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 4 of 31
The response of these “smart” polymers can be induced by a variety of environmental triggers,
such as ionic strength, light, magnetic field, pH, electric field and temperature [1,8,15,16,20,27,29-37].
From a biomedical standpoint, the favored “smart” polymers are generally those sensitive to pH and/or
temperature changes [30]. The most widely studied class of stimuli responsive polymers are
thermoresponsive polymer systems; as the name suggests, these systems undergo conformational
changes in response to temperature [16,30].
3.1
THERMORESPONSIVE POLYMERS.
Thermoresponsive polymers have a critical solution temperature, at which a significant phase
change occurs. Polymers whose water solubility increases with temperature are described as having
an upper critical solution temperature (UCST) or a higher critical solution temperature (HCST) and
solutions of these polymers appear biphasic below this critical temperature. Conversely, polymers
for which the solubility decreases with increasing temperature often have a lower critical solution
temperature (LCST) where the solutions transition to a biphasic state. This occurs because the
polymer becomes less solvated as the temperature increases [16,22,30,38]. Below the LCST, the
polymer is soluble in aqueous solutions due to the domination of hydrophilic interactions (i.e.
hydrogen bonding between the polymer and water) over hydrophobic (intramolecular) interactions,
and thus it typically assumes a relaxed coil-like conformation. Raising the temperature above the
LCST results in an increased dominance of the hydrophobic interactions, causing the
collapse/contraction of the polymer. This leads to the adoption of a more globule-like conformation
which minimizes the polymer-water contact and can eventually lead to precipitation from solution
[30,39,40].
In the case of polymer solutions with a UCST, the entropy of mixing is usually large and positive
but is dominated by enthalpic contributions at low temperatures. When the temperature increases,
the entropic contribution increases, and eventually surpasses the enthalpic contribution at the UCST,
resulting in a negative Gibb’s free energy. Therefore in these polymer systems, higher temperatures
enhance solubility [38]. For polymer solutions possessing a LCST, H-bonding between polymer
polar groups and water molecules are the driving force for solvation at low temperatures, resulting in
a large, dominant, negative enthalpy of mixing. In this state, the polymer is ordered, leading to an
unfavorable negative entropy contribution, but overall the system is stable in this mixed form below
its LCST due to the large enthalpic contribution. It has been suggested that the phase separation at
the LCST of a polymer can be attributed to entropic effects [41]. At higher temperatures the
contribution from entropy (displacement of water from the polymer matrix) surpasses the exothermic
enthalpy contribution from hydrogen bonding between polar groups in the polymer and water
molecules [8,27,30,41,42]. It is this balance between entropy and enthalpy that causes the polymer
Annual Volumes, Vol. 8, pp. 97-126, (2015). ISBN: 978-3-319-24607-9 (Hardcover), 978-3-319-24609-3 (ebook) Springer.
Page 4 of 31
The response of these “smart” polymers can be induced by a variety of environmental triggers,
such as ionic strength, light, magnetic field, pH, electric field and temperature [1,8,15,16,20,27,29-37].
From a biomedical standpoint, the favored “smart” polymers are generally those sensitive to pH and/or
temperature changes [30]. The most widely studied class of stimuli responsive polymers are
thermoresponsive polymer systems; as the name suggests, these systems undergo conformational
changes in response to temperature [16,30].
3.1
THERMORESPONSIVE POLYMERS.
Thermoresponsive polymers have a critical solution temperature, at which a significant phase
change occurs. Polymers whose water solubility increases with temperature are described as having
an upper critical solution temperature (UCST) or a higher critical solution temperature (HCST) and
solutions of these polymers appear biphasic below this critical temperature. Conversely, polymers
for which the solubility decreases with increasing temperature often have a lower critical solution
temperature (LCST) where the solutions transition to a biphasic state. This occurs because the
polymer becomes less solvated as the temperature increases [16,22,30,38]. Below the LCST, the
polymer is soluble in aqueous solutions due to the domination of hydrophilic interactions (i.e.
hydrogen bonding between the polymer and water) over hydrophobic (intramolecular) interactions,
and thus it typically assumes a relaxed coil-like conformation. Raising the temperature above the
LCST results in an increased dominance of the hydrophobic interactions, causing the
collapse/contraction of the polymer. This leads to the adoption of a more globule-like conformation
which minimizes the polymer-water contact and can eventually lead to precipitation from solution
[30,39,40].
In the case of polymer solutions with a UCST, the entropy of mixing is usually large and positive
but is dominated by enthalpic contributions at low temperatures. When the temperature increases,
the entropic contribution increases, and eventually surpasses the enthalpic contribution at the UCST,
resulting in a negative Gibb’s free energy. Therefore in these polymer systems, higher temperatures
enhance solubility [38]. For polymer solutions possessing a LCST, H-bonding between polymer
polar groups and water molecules are the driving force for solvation at low temperatures, resulting in
a large, dominant, negative enthalpy of mixing. In this state, the polymer is ordered, leading to an
unfavorable negative entropy contribution, but overall the system is stable in this mixed form below
its LCST due to the large enthalpic contribution. It has been suggested that the phase separation at
the LCST of a polymer can be attributed to entropic effects [41]. At higher temperatures the
contribution from entropy (displacement of water from the polymer matrix) surpasses the exothermic
enthalpy contribution from hydrogen bonding between polar groups in the polymer and water
molecules [8,27,30,41,42]. It is this balance between entropy and enthalpy that causes the polymer