Polarity, octanol-water partition coefficient

Closely related to water solubility as a polarity measure is the partition coefficient of a substance between water and an immiscible organic solvent. Most commonly the organic solvent is selected to be n-octanol, and the symbol P is given to the octanol/water partition coefficient. Then log P is a quantitative measure of hydro-phobicity and, therefore, of nonpolarity. Table 8-3 gives log P values for many of... 

The toxicological or cumulative effect of illicit drugs on the ecosystems has not been studied yet. Moreover, their fate and transport in the environment is to a big extent still unknown. Due to their physical-chemical properties (octanol-water partition coefficient, solubility, etc.) some of them, such as cannabinoids, are likely to bioaccumulate in organisms or concentrate in sediments whereas the rest, much more polar compounds, will tend to stay in aqueous environmental matrices. However, continuous exposure of aquatic organisms to low aquatic concentrations of these substances, some of them still biologically active (e.g., cocaine (CO), morphine (MOR) and MDMA) may cause undesirable effects on the biota. 

An important factor in determining the course of uptake, transport, and distribution of xenobiotics is their polarity. Compounds of low polarity tend to be lipophilic and of low water solubility. Compounds of high polarity tend to be hydrophilic and of low fat solubility. The balance between the lipophilicity and hydrophilicity of any compound is indicated by its octanol-water partition coefficient (K J, a value determined when equilibrium is reached between the two adjoining phases ... 

Polar surface area (PSA) - defined simply as the part of a molecular surface that is polar - is probably, together with the octanol-water partition coefficient, one of the most important parameters used to characterize the transport properties of drugs. PSA has been shown to provide very good correlations with intestinal... 

The log octanol-water partition coefficient (log Pq/w) probably is the most frequently used physicochemical parameter in medicinal chemistry [101 104]. Octanol, with a polar head and a flexible, nonpolar tail, has hydrogen-bonding capabilities and amphilicity similar to... 

In this model, one can argue that a peptide must have both an affinity for the interface (favorable n-octanol partition coefficient) and small desolvation energy (favorable A log PC) in order to efficiently cross a cell membrane. On the other hand, this model also predicts that a peptide with a large n-octanol/water partition coefficient and large desolvation energy, due to a significant number of polar groups, should adsorb and remain at the membrane interface. Both of these predicted events have been observed in the laboratory. 

Seydel, J. K., H-bond contribution to octanol-water partition coefficients of polar compounds, Quant. Struct.-Act. Relat. 1995, 34, 433-436. 

Absorption, in general, is treated as a physicochemical transport process based on computations of logP (the octanol/water partition coefficient) and solubility governed by factors such as polar surface area on the molecule. It is conceivable that SNPs in drug transporter genes will affect the pharmacokinetic properties of compounds and, therefore, these may have to be taken into consideration in the design process. 

The relationship between the herbicidal activity of 1,2,5-oxadiazole iV-oxides and some physicochemical properties potentially related to this bioactivity, such as polarity, molecular volume, proton acceptor ability, lipophilicity, and reduction potential, were studied. The semi-empirical MO method AMI was used to calculate theoretical descriptors such as dipolar moment, molecular volume, Mulliken s charge, and the octanol/water partition coefficients (log Po/w) <2005MOL1197>. 

Helweg, C., Nielson, T., Hansen, RE. (1997) Determination of octanol-water partition coefficients of polar polycyclic aromatic (NPAC) by high performance liquid chromatography. Chemosphere 34, 1673-1684. 

Once estrogens and progestagens have reached the waterways, a series of processes, such as, photolysis, biodegradation, and sorption to bed-sediments, can contribute to their elimination from the environmental water. Given the relatively low polarity of these compounds, with octanol-water partition coefficients mostly between 103 and 105, sorption to bed-sediments appears to be a likely process. Kd values calculated for estriol, norethindrone, and progesterone in a Spanish river (479,128, and 204, respectively) as the ratio between the sediment concentration (ng kg-1) and the water concentration (ng L 1) indicate that, in fact, these compounds exhibit a general tendency to accumulate in sediments. 

As the logarithm of 1-octanol-water partition coefficient (log P) describes the hydrophobicity of molecules and the retention of solutes in RP-HPLC depends on the hydrophobicity, a strong correlation can be expected between the log V value and the retention of solutes in RP-HPLC. Besides log P, a considerable number of physicochemical parameters have been tested for their capacity to predict retention in RP-HPLC. Thus, Snyder s polarity index, fraction of positively and negatively charged surface area, molecular bulkiness, nonpolar surface area, electron donor and acceptor capacity, various ster-ical parameters, and the energy of highest occupied molecular orbit have all been included in QSRR calculations. 

A mass transfer coefficient determined from some subsurface soil column elution studies was inverse log-linearly related to the octanol-water partition coefficient (i.e., K0Vf) for closely related compounds, and polarity in the molecule caused an additional decline in the mass transfer coefficient. 

The measurement of the solubility of drugs in polar and non-polar media is very important in the pharmaceutical field. One method proposed to describe this solubility is the partition coefficient between octanol and water. The mathematical calculation of an octanol-water partition coefficient from values for functional groups was first proposed by Hansch et al. as Hansch s n constants,1 and was later developed by Rekker as hydrophobic fragmental constants (logP).2 This method was further improved by the use of molecular connectivities.17 The prediction of logP values can be performed by either a computer program or by manual calculation. For example, approximate partition coefficients (log P) have been calculated by Rekker s method ... 

GIT gastrointestinal tract PSA polar surface area log P octanol/water partition coefficient. 

ClogP, computed logP (octanol-water partition coefficient of neutral species) HBA, number of H-bond acceptors HBD, number of H-bond donors MW, molecular weight PSA, polar surface area RNG, number of rings RTB, number of rotatable bonds. 

Adsorption may occur in a combination of three possible mechanisms hydrophobic expulsion, electrostatic attraction, and complexation. Most nonpolar compounds, such as various organics, adsorb by this mechanism, and the degree of partitioning is correlated to the octanol/water partitioning coefficient, Kou, Polar substrates such as various metals sorb via electrostatic attraction and complexation. Table 13.1 shows the typical sorption mechanisms and typical examples. 

For neutral organic compounds, in soils having a low clay/organic carbon ratio, sorption coefficients tend to increase as the hydrophobicity of the compound increases. Aqueous solubility or octanol/ water partition coefficients often are used as indicators of a compound s hydrophobicity. An increase in polarity, number of functional groups, and ionic nature of the chemical will increase the number of potential sorption mechanisms for a given chemical (Garbarini and Lion, 1985). For ionizable compounds, pKa is of particular importance because it determines the dominant form of a chemical at the specific environmental pH. 

Most log P values are determined with 1-octanol as the nonpolar solvent. Sometimes octanol-water partition coefficients are denoted Pow to make the nonpolar solvent more explicitly clear. Octanol effectively imitates many lipid membranes, especially those in the small intestine, where most drugs are absorbed. Other solvents are better suited to model other tissues in the body. Chloroform is more polar than octanol and simulates partitioning in oral tissues. Olive oil is less polar than octanol and models the blood-brain barrier. 

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