Hydrophobic effect enthalpy changes

HYDROPHOBIC INTERACTIONS. These bonding interactions arise from the tendency of nonpolar side chains of amino acids (or lipids) to reside in the interior, nonaqueous environment of a protein (or membrane/ micelle/vesicle). This process is accompanied by the release of tightly bound water molecules from these apolar side-chain moieties. The hydrophobic effect is thermodynamically driven by the increased disorder i.e., A5 > 0) of the system, thereby overcoming the unfavorable enthalpy change i.e., AH < 0) for water release from the apolar groups. 

How then can we account for the high degree of internal order routinely found within globular proteins We believe that combinations of the wide variety of electrostatic interactions reviewed above determine the precise three-dimensional structure of the interior of a protein. We argue that the sum of these interactions produces, at least in part, the enthalpy change on protein folding that is independent of the hydrophobic effect. Crystal structures of small organic compounds provide a useful model of protein interiors, and we now discuss some recent theoretical studies of these systems. 

As mentioned earlier, proteins are subject to cold denaturation because they exhibit maximal stability at temperatures greater than 0°C. The basis of this effect is the reduction in the stabilizing influence of hydrophobic interactions as temperature is reduced. Recall that the burial of hydrophobic side-chains in the folded protein is favored by entropy considerations (AS is positive), but that the enthalpy change associated with these burials is unfavorable (AH, too, is positive). Thus, as temperature decreases, there is less energy available to remove water from around hydrophobic groups in contact with the solvent. Furthermore, as temperature is reduced, the term [— TAS] takes on a smaller absolute value. For these reasons, the contribution of the hydrophobic effect to the net free energy of stabilization of a protein is reduced at low temperatures, and cold-induced unfolding of proteins (cold denaturation) may occur. 

In 1987 [8] and again in 1993 [9], it was pointed out that the hydrophobic liquid model could not be entirely adapted to protein folding, since it completely fails to explain the effects of pressure. Kauzmann points out that volume and enthalpy changes are equally fundamental properties of the unfolding process, and no model can be considered acceptable unless it accounts for the entire thermodynamic behaviour In his Reminiscences from a Life in Protein Physical Chemistry [10], Kauzmann further states ... 

The folding process can occur when the combination of the entropy associated with the hydrophobic effect and the enthalpy change associated with hydrogen bonds and van der Waals interactions makes the overall free energy negative. 

Two main sources of entropy may have been suggested. The first is related to the so-called hydrophobic effect, which was initially established from a consideration of the free energy enthalpy and entropy of transfer of hydrocarbon from water to a liquid hydrocarbon. Some results are listed in Table 3.4 this table also includes the heat capacity change ACp on transfer from water to a hydrocarbon, as well as that is the heat capacity in the gas phase. It can be seen from the... 

The inclusion of a guest in a CD cavity consists basically of a substitution of the included water molecules by the less polar guest. The process is energetically favored by the interactions of the guest molecule with the solvated hydrophobic cavity of the host. In this process entropy and enthalpy changes have an important role [9]. In spite of the fact that the driving force of complexation is not yet completely understood, it seems that it is the result of various effects [9] ... 

The hydrophobic effect is relatively easy to understand, at least semi-quantitatively. It arises because water, at room temperature, makes sufficiently strong HBs among its molecules that are energetically favorable. So, water reorganizes itself around a non-polar solute to maintain its HB network and this costs entropy. This physical picture changes at higher temperature, as we discuss below. At room temperature (around 25°C), the enthalpy of solvation of a non-polar solute... 

The difficulty with the lattice models of hydrophobicity is that they do not do full justice to the HB network of water. However, a molecular-level theory is also rather difficult because the hydrophobic effect is a complex collective phenomenon involving many water molecules. The hydrophobic solute perturbs the HB network of water, resulting in a change of both entropy and enthalpy of the solute-solvent... 

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