Supplementary data for article: Matijević, B. M.; Vaštag, T. T.; Apostolov, S. L.; Milčić, M. K.; Marinković, A. D.; Petrović, S. D. N-(Substituted Phenyl)-2-Chloroacetamides: LSER and LFER Study, 2015. https://doi.org/10.1016/j.arabjc.2015.09.008

Supplementary material for: [https://doi.org/10.1016/j.arabjc.2015.09.008]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/293

Supplementary data for the article: Mrđan, G. S.; Vastag, G. G.; Škorić, D. Đ.; Radanović, M. M.; Verbić, T. Ž.; Milčić, M. K.; Stojiljković, I. N.; Marković, O. S.; Matijević, B. M. Synthesis, Physicochemical Characterization, and TD–DFT Calculations of Monothiocarbohydrazone Derivatives. Structural Chemistry 2021, 32 (3), 1231–1245. https://doi.org/10.1007/s11224-020-01700-y.

Supplementary material for: [https://doi.org/10.1007/s11224-020-01700-y]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/4453

Supplementary data for article: Matijević, B. M.; Vaštag, T. T.; Apostolov, S. L.; Milčić, M. K.; Marinković, A. D.; Petrović, S. D. N-(Substituted Phenyl)-2-Chloroacetamides: LSER and LFER Study, 2015. https://doi.org/10.1016/j.arabjc.2015.09.008

Supplementary material for: [https://doi.org/10.1016/j.arabjc.2015.09.008]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/293

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

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 F-254s) 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, R-M(0), determined by RP-TLC method, are similar to the standard measure of lipophilicity, log P, which makes this method appropriate for predicting lipophilicity

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, R-M(0), of examined chloroacetamides was correlated with the standard measure of lipophilicity, log P, and with pharmacokinetic predictors such as human effective permeability in jejunum, P-eff, 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 R-M(0) determined by RPTLC could be used as a descriptor to estimate the potential biological activity of N-(substituted phenyl)-2-chloroacetamides

Thin-layer chromatography on reversed phase in the characterization of retention behaviour, lipophilicity, and pharmacokinetics of cyanoacetamide derivatives

Biological activity of a molecule is closely related to its lipophilicity. This significant parameter was determined for a group of potentially bioactive N-(4-phenylmonosubstituted)-2-cyanoacetamides applying thin-layer chromatography on reversed phase (RP-TLC) in mixtures of water and two organic modifiers separately, i-propanol and dioxane. The effect of the chemical structure of derivatives and the influence of the applied organic modifier on their retention were studied. The determined chromatographic retention constants, R-M(0), and the chromatographic parameter, m, of compounds were correlated with software calculated partition coefficients, log P as the standard measure of lipophilicity and with different pharmacokinetic predictors applying classical linear and multiple regression analysis. By classical linear regression analysis in both water-modifier systems only R-M(0)-log P and m-log P correlations were established (average r, 0.909 and 0.826). All studied relationships were enhanced by molecular descriptors that fulfilled the modified Lipinski's rule of five. Thereby, the performed multiple regression analysis gave better correlations (for R-M(0)-log P and m-log P average r(2), 0.994 and 0.993; for R-M(0)-pharmacokinetic parameters and m-pharmacokinetic parameters average r(2) 0.978 and 0.980). The obtained results indicate that the chromatographic parameters, R-M(0) and m determined by RP-TLC at given conditions could be used successfully for the description of lipophilicity and the evaluation of pharmacokinetic properties of N-(4-phenylmonosubstituted)-2-cyanoacetamides as potential bioactive molecules

Solvatohromizam N-aril-fenilacetamida

Amide derivates are biologically active compounds and they are widely used in all spheres of life. Therefore, it is very important to know their physical-chemical properties. In this work the influence of characteristics and nature of the solvent on the absorption spectra of N-aryl-phenylacetamide was investigated, in order to obtain information about their solvatochromic properties. The spectra of the compounds were recorded in 15 solvents, with different properties, in the wavelength range from 200 to 400 nm. The effect of the solvents on the absorption spectra of N-aryl-phenylacetamide was analyzed by using Kamlet-Taft's solvatochromic model. Also, in order to obtain detailed information on the type and dominance of the interactions that occur between the compound and the surrounding medium, correlations were made with absorption maxima and Hansen's solvent parameters. In addition to the effect of solvent, the impact of the chemical structure on the spectral behavior of tested amide derivatives was analyzed.Derivati amida su biološki aktivna jedinjenja i imaju široku primenu u svim sferama života. Zbog toga je veoma važno poznavati njihova fizičko-hemijska svojstva. U ovom radu ispitivan je uticaj osobina i prirode rastvarača na apsorpcione spektre N-aril-fenilacetamida radi dobijanja informacija o njihovim solvatohromnim svojstvima. Spektri ispitivanih jedinjenja su snimljeni u 15 rastvarača različitih osobina, u opsegu talasnih dužina od 200 do 400 nm. Uticaj rastvarača na apsorpcione spektre N-aril-fenilacetamida analiziran je pomoću Kamlet-Taft-ovog solvatohromnog modela. Takođe, radi dobijanja detaljnijih informacija o vrsti i dominantnosti interakcija koje se javljaju između jedinjenja i okolnog medijuma, urađene su korelacije apsorpcionih maksimuma sa Hansen-ovim parametrima rastvarača. Pored uticaja rastvarača analiziran je i uticaj hemijske strukture na spektralno ponašanje ispitivanih derivata amida

Proučavanje fizičko-hemijskih svojstava novosintetisanih derivata uracila

Uracil derivatives are potentially biologically active compounds, so the investigation of their physical and chemical properties is very important for their further application. In this work a series of newly synthesized derivatives of uracil was investigated by applying the spectrophotometric method. The absorption spectra were recorded in seventeen solvents with different properties. The effect of solvent was interpreted by Kamlet-Taft solvatochromic model. The dominance and the types of interactions that occur between the investigated derivatives and solvent were interpreted by applying the multiple linear correlation obtained values of absorption maxima and Hansen's solvent parameters. In addition to the effect of solvent, the influence of substituents in the molecule on absorption spectra was studied by applying Hammett equation.Derivati uracila predstavljaju potencijalno biološki aktivna jedinjenja, pa je ispitivanje njihovih fizičko- hemijskih svojstava veoma značajno za njihovu dalju primenu. U ovom radu je ispitana serija novosintetisanih derivata uracila primenom spektrofotometrijske metode. Apsorpcioni spektri su snimljeni u sedamnaest rastvarača različitih svojstava. Uticaj rastvarača na apsorpcione spektre tumačen je primenom Kamlet-Taft-ovog solvatohromnog modela. Dominantnost i vrste interakcija koje se javljaju između ispitivanih derivata i rastvarača analizirane su metodom višestruke linearne korelacije dobijenih vrednosti položaja apsorpcionih maksimuma i Hansen-ovih parametara rastvarača. Pored uticaja rastvarača, tumačen je i uticaj supstituenta prisutnog u molekulu na apsorpcione spektre pomoću Hammett-ove jednačine

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, H-1 and C-13 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 Catalan 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