Estimation of lipophilicity parameters of 3,5-di-tert-butylpyrocatechol by reverse phase HPLC
Abstract
Lipophilicity is one of the important parameters influencing the biological activity of compounds. In practice, this parameter is estimated using the distribution coefficient (logP) of the compound between the non-polar phase (n-octanol) and water. The main method of experimental determination of logP is the shaking flask method. However, in the case of the poor solubility of the studied compounds in water, the determination of logP using direct method is complicated, due to the difficulty of accurate determination of too low concentrations. In this case, indirect methods, including liquid chromatography, are successfully used for the estimation of logP. The lipophilicity of 12 new derivatives of 3,5-di-tert-butylpyrocatechol was determined using reverse-phase high-performance liquid chromatography. A methanol-water mixture was used as the mobile phase, and Separon Si C18 was used as the adsorbent. It is known that pyrocatechol derivatives have a wide range of biological activity; recently a large number of studies have been devoted to the investigation of their antioxidant properties. For each derivative of 3,5-di-tert-butylpyrocatechol (1-12) a linear relationship between the retention factor lg k and volume fraction of organic modifier φ in the mobile phase was established. By extrapolation of the retention to φ=0 using linear dependences, the lg k0 values were estimated and logP parameters were calculated. It was found that most of the studied derivatives of 3,5-di-tert-butylpyrocatechols have an octanol/water distribution coefficient log P in the range from 6 to 8. For compounds 1, 3, and 4 logP values turned out to be close to 4, which allows them to be considered as being promising for further study of antioxidant activity. Additionally, lipophilicity parameters log P of derivatives of 3,5-di-tert-butylpyrocatechol (1-12) were evaluated using the Kowwin and Molinspiration calculation methods. Comparison of experimental and calculated logP values showed good convergence of the results, while for most compounds the closest experimental and calculated values were shown by the Molinspiration method (the deviation did not exceed 10%).
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References
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