Hydrophobic effect, thermodynamic

Errors of this magnitude make the useful prediction of free energies a difficult task, when differences of only one to three kcal/mol are involved. Nevertheless, within the error limits of the computed free energy differences, the trend is that relative to 8-methyl-N5-deazapterin or 8-methyl-pterin, the compounds methyl substituted in the 5, 6 or 7 positions are thermodynamically more stable when bound to DHFR largely by virtue of a hydrophobic effect, i.e. methyl substitution reduces the affinity of the ligand for the solvent more than it reduces affinity for the DHFR active-site. The stability of ligand binding to DHFR appears to be optimal with a 6-methyl substituent additional 5-methyl and/or 7-methyl substitution has little effect... 

Cantor and SchimmeP provide a lucid description of the thermodynamics of the hydrophobic effect, and they stress the importance of considering both the unitary and cratic contributions to the partial molal entropy of solute-solvent interactions. Briefly, the partial molal entropy (5a) is the sum of the unitary contribution (5a ) which takes into account the characteristics of solute A and its interactions with water) and the cratic term (-R In Ca, where R is the universal gas constant and ( a is the mole fraction of component A) which is a statistical term resulting from the mixing of component A with solvent molecules. The unitary change in entropy 5a ... 

In general, the standard enthalpy of micellization is large and negative, and an increase in temperature results in an increase in the c.m.c. the positive entropy of micellization relates to the increased mobility of hydrocarbon side chains deep within the micelle as well as the hydrophobic effect. Hoffmann and Ulbricht have provided a detailed account of the thermodynamics of micellization, and the interested reader will find that their tabulated thermodynamic values and treatment of models for micellar aggregation processes are especially worthwhile. 

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. 

Following this, the thermodynamic arguments needed for determining CMC are discussed (Section 8.5). Here, we describe two approaches, namely, the mass action model (based on treating micellization as a chemical reaction ) and the phase equilibrium model (which treats micellization as a phase separation phenomenon). The entropy change due to micellization and the concept of hydrophobic effect are also described, along with the definition of thermodynamic standard states. 

Rowe, E. S., F. Zhang, T. W. Leung, J. S. Parr, and P. T. Guy, Thermodynamics of membrane partitioning for a series of n-alcohols determined by titration calorimetry Role of hydrophobic effects , Biochemistry, 37,2430-2440 (1998). 

The strategy used in this review to dissect specific fundamental interactions is to isolate first the hydrophobic effects and subsequently other interactions. Within this context the hydrophobic effect is defined as that contribution to the overall thermodynamics of a process that is proportional to the amount of apolar surface that becomes exposed to the solvent (Hermann, 1972 Gill and Wadso, 1976 Livingstone etal, 1991). The apolar surface area exposed to solvent can be computed using various algorithms (Lee and Richards, 1971 Hermann, 1972 Shrake and Rupley, 1973 Connolly, 1983) that yield the accessible surface area (ASA) in units of square angstroms (A2). 

With the hydrophobic effect defined as the contribution to the thermodynamics that is proportional to the exposure of apolar surface area, it is then possible for a set of homologous compounds to separate the hydrophobic contribution from all other effects by plotting any thermodynamic function (for instance, AH0) versus the number of apolar hydrogens (or the apolar surface area) that become exposed to the solvent on transfer. To the extent that the other interactions make a constant contribution to the thermodynamics,... 

As discussed above, the thermodynamics of the hydrophobic effect are seen to be proportional to the apolar surface area exposed to the solvent. Based on the absence of a size dependence of AS0 on transfer... 

The tendency for hydrocarbon chains to become remote from the polar solvent, water, is known as the hydrophobic effect (Chap. 4). Hydrocarbons form no hydrogen bonds with water, and a hydrocarbon surrounded by water facilitates the formation of hydrogen bonds between the water molecules themselves. The bulk water is more structured than it is in the absence of the hydrocarbon i.e., it has lost entropy (Chap. 10) and is thus in a thermodynamically less favorable state. This state is obviated by the hydrocarbon being organized so that it is remote from water, thus rendering the water molecules near to it less ordered. Thus the hydrophobic effect is said to be entropically driven. 

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