A.M. Barbaro

Partition data of penicillins determined by means of reversed-phase thin-layer chromatography

Abstract The RM values of II penicillins were measured by means of a reversed-phase thin-layer chromatographic method with various concentrations of acetone in the mobile phase. RM values were calculated by interpolation or extrapolation from the ranges of linearity between RM values and composition of the mobile phase. The influence of substituent groups on the RM values of the penicillins and disagreement with Σπ values are pointed out.

Determination of lipophilicity by means of reversed-phase thin-layer chromatography: II. Influence of the organic modifier on the slope of the thin-layer chromatographic equation

The RM values measured for a series of steroids were very close to those determined more than 15 years ago using the same chemicals. This finding supports the reliability of RM values as a lipophilicity parameter. However, the point at issue in this work was the influence of the organic solvent in the mobile phase on the slopes of the TLC equations. In fact, the slopes of the TLC equations were shown to be related to the reciprocal of the solvent strength (1/E0). As a consequence, the ratio between the slopes of the TLC equations in different solvent systems are close to the ratio between the 1/E0 values for the corresponding solvent pairs. A further interesting aspect seems to arise from the analysis of the equations correlating slopes and intercepts of the TLC equations. In particular, the ratios between the b values of such equations in different solvent systems are close to the ratios between the corresponding E0 values.

RM and log P values of 5-nitroimidazoles

Abstract The chromatographic RM values of a series of nitroimidazoles and their log P values were determined in view of a study of their structure-activity relationships as mutagenic agents. The equations describing the relationship between RM and log P values show a low correlation coefficient. The introduction of the molar refractivity of the R1 and R2 groups yields a significant improvement in the correlation coefficient. The molar refractivity could be an expression of the adsorption activity of the silica gel layer.

Study of the lipophilic character of xanthine and adenosine derivatives. I: RM and log P values

Abstract The RM values of a series of xanthine and adenosine derivatives were measured using silicone reversed-phase thin-layer chromatographic (TLC) and C18 reversed-phase high-performance TLC systems. The two series of data were well correlated. Both were compared with experimental log P and calculated CLOGP values. For xanthine derivatives a good linear relationship was shown between the RM values from the two chromatographic systems and the log P or CLOGP data. For adenosine derivatives the CLOGP values had to be corrected in order to fit the data to the same equation. The TLC data proved to be reliable parameters for describing the lipophilic properties of the test compounds.

Study of lipophilic character of serotonergic ligands

Abstract The R M values of a series of serotonergic derivatives were measured using a reversed-phase TLC system with acetone, acetonitrile or methanol as the organic modifier of the mobile phase. As regards the basic aspects of the chromatographic technique, the series of compounds studied here behave in quite the same way as the previoulsy investigated series of chemicals, i.e. a very good correlation is found between the experimental and extrapolated R M values as well as between the extrapolated R M values from different organic solvent systems; the relationship between intercepts and slopes of the TLC equations in series of congeneric compounds; the influence of the organic modifier on the slopes of the TLC equations. The R M values from the above system were shown to be correlated with those obtained with a C 18 high-performance TLC. Finally, both chromatographic parameters were compared with calculated octanol-water log P values.

Determination of lipophilicity by means of reversed-phase thin-layer chromatography. III: Study of the TLC equations for a series of ionizable quinolone derivatives

The RM values of a series of antibacterial quinolones were measured at pH 9.0 and 1.2 using a reversed-phase TLC system with acetone, methanol or acetonitrile as the organic modifier of the mobile phase and silicone DC 200 as the impregnating agent of the silica gel layer. The data obtained provide a further contribution to the assessment of the basic aspects of the chromatographic determination of lipophilicity for ionizable compounds. The very good correlations between experimental and extrapolated RM values support the validity of the extrapolation technique. The overlapping of the extrapolated RM values from three different systems show that they are not dependent on the nature of the organic solvent. In a series of congeneric compounds there is a relationship between intercepts (a) and slopes (b) of the TLC equations. Factors affecting chromatographic congenerity are discussed. The slopes of the TLC equations and those of the equations correlating the parameters a and b are related to the solvent strength of the organic modifiers.

Mutagenicity of a series of 25 nitroimidazoles and two nitrothiazoles in Salmonella typhimurium

Twenty-five 5-nitroimidazole and two 5-nitrothiazole derivatives were tested for mutagenicity as well as for antibacterial activity in Salmonella typhimurium TA-100 strain. Many of these compounds such as metronidazole, azanidazole, nimorazole, carnidazole, ornidazole, tinidazole, etc are extensively used in human chemotherapy, and some of them were recently synthetized for possible clinical trials as hypoxic cell specific radiosensitizers. Both mutagenic and antibacterial activity were shown for 22 of the test compounds. The high correlation between mutagenic and antibacterial activity supports the hypothesis of a same mechanism for both activities. The present results confirm that the mutagenicity of the nitroheterocyclic compounds is not separated from other biological activities, such as antimicrobial activity.

Relationship between the chromatographic behaviour of dermorphin-related oligopeptides and the composition of the mobile phase in reersed-phase thin-layer chromatography: comparison of extrapolated RF values

Abstract The RT>F values of a series of dermorphin-related oligopeptides were determinded in two reversed-phase thin-layer chromatographic systems, the mobile phase being an aqueous buffer alone or mixed with various amounts of methanol or acetone. The linear relationship between the chromatographic behaviour and the composition of the mobile phase yielded very similar extrapolated RF values at 0% of organic solvent in both systems. This shows that the extrapolated RF values are independent of the nature of the organic solvent. In other words, the extrapolated RF values should be related to the partitioning of the compounds between water and silicone oil in a standard system where all the compounds can be compared.

Study of the lipophilic character of a series of β-carbolines

Abstract The lipophilic character of a series of β-carbolines has been studied. The RM values were measured by means of a reversed-phase thin-layer chromatographic (TLC) technique and compared with the RM values obtained by high-performance TLC (HPTLC), the log k′ obtained by high-performance liquid chromatography (HPLC), and the log P values. The best equation shows a very good linear relationship between our RM values and the classical log P values obtained using an octanol—water system. The choice of a pH of 13.0 for the TLC system allowed the measurements of the RM values of molecules in their non-ionized form. The deviations from the linear relationship shown by the RM(HPTLC) and log k′ values of two compounds were due to the fact that both compounds were at least partially ionized at the pH of 7.0 at which the HPTLC and HPLC determinations were carried out.

RM values of naphthols and acetophenones in structure-activity studies.

The RM values of naphthols obtained in a chromatographic system where the stationary phase consisted of a silica gel G layer impregnated with silicone oil are much more closely related to the log P values in an octanol-water system than the RM values determined on polyamide layers. Similarly, the RM values of a series of acetophenones in the silicone system are closely related to their log P values. The equations describing the structure-activity relationship indicate the importance of lipophilic character and halogen substitution in determining the hemolytic activity and the acute toxicity of compounds.