Abstract
Walter Kauzmann’s classic 1948 review of liquid supercooling and glass formation drew attention to the temperatures
at which (by extrapolation) enthalpies and entropies of liquid and crystal phases would appear to become equal. In
the temperature–pressure (T, p) plane, the collection of such ‘Kauzmann temperatures’ generate characteristic curves.
The present study examines the connection of those Kauzmann loci to equilibrium inverse melting phenomena, i.e.
cases where isobaric heating causes freezing of the liquid. Such cases are associated with local minima or maxima in
the melting curve pm(T), and we point out the possible relevance of melting curve maxima to the thermodynamics
of protein folding. Both equal-enthalpy and equal-entropy Kauzmann curves must pass through melting curve extrema.
Three thermodynamic identities have been obtained to describe the vicinity of these points; they involve, respectively,
the slopes of the two Kauzmann curves, and the second temperature derivative of the melting pressure. The second
of these three equations is formally identical to the first Ehrenfest relation for second-order phase transitions, but
carries no phase-transition implication. For purposes of specific numerical illustration, the inverse-melting behavior
displayed by 3He at low temperature has been analyzed in detail.
䊚 2003 Elsevier Science B.V. All rights reserved.
0301-4622/03/$ - see front matter 䊚 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016/S0301-4622Ž03.00089-9
212 F.H. Stillinger, P.G. Debenedetti / Biophysical Chemistry 105 (2003) 211–220
that several recent comprehensive reviews also involves ambient pressure. However, a comprehen-
exist, documenting the experimental and theoreti- sive view of the properties of those metastable
cal advances that have been made subsequent to states includes the effects of varying pressure,
1948 w2–6x. extending even into the negative pressure (isotro-
Professor Kauzmann stressed the significance of pic tension) regime w13,14x. In the analysis pro-
the experimental fact that, for most liquids, upon vided below, we shall be interested in examining
supercooling the constant-pressure heat capacity behavior in the temperature–pressure (T,p) plane.
CpŽl.ŽT. exceeds that of the thermodynamically As examples, the two temperatures just mentioned
define curves TK(p) and TH(p) in that plane. These
stable crystal phase CpŽc.ŽT., with the discrepancy functions can be grouped with, but remain distin-
widening with increasing extent of supercooling. guished from, the familiar thermodynamic melting
Consequently, reduction in absolute temperature T temperature Tm(p), and the experimental conven-
causes the metastable liquid to lose both entropy tion-dependent glass-transition temperature Tg(p).
and enthalpy faster than does the stable crystal. Our primary objective in this paper is to elabo-
Although a glass transition or crystal nucleation rate upon an earlier suggestion w8x, specifically
event typically would intervene to frustrate contin- that comprehensive understanding of the many-
uation of this trend to very low temperature, body phenomena underlying the Kauzmann para-
smooth and ‘reasonable’ extrapolation of the heat dox should include analysis of ‘inverse melting’.
capacities indicates that the entropy of the super- This unusual and counter-intuitive phenomenon
cooled liquid would equal that of the crystal at a involves liquids at thermodynamic equilibrium that
positive ‘Kauzmann temperature’ TK. Further crystallize upon isobaric addition of heat, the
reduction in temperature toward absolute zero, reverse of the usual situation. The relevance to
following the same extrapolation, would then pro- supercooling and glass formation is that these cases
duce a non-crystalline state with entropy substan- permit straightforward identification of a Kauz-
tially below that of the stable crystal phase, in mann TK(p) curve, at least one point of which lies
clear violation of the third law of thermodynamics on the equilibrium melting curve Tm(p). This
w7x. This conundrum has traditionally been called avoids the usually encountered uncertainty associ-
the ‘Kauzmann paradox’ w8x. An analogous enthal- ated with heat capacity extrapolation below a glass
py crossing would occur (at least for ‘fragile’ glass transition temperature, one consequence of which
formers w3,4x) at another temperature, TH (where has been argument in the literature w15–17x over
0-TH-TK), implying that the corresponding prob- whether or not a thermodynamic ‘ideal glass tran-
lematical non-crystalline state at Ts0 would also sition’ in principle should exist close to TK(p).
be substantially lower in enthalpy than the crystal. Section 2 identifies some known real-substance
The notion that a supercooled liquid might run examples of the inverse melting phenomenon.
