Analysis of positional isomers of 2-3-4-alkoxyphenylcarbamic acid derivatives by a combination of TLC and IMS.

In this study, we have demonstrated a separation of positional isomers of some derivatives of alkoxyphenylcarbamic acid. These compounds belong to drugs with local anesthetics activity. The low volatility compounds were analysed by a Thin Layer Chromatography (TLC) and Ion Mobility Spectrometry (IMS) using diode laser desorption for sample introduction to IMS. This combined approach allowed the identification of compounds. Also, we have carried out IMS studies of all compounds and determined their ion mobilities The ion mobilities were increasing with the geometry change from position ortho to para of alkoxy chain, which is in agreement with their different collision cross section (CCS).

Determination of Critical Micellar Concentration of Homologous 2-Alkoxyphenylcarbamoyloxyethyl-Morpholinium Chlorides.

The critical micellar concentrations of selected alkyloxy homologues of local anesthetic 4-(2-{[(2-alkoxyphenyl)carbamoyl]oxy}ethyl)morpholin-4-ium chloride with nc = 2, 4, 5, 6, 7, 8, and 9 carbons in alkyloxy tail were determined by absorption spectroscopy in the UV⁻vis spectral region with the use of a pyrene probe. Within the homologous series of the studied amphiphilic compounds, the ln(cmc) was observed to be dependent linearly on the number of carbon atoms nc in the hydrophobic tail: ln(cmc) = 0.705⁻0.966 nc. The Gibbs free energy, necessary for the transfer of the methylene group of the alkoxy chain from the water phase into the inner part of the micelle at the temperature of 25 °C and pH ≈ 4.5⁻5.0, was found to be −2.39 kJ/mol. The experimentally determined cmc values showed good correlations with the predicted values of the bulkiness of the alkoxy tail expressed as the molar volume of substituent R, as well as with the surface tension of the compounds.

[Study of local anaesthetics: Part 206* Micellization of selected of quaternary ammonium salt derived from heptacaine]. / Stúdium lokálnych anestetík: Cast 206* Micelizácie vybraných kvartérnych amóniových solí odvodených od heptakaínu.

Micellization of selected quaternary ammonium compounds derived from heptacaine have been studied by absorption spectroscopy in the UV/VIS spectral region with the use of a pyrene probe. The compounds studied in the aqueous solution have been marked as H22, H26, H27, H29, H34, H + Al and H + B and the derivative marked as H34 was studied in a 3 mol/l ethanol solution at the temperature of 25 °C. In the homologous series of the studied bromides H22, H26, H27 and H29, cmc was observed to be dependent on the number of carbon atoms nc in the hydrophobic chain: ln (cmc) = -3.131-0.421nC. The Free Gibbs energy necessary for the transfer of a methyl group of the alkyl chain from the water phase to the inner part of the micelle at the temperature of 25 °C is (-0.421 ± 0.034)RT.

[Study of local anaesthetics: part 204* determination of critical micelle concentrations of selected derivatives of pyrrolidino-m-alkoxyphenylcarbamic acid using pyrene as a probe]. / Stúdium lokálnych anestetík: cast 204* determinácia kritických micelových koncentrácií vybraných m-alkoxysubstituovaných pyrolidínoetylesterov kyseliny fenylkarbámovej vyuzitím pyrénu ako sondy.

The critical micelle concentrations of the studied derivatives of pyrrolidino-m-alkoxyphenylcarbamic acid in aqueous media at 25 °C were determined using the UV/VIS absorption spectroscopy method with pyrene as a probe. In the absorption spectra of the derivatives and pyrene, there were examined unmasked pyrene peaks, at wavelength of 336 and 320 nm for VIII Z, XIV Z and XVII Z, and in addition at 308 nm for XXIX Z. The critical micelle concentrations were defined from the plots of the sum of the unmasked pyrene peaks against the surfactant concentration that had a sigmoidal character of Boltzmann type. The cmc values of the derivatives were exponentially dependent on the number of carbons in the hydrophobic chain. From the plot of ln (cmc) against the number of carbons n with the equation ln (cmc) = -0.146-0.691n, the value of the Gibbs free energy of transfer of each methylene group of the alkoxychain from the aqueous phase into the internal hydrophobic volume of micelle was also defined: δΔG(CH(2)) = (-0.691 ± 0.023)RT. Building on the obtained results, the spherical micelle forming in the solution can be assumed.

Antimicrobial effect of para-alkoxyphenylcarbamic acid esters containing substituted N-phenylpiperazine moiety.

