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Comparison of the physicochemical properties of macrocyclic antibiotics as potential chiral selectors
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Since their introduction by Armstrong in 1994, macrocyclic antibiotic-based chiral stationary phases have proven their applicability for the chiral resolution of various types of racemates. The unique structure of macrocyclic glycopeptides and their large variety of interactive sites (e.g., hydrophobic pockets, hydroxyl, amino and carboxyl groups,...
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Helicenes are interesting chiral molecules without asymmetric carbon atoms but with intrinsic chirality. Functionalized 5-Aza[5]helicenes can form non-covalent complexes with anticancer drugs and therefore be potential carriers. The paper highlights the different structural selectivity for DNA binding for two enantiopure compounds and the influence...
Citations
... In our study, a vancomycin-based chiral stationary phase was used. Using this macrocyclic glycopeptide molecule as a stationary phase results in a myriad of possible interaction mechanisms available to the analyte due to the chemical variety of moieties present on the vancomycin structure (hydrogen-bonding, electrostatic and short-distance van der Waals interactions) [38]. The Pirkle's rule states that three points of contact must be made for a unique enantiomeric chemical interaction to take place [39]. ...
Purpose:
Methorphan exists in two enantiomeric forms including dextromethorphan and levomethorphan. Dextromethorphan is an over-the-counter antitussive drug, whereas levomethorphan is strictly controlled as a narcotic drug. Chiral analysis of methorphan could, therefore, assist clinicians and forensic experts in differentiating between illicit and therapeutic use and in tracing the source of the drug.
Methods:
A method for enantiomeric separation and quantification of levomethorphan and dextromethorphan in human hair was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hair was extracted in hydrochloric acid/methanol (1:20, v/v). The supernatant were separated using a Supelco Astec Chirobiotic™ V2 column (250 × 2.1 mm, i.d., 5 μm particle size) and analyzed on a triple quadrupole linear ion trap mass spectrometer in multiple reaction monitoring mode.
Results:
The limits of detection for dextromethorphan and levomethorphan were 2 and 1 pg/mg, respectively; the lower limit of quantification was 2 pg/mg for both drugs. Good linearity (r > 0.995) was observed for both analytes over the linear range. Precision values were below 10% for both analytes; accuracy values ranged from 87.5 to 101%. The extraction recoveries were 78.3-98.4%, and matrix effects were 70.5-88.6%. This method was applied to human hair samples from 120 people suspected of methorphan use to further distinguish the drug chirality. Dextromethorphan was detected in all 120 samples at a concentration range of 2.7-19,100 pg/mg, whereas levomethorphan was not detected in any sample.
Conclusions:
A sensitive quantitative method was established for the enantiomeric separation of dextromethorphan and levomethorphan in hair. This is the first study to achieve chiral analysis of methorphan in human hair.
... Teicoplanin has an isoelectric point of ~ 3.5, and electrostatic interactions are considered one of the dominant interactions occurring between the analytes and stationary phase. As the chiral selector itself is ionizable, changes to pH affects its degree of ionization as well as the analyte (Ilisz et al. 2013). Teicoplanin has been successfully applied for the simultaneous enantioseparation of indoprofen, naproxen, ketoprofen and ibuprofen as well as its metabolites carboxyibuprofen and 2-hydroxyibuprofen (Camacho-Muñoz and Kasprzyk-Hordern 2017). ...
Non-steroidal anti-inflammatory drugs (NSAIDs) are found in the aquatic environment globally. Such drugs including naproxen, ibuprofen and ketoprofen are chiral molecules. Enantiomers of those drugs have identical physicochemical properties but can behave and interact differently in chiral environments due to differences in their three-dimensional shape. This results in enantiospecific differences in environmental fate and toxicity, which is often overlooked. Therefore, we review the analytical methods, occurrence and fate, and toxicity of chiral non-steroidal anti-inflammatory drugs at the enantiomeric level. The advancement of enantioselective chromatography methods, particularly the use of polysaccharide-based stationary phases, has enabled trace determination of enantiomers in complex environmental matrices. Macrocosm and microcosm studies of engineered and natural environments revealed that such drugs can undergo both enantioselective degradation and chiral inversion. Enantioselectivity has been reported during wastewater treatment, in surface waters and in agricultural soils. The use of microcosms spiked with individual enantiomers over racemates is essential to evaluate these degradation and inversion fate processes. The chiral inversion process whereby one enantiomer converts into its antipode can be significant if the more toxic enantiomers are formed. Existing enantiospecific effect studies report less than an order of magnitude difference in enantiomer toxicity. However, toxicity data for enantiomers are limited and further research is needed to better appreciate the environmental risk at the enantiomeric level.
... Most quinoles are racemic and, hence, are separated because only one enantiomer is pharmaceutically active, while the other may be toxic, ballast, or inactive. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Therefore, to avoid the toxicities, side effects, and other problems, these quinolones should be administered in the form of pharmaceutically active pure enantiomers. The scientists, clinicians, industrialists, and government authorities are asking data on the chiral resolution of biologically important molecules including quinolones. ...