out of available molecular configurations at, or Interestingly, this listing cites an example drawn
near, a Kauzmann temperature TK, should have from protein physical chemistry, another subject
implications beyond thermodynamics, and so has toward which Walter Kauzmann has contributed
long influenced the interpretation of flow and fundamental insights w18x. Section 3 analyzes ther-
relaxation behavior. As an example, this has tended modynamic relations for the two phases exhibiting
to provide legitimacy to the presence of a the inverse-melting property, and deduces families
divergence temperature T0)0 in the of curves in the T,p plane that describe constant
Vogel–Tammann–Fulcher (‘VTF’) expression for entropy differences (generalized Ehrenfest rela-
the temperature dependence of shear viscosity tions), as well as curves of constant enthalpy
w9–11x. It also underlies the conceptual basis of differences, between the two phases of interest.
the Adam–Gibbs theory of relaxation phenomena Section 4 is devoted to the specific case of the
w12x. lighter helium isotope 3He and its inverse melting
For obvious reasons, the majority of the exper- behavior. Final remarks have been collected into a
imental studies of supercooled liquids and glasses concluding Section 5, where we speculate on the
F.H. Stillinger, P.G. Debenedetti / Biophysical Chemistry 105 (2003) 211–220 213
The three points B, D and E are distinguished possesses a maximum of the type depicted in Fig.
by vanishing of the melting curve slope: 1 by point D and its neighborhood. The crystalline
phase in coexistence with the liquid has been
dpmŽT.ydTs0 ŽB,D,E. (2.3) reported to be tetragonal. This melting maximum
occurs at approximately 425 K and 6.5 kbar. The
These points thus are all associated with vanishing P4MP1 and helium isotope examples have been
entropy change: mentioned in a previous publication as relevant to
the Kauzmann paradox issue w8x.
SŽl.ySŽc.s0 ŽB,D,E. (2.4) Although smaller by many orders of magnitude
than macroscopic phases, individual protein mol-
because the difference in molar volumes can never ecules in solution possess, nevertheless, a large
be infinite. Consequently, these are ‘Kauzmann number of internal conformational degrees of free-
points’ occurring as natural loci in the equilibrium dom. The rather sharp transition between the struc-
phase diagram. Their existence does not hinge turally organized and biologically relevant native
upon the legitimacy of long heat capacity extrap- form, and the large group of biologically inactive
olations that are obliged to cross glass transitions. denatured forms, provides a strong analogy to the
Section 3 utilizes this identification to trace out conventional melting transition. It is therefore sat-
‘Kauzmann curves’ TK(p) as they pass through isfying to notice that at least one protein, ribonu-
these kinds of distinguished points. Notice also clease A, displays a ‘melting’ curve in the T,p
that B, D and E must lie on vanishing–enthalpy plane with a maximum of type D in Fig. 1. This
curves TH(p). This follows from the fact that at maximum is located approximately at 283 K and
any point along the melting curve, the chemical 4.0 kbar, with the native form lying below the
potentials of the coexisting phases are equal, and maximum, and the denatured form above the
hence the respective enthalpy and entropy differ- maximum w30x. Starting at a slightly lower tem-
ences satisfy DHsTDS. perature and pressure, an initially denatured mol-
With this schematic analysis as background, we ecule can be induced to renature at constant
can now classify examples of inverse melting that pressure by raising the temperature. By semantic
have been reported in the published literature. The analogy to the phrase ‘inverse melting’, this pro-
best-documented examples of inverse melting are cess might well be called ‘inverse denaturation’.
the two helium isotopes 3He w23x and 4He w24,25x Liquid crystals also supply a useful analogy to
at low temperature. Both isotopes display melting inverse melting. Basing his remarks on data report-
curves that qualitatively resemble the neighbor- ed by Cladis et al. w31x, Johari has pointed out
hood of point B in Fig. 1, but they differ signifi- that the first-order phase boundary between the
cantly from one another in quantitative detail. The smectic-A and nematic phases of 4-cyano-49-octyl-
3
He example has its zero-slope minimum at oxybiphenyl also exhibits a maximum in the T,p
approximately 0.315 K and 29.3 bar, with normal plane (type D in Fig. 1) w32x. This maximum
(i.e. non-superfluid) liquid in coexistence with occurs at approximately 350 K and 2100 bar. In
body-centered cubic crystal. By contrast, the 4He fact, the observed phase boundary is analogous to
minimum is very shallow, occurs at approximately a larger portion of the schematic curve in Fig. 1
0.8 K and 26.2 bar, and has superfluid liquid in that includes a point of equal molar volumes for
coexistence with hexagonal-close-packed crystal. the two coexisting phases (type C in Fig. 1).