In current research, nine basic esters of para-alkoxyphenylcarbamic acid with incorporated 4-(4-fluoro-/3-trifluoromethylphenyl)piperazin-1-yl fragment, 6i-6m and 8f-8i, were screened for their in vitro antimicrobial activity against Candida albicans, Staphylococcus aureus and Escherichia coli, respectively. Taking into account the minimum inhibitory concentration assay (MIC), as the most active against given yeast was evaluated 8i (MIC = 0.20 mg/mL), the most lipophilic structure containing para-butoxy and trifluoromethyl substituents. Investigating the efficiency of the compounds bearing only a single atom of fluorine and appropriate para-alkoxy side chain against Candida albicans, the cut-off effect was observed. From evaluated homological series, the maximum of the effectiveness was noticed for the stucture 6 k (MIC = 0.39 mg/mL), containing para-propoxy group attached to phenylcarbamoyloxy fragment, beyond which the compounds ceased to be active. On the contrary, all the tested molecules were against Staphylococcus aureus and Escherichia coli (MICs > 1.00 mg/mL) practically inactive.

Study of local anaesthetics: part 201. Determination of the critical micellar concentration of pentacaine hydrochloride from the measurements of UV absorption of pyrene in methanol solutions.

The formation of micelles of the local anaesthetic pentacaine hydrochloride (K 1902) in methanol solutions at two concentrations was investigated by measuring the absorbance of pyrene in surfactant solution. The absorbance vs. surfactant concentration profiles for all the major UV spectral peaks of pyrene have been found to be sigmoidal in nature which were analyzed according to Sigmoidal-Boltzmann equation to evaluate the cmcs values of the studied systems. The influence of the methanol concentration on the critical micellar concentration was studied. The observed critical micellar concentration rises with an increasing of alcohol.

Antimicrobial effect of para-alkoxyphenylcarbamic acid esters containing substituted N-phenylpiperazine moiety

In current research, nine basic esters of para-alkoxyphenylcarbamic acid with incorporated 4-(4fluoro-/3-trifluoromethylphenyl)piperazin-1-yl fragment, 6i-6m and 8f-8i, were screened for their in vitro antimicrobial activity against Candida albicans, Staphylococcus aureus and Escherichia coli, respectively. Taking into account the minimum inhibitory concentration assay (MIC), as the most active against given yeast was evaluated 8i (MIC = 0.20 mg/mL), the most lipophilic structure containing para-butoxy and trifluoromethyl substituents. Investigating the efficiency of the compounds bearing only a single atom of fluorine and appropriate para-alkoxy side chain against Candida albicans, the cut-off effect was observed. From evaluated homological series, the maximum of the effectiveness was noticed for the stucture 6 k (MIC = 0.39 mg/mL), containing para-propoxy group attached to phenylcarbamoyloxy fragment, beyond which the compounds ceased to be active. On the contrary, all the tested molecules were against Staphylococcus aureus and Escherichia coli (MICs > 1.00 mg/mL) practically inactive.

Antimicrobial activity of meta-alkoxyphenylcarbamates containing substituted N-phenylpiperazine fragment

In the present investigation, the basic esters of meta-alkoxyphenylcarbamic acid bearing variously substituted N-phenylpiperazine fragment were screened for their in vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans, respectively. The most effective against Escherichia coli was found the compound 6d (MIC=195,3 μg/mL) bearing simultaneously para-fluoro substituent at the 4‑phenylpiperazin-1-yl core and meta-methoxy side chain in the lipophilic part of the molecule. From whole analyzed set of the molecules the substance 8e with propoxy side chain forming meta-alkoxyphenylcarbamoyl fragment and lipophilic, sterically bulky meta-trifluoromethyl group attached at N-phenylpiperazine moiety was evaluated as the most active against Candida albicans (MIC=97,7 μg/mL). On the contrary, all investigated structures were practically inactive against Staphylococcus aureus (MIC>1000 μg/mL).

[Analytical profile of mono[{3-[4-(2-ethoxyethoxy)-benzoyloxy]-2-hydroxypropyl}-tert-butylammonium] fumarate]. / Analytické hodnotenie mono[{3-[4-(2-etoxyetoxy)- -benzoyloxy]-2-hydroxypropyl}-terc-butylamónium]fumarátu.

The present paper aims at a complex spectral and physicochemical evaluation of mono[{3-[4-(2-eth-oxyethoxy)-benzoyloxy]-2-hydroxypropyl)-tert-butyl-ammonium] fumarate, the potential ultra-short acting blocker of beta1-adrenergic receptors. The identity of the evaluated compound (labelled as UPB-2) was confirmed by 1H-, 13C-NMR and IR spectral data as well. The estimated physicochemical parameters included melting point data, solubility in various media, purity checking (adsorption thin-layer chromatography), surface activity determination (non-direct Traube stalagmometric method), acidobasic characteristics (pKa value determination by alkalimetric titration), log epsilon values estimation (spectrophotometrically in UV/VIS region) and a study of the influence of acidic and alkaline media towards the stability of UPB-2. Other experimentally estimated values were lipohydrophilic descriptors using RP-HPLC (log k') and the log PexpS in various lipohydrophilic media by the shake flask method. Based on the log Pexp readouts, the ability to permeate across the brain-blood barrier was predicted. For the content determination of UBP-2 the RP-HPLC (reversed-phase HPLC), the method of an internal standard and UV/VIS spectrophotometry at the wavelength of 260 nm (aqueous medium) and at 258 nm (methanolic medium) was applied.

