Małgorzata Janicka

Thermodynamic Description of Liquid-Solid Chromatography Process in the Optimization of Separation Conditions of Organic Compound Mixture

Abstract Continuous interest in chromatographic methods as analitical techniques of different compounds separation gives rise to studies on theoretical description of chromatographic systems and, at the same way, to the selection of the best way of the prediction of chromatographic separation results. The main problem of theoretical studies in adsorption chromatography is to describe precisely correlations between retention parameters of given solute and mobile phase composition. In present paper the effort was made to use thermodynamic description of adsorbent - binary solvent - substance systems for theoretical predictions of analytical separation results in high-performance liquid column and thin-layer chromatography. The attention was paid to the possibility of using thin-layer chtomatography as a method of an initial choice of chtomatographic process optimization.

Reversed-phase liquid chromatography with octadecylsilyl, immobilized artificial membrane and cholesterol columns in correlation studies with in silico biological descriptors of newly synthesized antiproliferative and analgesic active compounds

Reversed-phase liquid chromatography (RPLC) with different stationary phases, i.e., octadecylsilyl, immobilized artificial membrane and immobilized cholesterol, was used to study lipophilicity of 56 newly-designed 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones and 2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-diones with potential anti-proliferative, anti-metastatic and analgesic activities. Extrapolated retention parameters that correspond to pure buffer as the mobile phase, i.e., logkw values are used as chromatographic lipophilicities. The lipophilic properties of compounds also are characterized by computed logP values and basic pharmacokinetic descriptors calculated in silico with the use of ACD/Percepta software according to Abrahams linear solvation energy relationship. Chromatographic and partitioning parameters are compared with biological descriptors using principal component analysis (PCA), and similarities and dissimilarities between variables and compounds are described. Highly significant, predictive relationships between biological descriptors and chromatographic parameters are obtained. Reversed parabolic relationships, which have very good statistical quality between various biological descriptors, i.e., logKsc, logKp, logBB, and logKhsa, and the logkw values, indicate the advantages of a cholesterol column in comparison with immobilized artificial membrane and octadecylsilyl stationary phase.

Comparison of different properties — log P , log kw , and ϕ 0 — as descriptors of the hydrophobicity of some fungicides

Log P, log kw, and ϕ0, are proposed and compared as descriptors of the hydrophobicity of twenty-two dihydroxythiobenzanilides — organic substances with antifungal properties. The log P values were calculated using theoretical methods proposed at http://146.107.217.178/lab/alogps. Chromatographic data log kw and ϕ0, were calculated from experimental TLC results obtained on RP-18W and RP-CN bonded stationary phases with methanol or acetone as organic modifiers. In addition to extrapolation, a numerical method based on Ościk’s linear equation was used for calculation of log kw values. The effect of mobile and stationary phase properties on the chromatographic data was studied and calculated hydrophobicity was compared with the biological activity of the test substances.

Chromatographic evaluation of the lipophilicity of N-phenyltrichloroacetamide derivatives using micellar TLC and OPLC

Micellar liquid chromatography (MLC) has been used to study the lipophilicity of eight newly synthesized N-phenyltrichloroacetamide derivatives. Because the lipophilicity of a substance determines its retention and its interactions with micelles, chromatographic data calculated from experimental results — km (log km) — were compared with partition coefficients log P calculated from the molecular structures of the solutes. Micellar mobile phases containing Brij 35 and tetrahydrofuran, alkyl-bonded stationary phases, and two planar chromatography techniques — thin-layer chromatography (TLC) and over-pressured-layer chromatography (OPLC) — were used in the experiments. According to results obtained from the OPLC studies, especially, log km values are excellent descriptors of the lipophilicity of the compounds. Very good linear relationships between log km and log P were obtained by use of this technique (R in the range 0.917–0.987).

Thin-layer and overpressured-layer chromatography for evaluation of the hydrophobicity of s -triazine derivatives

The retention factor in pure water, log kw, is proposed as a measure of the hydrophobicity of s-triazine derivatives. In these studies two reversed-phase techniques, thin-layer chromatography (TLC) and overpressured-layer chromatography (OPLC), were used. The effects of the chromatographic system, i. e. mobile and stationary phase properties, on log kw were analyzed to select the best system for determination of the hydrophobicity of the compounds. In TLC the chemically bonded phases RP-18 and RP-CN were used as stationary phases and acetone, acetonitrile, tetrahydrofuran, and dioxane as organic modifiers of the mobile phases. In OPLC RP-8 and RP-18 stationary phases and water-acetonitrile mobile phases were used. The values of log kw, determined by linear extrapolation and by the new method based on Oscik’s equation, were compared with log P values calculated by different theoretical methods. In TLC the best linear correlations between log P and log kw were observed for water-dioxane as mobile phase on both RP-18 and RP-CN stationary phases whereas in OPLC very good relationships were obtained for all the systems applied. Better functions for correlation of log P with log kw were obtained for log kw values determined by the method developed from Oscik’s equation.

