Gyöngyi Vastag

Effect of the physicochemical properties of N,N -disubstituted-2-phenylacetamide derivatives on their retention behavior in RP-TLC

The chromatographic behavior of some N,N-disubstituted-2-phenyl-acetamide derivatives has been studied on the chemically bonded stationary phase RP-Clg with acetone, acetonitrile, tetrahydrofuran, dioxane, methanol, ethanol, 1-propanol, and 2-propanol as organic modifiers of aqueous mobile phases. The retention observed with different mobile-phase modifiers was correlated. The effects of different physicochemical properties of the compounds on retention behavior when chromatographed with aqueous mobile phases containing protic and aprotic modifiers were also studied. Multiple linear regression analysis was used to correlate chromatographic retention constants of the compounds with physicochemical properties. The chromatographic lipophilicity RM0 (determined by linear extrapolation) was correlated with log P values calculated by use of different theoretical methods. Good relationships were obtained for all the systems investigated. Good correlation was obtained between lipophilicity measured chromatographically and biological activity predictors.

Multivariate analysis of chromatographic retention data and lipophilicity of phenylacetamide derivatives.

One of the most important physicochemical parameters of a molecule that determines its bioactivity is its lipophilicity. Cluster analysis (CA), principal component analysis (PCA), and sum of ranking differences (SRD) were used to compare the lipophilic parameters of twenty phenylacetamide derivatives, obtained experimentally as chromatographic retention data in the presence of different solvents and calculated by different mathematical methods. All the applied methods of multivariate analysis gave approximately similar grouping of the studied lipophilic parameters. In the attempt to group the investigated compounds in respect of their lipophilicity, the obtained results appeared to be dependent on the applied chemometric method. The CA and PCA, grouped the compounds on the basis of the nature of the substituents R1 and R2, indicating that they determine to a great extent the lipophilicity of the investigated molecules. Unlike them, the SRD method could not be used to group the studied compounds on the basis of their lipophilic character.

Establishing Dependences between Different Lipophilic Parameters of New Potentially Biologically Active N-Substituted-2-Phenylacetamide Derivatives by Applying Multivariate Methods

Lipophilicity, a very important parameter in the potential biological activities of molecules, was investigated for newly synthesized N-substituted-2-phenylacetamide derivatives. The determination was carried out in two ways: first experimentally, by applying thin-layer chromatography (TLC) on reversed-phase TLC (RPTLC) RP18F254s in the presence of one protic (methanol) and one aprotic solvent (acetonitrile) and then mathematically, by using different software packages. The intercept of the linear dependence between volume fractions of the organic solvent and the retention parameters obtained by TLC is known as the retention chromatographic constant, R(M)(0), while the slope represents the m value. In order to establish the dependences between the partition coefficient, log P as the standard measure of lipophilicity and the alternative lipophilic parameters obtained experimentally by TLC, R(M)(0) and m values, linear regression analysis and multivariate methods, cluster analysis (CA) and principal component analysis (PCA), were used. All applied methods gave approximately similar results. Although there is a linear dependence between the two chromatographic parameters, the retention constant, R(M)(0), and the m values, only R(M)(0) shows suitable similarity with the standard measure of lipophilicity of the investigated N-substituted-2-phenylacetamide derivatives at the given conditions. The existence of this resemblance proves that the chromatographic retention constant, R(M)(0), obtained by RPTLC could be successfully used for the description of lipophilicity of investigated compounds. On the other hand, the results confirmed that the applied linear regression analysis and the multivariate analysis (CA and PCA) have the ability to compare lipophilic parameters of the investigated phenylacetamide derivatives obtained in different ways.