A new HPLC method was developed for the enantio-separation and chiral recognition mechanism of quinolones (lomefloxacine, ofloxacine, primaquine and quinacrine) on Vancomycin CSP. The column used was Chirabiotic V column (150 x 4.6 mm, 5.0 μm) with two mobile phases i.e. (I) MeOH:ACN:H2O:TEA (50:30:20:0.1%) and (II) MeOH:ACN: H2O:TEA (70:10:20:0.1%) at 1.0 mL/minute flow rate with various UV detection. The values of retention, separation and resolution factors in a solvent system I were ranged from 2.20 to 5.05, 1.70 to 1.96 and 1.75 to 2.20 while these values were 1.93 to 6.85, 1.62 & 2.01 and 2.30 & 2.40 in solvent system II. The limits of detection and quantification were ranged from 8.0 to 10.5 µg and 24.4 to 33.5 µg. The resolution was controlled mainly by π-π interactions along with other forces like hydrogen bonding, van der Waal’s forces, steric effects, etc. The determination of the chiral recognition mechanism may be beneficial to separate other racemates successfully. The method is fast precise and efficient and may be utilized to analyze enantiomers of the reported quinolones.
... Most quinoles are racemic and, hence, are separated because only one enantiomer is pharmaceutically active, while the other may be toxic, ballast, or inactive. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Therefore, to avoid the toxicities, side effects, and other problems, these quinolones should be administered in the form of pharmaceutically active pure enantiomers. The scientists, clinicians, industrialists, and government authorities are asking data on the chiral resolution of biologically important molecules including quinolones. ...
New chiral high‐performance liquid chromatography (HPLC) method for the enantiomeric resolution of quinolones is developed and described. The column used was Chirobiotic T (150 × 4.6 mm, 5.0 μm). Three mobile phases used were MeOH:ACN:Water:TEA (70:10:20:0.1%), (60:30:10:0.1%), and (50:30:20:0.1%). The flow rate of the mobile phases was 1.0 mL/min with UV detection at different wavelengths. The values of retention, resolution, and separation factors ranged from 1.5 to 6.0, 1.80 to 2.25, and 2.86 to 6.0, respectively. The limit of detection and quantification ranged from 4.0 to 12 ng and 40 to 52 ng, respectively. The modeling studies indicated strong interactions of R‐enantiomers with teicoplanin chiral selector than S‐enantiomers. The supra molecular mechanism of the chiral recognition was established by modeling and chromatographic studies. It was observed that hydrogen bondings and π‐π interactions are the major forces for chiral separation. The present chiral HPLC method may be used for enantiomeric resolution of quinolones in any matrices.
... Using this macrocyclic glycopeptide molecule as a stationary phase results in a myriad of possible interaction/retention mechanisms available to the analyte due to the chemical variety of moieties present on the vancomycin structure ( Figure 2) (14). For this particular CSP these interactions may comprise: inclusion into the hydrophobic pocket, π-π complexation, dipole stacking, hydrogen-bonding, electrostatic and short-distance van der Waals interactions and steric effects (15,16). The Pirkle's rule states that three points of contact must be made for a unique enantiomeric chemical interaction to take place (17,18). ...
To determine the true enantiomeric composition of methamphetamine urine drug testing results, chiral separation of dextro
(d) and levo (l) enantiomers is necessary. While enantiomeric separation of methamphetamine has traditionally been accomplished using gas
chromatography–mass spectrometry (GC–MS), chiral separation of d- and l-methamphetamine by chiral stationary phase (CSP) liquid chromatography–mass spectrometry/mass spectrometry (LC–MS-MS) has
proved more reliable. Chirally selective detection of methamphetamine by GC–MS is often performed using l-N-trifluoroacetyl-prolyl chloride (TPC). l-TPC, a chiral compound, is known to have impurities that can affect the chiral composition percentages of the methamphetamine
sample, potentially leading to inaccurate patient results. The comparative analysis of the samples run by GC and LC methods
showed preferential bias of the GC method for producing error rates, consistent with previous research, of 8–19%. The CSP-LC–MS-MS
method produces percent deviation errors of <2%. Additionally, the GC method failed to produce results that were 100% d- or l-isomer even for enantiomerically pure standards. A higher rate of d- and l-methamphetamine isomer racemization is seen in samples when analyzed by GC–MS using l-TPC-derivatizing agent. This racemization is not seen when these samples are tested with CSP-LC–MS-MS. Thus, a more accurate
method of enantiomeric analysis is provided by CSP-LC–MS-MS.
... grupy hydroksylowe, aminowe, karboksylowe, aromatyczne i halogenki. To właśnie grupy funkcyjne odpowiedzialne są za ich selektywność, a modyfikowanie struktury molekularnej tych związków chemicznych może zwiększać ich możliwości zastosowania [38]. Jako chiralne fazy stacjonarne stosuje się glikopeptydy, ansamycyny i tiostrepton. ...
http://dach.ich.uph.edu.pl/cs/download/cs_vol7_no2/_cs_2015_99-128.pdf
... HPLC enantioseparations of -amino acids have been performed by both indirect and direct methods. In the past decade, new types of chiral derivatizing agents and chiral stationary phases (CSPs) have been introduced for the enantioseparation of -amino acids and the results have been surveyed in several review papers [17][18][19][20][21][22][23][24][25][26][27][28]. The enantioselectivities of different macrocyclic glycopeptide-based CSPs have been compared by the application of monoterpene-based 2-aminocarboxylic acids [29]. ...
