Borko Matijević

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.

Solvent and structural effects on the UV absorption spectra of N-(substituted phenyl)-2-cyanoacetamides

UV absorption spectra of N-(substituted phenyl)-2-cyanoacetamides have been recorded in the range 200-400 nm in the set of selected solvents. The solute-solvent interactions were analyzed on the basis of linear solvation energy relationships (LSER) concept proposed by Kamlet and Taft. The effects of substituents on the absorption spectra were interpreted by correlation of absorption frequencies with Hammett substituent constant, σ. It was found that substituents significantly change the extent of conjugation. Furthermore, the experimental findings were interpreted with the aid of ab initio B3LYP/6-311G(d,p) method. Electronic energies was calculated by the use of 6-311++G(3df,3pd) methods with standard polarized continuum model (PCM) for inclusion of the solvent effect.

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

Solvatochromism of Thiouracil Azo Dyes

A series of sixteen synthesized thiouracil azo dyes was obtained by condensation of arylazo acetoacetic esters with thiourea. Purified products were characterized by UV–Vis, FT–IR, 1H and 13C NMR spectroscopy. The UV–Vis absorption spectra of all synthesized compounds were recorded in nineteen solvents of different properties. The study and analysis of the spectral data of azo dyes generally indicate that the tautomeric equilibrium is shifted to the hydrazone tautomeric form in the solid state. Linear solvation energy relationships describe solvent influence on solvatochromism of the hydrazone form with the use of the Catalán model. Linear free energy relationships were applied in the form of single substituent parameter model to analyze substituent electronic effects on the spectral behavior of the compounds by Hammett’s equation. The correlations obtained with aid of theoretical calculations give insight into the influence of molecular conformation on the transmission of substituent effects, as well as different solvent–solute interactions.

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.

Interpretation of the results of surface water quality applying multivariate analysis

Monitoring of surface water, through the analysis of physical-chemical and chemical parameters is a very important factor in the control of water quality and the health of living beings. Surface water quality is largely determined by the nature (atmospherics) and anthropogenic processes (discharge of municipal and industrial waste water). The results of monitoring of surface water are usually too expensive and difficult for correct interpreting, due to the spatial and temporal variations in water quality. By applying Multivariate statistical analysis can achieve significant reductions of the ampleness of the available data and the better interpretation of the obtained results about the quality and ecological status/potential of water. In this paper, were analyzed selected results of the analysis of surface water in AP Vojvodina in 2011 year by using multivariate statistical analysis (cluster analysis and principal components analysis). These techniques allow the interpretation of the results of the monitoring program of investigated surface water bodies and simultaneous identification of registered influence and potential sources of pollution on the quality of the given water bodies. With both methods applied and the division of water bodies tested in the same manner at the origin (natural and artificial) and on the basis of territorial belonging monitoring stations (Banat and Backa). Individual variations are discussed in corresponding differences in individual measuring stations in relation to others. Application of the given method, a grouping of the examined indicators of water quality in the following factors: hydro-chemical factor, ecological factor, the factor point pollution and diffusion. The obtained results confirm the initial hypothesis that the use of different statistical methods can identify the main factors that have an impact on the ecological status and ecological potential of water bodies and to improve the existing monitoring. In addition, analysis of the extracted surface water bodies where it is necessary to implement simultaneous monitoring of the biological quality elements to determine whether chemical parameters ensure the functioning of ecosystems. [Projekat Ministarstva nauke Republike Srbije, br. ОI-172013 i br. III43005]

Metal Complex Formation in Melts of Acetamide-Ammonium Nitrate-Water Mixtures, Part I. Cobalt(II) Chloride Complexes

The complex formation between cobalt(II) and chloride ions in molten NH4NO3・2.61H2O, NH4NO3・CH3CONH2・1.61H2O and NH4NO3・2.61CH3CONH2 has been investigated. Absorption spectra of cobalt(II) chloride containing variable amounts of ammonium chloride were recorded at 45 to 60 °C. In the absence of chloride, the solutions show spectra typical for octahedral co-ordination of cobalt(II). Addition of chloride caused a shift of the absorption maximum toward lower energies and an increase of the molar absorption coefficient with increasing chloride concentration. The position of the absorption maximum and the intensity of the absorption indicate tetrahedral or severely distorted octahedral co-ordination. The stability constants for [Co(NO3)4]2−, [Co(NO3)2Cl2]2− and [CoCl4]2− complex formation in NH4NO3・2.61CH3CONH2 are reported.