Peptide model systems: Correlation between thermophilicity and hydrophilicity

Abstract

In recent years, the response of biomolecules to a temperature gradient has been utilized to monitor reactions of biomolecules, but the underlying mechanism is not well understood due to the complexity of the multicomponent system. To identify some underlying principles, we investigate the thermal diffusion of small amide molecules in water systematically. We re-analyze previous measurements of urea and formamide and compare the results with acetamide, N-methylformamide, and N,N-dimethylformamide, amides with a lower hydrophilicity. It turns out that less hydrophilic substances do not show the typical temperature dependence of water soluble macromolecules. Analyzing temperature and concentration dependent measurements using an empirical expression originally derived for nonpolar mixtures, we find that the so-called isotope contribution depends strongly on the hydrophilicity of the solute. This can be qualitatively understood by comparing with molecular dynamic simulations of Lennard-Jones fluids. The hydrophobic/hydrophilic balance also influences the structure in the fluid and with that the thermal expansion coefficient, which correlates with the thermal diffusion coefficient. Furthermore, we observe a clear correlation of the temperature and concentration dependence of the Soret coefficient with the hydrophilicity, which can be quantitatively described by the partition coefficient log P.

Thermophoresis: The Case of Streptavidin and Biotin

“…of biotin and compared it with the other investigated systems [1,9]. Note that, at pH 7.4, biotin is negatively charged leading to log P = 3.4 [41].…”

“…This equation describes many diluted solutions of water soluble solutes well: the Soret coefficient is low, often even negative at low temperatures, then rises, approaching a constant value at high temperatures. On the other hand, for less hydrophilic solutes and for solutions with high concentrations, a decrease of S T with temperature has been observed [3,9,12]. This has been connected to reduced interactions between solute and solvent, through reduced attraction between the components.…”

“…Another important factor is the interaction of a molecule or a colloid with the surrounding solvent. This contribution has significant influence on thermodiffusion in polar solvents and is expected to be relevant for biomolecules in aqueous solutions, where interactions are dominated by hydrogen bonds [7][8][9]. It has been observed that thermodiffusion of biomolecules changes strongly when conformational changes occur, for example due to a ligand binding to a protein [10] or due to protein unfolding [11].…”

“…It has been observed that thermodiffusion of biomolecules changes strongly when conformational changes occur, for example due to a ligand binding to a protein [10] or due to protein unfolding [11]. This is often explained with structural changes in the hydration shell [3,9,12]. Microscale thermophoresis (MST) exploits this sensitivity of thermophoresis to conformational changes to measure equilibrium binding constants [4].…”

“…It turns out that the hydrophilicity of the solute (or hydrophobicity, if the affinity is small) plays an important role in the thermophoresis of aqueous systems. One of the most frequently used parameters to describe hydrophilicity is the 1-octanol partition coefficient P. It was found that temperature dependence of S T correlates with the log P of the solute [9,12]. For lower log P-values, a stronger change of the Soret coefficient with temperature is observed.…”