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In our earlier studies, we demonstrated an ability of selected enantiomeric profen drugs (e.g., S-(+)-ibuprofen, S-(+)-naproxen, and S-(+)- and R-(−)-flurbiprofen) and one amino acid (i.e., L-α-phenylalanine) to undergo oscillatory transenantiomerization when dissolved in simple, low molecular weight solvents (e.g., water, ethanol, dichloromethane,...
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... Our own research interests have been focused for over a decade now on spontaneous behavior of proteinogenic α-amino acids in the abiotic aqueous liquid systems and we were the first ones to report on spontaneous oscillatory chiral inversion [15][16][17][18] and spontaneous oscillatory peptidization [19][20][21][22][23][24][25] of a number of amino acids. Based on the results of these studies and aiming to gain deeper understanding of molecular mechanisms governing the aforementioned oscillatory phenomena, we decided to scrutinize an impact of heavy water (D 2 O) upon them. ...
This is our follow-up study carried out in an order to collect experimental evidence regarding the impact of heavy water (D2O) on the spontaneous oscillatory peptidization of l-proline (l-Pro). Our earlier studies have been focused on the two sulfur-containing proteinogenic α-amino acids, i.e., l-cysteine (l-Cys) and l-methionine (l-Met), and it seemed interesting to assess the effect induced by D2O on one more proteinogenic α-amino acid, i.e., l-Pro. It needs to be added that unlike l-Met, but similar to l-Cys, the oscillatory peptidization of l-Pro dissolved in the organic-aqueous solvent characterizes with the circadian rhythm. As analytical techniques, we used high-performance liquid chromatography with the evaporative light-scattering detection (HPLC-ELSD), mass spectrometry (MS), scanning electron microscopy (SEM), and turbidimetry. The obtained results can in certain sense be viewed as analogous to those earlier reported for l-Cys and l-Met by demonstrating that heavy water considerably hampers the oscillatory peptidization of l-Pro. However, an unexpected observation was also made than unlike the cases with l-Cys and l-Met, the observed hampering effect of D2O on the oscillatory peptidization of l-Pro is not monotonously dependent on the concentration of D2O in the system, but it is the strongest pronounced for 10% (v/v) D2O in the employed binary methanol–water solvent (with the investigated proportions of D2O in this solvent changing from 0 to 30%). Although we have no rational explanation for this striking effect, we believe that it should not pass unnoticed and therefore it is emphasized in this study. Maybe this firm quantitative result will prove an inspiration for future researchers interested in getting a deeper insight into the role of D2O in life processes, and more specifically in the kinetic and the mechanistic aspects thereof.
... [3][4][5] Due to spontaneous peptidization, instead of a given amino acid, a variety of the oligopeptides are rapidly formed, which make the direct amino acid separation a challenging task. As discussed in papers, [3][4][5] spontaneous peptidization of amino acids is oscillatory in nature and it is accompanied by spontaneous oscillatory chiral conversion of the same compounds, [6][7][8] which additionally contributes to the structural instability of amino acids and is illustrated by Scheme 1. ...
... Proline in the monomeric form is the only amino acid which reacts with ninhydrin to produce yellow spots, [12] whereas all the remaining amino acids, peptides and proteins yield the pink or purple spots. On the chromatograms showed in Figure 1a-c, from the left to the right we can see four DL-proline spots (1-4) followed by four L-proline spots (5)(6)(7)(8). The applied sample aliquots in each case were 5 mL, and the respective concentrations were 0.2 mg mL À1 (Figure 1a), 1.0 mg mL À1 (Figure 1b), and 2.0 mg mL À 1 (Figure 1c). ...
Direct enantioseparation of underivatized amino acids dissolved in the aqueous and nonaqueous solvents by means of the chiral TLC is a difficult analytical task. Most often such enantioseparations are carried out for the derivatized amino acids, or by means of the ion-exchange chromatography or electrophoresis. The main reasons of the aforementioned difficulty seem an ability of the chiral low molecular weight carboxylic acids (amino acids included) to undergo spontaneous condensation and spontaneous chiral conversion, as confirmed, for example, by the results of our earlier studies. In this study, we provide an experimental evidence of rapid peptidization of L-proline and DL-proline obtained by means of the two different TLC systems, additionally confirmed by LC/MS and 1H NMR spectroscopy. Additionally, a novel TLC system for the direct enantioseparation of DL-proline is proposed, which considerably outperforms earlier elaborated systems. Finally, relevant practical conclusions are drawn.