APPLICATION OF CHEMOMETRIC METHODS IN EXAMINING OF THE RETENTION BEHAVIOR AND LIPOPHILICITY OF NEWLY SYNTHESIZED CYANOACETAMIDE DERIVATIVES

Lipophilicity, as an important molecules property, was analyzed on a series of newly synthesized N-(4-phenylmonosubstituted) cyanoacetamides, by applying the reversed phase thin-layer chromatography (RP-TLC), RP TLC18, in the presence of different organic modifiers in various concentrations (ethanol, n-propanol, acetone and tetrahydrofuran) and by mathematical method, using different software packages. The effect of the chemical structure as well as influence of the applied organic solvents on retention behavior of investigated derivatives was studied. Using different chemometric methods as linear regression analysis, principal component analysis and sum of ranking differences, experimentally determined lipophilicity of investigated compounds (chromatographic retention constant ) was correlated with partition coefficients, log P, as a standard measure of lipophilicity, calculated by applying different computational techniques. The obtained results indicate that all used methods gave approximately similar grouping of the studied lipophilic parameters and demonstrated that the chromatographic retention data are in a good agreement with standard measure of lipophilicity. This fact confirm that chromatographic retention parameter of the investigated N-(4-phenylmonosubstituted) cyanoacetamides obtained by RP-TLC could be used for the description of their lipophilicity.

Chemometric approach in studying of the retention behavior and lipophilicity of potentially biologically active N-substituted-2-phenylacetamide derivatives

The potential biological activity of a molecule largely depends on its lipophilicity. The lipophilicity of derivatives of N-substituted-2-phenylacetamide was investigated experimentally, by applying thin-layer chromatography on reversed phase (RP-TLC on RP 18 F254s) in the presence of ethanol and dioxane and by using relevant software packages. In order to establish dependence between lipophilicity obtained in different ways, linear regression analysis and multivariate methods were used. Approximately similar groupings of lipophilic parameters and tested compounds were registered in case of both chemometric methods. The obtained results confirm the fact that the applied linear regression analysis and multivariate analysis provide opportunities for comparing chromatographic retention data and lipophilic parameters of the investigated phenylacetamide derivatives. Results suggest that the lipophilicity of investigated molecules largely depends on the nature of the substituents linked to nitrogen atom and on the other hand that the chromatographic retention constants, RM0, determined by RP-TLC method, are similar to the standard measure of lipophilicity, log P, which makes this method appropriate for predicting lipophilicity.

Structure‐interaction relationship study of N‐(4‐phenylsubstituted) cyanoacetamides by multivariate methods

Derivatives of amides belong to a very attractive group of compounds due to a broad spectrum of different biological activities. The type of molecule activity significantly depends on its interactions with the environment, which on the other hand largely depends on the nature of the substituent attached to the basic molecule as well as of solvents properties. In this work, the influence of the mentioned parameters on the interaction ability of the group of N‐(4‐phenylsubstituted) cyanoacetamides is investigated by using multivariate methods, based on the results obtained by reverse‐phase thin‐layer chromatography and ultraviolet absorption spectroscopy. Results obtained by the used chemometrics methods are very similar, within which the principal component analysis has provided the most detailed information. The obtained results suggest that the interactions of the investigated compounds are dominantly regulated by the polarity of the used solvents and their proton donor ability inside the chromatographic measurements, while in the case of the spectrophotometric data, the solvents hydrogen bond ability has the greatest impact on the future interaction capability of the investigated cyanoacetamides. In the case of the substituent effect which is attached to the benzene ring, the greatest impact on the future interaction ability of the investigated cyanoacetamides is the orientation effect of ring substituent. Based on all the obtained results, it can be noticed that the used multivariate methods are able to detect effects of the substituent and solvent properties on the future interaction ability of the investigated derivatives. Copyright

Chromatographic and Computational Assessment of Potential Biological Activity of N-(Substituted Phenyl)- 2-Chloroacetamides Applying Multivariate Methods

The lipophilicity of the newly synthesized N-(substituted phenyl)-2-chloroacetamides, as the most commonly used molecular descriptor of a potential biological activity was the subject of research. The lipophilicity of the tested derivatives was determined by applying the reversed-phase thin-layer chromatography (RPTLC18F254s) in mixtures of water and one protic (n-propanol) and one aprotic (acetonitrile) solvent, as well as mathematically. The effects of the substituent on the lipophilicity of chloroacetamides were discussed. The obtained chromatographic retention constant, , of examined chloroacetamides was correlated with the standard measure of lipophilicity, log P, and with pharmacokinetic predictors such as human effective permeability in jejunum, Peff, plasma protein binding, PPB, and distribution through blood-brain barrier, log BBB, using linear regression analysis and two multivariate methods, cluster analysis and principal component analysis. All the applied methods gave very similar results, and all the procedures also confirmed the fact that determined by RPTLC could be used as a descriptor to estimate the potential biological activity of N-(substituted phenyl)-2-chloroacetamides.

