Substituents hydrophobic

The substituent hydrophobicity constant, based on partition coefficients analogs to Hammet constants ... 

Substituent electronic constants used to derive simple QSRR for real retention prediction potency have seldom succeeded. A wider application in that respect found the Hansch substituent hydrophobic constants, n 8], and Dross et al. [64] or Hansch and Leo [65] fragmental hydrophobic constants, /. The sums of these constants (plus corrections due to intramolecular interactions) account for the retention in reversed-phase liquid chromatographic systems [7,12). 

Fortunately, partition coefficients can be calculated by knowing the contribution that various substituents make to hydrophobicity. This contribution is known as the substituent hydrophobicity constant (it). 

The substituent hydrophobicity constant is a measure of how hydrophobic a substituent is, relative to hydrogen. The value can be obtained as follows. Partition coefficients are measured experimentally for a standard compound with and without a... 

QSAR equations relating biological activity to the partition coefficient P have already been described, but there is no reason why the substituent hydrophobicity constant tt cannot be used in place of P if only the substituents are being varied. 

The water solubility of quaternaries primarily depends on the nature of R substituents (hydrophobic chain lengths, polarity, etc.). Quaternaries carrying two or more long hydro-phobic chains have very poor water solubility. On the other hand, iST-alkyltrimethyl ammonium salts and short-chain dialkyl or alkyl/aryl (e.g., benzylalkyl) dimethyl ammonium salts often show much better solubility. 

Lipid type Substituents Hydrophobic (chain length) Hydrophilic (pK) Composite lipid... 

The hydrophobic constant r is a measure of the contribution of a substituent X to the lipophilidty of compound R-X compared with R-H. The constant representing the solvent/solvent system, analogously to Hammett s p constant for the reaction type, was arbitrarily set to 1 for octanol/water and thus does not appear in Eq. (7). The lipophilidty constant ti allows the estimation of log P values for congeneric series of compounds with various substituents (see Eq. (8)). 

Cosurfactant requirements can be minimized usiag a surfactant having a short-branched hydrophobe or a branched-alkyl substituent on an aromatic group (232,234) and a long ethoxy group chain (234). Blends of surfactants optimized for seawater or reservoir brine salinity include linear alkyl xylene sulfonate—alcohol ether sulfate mixtures (235). 

GeneraHy, hydrophobic substituents on the pyridine ring reduce water solubHity, polar ones capable of hydrogen bonding as acceptor or donor, iacrease it. 

Other solvents can be divided into several classes. In hydrogen bond-breaking solvents (dipolar aprotics), the simple amino, hydroxy and mercapto heterocycles all dissolve. In the hydrophobic solvents, hydrogen bonding substituents greatly decrease the solubility. Ethanol and other alcohols take up a position intermediate between water and the hydro-phobic solvents (63PMH 1)177). 

From the data reported in (63PMH(l)177) it was concluded that hydrophobic substituents reduce the solubility of pyrazole in water (at 20 °C pyrazole, 1 part in 2.5 3,5-dimethyl-pyrazole, 1 part in 52). Another determination gives the following values for the solubilities of pyrazole at 25 °C in water, benzene and cyclohexane (expressed as g/100 g of solvent) 130, 18 and 3 (66AHC(6)347). Indazole is soluble in hot water and most organic solvents, but less so in cold water. 

The binding site is located at the tip of the subunit within the jelly roll structure (Figure 5.23). The sialic acid moiety of the hemagglutinin inhibitors binds in the center of a broad pocket on the surface of the barrel (Figure 5.24). In addition to this groove there is a hydrophobic channel that can accomodate large hydrophobic substituents at the C2 position of sialic acid (Figures 5.22 and 5.24). 

Figure S.22 Chemical formula for sialic acid (a-5-n-acetylneuramlnlc acid) drawn In approximately the same orientation as the ball and stick models in Figure 5.24. Ri and Rz which are H atoms in sialic acid, denote substituents introduced to design tightly bound inhibitors. These are large and hydrophobic as shown in Figure 5.24.

Figure 5.24 Space-filling model (green) of the sialic acid binding domain of hemagglutinin with a bound inhibitor (red) Illustrating the different binding grooves. The sialic acid moiety of the Inhibitor binds in the central groove. A large hydrophobic substituent, Ri, at the Cz position of sialic acid binds in a hydrophobic channel that runs from the central groove to the bottom of the domain. (Adapted from S.J. Watowich et al.. Structure 2 719-731, 1994.)...

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