... These investigations were carried out with the aid of the chiral thin-layer chromatography (chiral TLC) and polarimetry. Then, the analogous results were reported for the selected optically pure amino acids [4][5][6] and hydroxy acids [7,8]. Ultimately, a generalizing conclusion was drawn that the spontaneous oscillatory chiral conversion might be inherent in the whole class of chiral low-molecular-weight carboxylic acids (e.g., those which can formally be derived from acetic, propionic, and butyric acids). ...
In our earlier studies performed with the use of thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), polarimetry, and several other instrumental techniques, we have provided abundant experimental evidence for the oscillatory chiral conversion and the oscillatory condensation of the low-molecular-weight carboxylic acids from the groups of profen drugs, amino acids, and hydroxy acids. We have also proposed several kinetic-diffusive models aimed at elucidation of these striking phenomena, which in the diffusive term assumed contribution from the density inhomogeneity of the investigated liquid systems. Moreover, each model laid special emphasis on the importance of cyclic H-bonded carboxylic acid homodimers of the SS and RR type. In this paper, we introduce a simple experimental approach enabling convenient registration of the density inhomogeneity in the S(+)-naproxen solution prepared in 70% aqueous ethanol. To this effect, we use a zooming scanner that is able to scan this solution in a Petri dish placed in UV light (λ = 254 nm). Scanning in the selected time intervals allows tracing the dynamics of supramolecular aggregation of the investigated profen drugs. The mobility of these aggregates can probably result from the energy released in the process of chemical polycondensation. The obtained results seem to correlate well with those originating from HPLC, and the relevant conclusions are drawn. It seems possible that the zooming scanner can prove helpful in monitoring some other interesting chemical processes as well, thus contributing to the studies on the mechanism and kinetics of the nonlinear organic reactions.
... This extraordinary behavior of the aryl-substituted propionic acids instigated our interest in other chiral propionic acid derivatives from the classes of amino acids and hydroxy acids. To this effect, we performed the analogous chromatographic investigations with the organic-aqueous solutions of L-alanine [14], L-αphenylalanine [15], and tyrosine [4], using the chiral TLC with densitometric detection as the primary analytical tool to trace instabilities of the respective retardation parameter (R F ) values and those of the concentration profile intensities and shapes. With amino acids, once again these two striking instabilities were confirmed (as shown, e.g., in Figures 3 and 4). ...
... In fact, with the most examined solutions, the polarimetric evidence of the changing specific rotation ([α] D ) values in the function of time was provided in papers [3][4][5][6][7][10][11][12][13][14][15][16][17][18][19][20]. However, in most cases, the respective measurements have been carried out pointwise with use of a simple noncontinuous polarimetric registration. ...
Oscillatory reactions are a narrow reaction type among the entity of chemical reactions and those involving purely organic compounds make a small contribution to an overall number of all known oscillatory reactions. The most abundant type is purely inorganic and mixed inorganic-organic oxidation-reduction reactions, basically because monitoring them is relatively easy (e.g., with use of potentiometric measurements). Investigation of the organic reactions can be more demanding, and then chromatography is an analytical technique of choice. In this paper, we provide an overview of chromatographic evidence with oscillatory reactions discovered in our laboratory in the course of the last several years that involve the low-molecular-weight carboxylic acids (profen drugs, amino acids, and hydroxy acids). The investigated processes comprise the oscillatory chiral conversion and the oscillatory condensation, spontaneously running in the aqueous and nonaqueous abiotic media, and they were traced with use of TLC and HPLC coupled with different detector types.
... The remarkable phenomenon of spontaneous in vitro oscillatory chiral conversion of selected profens, amino acids, and hydroxy acids has been the focus of our attention for some time. We first observed oscillatory chiral conversion in selected profens: S(+)-ibuprofen, S (+)-naproxen, S,R(±)-2-phenylpropionic acid, S(+)-flurbiprofen , R(-)-flurbiprofen, and S,R(±)-ketoprofen123. Later we described an analogous behavior in several amino acids: L-alanine, L-a-phenylalanine, and L-tyro- sine456. We have characterized similar phenomena in selected hydroxy acids [7,8] (L-lactic acid, R-a-hydroxybutyric acid, S-a-hydroxybutyric acid, R-mandelic acid, and S-mandelic acid) as well. ...
... The experimental results presented here demonstrate that phenylglycine, which exists largely in the form of hydrogen-bonded dimers, can undergo a condensation reaction in ethanol-water solution to produce higher oligomers. The reaction occurs in a nonmonotonic fashion and is apparently linked with the oscillatory chiral conversion of amino acids reported previously456 . The S-and Renantiomers appear to differ somewhat in their dynamics, a phenomenon that may arise from the presence of different amounts of trace impurities in the commercial samples . ...
