Article pubs.acs.org/JPCB
Amino Acid Solvation in Aqueous Kosmotrope Solutions: Temperature Dependence of the L-Histidine−Glycerol Interaction Andrey V. Kustov,*,† Nataliya L. Smirnova,† Roland Neueder,‡ and Werner Kunz‡ †
Institute of Solution Chemistry of Russian Academy of Sciences, Ivanovo, Russian Federation Institute of Physical and Theoretical Chemistry, University of Regensburg, D-93040 Regensburg, Germany
‡
ABSTRACT: We have studied thermodynamics of interaction between the aromatic amino acid L-histidine and glycerol, which is one of the most important stabilizing agents for proteins in water. The pair and triplet interaction parameters have been extracted from enthalpy and solubility data using standard thermodynamic manipulations in a wide temperature range. Our results indicate for the first time that the L-histidine−glycerol pair and triplet interactions are characterized by rather small enthalpy and entropy changes, which do not depend on temperature in either cold or hot water. These temperature-independent enthalpies and entropies of interaction lead to zero heat capacity changes during the amino acid transfer from water to both dilute and rather concentrated aqueous glycerol solutions. We attribute this behavior to a delicate balance between contributions from hydrophobic and hydrophilic fragments in the solute molecules. This unique feature appears to be the major reason that thermodynamics of pair and triplet interactions are nearly identical at standard and physiological temperatures.
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INTRODUCTION The study of the interactions between simple biological solutes and nonelectrolytes in aqueous solutions appears to be of fundamental importance to understand the factors that determine the stability of biopolymers in living systems.1−4 The main goal of most of the thermodynamic studies over the several decades5−12 was to obtain the detailed experimental information on the energetics of the interaction between amino acids, amides or their derivatives with nonelectrolyte molecules. These interactions and the corresponding energies generally determine what is currently called the molecular recognition process. However, most of these efforts deal with the behavior of highly soluble amino acids or their derivatives in aqueous solutions at the standard temperature only. Therefore, it is not quite clear whether the results obtained at 298 K for a rather restricted set of solutes can reflect correctly the behavior of biosystems at 310 K. Recently13,14 we have shown that enthalpic and entropic parameters of pair interaction of urea with two aromatic amino acids, L-phenylalanine and L-histidine, in water reveal anomalous temperature changes. Both parameters pass through maxima in the temperature range of 300−308 K, indicating that the heat capacity of the solute-denaturant pair interaction changes in sign. This solute behavior is found to be closely related to properties of pure water because the extrema observed arise in the region, where the temperature dependence of the heat capacity of pure water passes through a minimum. It has been also emphasized that for slightly hydrophobic species enthalpic and entropic parameters of solute−solute pair interactions appear to be nearly identical at 298 and 310 K. However, for the interaction between more hydrophobic L-phenylalanine and L-alanine with dimethylformamide (DMF) they differ strongly. © 2012 American Chemical Society
In the present Article, we give a deeper insight into the temperature dependence of the amino acid−nonelectrolyte interaction in water in the case of L-histidine and glycerol solutions over the physiological temperature range. Glycerol is known to be one of the most important cryoprotectants for different organisms and reveals high activity to maintain the structure of biological macromolecules.1,2,15 It has been shown that both glycerol and sugars indirectly stabilize the native structure of globular protein due to preferential hydration of the protein domain even at high nonelectrolyte concentrations.1−3 This thermodynamically unfavorable protein−solvent interaction induces the minimization of the surface contact between protein and nonelectrolyte molecules, which stabilizes more folded conformations. Here our efforts are mainly directed toward obtaining thermodynamic information on the L-histidine interactions with one or two glycerol molecules in a dilute aqueous solution using a virial expansion technique to elucidate some of the features that contribute to the protein−nonelectrolyte interactions in water−glycerol mixtures.
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EXPERIMENTAL SECTION Distilled water was treated with basic potassium permanganate and then distilled twice in a quartz still to reach the electric conductivity of 1 × 10−5 S·m−1. Glycerol (Aldrich, > 99.5%) was stored with freshly dried 4 Å molecular sieves and then used without further purification. L-Histidine (free base, MP Biomedicals, >99%) and L-phenylalanine (Carl Roth, >99.5%) were dried in vacuum at 343 K for several days and used Received: December 16, 2011 Revised: January 15, 2012 Published: January 25, 2012 2325
dx.doi.org/10.1021/jp2121559 | J. Phys. Chem. B 2012, 116, 2325−2329
The Journal of Physical Chemistry B
Article
Table 1. Standard Enthalpies of Solution ΔH0 (sol) in kilojoules per mole for L-Histidine in Water−Glycerol Mixtures at 288.15−328.15 K ΔH0 (sol)
XGla 288.15 K
13.76
0.01011 0.02014 0.03675 0.04652 0.06805 0.08072 0.1003
13.76 ± 0.0516 13.97 14.12 14.31 14.38 14.47 14.49 14.49
0
318.15 K
0.00461 0.009900 0.01691 0.02363 0.03874 0.0497 0.08113 0.1014
308.15 K 14.15 14.22 ± 0.0616 14.32,12 13.966 14.34 14.52 14.75 14.76 14.81 14.82 14.84 14.84
0.00774 0.02059 0.04729 0.04921 0.07806 0.08801 0.1069 0.1201
0
0
16.60 16.59 ± 0.0717 16.71 16.85 17.01 17.14 17.23 17.26 17.28 17.29
0.00513 0.01269 0.02413 0.03664 0.05498 0.06649 0.08810 0.1179
14.90
0.01035 15.12 0.01887 15.24 0.02782 15.36 0.04368 15.48 0.05381 15.53 0.06605 15.59 0.08186 15.60 0.09318 15.60 298.15 (L-phenylalanine) 0 8.30 ± 0.03 8.23,13 8.287 0.01806 9.21 0.03306 9.79 0.04996 10.52 0.06123 10.95 0.07825 11.60 0.08914 11.90
328.15 K 15.79 15.76 ± 0.0416 15.90 16.00 16.12 16.21 16.37 16.44 16.52 16.52
ΔH0 (sol)
XGl
298.15 K
0
0
ΔH0 (sol)
XGl
a
From here on it denotes the glycerol mol fraction and errors represent the twice standard deviation. The coefficients of eq 2 for L-histidine are: A0 = 13.76(0.004), A1 = 21.95 (0.37), A2 = −219.4(9), A3 = 727.0(59), sf = 0.004 kJ/mol (288 K); A0 = 14.16(0.01), A1 = 22.14 (0.98), A2 = −249.4 (20), A3 = 937.3 (111), sf = 0.01 kJ/mol (298 K); A0 = 14.90(0.01), A1 = 22.01 (1), A2 = −236.4 (25), A3 = 864.3(178), sf = 0.01 kJ/mol (308 K); A0 = 15.80(0.003), A1 = 22.93 (0.36), A2 = −242.1 (9), A3 = 852.2(52), sf = 0.005 kJ/mol (318 K); and A0 = 16.60(0.004), A1 = 22.42 (0.34), A2 = −248.3 (8), A3 = 913.6(40), sf = 0.005 kJ/mol (328 K). Values in brackets represent the standard deviation.
solute molality of 0.007 to 0.02 mol/kg. On the basis of results of our previous studies (see refs 13, 14, and 16), the overall uncertainty of the ΔH0 (sol) values is estimated to be
