Hydrophobic effect substitution

The hydrophobicity index is also suitable for correlating the cM values of various substituted sodium alkane 1-sulfonates [68]. The perfluoroalkyl substituent, e.g., 8 17 has a pronounced hydrophobic effect (/ = 1.66 at 75°C, sodium salt), whereas the hydrophilic disulfonates have values distinctly below 1 (for a-disulfonates, / = 0.75 was derived [70]). Further, it was somewhat surprisingly shown that substituents like 1-hydroxymethyl, 3-hydroxyethoxy, or even the hydroxyethoxyethoxy groups have hydrophobic effects. 

Hydrolysis of diphenyl phosphorochloridate (DPPC) in 2.0 M aqueous sodium carbonate is also believed to be a two-phase process. DPPC is quite insoluble in water and forms an insoluble second phase at the concentration employed (i.e. 0.10 M). It seems highly significant that the hydrophobic silicon-substituted pyridine 1-oxides (4,6,7) are much more effective catalysts than hydrophilic 8 and 9. In fact, 4 is clearly the most effective catalyst we have examined for this reaction (ti/2 < 10 min). Since derivatives of phosphoric acids are known to undergo substitution reactions via nucleophilic addition-elimination sequences 1201 (Equation 5), we believe that the initial step in hydrolysis of DPPC occurs in the organic phase. Moreover, the... 

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... 

A classical Hansch approach and an artificial neural networks approach were applied to a training set of 32 substituted phenylpiperazines characterized by their affinity for the 5-HTiA-R and the generic arAR [91]. The study was aimed at evaluating the structural requirements for the 5-HTiA/ai selectivity. Each chemical structure was described by six physicochemical parameters and three indicator variables. As electronic descriptors, the field and resonance constants of Swain and Lupton were used. Furthermore, the vdW volumes were employed as steric parameters. The hydrophobic effects exerted by the ortho- and meta-substituents were measured by using the Hansch 7t-ortho and n-meta constants [91]. The resulting models provided a significant correlation of electronic, steric and hydro-phobic parameters with the biological affinities. Moreover, it was inferred that the... 

Hansch constant — A measure of the capability of a solute for hydrophobic (lipophilic) interaction (see - hydrophobic effect) based on the partition coefficient, P, for distribution of the solute between octan-l-ol and water. The most general way of applying P in correlation analysis, etc. is as logP, but the behavior of substituted benzene derivatives maybe quantified by a substituent constant scale, n, which is defined in a way analogous to the Hammett a scale. There are various n scales, depending on the substrate series used as reference. See also - hy-drophilicity. 

Pakula, A. A., and Sauer, R. T. Reverse hydrophobic effects relieved by amino-acid substitutions at a protein surface. Nature (London) 344, 363-364 (1990). Baker, E. N., and Hubbard, R. E. Hydrogen bonding in globular proteins. Prog. Biophys. Molec. Biol. 44, 97-179 (1984). 

The oxidation of aromatic hydrocarbons to oxygen-containing derivatives is of the same theoretical and practical interest as the oxidation of saturated hydrocarbons. The application of transition-metal compounds in combination with PT catalysts leads to rather interesting results. The hydroxylation of benzene with aqueous H2O2 is catalyzed by an Fe /catechol pair [106]. Hydrophobic 4-substituted catechols are the most effective. Using this method, one can obtain phenol under mild conditions. No reaction occurs in the absence of the one of the catalysts. 

Polymerization of phthalocyanines in water occurs for derivatives substituted with oligo (ethylene oxide) side-chains (27c).167 168 In the lyotropic mesophases in water supramolecular polymers are present, and a comparative aggregation study between tetraphen-ylporphyrins and phthalocyanines proved the polymerization of the phthalocyanines to be stronger.168 The strong arene—arene interactions and the flatness of the aromatic core in the phthalocyanines causes them to aggregate more strongly, also mediated by the additional hydrophobic effect. 

Since the adenine moiety is bound with its NH2 group pointing out from the protein and with N-1 pointing into the hydrophobic pocket, substitutions at these two nitrogens have different effects (21S). The N -hydroxyethyl-substituted analog is almost as active as NAD whereas the corresponding N-1 substituted analog possesses lower enzymic activity. 

The next selection criterion concerns the polarity of the selected cavity. In the most favorable case, it should contain hydrophobic residues to favor the design of lipophilic inhibitors. The addition of hydrophobic substitutions (taking care to ensure their solubility) is an effective way of improving the potency of an inhibitor thanks to the hydrophobic effect. It has been shown that electrostatic interactions are important for the rate of association, but not for the stability of protein complexes [20], Furthermore, electrostatic interactions are weakened by the high dielectric constant of water. It might therefore be more difficult to identify inhibitors that bind tightly to the target cavity when it is essentially polar. 

Presence of hydrophobic (lipophilic) substitution on the A-ring Regional isomerism in ring A appeared to have only a slight effect on... 

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