In earlier studies, we showed that certain low-molecular-weight carboxylic acids (profens, amino acids, hydroxy acids) can
undergo spontaneous in vitro chiral conversion accompanied by condensation to from oligomers, and we proposed two simple models to describe these processes.
Here, we present the results of investigations using non-chiral high-performance liquid chromatography with diode array detector
(HPLC-DAD) and mass spectrometry (MS) on the dynamics of peptidization of S-, R-, and rac-phenylglycine dissolved in 70% aqueous ethanol and stored for times up to one year. The experimental results demonstrate
that peptidization of phenylglycine can occur in an oscillatory fashion. We also describe, and carry out simulations with,
three models that capture key aspects of the oscillatory condensation and chiral conversion processes.
... In papers, [1][2][3] we reported on the chiral conversion of S-(þ)-ibuprofen, S-(þ)-naproxen, S,R-(AE)-2phenylpropionic acid, S-(þ)-flurbiprofen, R-(-)-flurbiprofen, and S,R-(AE)-ketoprofen. In papers, [4][5][6] we reported on the analogous behavior of L-alanine, L-a-phenylalanine, and L-tyrosine. [4][5][6] In papers, [7,8] the oscillatory chiral conversion of the selected hydroxy acids, i.e., L-lactic acid, R-a-hydroxybutyric acid, S-a-hydroxybutyric acid, R-mandelic acid, and S-mandelic acid, was confirmed. ...
... In papers, [4][5][6] we reported on the analogous behavior of L-alanine, L-a-phenylalanine, and L-tyrosine. [4][5][6] In papers, [7,8] the oscillatory chiral conversion of the selected hydroxy acids, i.e., L-lactic acid, R-a-hydroxybutyric acid, S-a-hydroxybutyric acid, R-mandelic acid, and S-mandelic acid, was confirmed. Most of the reported cases of chiral conversion took place with acid samples dissolved in aqueous ethanol. ...
... Owing to the results of our earlier studies, nowadays the phenomenon of the spontaneous oscillatory in vitro chiral conversion of the lowmolecular weight carboxylic acids seems relatively common, which made us curious to know the scope of its universality and the structural limits thereof. All cases of the oscillatory chiral conversion so far described in papers, [1][2][3][4][5][6][7][8] referred to carboxylic acids with the asymmetry center in position a, hence neighboring carboxylic functionality. It was the aim of this study, to examine one more low molecular weight hydroxy acid, this time with the hydroxyl group placed in position b, hence with the asymmetry center separated with one methylene unit from carboxyl functionality acting as spacer. ...
Earlier we have shown that chiral aliphatic hydroxy acids, i.e., L-lactic acid, R-α-hydroxybutyric acid, and S-α-hydroxybutyric acid, can undergo oscillatory in vitro chiral conversion, exhibiting oscillatory changes in the chromatographic retention parameter (R F ) and the specific rotation ([α] D ) for the periods of two or even many more weeks after preparation of the solutions in aqueous ethanol. As the phenomenon of spontaneous oscillatory chiral conversion with low molecular weight carboxylic acids dissolved in the abiotic aqueous media seems to be of a relatively general nature, it made us curious to examine steric limitations of this process. One essential question that we posed in this study regards the impact of the distance between the carboxylic group of the acid and the asymmetry center in the chiral molecule on its ability to undergo chiral conversion. With the earlier examined lactic acid and two α-hydroxybutyric acids, the hydroxyl group was placed in position α, hence the asymmetry center was directly neighboring the carboxylic group. It was the aim of this study, to examine one more low molecular weight hydroxy acid with the hydroxyl group placed in position β, hence with the asymmetry center separated by one methylene unit from carboxyl functionality acting as spacer. To this effect, we selected R-β-hydroxybutyric acid and investigated its ability to undergo a spontaneous oscillatory in vitro chiral conversion in the abiotic aqueous medium, for this purpose using thin layer chromatography and polarimetry as the best suiting analytical techniques. It was experimentally established that R-β-hydroxybutyric acid – similar to the earlier scrutinized α-hydroxy acids – can undergo the oscillatory chiral conversion and the methylene spacer between the carboxyl and the hydroxyl functionality cannot prevent this particular compound from undergoing steric conversion.
... Our experiments were performed on samples of these dissolved in low-molecular-weight solvents, basically ethanol-water mixtures. The results obtained are reported elsewhere [11,12]. Chiral inversion of the amino acids is represented in simplified form as: L-amino acid ↔ keto-enol tautomer ↔ D-amino acid (1) A detailed model of the oscillator was proposed [11], providing the basis of a mechanistic understanding of the oscillatory chiral inversion of the profens and amino acids. ...