Multivariate assessment of azo dyes' biological activity parameters

Lipophilicity as key molecular descriptor of potential biological activity for selected derivatives of azo dyes was determined mathematically, by using relevant software packages and by reversed-phase thin-layer chromatography (RPTLC) on C18 and cyano modified carriers in mixtures of water/n-propanol and water/acetone. The obtained chromatographic parameters, RM0 and m, of the examined azo dyes were correlated with the standard measure of lipophilicity, log P, important pharmacokinetic predictors and selected toxicity parameters applying linear regression analysis. Thereby, good correlations for each applied system were obtained (average correlation coefficient, r, 0.944, 0.885 and 0.919). Also, the correlations between the studied parameters of azo dyes were examined applying two multivariate methods (Cluster Analysis and Principal Component Analysis). It was shown that the polarity of the substituent, and to a lesser extent its electronic effects has the greatest influence on the studied parameters of the azo dyes derivatives. Multivariate methods pointed out the similarity of the chromatographic retention constant, RM0, with the parameters of lipophilicity, unlike the chromatographic parameter m, which exhibits better agreement with the toxicity parameters.

Quantitative structure—retention relationships modeling and multivariate data analysis of lipophilicity data of new spirohydantoin derivatives

Modeling properties of newly synthesized compounds is important for both understanding their activity and predicting their interactions. This paper describes the evaluation of the lipophilicity of the newly synthesized cycloalkylspiro-5-hydantoins by experimental and calculation methods. The chromatographic lipophilicity (RM0) of the analyzed compounds was determined by reversed-phase liquid chromatographic system consisting of RP-18 stationary phase and methanol—water mobile phase. Correlation coefficients between RM0 values and the predicted log P were above 0.93, indicating a strong linear relationship between the variables. Multivariate data analysis applied in this study enabled the comparison of the lipophilicity and the structure of the investigated compounds using solely information obtained from thin-layer chromatography. Hierarchical clustering analysis (HCA) reveals a high similarity between RM0 and miLogP whereas squared log Ps such as ALOGP2 and MLOGP2 were distinct from RM0. HCA classifies the investigated compounds into three clusters according to lipophilicity. Principal component analysis (PCA) yields two principal components which explained >99.19% total variance. The changes in the lipophilicity of the substituents attached in the molecule are reflected in the value of PCs. An increase in the lipophilicity of spiro substituent results in a decrease of values of both PC1 and PC2. The increase in the lipophilicity of R substituent decreases the value of PC1 and increases the value of PC2. The positive value of PC1 is typical for the compounds with the electron withdrawing groups such as CN, NO2, or OCH3.

QSRR approach in examining selected azo dyes

ABSTRACT Azo dyes as the most numerous and widely applied class of synthetic dyes in various industries at the same time represent the great polluter of the aquatic systems and environment. Most of them are hydrophobic and resistant to degradation, but also they express diverse biological activity. The preliminary examinations of the bioactivity of the compounds include the estimation of their lipophilicity. The lipophilicity, as the key molecular descriptor for assuming an activity in a biological system for group of thiouracil azo dyes, was determined by the reversed-phase thin-layer chromatography (RPTLC18F254s) in different mixtures of water and (ethanol, i-propanol, dioxane, tetrahydrofurane) and mathematically using relevant software packages. The insight into the relationship between the chromatographic retention parameters, and m of azo dyes with the partition coefficient log P, was attained by applying the linear regression analysis, Cluster analysis, and principal component analysis. All the applied methods have resulted in good agreements of the studied lipophilicity parameters of azo dyes. Also, these methods provided significant informations about the influence of the organic modifier on one side as well as the impact of the polarity and the electronic effect of substituent of examined dyes on their lipophilicity. GRAPHICAL ABSTRACT