Lipophilicity property example

As In the case of the examples given in Tables I and III, the N-thiocarbamate derivatives were generally equal to the parent methylcarbamate in toxicity to house flies, particularly after taking into consideration Increase in molecular weights. Except for the methomyl and oxan l derivatives, substantial improvement in mosquito larvlcldal activity again appeare d to be a function of the lipophilic properties of the derivative. With the exception of the oxanyl derivatives, the data clearly indicate that the N-thiocarbamate derivatives are markedly less toxic to the white mouse than the parent methylcarbamate. Since... 

Analogous gel matrices of liquid crystalline lamellar phases can also be formed with non-ionic mesogens, for example, with the combination of cetyl/stearyl alcohol and ethoxylated fatty alcohol, provided the hydrophilic and lipophilic properties of the surfactant molecules are more or less balanced to favor the formation of lamellar structures. 

According to Eqnation 9.3, solubilization shonld increase with decreasing interfacial tension y between the micelles and water. It is known that interfacial tension decreases as a surfactant s hydrophilic and lipophilic properties become more nearly balanced, for example, as salinity or hardness of the aqneons phase increases in the case of ionic surfactants. Solubilization increases nnder these conditions as well, so that the predicted trend is in qualitative agreement with experimental data. 

Fig. 22.4 Molecular properties can be divided into experimental (subdivided into biological and physicochemical) and in silico (subdivided into structural and substructural) properties, physicochemical and biological properties. Examples of experimental data are IC50 (binding affinity), MIC (antibacterial minimum inhibition concentration), LD50 (lethal dose), Vd (volume of distribution), F% (bioavailability), pKg (ionization constant), log P (partition coefficient from shake flask determination), log kn,(lipophilicity from HPLC measurement), A (hydrogen bond capability), solubility. Examples of calculated properties, either for whole molecule or for substituents or buildings blocks, are MW (molecular weight), MR (molar refractivity), molecular volume, PSA (polar surface area), HA (number of H-bond acceptors), HD (number of H-bond donors), CLOGP (calculated log P values), L (substituent length), B5 (substituent width), cr (Hammett constant), F, R (field and resonance parameters), TT (Hansch constant), f (hydrophobic fragmental constant).

The principal components derived from the activities can be correlated to physicochemical properties using MLR. Thus it was found that component one appears to be dominated by electronic factors (equation 12), while in component two transport (lipophilicity) properties (equation 13) play a role. The following parameters are used Appm(NH2) is the NMR chemical shift of the amino protons relative to the unsubstituted congener, / is the fraction ionized at pH 7.4, and log k is the lipophilicity measured by HPLC. Equation (13) shows an example of a nonsignificant constant term, since the standard deviation is larger than the term itself. In such cases the equation should be forced through the origin. 

After intravenous dosing, the half-life of tylosin is short in all species, 1.1, 2.1, 3.0, and 4.0 h, respectively, in calves, sheep, goats, and pigs." ° Tylosin penetrates readily into milk and is slowly cleared from the mammary gland, so that its use in lactating cattle is not recommended. In fact, this property extends to other macrolides, due to their basic nature and lipophilic properties. For example, the half-life of tilmicosin in cows is approximately 1 h, but concentrations in milk exceed 0.8 mg/1 for 8-9 days after a single subcutaneous dose of 10 mg/kg. 

It is important to note that the structure and stability of a microemulsion system may be affected by the solubilized drug. The effect of the drug on the microemulsion stability and structure depends on the properties of the drug, notably its lipophilicity. For example. 

Intensive work has been carried out in order to estab lish a relationship between emulsion properties and the properties of surfactant systems. The classical HLB (hydrophile-lipophile balance) concept is widely used in emulsion science to describe the balance of the hydrophilic and lipophilic properties of a surfae tant at oil/water interfaees. The HLB value deter mines flie emulsion inversion point (EIP) at which an emulsion ehanges from W/O to 0/W type. This was of particular importance for nonionic surfactants that change their properties with ehanges in tempera ture (59). Various NMR techniques have provided significant contributions to this basic understanding of surfactant systems and some of those were reviewed in Ref. 7. The usefulness of NMR techni ques in studying surfactant solutions lies in the direct information they provide about the microstracture ofmicroheterogeneous systems (8,60— 64). It is beyond the scope of this chapter to summarize the use of NMR techniques in the study of surfactant systems, but we will present some representative examples related to emulsions. 

Methadone undergoes hepatic metabolism and renal excretion. Because of its ionized and lipophilic properties, changes in the pH of the urinary tract can 28 be an important determinant in the elimination of methadone. For example, at a urinary pH above 6,... 

Lipophilicity is undoubtedly the most important physicochemical property used in drug design and QSAR studies. > Besides numerous experimental parameters, calculated lipophilicity properties play an important role in QSAR and drug design, as illustrated by the large number of publications devoted to such applications. Because it is impossible here to provide an exhaustive overview of these applications, we focus our attention on a few examples, giving a flavor of what can be performed with computed lipophilicity properties. 

Several approaches to the evaluation of the hydrophilic-lipophilic properties of chemical compounds are known from the literature. For example, in order to evaluate the HLB of surfactants, Davies developed a system based on the analysis of group numbers. The "group number" characterizes the contribution of each specific functional group to the energy that would be required if a solvent molecule were changed from water to an organic solvent. 

Dmg distribution into tissue reservoirs depends on the physicochemical properties of the dmg. Tissue reservoirs include fat, bone, and the principal body organs. Access of dmgs to these reservoirs depends on partition coefficient, charge or degree of ionization at physiological pH, and extent of protein binding. Thus, lipophilic molecules accumulate in fat reservoirs and this accumulation can alter considerably both the duration and the concentration—response curves of dmg action. Some dmgs may accumulate selectively in defined tissues, for example, the tetracycline antibiotics in bone (see Antibiotics,tetracyclines). 

A chemical must have certain physicochemical properties to elicit an endocrine disrupting effect. For example, the ability to enter the body and to cross the cell membrane into the cellular medium requires a degree of lipophilicity. Fipophilic potentials may be compared by reference to the chemical s octanol-water coefficient (usually expressed as log K ). This property, together with molecular size and chemical structure, has an important influence on the bioacciimiilation... 

Lead tetramethyl and lead tetraethyl are covalent lipophilic liquids of low water solubility. Certain inorganic forms of lead, for example, lead tetrachloride, have similar properties, but other forms such as lead nitrate and lead dichloride are ionic and water soluble. Covalent and lipophilic forms of lead, like lipophilic forms of organomercury and organotin, can readily cross membranous barriers such as the... 

A close relationship exists between physicochemical properties of pigment molecules and their ability to be absorbed and thus to exhibit biological functions. Carotenoids are hydrophobic molecules that require a lipophilic environment. In vivo, they are found in precise locations and orientations within biological membranes. For example, the dihydroxycarotenoids such as lutein and zeaxanthin orient themselves perpendicularly to the membrane surface as molecular rivets in order to expose their hydroxyl groups to a more polar environment. 

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