Solvation is further
encouraged by a type of hydrophobic hydration, where the water molecules surround the a-polar
isopropyl entities in a cage-like structure [50]. As the temperature is increased towards the LCST,
intramolecular hydrogen bonding between carboxyl and amide groups on the PNIPAm chains result in
the interruption of hydrogen bonding of these groups with water molecules, ultimately resulting in the
chain adopting a collapsed conformation, driving out the water, and causing the polymer to precipitate
out of solution [49]. These properties of PNIPAm and its copolymers make them applicable to a
diverse range of pharmaceutical and biomedical applications [5,13,51,52].
Figure 3: Chemical structure of PNIPAm [22].
The thermoresponsive behavior of PNIPAm may be altered by the introduction of hydrophobic or
hydrophilic groups into the polymer structure. By copolymerization with more hydrophobic
monomers, like N-tBAAm (N-tert-butylacrylamide), the LCST of the polymer is shifted to lower
temperatures while copolymerization with more hydrophilic monomers, like AAm (acrylamide),
increases the LCST [26]. Rochev and co-workers have synthesized a series of copolymers based on
N-isopropylacrylamide (NIPAm) and N-tBAAm. Increasing the amount of the hydrophobic
monomer (from a mole ratio of 0 to 50 %) increases hydrophobicity and therefore lowers the LCST
(from 33 to ~10 °C) [53]. It was also observed that cell adhesion, cell growth properties and drug
elution from cast NIPAm/N-tBAAm copolymer films were all dependent on the copolymer
Annual Volumes, Vol. 8, pp. 97-126, (2015). ISBN: 978-3-319-24607-9 (Hardcover), 978-3-319-24609-3 (ebook) Springer.
Page 6 of 31
Of the family of poly(N-substituted acrylamides), PNIPAm (Figure 3) is probably the most widely
known and studied. PNIPAm is a chemical isomer of poly-leucine, in that it has the polar peptide
group in its side chain rather than in the hydrocarbon backbone [45]. In aqueous solution, PNIPAm
has a LCST of 32C; at this temperature it undergoes a sharp and reversible coil-to-globule phase
transition from a hydrophilic to a more hydrophobic state, forcing water from the matrix
[3,7,14,16,27,46-48]. This phenomenon occurs due to the domination of entropic over enthalpic
effects as the temperature increases above the LCST [30,42]. Below the LCST, PNIPAm chains exist
in an extended coil conformation, and solvation is driven by the enthalpic gain from intermolecular
hydrogen bonding between the PNIPAm chains and water molecules [16,49]. Solvation is further
encouraged by a type of hydrophobic hydration, where the water molecules surround the a-polar
isopropyl entities in a cage-like structure [50]. As the temperature is increased towards the LCST,
intramolecular hydrogen bonding between carboxyl and amide groups on the PNIPAm chains result in
the interruption of hydrogen bonding of these groups with water molecules, ultimately resulting in the
chain adopting a collapsed conformation, driving out the water, and causing the polymer to precipitate
out of solution [49]. These properties of PNIPAm and its copolymers make them applicable to a
diverse range of pharmaceutical and biomedical applications [5,13,51,52].
Figure 3: Chemical structure of PNIPAm [22].
The thermoresponsive behavior of PNIPAm may be altered by the introduction of hydrophobic or
hydrophilic groups into the polymer structure. By copolymerization with more hydrophobic
monomers, like N-tBAAm (N-tert-butylacrylamide), the LCST of the polymer is shifted to lower
temperatures while copolymerization with more hydrophilic monomers, like AAm (acrylamide),
increases the LCST [26]. Rochev and co-workers have synthesized a series of copolymers based on
N-isopropylacrylamide (NIPAm) and N-tBAAm. Increasing the amount of the hydrophobic
monomer (from a mole ratio of 0 to 50 %) increases hydrophobicity and therefore lowers the LCST
(from 33 to ~10 °C) [53]. It was also observed that cell adhesion, cell growth properties and drug
elution from cast NIPAm/N-tBAAm copolymer films were all dependent on the copolymer