Antimicrobial activity of meta-alkoxyphenylcarbamates containing substituted N-phenylpiperazine fragment.

In the present investigation, the basic esters of meta-alkoxyphenylcarbamic acid bearing variously substituted N-phenylpiperazine fragment were screened for their in vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans, respectively. The most effective against Escherichia coli was found the compound 6d (MIC=195,3 µg/mL) bearing simultaneously para-fluoro substituent at the 4-phenylpiperazin-1-yl core and meta-methoxy side chain in the lipophilic part of the molecule. From whole analyzed set of the molecules the substance 8e with propoxy side chain forming meta-alkoxyphenylcarbamoyl fragment and lipophilic, sterically bulky meta-trifluoromethyl group attached at N-phenylpiperazine moiety was evaluated as the most active against Candida albicans (MIC=97,7 µg/mL). On the contrary, all investigated structures were practically inactive against Staphylococcus aureus (MIC>1000 µg/mL).

[Synthesis and basic physicochemical properties of 1-[3-(Y-alkoxyphenylcarbamoyloxy)-2-hydroxypropyl]-4-(2-methylphenyl)piperazinium chlorides]. / Syntéza a základné fyzikálno-chemické vlastnosti 1-[3-(Y-alkoxyfenylkarbamoyl- oxy)-2-hydroxypropyl]-4-(2-metylfenyl)- piperazíniumchloridov.

1-[3-(Y-Alkoxyphenylcarbamoyloxy)-2-hydroxypropyl]-4-(2-methylphenyl)piperazinium chlorides (labelled as 7a-7d) were prepared within a complex study of the relationships between the chemical structure, physicochemical properties and biological (antiarrhythmic, antihypertensive) activity of dual acting compounds. Chemical structures of basic forms (labelled as 7a2C-7d2C) and appropriate monochlorides (labelled as 7a-7d) were confirmed by 1H-NMR, 13C-NMR, MS and IR spectral and elemental analysis. The estimated physicochemical parameters included the melting point data, solubility profile in various media, purity checking (adsorption thin-layer chromatography), surface activity determination (Traube stalagmometric method), acidobasic characteristics (pKa value determination by alkalimetric titration) as well as the log epsilon values estimation by UV/VIS spectrophotometry. Other experimental values under consideration were lipohydrophilic characteristics using reversed-phase thin-layer chromatography (R(M) readouts) RP-HPLC (log k' data) and the log P(exp) s estimated in octan-1-ol/phosphate buffer medium.

[Analytical evaluation of mono[{3-[4-(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropylammonium]fumarate]. / Analytické hodnotenie mono[{3-[4-(2- -etoxyetoxy)-benzoyloxy]-2- -hydroxypropyl}-izo- propylamónium]fumarátu.

The present paper deals with a complex spectral and physicochemical evaluation of mono[{3-[4-(2-etoxyetoxy)-benzoyloxy]-2-hydroxypropyl}-isopropylammonium]fumarate, a potential ultrashort acting beta1-blocker. The identity of the substance under study (labelled as UPB-1) was confirmed by 1H- and 13C-NMR spectra as well as IR spectrometry. The determined fundamental physicochemical characteristics included the determination of the melting point, solubility in a spectrum of solvents, verification of purity (adsorption thin-layer chromatography), determination of surface activity (Traube's stalagmometric method), acidobasic characteristics (pK(a) value by means of alkalimetric titration), determination of log epsilon values using spectrophotometry in UV/VIS region, as well as the evaluation of the effect of acid and basic media on the stability of the substance under the study. Other experimentally determined parameters were lipohydrophilic characteristics essayed by means of RP-HPLC (log k'), and the shake-flask method was employed to determine the values of the partition coefficients P(exp) (resp. log P(exp)) in different lipohydrophilic media. On the basis of log P(exp-) data, the ability of the substance to penetrate the hematoencephalic barrier was predicted. To determine the UPB-1 content, RP-HPLC (reversed-phase HPLC) method of the internal standard and UV/VIS spectrophotometry at the wavelength of 260 nm (aqueous medium) and 258 nm (methanol medium) were used.

[Study of local anesthetics--part 195. Study of micellization of pentacainium chloride in methanol and ethanol solutions]. / Stúdium lokálnych anestetík--cast' 195. Stúdium micelizácie pentakaíniumchloridu v metanoloých a etanolových roztokoch.

The critical micellar concentrations of pentacainium chloride in methanol and ethanol solutions with different concentrations were determined by the spectrophotometric method in the UV region of the spectrum at the temperature range of T = 278.15-308.15 K and pH = 4.5-5.0. The dependence of cmc on temperature T turned out to be U-shaped. The influence of the n-alkanols, methanol and ethanol, on the critical micellar concentration was studied. The cmc values show that micelle formation occurred more easily in methanol than in ethanol solutions. Simultaneously the influence of various concentrations of alcohols was studied. The critical micellar concentration rises with an increasing concentration of alcohol up to some value, then cmc decreases.