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1

Condensation oscillations in the condensation of mandelic acid

Sajewicz M., Gontarska M., Kronenbach D., Berry E, Kowalska T.

Acta Chromatographica

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2012

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Vol. 24, no. 1

1--13

EN

In our earlier studies, we were the first to discover a spontaneous chiral conversion of the low-molecular-weight carboxylic acids dissolved in aqueous media, running in vitro. The investigated chiral carboxylic acids belong to the classes of profen drugs, amino acids, and hydroxy acids. Then, the spontaneous chiral conversion running in vitro and accompanied by the spontaneous condensation of the discussed compounds was discovered. From the literature, we learnt that spontaneous condensation of certain chiral compounds sometimes can be oscillatory in nature. Thus, we considered it noteworthy to check if spontaneous condensation of the chiral low-molecular-weight carboxylic acids follows a linear or a nonlinear dynamic pattern. In this paper, we present the results of our studies on the dynamics of condensation of S-, R-, and rac-mandelic acid, carried out with the aid of the high-performance liquid chromatography with the diode-array detection (HPLC-DAD), and with the aid of mass spectrometry (MS). The obtained data furnish reliable evidence that condensation of mandelic acid is oscillatory in nature. Finally, a theoretical model is recalled, which jointly describes the oscillatory chiral conversion and the oscillatory condensation with S-, R-, and rac-mandelic acid.

2

On the spontaneous condensation of profens, with ketoprofen as an example

Matlengiewicz M, Sajewicz M., Gontarska M., Kronenbach D., Kowalska T.

Acta Chromatographica

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2010

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Vol. 22, no. 1

81--90

EN

In a series of recently published full-length papers and short communications we attempted to gain deeper insight into elementary reactions which might contribute to the non-linear nature of the spontaneous chiral conversion of low-molecular-weight carboxylic acids. Earlier, we succeeded in demonstrating that amino acids and hydroxy acids can undergo spontaneous peptidization and spontaneous esterification (both regarded as condensation), respectively, when dissolved in 70% aqueous ethanol. In this study we provide experimental proof from thin-layer chromatography and 13 C NMR spectroscopy of spontaneous condensation of profens, with ketoprofen as an example. It can be expected that other profen drugs undergo an analogous condensation. In the future, an analogy between the ability of amino acids, hydroxy acids, and profens to undergo spontaneous peptidization or condensation (as reported in our papers), and the ability of selected organosilanols to undergo the spontaneous oscillatory condensation (as reported elsewhere), might prove essential for better understanding of detailed mechanism of the spontaneous oscillatory in-vitro chiral conversion of the selected low-molecular-weight carboxylic acids.

3

On the spontaneous condensation of selected hydroxy acids

Sajewicz M., Matlengiewicz M., Kronenbach D., Gontarska M., Kowalska T.

Acta Chromatographica

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2009

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Vol. 21, no. 2

259--271

EN

In a previous study we provided thin-layer chromatographic, polarimetric, and other experimental evidence that phenylglycine can undergo easy spontaneous peptidization in abiotic aqueous media. From our unpublished results it is apparent that this behaviour is also characteristic of some other amino acids (e.g., alanine and phenylalanine). It seems highly probable that this abiotic peptidization of amino acids dissolved in aqueous media is directly linked to their ability to undergo spontaneous oscillatory chiral conversion. In our earlier research it was also shown that spontaneous oscillatory chiral conversion was characteristic not only of amino acids but also of several other classes of carboxylic acid, including profen drugs and hydroxy acids. We therefore decided to check whether selected chiral hydroxy acids — lactic acid and mandelic acid — previously recognized for their ability to undergo spontaneous oscillatory chiral conversion, could also furnish the respective polyacids. Condensation of hydroxy acids can be viewed as a reaction fully analogous with peptidization of amino acids and, hence, it seemed to us highly probable that it also can be triggered by oscillatory chiral conversion. In our study, we used thin-layer chromatography and 13 C NMR spectroscopy to check whether formation of polylactic acid and polymandelic acid occurred in stored solutions of lactic and mandelic acids. By means of polarimetry with continuous recording we provided experimental evidence that all three hydroxy acids investigated (i.e. L -(+)-lactic acid, S -(+)-mandelic acid, and R -(−)-mandelic acid) undergo continuous chiral conversion. From the thin-layer chromatographic results obtained it was apparent that — similar to the spontaneous and instantaneous peptidization of amino acids — the hydroxy acids investigated also undergo easy condensation to form the respective polyacids. 13 C NMR spectroscopy provided additional experimental confirmation of this.

