The Determination Of The Lipophilic Parameters

Category: VI Ukrainian-Polish Symposium

THE DETERMINATION OF THE LIPOPHILIC PARAMETERS

OF THE CONGENERIC SERIES OF THE BENZTIAZOLES

BY CHROMATOGRAPHIC

AND SPECTROPHOTOMETRIC METHODS

A. Persona1, A. Niewiadomy2, Z. Fekner1, B. Senczyna2

1Faculty of Chemistry, Maria Curie-Sklodowska University,

Maria Curie-Sklodowska sq. 3, 20-031 Lublin, Poland

2Department of Chemistry, University of Agriculture,

Akademicka st. 15, 20-950 Lublin, Poland

The discovery of novel pesticide molecule is a long, expensive and tortuous process with no guarantee of success. Clearly, out of the almost infinite number of possible compound, only a finite number can be synthesized and tested. Of course, there is essential problem, which of those compounds should be chosen. The aim of QSAR is to find predictive relationship between quantitative descriptions of physical properties of compounds and biological system under consideration. Lipophilicity is an important factor affecting the distribution and fate of bioactive molecules. Increased lipophilicity has been shown to correlate with increased biological activity, poorer aqueous solubility, increased storage in tissues and more rapid metabolism and elimination. Benztiazoles are found to show strong biological activity as antimicrobal, antimycotic and tuberculostatic agents. In addition, they are relatively weakly toxic to higher organisms.

Figure1. The chemical structure of investigated benztiazoles. R1¸R6=-H, -F, -Cl, -Br, -I, -OH, -NO2, -CF3, -COOH, -CH3, etc.

The spectrophotometric investigations of the permeation process of the new congomeric group of the benztiazoles (Fig.1) were performed. The

UV/VIS spectra were obtained by use of UV530 JASCO spectrophotometer equipped with Peltier\’s thermostat and stirring speed control of the solution in cuvette. The time required to that the absorbance in investigated system decreases to the values of the half of the starting values, as the effect of passing the analyte to the octanol phase, was defined as the parameter t connecting the permeation rate of analyte from aqueous-methanol phase to octanol with lipophilicity of investigated compound. In order to convert the experimentally defined values of  on typical in QSAR accepted parameter logP (logarithm of distribution coefficient of determined substances in n-octanol-water system) the calibration equation was obtained on the basis of experimental  data for standards.

The HPLC analysis was performed on Knauer-WellChrom chromatograph with spectrophotometric detector (l=320nm) using C-18 column (Vertex 300×4mm, Eurosal-Bioselect 300A, 5mm, endcapped). The logPexp values obtained by spectrophotometric method were correlated with values of logkw and Fo for investigated benztiazoles.

The theoretical values of logP were calculated according to fragmentation methods introduced by Crippen [1], Viswanadhan [2] and Broto [3].

Spectrophotometrically obtained values of logP were compared with theoretical ones with success (the correlation was also good).

These facts suggest that spectrophotometrically determined parameter  may be regarded as alternative liphophilicity determinant of biological activity of substances.

References

1. Ghose A.K., Crippen G.M, J. Chem. Inf. Comput. Sci. 27(1987)21.

2. Viswanadhan V.N., Ghose A.K., Revankar G.R., Robins R.K., J. Chem. Inf. Comput. Sci. 29(1989)163.

3. Broto P., Moreau G., Vandycke C., Eur. J. Med. Chem. - Chim. Ther. 19(1984)71.



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