Optimum lipophilicity

Another extensively investigated field in QSAR are mutagenic agents [325 — 328, 757 — 760]. The QSAR equations of a series of l-(X-phenyl)-3,3-dialkyltriazenes show that mutagenic activity (and presumably carcinogenicity) can be minimized with relatively little loss in antitumor potency. While such hints are useful, they should not be overemphasized lipophilicity optima can be significantly different in isolated cells and in whole animals. 

However, the parabolic model is still valuable for structure-activity analyses. It is the simpler model, easier to calculate, and most often a sufficient approximation of the true structure-activity relationship. The calculation of bilinear equations is relatively time-consuming, as compared to the parabolic model strange results may be obtained in ill-conditioned data sets. On the other hand, in many cases the, bilinear model gives a better description of the data, especially if additional physicochemical parameters are included in the regression equation. The lipophilicity optimum of symmetrical curves is precisely described by both, the parabolic model (optimum log P = — b/2a) and the bilinear model (optimum log P = — log P). In the case of unsymmetrical curves the site of the lipophilicity optimum is described much better by the bilinear model (optimum log P = log a — log p — log (b — a) eq. 93) than by the parabolic model. 

Eq. 180 was derived for the antitumor activities of 9-anilinoacridines (43) [789]. The coefficients of the n terms indicate that activities fall off more rapidly for the hydrophilic analogs as the parent compound has a log P value of about 4.8, the lipophilicity optimum can be estimated to be close to log P = 0. 

In the 2,5-dimethoxy substituted series, when the 4-substituent is alkoxy, a methoxy group gives optimum activity. (Compare, for example, TMA-2 and MEM in Table 1.) The 4-ethoxy group does not lead to an increase in activity, despite increased lipophilicity. This is in sharp contrast to 3,4,5-substituted compounds (discussed below), where an analogous transformation leads to an activity increase of nearly an order of magnitude. 

Dyeing conditions are usually controlled to give a moderate initial rate of dyeing for optimum levelling, followed by a gradual lowering of pH by acid release to achieve as much exhaustion as possible at the end of the process. Selection of the preferred initial pH and rate of acidification is determined by the affinity of the dyes at neutral pH values. Neutraldyeing affinity is dependent on the structural features and hydrophilic-lipophilic balance of the dye molecule. 

In the process of realizing product quality factors by changing product formulation, the relevant performance indices have to be determined. The determination process in turn requires experience and technical expertise. For detergent products the performance indices need to be considered include (1) optimum hydrophilic-lipophilic balance, HLB0p (2) critical micelle concentration, CMC (3) soil solubilization capacity, S (4) Krafft point,... 

Optimum hydrophilic- lipophilic Weight percentage of hydrophilic group in surfactant molecule, Whvdro HLB = 5... 

The addition of an alcohol to the basic two-phase system increases the apparent extraction of base into the organic phase, but it is generally acknowledged that it is the alkoxide anion which is being transferred [e.g. 43-50]. Optimum conditions for this co-catalytic effect requires the formation of highly lipophilic and highly basic alkoxides anions, either in the aqueous phase or at the interface. 

In all of these data what requires explanation is the effectiveness of the dodecyl chain, the decreasing activity with increasing ethylene oxide chain length above EiQ-14 the increase in activity when we move from a very hydrophobic surfactant with short ethylene oxide chain to the optimum, and the decrease in activity with increasing lipophilicity of compounds with alkyl chain lengths greater than Cl2. 

This last case is a combination of the two previous ones, in which the pH has an opposite effect on two surfactants. As shown in Fig. 17 (upper part) and discussed in Sect. 5.2 an increase in pH increases the ionization of the fatty acid, i.e., the proportion of the ionized hydrophilic soap, and hence the hy-drophilicity of the acid-soap mixture in the water phase and consequently at the interface. At low pH, the acid, i.e., a lipophilic nonionic surfactant, prevails, whereas at high pH, it is the hydrophilic soap that dominates the formulation. The pH at which about half of the interfacial mixture is acid and half soap, i.e., the pH at which the interfacial mixture is at optimum formulation (and three-phase behavior is exhibited), is called pH in Fig. 17. 

Though there are no drugs yet on the market from this particular system, the pyridine-pyridinium redox CDS has been widely exploited experimentally to deliver hormones and drugs to the brain (Bodor and Farag, 1984 Shek ef al., 1987). By using a variety of groups, R, in 27 from, for example, methyl through to octyl, the lipophilicity can be adjusted to provide optimum properties for passive transport. 

The temperature (or salinity) at which optimal temperature (or optimal salinity), because at that temperature (or salinity) the oil—water interfacial tension is a minimum, which is optimum for oil recovery. For historical reasons, the optimal temperature is also known as the HLB (hydrophilic—lipophilic balance) temperature (42,43) or phase inversion temperature (PIT) (44). For most systems, all three tensions are very low for Tlc < T < Tuc, and the tensions of the middle-phase microemulsion with the other two phases can be in the range 10 5—10 7 N/m. These values are about three orders of magnitude smaller than the interfacial tensions produced by nonmicroemulsion surfactant solutions near the critical micelle concentration. Indeed, it is this huge reduction of interfacial tension which makes micellar-polymer EOR and its SEAR counterpart physically possible. 

The lipophilicity of the drug, as reflected by its w-octanol/buffer partition coefficient (PC), with the optimum PC being in the range 10-100. 

Abstract A novel colorimetric method, digital color analysis (DCA), was proposed using a digital color analyzer and was applied to various quantitative analyses using chromatic-ity coordinates and suitable sensors for visual colorimetry based on the characteristics of human visual perception by virtual simulations based on digital color information. On the basis of DCA, we developed a visual colorimetric sensor for Li+, NH4+ and protein determination by the mixing of two kinds of lipophilic dyes, whose optimum mixing ratio... 

The NH4+ sensing film optode was fabricated from TD19C6, KD-M13, K-TCPB, and NPOE under optimum conditions, which correspond to the NH4+ ionophore, the color-changeable dye of pfCa 7.9, the lipophilic anionic additive, and a membrane solvent, respectively, included in a PVC membrane [23,24], These chemical structures are shown in Fig. 13. KD-M13 becomes yellow in its protonated form and turns blue in the deprotonated form. When the quantity of the protonated form of the dye equals that of the deprotonated form, the mixture becomes green. 

The hydrophile-lipophile balance (HLB) system is the measure of the surfactant s polarity as well as other physical properties of surfactants and the emulsifying materials. The more lipophilic the surfactant is, the lower the HLB values will be. Table 4.5 empirically classifies and compares surfactants according to their optimum use. Table 4.6 shows the HLB values for a selected group of surfactants. The HLB value of the surfactant or surfactant mixture should be matched with that of the oil or the mixture of oils to ensure a stable emulsion. The required HLB values of a... 

According to Kaur and Smitha [36], the optimum lipophilicity for corneal absorption is found in drugs with an n-octanol-water partition coefficient between 10 and 100. For drugs with smaller partition coefficients (highly hydrophilic drugs), the lipophilic epithelium forms the rate-limiting barrier, whereas the hydrophilic stroma... 

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