Stereoselective HPLC separations of five sterically constrained monoterpene-based 2-aminocarboxylic acid enantiomers were carried out by using the newly developed zwitterionic chiral stationary phases Chiralpak ZWIX(+)™ and ZWIX(-)™ based on Cinchona alkaloid. In order to optimize the retention and enantioselectivity parameters, the ratio of the different organic solvents in the mobile phase and the nature of the acid and base additives (counter- and co-ions) were systematically varied. The effects of structure variants of the analytes on the resolution were investigated. The elution sequence was determined in all cases and was observed to be opposite on ZWIX(+)™ and on ZWIX(-)™. This article is protected by copyright. All rights reserved.
... For the enantioseparation of β-amino acids, new types of chiral derivatizing agents and chiral stationary phases (CSPs) have been applied, and the results of that work can be found in the literature. [9][10][11][12][13][14][15][16][17][18] Enantiomer separations are inherently challenging, because enantiomers have exactly the same properties in an anisotropic environment. Enantioseparation is usually achieved through the formation of transitional diastereomeric complexes between the analytes (selectand enantiomers, SAs) and the chiral selector (SO) as part of the CSP. ...
The effects of temperature on the chiral recognition of cyclic β-amino acid enantiomers on zwitterionic [Chiralpak ZWIX(+) and ZWIX(-)] chiral stationary phases were investigated. Experiments were performed at different mobile phase compositions and under 10°C column temperature increments in the temperature range 10-50°C. Apparent thermodynamic parameters and Tiso values were calculated from plots of ln k and ln α versus 1/T, respectively. Unusual temperature behavior was observed, especially on the ZWIX(-) column, where the application of MeOH/MeCN (50/50 v/v) containing 25 mM triethylamine and 50 mM formic acid as mobile phase led to nonlinear van't Hoff plots and increasing retention time with increasing temperature. On both columns, both enthalpically and entropically driven separations were observed. Chirality 00:000-000, 2014. © 2014 Wiley Periodicals, Inc.
The enantiomers of quinolone racemates were resolved using chiral crown ether within 8 minutes. Thermodynamics data and modeling results were used to determine chiral recognition mechanism. The column used was (+)-Crownpack column (250 mm × 4.6 mm, 5 µm) with three mobile phases I: ACN:Water (80:20) + 10 mM H2SO4 and 10 mM CH3COONH4, II: ACN:Water (80:20) + 20 mM perchloric acid and III: EtOH:Water (80:20) + 20 mM perchloric acid. The flow rate of the mobile phases was 1.0 mL/min with UV detection at different wavelengths. The ranges of retention (k), separation (α), and resolution (Rs) factors were 1.00 to 5.40, 1.37 to 2.00 and 1.50 to 3.30. The tailing factor was 1.o for all peaks with 900 to 2325 as the number of theoretical plates were 8.0 to 10.0 and 32.4 to 22.1 µg. The difference in enthalpy, entropy and free energy varied in the range of -0.350 to -0.024, 18.74 x 10⁻⁴ to 3.94 x 10⁻⁴ and -0.918 to -0.143, respectively. The thermodynamic and docking results showed chiral discrimination due to physical forces of amnio group cations penetration into the chiral cavity of the chiral selector following hydrogen bindings. The binding energy of S-enantiomers was higher than R-enantiomers; confirming stronger binding of S-enantiomers with CSP than R-enantiomers. The described chiral-HPLC method was used for the analysis of the quinolone enantiomers in urine samples and the results were quite satisfactory. Therefore, the reported method may be used for the enantiomeric separation of quinolone enantiomers in urine samples.
Sixteen pairs of enantiomeric dipeptides were separated on four chiral ion-exchanger-type stationary phases based on Cinchona alkaloids. Anion-exchangers (QN-AX, QD-AX) and zwitterionic phases [ZWIX(+)™ and ZWIX(-)™] were studied in a comparative manner. The effects of the nature and concentrations of the mobile phase solvent components and organic salt additives on analyte retention and enantioseparation were systematically studied in order to get a deeper insight into the enantiorecognition mechanism. Moreover, experiments were performed in the temperature range 10-50 °C to calculate thermodynamic parameters like changes in standard enthalpy, Δ(ΔH°), entropy, Δ(ΔS°), and free energy, Δ(ΔG°) on the basis of van't Hoff plots derived from the ln α vs. 1/T curves. Elution sequences of the dipeptides were determined in all cases and, with a few exceptions, they were found to be opposite on the pseudoenantiomeric stationary phases as of QN-AX/QD-AX and of ZWIX(+) and ZWIX(-). The stereoselective retention mechanism is based on electrostatically driven intermolecular interactions supported by additional interaction increments mainly determined by the absolute configuration of the chiral C8 and C9 atoms of the quinine and quinidine moieties.
