RELATIONSHIP BETWEEN THE CALCULATED PHYSICOCHEMICAL PARAMETERS AND REVERSED PHASE THIN-LAYER CHROMATOGRAPHIC RETENTION BEHAVIOR OF CARBOXAMIDE FUNGICIDES AND RELATED COMPOUNDS

Abstract

The lipophilicity of 6 carboxamide fungicides and 11 phenylbenzamide derivatives were determined by reversed phase layer chromatography (RP-TLC) employing silica and alumina as stationary phases impregnated with paraffin oil. Mixtures of methanol-water, acetonitrile-water, tetrahydrofurane-water, and acetone-water were used as mobile phases. The R_M0 and b values related to the molecular lipophilicity and to the specific hydrophobic surface area (b) of the solutes were calculated separately for each RP-TLC system and for each analyte. The correlations between the physicochemical parameters measured were calculated by linear regression analysis. The impact of the site and character of the substituent on the retention of analytes was assessed by Free-Wilson analysis.

The measured lipophilicity parameters were compared with 24 molecular descriptors computed applying free engines of the web. Calculations proved that the character of the stationary phase and the type of organic modifier exerted a negligible effect on the measured lipophilicity parameters. In the majority of cases the R_M0 and b values and computed molecular descriptors were intercorrelated, but the fitness of the points to the linear regression equation was not strong enough to replace the measured values with the computed ones. This finding indicates the importance of using not only computed but also measured parameters for the future studies of both quantitative structure retention relationship (QSRR) and quantitative structure activity relationship (QSAR) calculations.

Keywords:

• carboxamide fungicides
• phenylbenzamide derivatives
• lipophilicity
• reversed phase thin-layer chromatography
• specific hydrophobic surface area

ACKNOWLEDGMENT

This study was supported by the Hungarian Scientific Research Found and the National Office for Research and Technology.

Notes

Matrix A and Matrix B=Pearson's correlation coefficients of R_M0 values and specific hydrophobic areas, respectively (r_0.01 = 0.57, r_0.05 = 0.43, n = 17).

ACO = aceton, MEOH = methanol, ACN = acetonitrile, THF = tetrahyrofuran.

Al = aluminiumoxide, Si = silicagel. The parcial regression coefficients were calculated by Stepwise regression analysis involving experimental compounds 1–12 (r_0.05 = 0.46, FG = 11).

^a The Pearson's correlation coefficients between “in silico” molecural descriptors and lipophylicity parameters R_M0 as well as specific hydrophopbic area (SHA) were calculated applying Excel2003 statistical functions (r_0.05 = 0.43; r_0.01 = 0.57).

^b The following free programs, sets, and web engines were used for calculation of “in silico” descriptors: A=ACD, M=Molinspiration, T=VCCLab, S=Syrres, AC=Actelion, O=Osiris, C=Chemaxon.