Hydrophobicity Estimation for Organic Compounds

Another interesting possibility of MLC techniques is their application to the quantitation of physico-chemical properties of biologically active compounds in QSAR (quantitative structure-activity relationships) studies, especially for the prediction of hydrophobicity.

Hydrophobicity is commonly understood as a measure of the relative tendency of a solute to prefer a nonaqueous rather than an aqueous environment. Biological activity of many compounds, bioaccumulation of organic pollutants, and soil sorption of contaminants have all been correlated to the lipophilic character of the molecules concerned.

The quantitation of hydrophobicity has both diagnostic and predictive value in various disciplines such as drug design, toxicology and environmental monitoring.

Traditionally, the logarithm of the octanol-water partition coefficient (log POW) of the nonionized form of a solute has been the most common parameter used to measure the hydrophobicity. The standard 'shake-flask' method for determining partition coefficients in liquid-liquid systems has several serious disadvantages. This fact, together with the use of a bulk solvent such as octanol as a model for complex systems such as biomembranes, has been occasionally criticized and has instigated the search for other indirect methods for evaluating hydrophobicity. Among these methods, chromatographic techniques such as reversed-phase TLC and HPLC can be highlighted. From 1977 several QSRR (quantitative structure-retention relationships) studies have appeared in the literature relating the biological activity of a solute and its retention in a chromatographic system. Good linear relationships between the logarithm of the retention factor (log k) for series of organic compounds determined by RPLC and their log POW have been obtained.

The linear relationships obtained between log k determined by chromatographic techniques and log POW are based on the relationship existing between the logarithms of the distribution coefficients of a solute in two different systems, provided the interactions that the solute experiences in these systems are similar and the relationship can be expressed by an equation of the Collander type (log P i — ai log P2 + a2, where P1 and P2 are the distribution coefficients of the solute in the two different phases and a1 and a2 are constants).

The good linear correlations obtained between log k and log POW in RP-HPLC suggest that the Collander relationship is satisfied, that is, that the interactions of a solute in an aqueous-stationary phase system are similar to the interactions that the solute experiences in an aqueous-octanol one.

As micelles are considered to be simple chemical models for biomembranes, MLC has been investigated as an interesting possibility for evaluating the hydrophobicity of organic compounds. w-Octanol is an isotropic solvent in which the molecular size and shape of the molecules are not important factors; however, micellar systems, like biomembranes, have amphiphilic properties and are anisotropic media so that the size and shape of molecules influence their penetration through them. The solubilization (or partitioning of solute into micelles) closely resembles that of lipid bilayers and both of these are different from the two-phase octanol-water system.

log PrJ

1.8

1.6 -

1.4 -

1.2 -

<3)

O

1.0 -

0.8 -

0.6 -

0.4 -

18

4 9

0 16

8 05 O

2 0

0

log Pow

log Pow

Figure 9 Variation of k(A) and log k(B) with log Pow for a group of 23 benzene derivatives and polycyclic aromatic hydrocarbons in a 0.05 mol L~1 CTAB/3% n-propanol mobile phase. Key: 1, benzene; 2, benzylic alcohol; 3, benzamide; 4, toluene; 5, ben-zonitrile; 6, nitrobenzene; 7, phenol; 8, 2-phenylethanol; 9, chloro-benzene; 10, phenylacetonitrile; 11, 3,5-dimethylphenol; 12, naphthalene; 13, 1-naphthol; 14, 2-naphthol; 15, 1-naph-thylamine; 16, pyrene; 17, phenanthrene; 18, 2,3-benzofluorene; 19, fluorene; 20, fluoranthene; 21, acenaphthylene; 22, ace-naphthene; and 23, anthracene. Column: Spherisorb C8 (15 cm x4.0 mm i.d.). (Reproduced with permission from Garcia MA and Marina ML (1994) Study of the k' or logk' - log POW correlation for a group of benzene derivatives and polycyclic aromatic hydrocarbons in micellar liquid chromatography with a C8 column. Journal ofChromatographyA 687: 233-239, copyright Elsevier Science Publishers B.V.)

Contradictory results have been obtained concerning which of the two parameters (k or log k) best correlates with log POW in MLC. Figure 9 shows the variation of k (Figure 9A) and log k (Figure 9B) with log POW for a micellar mobile phase, 0.05 mol L_1 CTAB modified by 3% n-propanol, for a group of 23 benzene derivatives and polycyclic aromatic hydrocarbons. This figure shows that a good linear correlation between log k and log POW can be obtained for solutes with a low hydrophobicity, while, when high log POW values are attained, there exists a log POW value from which no further change for log k with log POW is obtained. This is due to the change in the retention mechanism of compounds from a three-equilibria mechanism to a direct-transfer mechanism from the micellar mobile phase to the stationary phase with increasing log POW for solutes. In fact, for highly hydrophobic compounds, which can become insoluble in water, the predominant equilibrium is the distribution between the micellar and stationary phases. Since these two phases are chemically similar, the distribution coefficient is close to unity and may become independent of solute hydro-phobicity. In this way the variation of log k with log POW is represented by a curve.

Solar Panel Basics

Solar Panel Basics

Global warming is a huge problem which will significantly affect every country in the world. Many people all over the world are trying to do whatever they can to help combat the effects of global warming. One of the ways that people can fight global warming is to reduce their dependence on non-renewable energy sources like oil and petroleum based products.

Get My Free Ebook


Post a comment