Use of thin-layer and over-pressured-layer chromatography to study the hydrophobicity of homologous s -triazines

Retention factors in pure water, log kw, determined by linear extrapolation and by a numerical method based on Ościk’s equation, and calculated values of log P have been compared as hydrophobicity indices for nine homologous s-triazines. In chromatographic studies thin-layer and over-pressured-layer chromatography were used. The effect of mobile phase pH on solute retention was investigated by use of different buffer-methanol mixtures. The effect of mobile and stationary phase properties on chromatographic behavior was also studied; three different organic modifiers (dioxane, acetoni-trile, and tetrahydrofuran) and two stationary phases (RP-8 and RP-18) were used. Correlations of calculated log P values and log kw with carbon number, nC, confirm the usefulness of chromatograph-ic techniques for studying the hydrophobicity of organic compounds.

Use of OPLC to study the biological activity of organic compounds

SummarySolute capacity factors in pure water, logkw, determined by the new method based on Ościks equation, are proposed as descriptors of the biological activity of some benzamides. Values of logkw determined by the new method and by parabolic extrapolation were compared with the minimum inhibitory concentration (MIC) of the compounds against six different dermatophytes, and correlations between logkw and log (1/MIC) values of the same substances were analysed. For all the dermatophytes and all the compounds very good linear correlations were obtained for retention factors determined by the method proposed in this study.

Retention–property relationships of 1,2,4‐triazoles by micellar and reversed‐phase liquid chromatography

The properties of 21 1,2,4-triazoles, relevant to their pharmacokinetics, were investigated using experimental methods and in silico calculations. The lipophilicities of the compounds were determined experimentally using reversed-phase chromatography and liquid chromatography with micellar mobile phases, or they were calculated in silico from their molecular structures. In the reversed-phase technique, an octadecylsilyl, immobilized artificial membrane and immobilized cholesterol were used as the stationary phases. Biological descriptors of compounds, i.e. log BB, log KHSA, Caco-2, and fu,brain, were determined in silico by using ACD/Percepta software. Principal component analysis was used to indicate similarities between chromatographic, partitioning, and biological variables. Highly significant relationships were determined to exist between the chromatographic parameters and the biological descriptors, especially for log BB and log KHSA. The chromatographic parameters measured on the cholesterol column were recommended for use in predicting the lipophilic and biological properties of the 1,2,4-triazoles that were tested.

Application of Ościk's Equation for Description of Solute Retention in RP HPLC and Calculation of Retention Factor in Water

Abstract Ościks Equation, assuming the partition displacement model for a chromatographic process is proposed, for the description of solute retention in reversed phase liquid chromatography. Moreover, a numerical method of calculation of solutes retention factors in water, derived from the linear form of this Equation is presented. Theoretical investigations are applied to the literature of the RP HPLC results obtained for a group of model solutes, i.e., alkyl benzene homologues and test substances of different polarities chromatographed using three chemically bonded stationary phases: RP-8 (octylsilyl-silica), ODS (octadecylsilyl-silica) and PLRP-S (polystyrene-divinylbenzene polymer, PS-DVB) and water-methanol and/or water-acetonitrile mixtures as effluents. Calculated chromatographic parameters were analyzed as hydrophobicity indices and related to experimental and calculated log P values.

Crucial Role of Formaldehyde and its Reaction Products in the Antiproliferative Activity of Some Potential Pesticides

A group of thirteen newly synthesized potential herbicides, N-aryl-trichloroacetamides or 2-(chlorophenoxy)acyl derivatives, have been initially investigated by reversed phase (RP) TLC. The lipophilicity of the substances was described by retention factors in water, log kw, calculated from experimental RP TLC data, and by log P values calculated by use of software. Biological activity was examined by use of the BioArena system of TLC separation then (micro)biological detection. The potential role of formaldehyde (HCHO) in the toxic antibacterial action of substances against Pseu-domonas savastanoi pv. phaseolicola bacterial cells was investigated. The effect of HCHO capturers (L-arginine and reduced glutathione) and Cu2+ ions on the bioactivity and mechanism of toxicity of the substances was examined. It was established that HCHO and its potential reaction products (e.g. 1O2, O3) are crucial in the mechanism of action of these molecules. Correlations between the lipophilicity and bioactivity of the test compounds were also analyzed. It seems that hydrophobicity is not the decisive factor affecting the bioactivity of these substances.