Hydrophobic effects parameters

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... 

From the models, when X2, and X4 decrease, the dissolution parameters increase. This can be explained by the hydrophobic effect of the ethylcellulose (X4). Furthermore, an increased effective drug surface area occurs when the particle size range and the UPF at the final compression are at minimal levels and an increase in dissolution rate occurs. The area under the dissolution curve is far above the optimum value (713% h). Another experimental design must be explored. 

In a parallel development, structural effects on the chemical reactivity and physical properties of organic compounds were modelled quantitatively by the Hammett equation 8). The topic is well reviewed by Shorter 9>. Hansen 10) attempted to apply the Hammett equation to biological activities, while Zahradnik U) suggested an analogous equation applicable to biological activities. The major step forward is due to the work of Hansch and Fujita12), who showed that a correlation equation which accounted for both electrical and hydrophobic effects could successfully model bioactivities. In later work, steric parameters were included 13). 

In Eq. 27, is the equilibrium constant (M-1). The four N-substituents are classified as E (R ) E (R2) E,(R3) E (R4). Hydrophobic substituent parameter, n, is evaluated by taking the H substituent as the reference, and summed for component four substituents. Since the steric effect of bulkiest R4 substituents is not significant, the ion-pairing is perhaps achieved in such a manner that the counter anion must approach from the least hindered side of the ammonium ions (11). 

Leo et al. indicated that the van der Waals volume is linearly related to hydro-phobicity for non-polar compounds expressed in terms of log P (octanol/water)66). Moriguchi et al. showed that the log P value is generally factored into two components attributable to hydrophilic effect of polar group and hydrophobic effect due to the net molar volume 67). Thus, the van der Waals volume could be a parameter related to solute-solvent interactions and partition coefficient. 

Pussemier et al. (1989) found that log Koc for 12 aryl N-methylcarbamates correlated significantly to a linear combination of two parameters, % hydrophobic effect (calculated from RP-HPLC measurements) and 8 Hildebrand solubility parameter. The authors also used data for 16 phenylureas and 13 anilides from Briggs (1981) and obtained similar results. 

Isothermal titration calorimetry (ITC) dilution experiments were used to measure association constants and thermodynamic parameters for the formation of dimers 15-15 (cf. Section 14.09.3.1) <20010L3221>. Aggregates 15-15 are highly associated at 298K and entropically driven. The change in heat capacity (ACp) for the formation of dimer 15-15 was determined by ITC measurements from 288 to 328 K yielding the negative value (ACp = — 185 6 cal mol-1 K 1). It was concluded that the dimerization process is driven by hydrophobic effect. 

It is assumed that the molecular properties responsible for biological activity can be separated into hydrophobic, electronic and steric effects, all of which are independent. It is further assumed that the hydrophobic effects are fully described by the parameter ir (23, 24, 25), the electronic effects by a (1, 4, 26), and the steric effects by Eg (10, 27). The relationship between biological activity and the parameters is expressed by equation 57 (28). 

Other associations have been investigated by the same methods. Lectin UE-I from Ulex europaeus (Section 15.4.3) and PT-II from Psophocarpus tetragonolobus both bind the H-type trisaccharide glycoside a-L-Fuc-(l—>2)-j3-D-Gal-(1—>4)-)3- D-GlcNAc-(l-OMe). With the Ulex lectin, the thermodynamic parameters are A/r "-29, TAS -20.5 kcal mol" . Again a decrease in entropy is observed. However, with the Psophocarpus lectin, the figures are ATT "- 5.4, TA5° -I- 0.8 kcal mol" . In the latter case, the small increase in entropy seems to indicate an important hydrophobic effect. 

Because the main driving force for surfactant self-association in polymer-surfactant mixed systems is the hydrophobic effect, the binding of surfactants to polyelectrolytes exhibits a similar dependence on the length of the alkyl chain as known for free micellization. Surfactants with longer hydrocarbon chains bind more strongly to polyions than those with shorter chains, and the binding starts a lower surfactant concentrations. In this context, a convenient parameter to characterize polyelectrolyte-surfactant systems is the critical aggregation concentration, cac, which is a counterpart of the well-known critical micellization concentration, cmc, but applies to solutions of surfactants in the presence of a polymer. It is defined as the... 

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