4

On the spontaneous abiotic peptization of phenylglycine in an aqueous medium

Sajewicz M., Gontarska M., Kronenbach D., Kowalska T.

Acta Chromatographica

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2009

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Vol. 21, no. 1

151-160

EN

In this report we provide thin-layer chromatographic evidence that phenylglycine dissolved in 70% aqueous ethanol and kept at ambient temperature (22°C) undergoes spontaneous peptization, as additionally confirmed by use of the biuret test. It was also shown that an important precondition for instantaneous peptization of phenylglycine is the simultaneous presence of the R and S antimers in solution, and the most spectacular peptization effect is obtained with racemic R,S -phenylglycine. An assumption is made that polycondensation of phenylglycine results from its ability to undergo spontaneous oscillatory chiral conversion and can be regarded as a step following enolization, and competitive with chiral conversion.

5

How to suppress the spontaneous oscillatory in-vitro chiral conversion of α-substituted propionic acids? A thin-layer chromatographic, polarimetric, and circular dichroism study of complexation of the Cu(II) cation with L -lactic acid

Sajewicz M., John E., Kronenbach D., Gontarska M., Wróbel M., Kowalska T.

Acta Chromatographica

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2009

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Vol. 21, no. 1

39-55

EN

In our earlier investigations we showed, for the first time, with numerous practical examples that α-substituted propionic acids dissolved in the low-molecular-weight solvents are able to undergo spontaneous oscillatory in-vitro chiral conversion. In this study, we focused on attempting to suppress the spontaneous oscillatory in-vitro chiral conversion of α-substituted propionic acids using, as example, L -lactic acid dissolved in water in the presence of copper(II) cations. Our intention was to check whether the coordinate covalent bonds between copper(II) and L -lactic acid ligands prevented the latter species from oscillatory chiral conversion. To do this we stored aqueous solutions of copper(II) acetate and lactic acid in the molar ratios 1:1, 1:2, and 1:3 for a long period of time. Scrutiny of possible chiral conversion of L -lactic acid was carried out by thin-layer chromatography (TLC), polarimetry, and circular dichroism (CD) spectroscopy. Seemingly contradictory results were obtained from our investigations. From the TLC data it was apparent that chelating of copper(II) cations with L -lactic acid molecules did not result in suppression of the spontaneous oscillatory in-vitro chiral conversion of the acid. It was also established that different molar proportions of copper(II) cation and L -lactic acid molecules had somewhat different effects on the dynamics of conversion. In contrast, from polarimetric and circular dichroism studies it was apparent that when L -lactic acid is dissolved in water in the presence of copper(II) cations almost no chiral conversion is observed. Hence a final conclusion was drawn that chelating of copper(II) cations with L -lactic acid stabilizes the chiral structure of the acid in solution. Intermolecular interactions between the copper(II)-L -lactic acid complex and the silica gel stationary phase evidently affects the structure of the complex, however, most probably resulting in partial "liberation" of L -lactic acid ligands. Thus the chiral structure-stabilizing effect of copper(II) cations is apparently weakened by the TLC system and the freed L -lactic acid molecules can undergo chiral conversion.

6

TLC study of the separation of the enantiomers of lactic acid

Sajewicz M., John E., Kronenbach D., Gontarska M., Kowalska T.

Acta Chromatographica

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2008

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Vol. 20, no. 3

367-382

EN

Enantiomer separation by TLC is still much less frequent than with other, mostly instrumental, chromatographic techniques. From a literature survey it is apparent that separation of the enantiomers of D,L -lactic acid is primarily of interest to the diary industry and that this particular separation is less frequently performed by chromatographic than by membrane techniques. As far as we are aware, before our studies only one report of TLC separation of the enantiomers of D,L -lactic acid was available in the literature; this is dated 1991 and describes the use of non-instrumental TLC only. In this study, we started by reproducing the TLC procedure originating from 1991, for this purpose using TLC with automatic sample application and densitometric detection. We managed to repeat the earlier procedure and to achieve full, i.e. baseline, separation of the enantiomers, with a remarkable distance between the two antimers. However, we revealed a significant drawback of this separation procedure - D -(-)-lactic acid was transported almost with the mobile-phase front and its densitometric quantification was barely possible because of the relatively high UV absorption of the mobile-phase front line. The reference method for separation of the enantiomers of D,L -lactic acid consisted in preliminary impregnation of commercial silica gel TLC plates with copper(II) acetate. In-situ formation of bidentate complexes of the D,L -lactic acid antimers with the Cu 2+ cation resulted in different mobilities of these complex cations in the planar chromatographic system. The objectives of this study were twofold - to investigate separation of the enantiomers of D,L -lactic acid with other transition metal cations (i.e., Co 2+, Ni 2+, and Mn 2+) used to impregnate the silica gel (to achieve resolution that might enable quantification of the two lactic acid antimers and not only the L -(+) enantiomer) and to gain deeper insight into the mechanism of separation with these metal cations. For purposes of comparison, we chromatographed D,L -lactic acid on non-impregnated silica gel layers. As a result, we managed to establish efficient separation conditions with the Ni 2+ and Co 2+ cations that outperformed the earlier established procedure involving the Cu 2+ cation, and - partially at least - to elucidate the mechanism of separation of the enantiomers of D,L -lactic acid by these TLC systems. The Mn 2+ cation proved unsuitable for the purpose. Finally, we managed to separate the enantiomers of D, L -lactic acid on non-impregnated silica gel layer also, which seems yet more proof of the microcrystalline chirality of silica gel used as stationary phase and of its substantial contribution to the enantiomer separation investigated.