... -results from our previous studies with L-phenylalanine and Ltyrosine [11,12]; ...
... If we compare these results with those obtained earlier for Lphenylalanine and L-tyrosine [11,12], it becomes clear that the behavior of L-alanine is different from that of the other two acids. The amplitude of the oscillations for L-alanine is less than for L-phenylalanine and greater than for L-tyrosine. ...
In recent TLC and polarimetric studies we showed, for the first time, the tendency of profen drugs to undergo spontaneous oscillatory chiral inversion in vitro. Because profen drugs are chiral propionic acid derivatives, we sought other chiral compounds with similar chemical structures and hence a similar tendency to spontaneously change their steric configuration. We have previously demonstrated that L-α-phenylalanine and L-tyrosine also undergo oscillatory in-vitro chiral inversion. We also demonstrated the effect of temperature and mixing on the process, and proposed a detailed model of the oscillator, providing the basis for mechanistic understanding of the oscillatory chiral inversion of these compounds. In this study we focused our attention on L-alanine, another amino acid with a chemical structure formally derived from propionic acid, and, again, by use of TLC and polarimetry, investigated the tendency of L-alanine to undergo oscillatory in-vitro chiral inversion when dissolved in neutral, acidic, and basic solvents. We also studied the effect of temperature and sample mixing. It was confirmed that L-alanine also undergoes chiral inversion. The dynamics of the process are specific to each compound.
We present an overview of our studies on the hampering effect of heavy water (D2O) on spontaneous oscillatory peptidization of selected proteinogenic α-amino acids. The investigated set of compounds included three endogenous and two exogenous species. The experiments were carried out with use of high-performance liquid chromatography (HPLC), mass spectrometry (MS) and scanning electron microscopy (SEM). These techniques were chosen to demonstrate spontaneous oscillatory peptidization of α-amino acids in an absence of D2O (HPLC) and the hampering effect of D2O on peptidization (HPLC, MS and SEM). The HPLC analyses were carried out at 21 ± 0.5°C with each α-amino acid freshly dissolved in the binary liquid mixture of organic solvent + H2O, 70:30 (v/v) or in pure D2O for several dozen hours or several hours, respectively. The analyses with use of MS and SEM were carried out, respectively, after 7 days and 1 month of sample storage period in the darkness at 21 ± 0.5°C and for these experiments, each α-amino acid was dissolved in the liquid mixture of organic solvent + X, 70:30 (v/v), where X: H2O + D2O in volume proportions from 30:0 to 0:30. The results obtained with use of HPLC, MS and SEM point out to the strong hampering effect of D2O on the oscillations and peptidization yields, yet the dynamics of these processes significantly depends on chemical structure of a given α-amino acid.
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.
Enantiomer separations have been one of the most important and, simultaneously, one of the most difficult to accomplish analytical (and technological) tasks, present at the top of separation scientists' agenda since the early sixties of the last century. Awareness of their importance has been awakened by an infamous case of the racemic drug thalidomide, a widely advertised sedative drug which had unexpected teratogenic activity in pregnant women that resulted in thousands of 'flipper babies' born in the late fifties and the early sixties in many countries around the world. Since that time, separation scientists have developed numerous methods for enantiomer separation, basically by use of gas chromatography (GC), high-performance liquid chromatography (HPLC), and capillary electrophoresis (CE). In this respect, planar chromatography has remained to a large extent an undervalued enantiomer separation technique, despite separation performance sufficient to separate a pair of enantiomers. The large number of GC, HPLC, and CE enantiomer separation strategies and methods developed are evidence that - once confronted with this particular and no doubt very important challenge - instrumental chromatographic techniques have lost if not face, then, to a large extent, their reputation as robust, universal, and efficient separation tools. In these circumstances, planar chromatography on silica gel seems a very promising and tempting alternative, basically because of the advantageous properties of microcrystalline silica gel and the 2D effective diffusion available only in planar chromatographic mode. Enhancement of the enantiomer separating power of the silica gel by simple mechanical impregnation with a properly chosen chiral selector, and additional coupling of this with efficient instrumental detection (e.g. densitometric, DAD, or mass spectrometric) can yield in a simple, robust, and universal tool for separation of enantiomers comparable with the long-established chromatographic enantiomer-separation techniques. In this mini review, favourable preconditions for silica-gel-based planar chromatographic separation of enantiomers which can elevate planar chromatography to the status of leading tool for separation of enantiomers are discussed. Further improvements which can enhance the enantiomer separation performance of chiral planar chromatography are also indicated.
