Intramolecular hydrophobic bonding

Hansch C., Anderson, S. (1967) The effect of intramolecular hydrophobic bonding on partition coefficients. J. Org. Chem. 32, 2583-2586. 

Favored conformations of maltose arrived at by free-energy calculations were in good agreement with those for the solid state and in solution.17-18 From thermal-expansibility experiments, it has been suggested that, in aqueous solution, the maltose molecule folds, and undergoes extensive, intramolecular, hydrophobic bonding.19... 

Table II shows some literature examples of the breakdown in additivity which can occur in flexible molecules (Compounds 1-4) or in sterically crowded molecules such as the diphenylmethanes (Compounds 5 and 6). In the first four cases, a dipole is probably interacting with polarizable 7r-electrons of the aromatic ring. In Compound 5, the overall shape probably prevents water molecules from forming a solvate iceberg between the two rings—a situation which can be considered an intramolecular hydrophobic bond. In Compound 6 a combination of intramolecular hydrophobic effects and possibly interaction of the side chain dipole with one or both aromatic rings leads to a wide discrepancy between experimentally determined and calculated log F values.

FIGURE 3. Dependence of molecular size on pH due to carboxylate repulsion (upper) and intramolecular hydrophobic bonding (lower). 

Some of the interactions that determine the three-dimensional structure of a protein molecule support a compact conformation, whereas others tend to expand the molecule. In aqueous solution hydrophobic parts of the protein are buried as much as possible in the interior of the molecule but in the adsorbed state the hydrophobic residues may be exposed to the sorbent surface, still shielded from water. Therefore, an expanded structure will be promoted upon adsorption if the compact structure in solution is stabilized by intramolecular hydrophobic bonding. More precisely, whether or not adsorbing protein molecules change their structure depends on the contribution from intramolecular hydrophobic bonding, relative to those from other interactions, to the overall stabilization of the structure in solution. In reference ( ) such an analysis of the structure determining factors has been made for HPA and RNase. It leads to the conclusion that HPA, more than RNase, is able to adapt its structure at sorbent surfaces. 

Interaction between hydrophobic amino acid residues stabilizes secondary structures such as a-helices and p-sheets. A reduction of the intramolecular hydrophobic bonding would cause a decrease of such secondary structures, which has indeed been found for, e.g.,... 

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