7

Investigation of the spontaneous oscillatory in-vitro chiral conversion of L -(+)-lactic acid

Sajewicz M., Gontarska M., Kronenbach D., Kowalska T.

Acta Chromatographica

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2008

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Vol. 20, no. 2

209-225

EN

In previous studies we focused our attention on the in-vitro oscillatory chiral conversion of selected profens and amino acids when dissolved in low-molecular-weight solvents. The results obtained encouraged us to check other propionic acid derivatives of biological importance and we therefore decided to investigate the tendency of L -(+)-lactic acid to undergo an analogous process of spontaneous oscillatory in-vitro chiral conversion. As far as we are aware, this type of investigation on lactic acid has not previously been conducted. In our studies, we used solutions of L -(+)-lactic acid in three different mixed solvents, ethanol-water, ethanol-glacial acetic acid, and ethanol-basic buffer (pH 9), in the volume proportion 7:3. The investigations were conducted by thinlayer chromatography (TLC) and polarimetry. The results obtained by TLC gave evidence of the spontaneous oscillatory chiral conversion of L -(+)-lactic acid solution. From TLC results alone it is hardly possible to judge whether this process commences in solution before chromatography, catalyzed by the solid-liquid interface of the TLC plate, or commences immediately on dissolution of the acid and occurs continuously without interruption, both outside and inside the chromatographic system. It is easy to believe that the highly active surface of the silica gel adsorbent acts as a catalyst of chiral conversion. From long-term polarimetric studies it was concluded that L -(+)-lactic acid also undergoes oscillatory chiral conversion in the bulk liquid phase at ambient temperature, i.e. outside the TLC system, although the rate is much lower than in TLC and the racemic mixture is obtained after approximately one month only. In TLC racemization is practically complete within one chromatographic run.

8

Study of the oscillatory in-vitro transenantiomerization of the antimers of flurbiprofen and their enantioseparation by thin-layer chromatography (TLC)

Sajewicz M., Gontarska M., Kronenbach D., Wojtal Ł., Grygierczyk G., Kowalska T.

Acta Chromatographica

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2007

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No. 18

226-237

EN

In our earlier studies on the spontaneous in-vitro oscillatory transenantiomerization of profens we investigated optically pure S-(+)-ibuprofen and S-(+)-naproxen and the racemic mixtures S,R-(š)-2-phenylpropionic acid and S,R-(š)-ketoprofen, which remained in a state of dynamic equilibrium between the two antimers yet also had the ability to transenantiomerize. In this study we have demonstrated, for the first time, the spontaneous oscillatory in-vitro transenantiomerization of S-(+)-flurbiprofen (an important non-steroidal anti-inflammatory drug, NSAID) and R-(-)-flurbiprofen, as monitored by polarimetry. It is also noteworthy that – as far as we are aware – this is the first report of separation of the enantiomers of flurbiprofen by TLC. This separation was achieved by two-dimensional development using a simple chromatographic system comprising a commercial silica gel layer impregnated with L-arginine as stationary phase and ethanol containing a few drops of glacial acetic acid as mobile phase. Unfortunately, this chromatographic system resulted in catalysis of structural conversion of the optically pure flurbiprofen enantiomer, either S-(+), or R-(-), to the scalemic or racemic mixture of the two antimers. This is an interesting contribution to general knowledge about the reactivity of this particular profen, although the spontaneous and rapid conversion observed prevents use of this TLC system for identification and quantification of individual flurbiprofen enantiomers.