Enthalpy change apolar

It is conceptually convenient to define the enthalpy changes with reference to the temperature at which the apolar contribution to the overall AH° is zero (Baldwin, 1986), so that the apolar enthalpy change AHap is simply... 

The tendency of apolar 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 water molecules from these apolar side-chain moieties. The effect is thermodynamically driven by the increased disorder (ie., AS > 0) of the system, thereby overcoming the unfavorable enthalpy change (ie., AH < 0) for water release from the apolar groups. 

Eaker and Porath studied the elution of amino acids on Sephadex 6-10 with particular focus on the eluant ionic strength and composition (e.g. acetic acid or pyridine content) (11). They described the gel as a "weak exchanger," thus accounting for effective separations of mixtures of up to seven amino acids. They noted that K ec increases with ionic strength, and attributed this effect to variations in the "effective size" of the ion, which includes the "electrical double layer and the hydration layer." In addition to discussing the effects of ionic sites on gel and solute, Eaker and Porath also discussed the "aromatic adsorption" of solutes with coplanar II electron systems, and the hydrophobic adsorption of partly apolar solutes (accompanied by a positive enthalpy change). They pointed out that such "short range" effects require "intimate contact" between solute and gel and are unlikely to occur in the presence of electrical repulsion. 

Now, if we assume that the active sites of these enzymes have a hydrophobic pocket at Sj as well as discrete subsites for substrate amino acids, we can explain these results by assigning different levels of importance to these different modes of interaction for the two enzymes. To account for the Pi specificity of FKBP, we not only assume a more prominent role for Pi-Si interactions but also that these interactions are characterized by dehydration of the Michaelis complex, E S, as it proceeds to the transition state, [E S]t. What we are suggesting here is that in E S, the Pi residue is not yet buried in Si and that the active site and the substrate are still at least partially solvated. As E S proceeds to [E S], the Pi residue becomes buried in the Si pocket and the residual water of solvation is expelled from the active site. This scenario can reasonably account for the large values of A/ft and ASt that we observe for reactions of FKBP, since the formation of hydrophobic contacts between apolar groups in aqueous solution is known to be accompanied by positive enthalpy and entropy changes (Nemethy, 1967). Likewise, to account for the lack of Pi specificity for CyP, we assume that subsite interactions play a more prominent role than do Pi—Si interactions. Thus, the Pi-Si hydrophobic interactions that dominate the thermodynamic parameters for FKBP have a smaller role for this enzyme. 

Dissolution of apolar compounds in water is accompanied by a strong positive change in the heat capacity of the system ACp > 0. It implies that H and TA S become more positive with increasing temperature (see Figure 4.6). As a result, Aj G is only slightly dependent on temperature. This is known as the enthalpy-entropy compensation. 

From a thermodynamic point of view, self-aggregation of amphiphilic molecules in apolar solvents involves a favorable enthalpic term due to intermolecular bonding counteracted by an unfavorable entropic term due to a partial loss of molecular translational and rotational degrees of freedom. Using vapor pressure osmometry, for example, it has been found that the enthalpies of formation of molecular aggregates of dodecylammonium propionate in benzene and cyclohexane are 83.4 kJ/mol and -57.4 kJ/mol, whereas the entropy changes for the same processes are -0.23 kJ/mol and -0.14 kJ/mol, respectively [2]. 

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