The 3He case will be examined in numerical detail Starting at the appropriate nematic state (possess-
in Section 4. ing just molecular orientational order), isobaric
A very different inverse-melting material has heating can cause the material to reorder into the
recently come to attention. This is the polymeric smectic-A phase (possessing both orientational and
substance poly(4-methylpentene-1), denoted more partial translational order).
simply as ‘P4MP1’ w26–29x. Published reports The reader should be warned that the scientific
indicate that its melting curve in the T,p plane literature also uses the phrase ‘inverse melting’ in
F.H. Stillinger, P.G. Debenedetti / Biophysical Chemistry 105 (2003) 211–220 215
a circumstance that is not directly relevant to the the expansions for the separate phases will appear
present study. In particular, kinetically-controlled as follows:
irreversible transformations of supersaturated alloy
crystals to amorphous solids under heat treatment HŽv.ŽT, p. s HŽv.ŽX. q CpŽv.ŽX. dTqVŽv.ŽX.
have been described this way w33x.
w
x
y1 y TX aŽv.ŽX.z~dpq... |
(3.4)
3. Generalized Ehrenfest relations
Recalling that the zero-slope point X has the
In order to present a proper thermodynamic property that molar enthalpies are exactly equal
characterization of inverse melting phenomena, it there, we deduce a linear expression for the differ-
will be useful and convenient to use leading terms ence in molar enthalpies of the liquid and crystal
of Taylor expansions for properties of interest. For phases that is locally valid in the vicinity of point
the moment, let X represent any zero-slope point X:
of the melting curve (such as B, D and E in Fig.
1). We shall suppose that thermodynamic functions
are well defined for both phases in the vicinity of HŽl.ŽT, p.yHŽc.ŽT, p.(wyCpŽl.ŽX.yCpŽc.ŽX.z~dT
x |
y1 y TX aŽc.ŽX.~z ∂dp |
through zero, to negative as temperature increases. As in the case of constant enthalpy difference, this
By contrast, the slope of the melting curve as it expression represents a family of parallel curves,
passes through E changes from negative to zero to indexed now by s. On account of the differing
positive with increasing temperature. These fea- denominators in Eqs. (3.14) and (3.6), the curves
tures imply that: of fixed enthalpy difference and of fixed entropy
difference will generally display distinct slopes.
CpŽl.ŽD.yCpŽc.ŽD.)0 (3.9) The ss0 curve from the family wEq. (3.14)x
passes through point X, and corresponds to vanish-
ing entropy difference. For this special ‘Kauzmann
and that curve’ the differential form of Eq. (3.14) then may
be written:
CpŽl.ŽE.yCpŽc.ŽE.-0 (3.10)
B dp E CpŽl.yCpŽc.
C F s (3.15)
D dT GDSs0 TwyaŽl.VŽl.yaŽc.VŽc.z~
x |
Fig. 2. Experimentally determined melting curve for 3He, in the neighborhood of its pressure minimum. Adapted from Dobbs w23x.
We close this Section 3 with a relationship This indicates that points B and E, exhibiting
obeyed by the melting curve itself, as it passes upward curvature in Fig. 1, must have a common
through one of the zero-slope points. When carried sign for the heat capacity difference, and the
to second order in temperature and pressure chang- volume difference, between the phases. By con-
es, the Taylor expansion of chemical potential is: trast, point D must entail opposite signs for these
quantities.
mŽdT,dp.smŽX.ySŽX.dTqVŽX.dp Distinct positive or negative signs in principle
BC
ŽX. E can occur for the various combinations of ther-
yC FŽdT.2qVŽX.aŽX.dTdp
p
modynamic quantities that appear as factors in the
D 2TX G
basic enthalpy and entropy Eqs. (3.7) and (3.15).
BV
ŽX.kTŽX. E Those signs jointly determine the signs of the
yC FŽdp.2q... (3.16) slopes of the enthalpy and entropy Kauzmann
D 2 G
curves as they pass through the zero-slope points
Along the melting curve, the chemical potentials of the melting curve. The slopes of those curves
of the two phases must be equal. Furthermore, in in principle can be either positive or negative, and
the immediate vicinity of the zero-slope points need not be the same for the vanishing-enthalpy
such as B, D and E, the pressure dp along the and vanishing-entropy loci at any given zero-slope
melting curve is proportional to (dT)2. By utilizing point of the melting curve.
these properties in connection with the Taylor
4. Melting curve for 3He
expansion wEq. (3.16)x, one obtains the following
expression for the second temperature derivative We now examine in quantitative detail the
of the melting curve at zero-slope points: inverse melting phenomenon for 3He. As men-
tioned earlier, a melting-curve minimum of type B
d2pm CpŽl.yCpŽc. in Fig. 1 is involved. This example has had a
s (3.17)
dT2 TŽVŽl.yVŽc.. notable technical application, specifically in the
‘Pomeranchuk refrigerator’ that attains millikelvin
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