Thermodynamic Description of Hofmeister Effects on the LCST of Thermosensitive Polymers

Cosolvent effects on protein or polymer
collapse transitions are
typically discussed in terms of a two-state free energy change that
is strictly linear in cosolute concentration. Here we investigate
in detail the nonlinear thermodynamic changes of
the collapse transition occurring at the lower critical solution temperature
(LCST) of the role-model polymer poly­(N-isopropylacrylamide)
[PNIPAM] induced by Hofmeister salts. First, we establish an equation,
based on the second-order expansion of the two-state free energy in
concentration and temperature space, which excellently fits the experimental
LCST curves and enables us to directly extract the corresponding thermodynamic
parameters. Linear free energy changes, grounded on generic excluded-volume
mechanisms, are indeed found for strongly hydrated kosmotropes. In
contrast, for weakly hydrated chaotropes, we find significant nonlinear
changes related to higher order thermodynamic derivatives of the preferential
interaction parameter between salts and polymer. The observed non-monotonic
behavior of the LCST can then be understood from a not yet recognized
sign change of the preferential interaction parameter with salt concentration.
Finally, we find that solute partitioning models can possibly predict
the linear free energy changes for the kosmotropes, but fail for chaotropes.
Our findings cast strong doubt on their general applicability to protein
unfolding transitions induced by chaotropes.