Displaying all 11 publications

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  1. Arsad SR, Maarof H, Wan Ibrahim WA, Aboul-Enein HY
    Chirality, 2016 Mar;28(3):209-14.
    PMID: 26708260 DOI: 10.1002/chir.22554
    A molecular docking study, using molecular mechanics calculations with AutoDock and semi-empirical PM3 calculations, was used to predict the enantiodiscrimination of heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCD) and ketoconazole (KTZ) enantiomers. A Density Functional Theory (DFT) single-point calculation at the level of B3LYP/6-311G (d,p) was performed for the PM3-optimized complexes to obtain more accurate binding energy and the electronic structures of the complexes. The difference in energies of the inclusion complexes between the KTZ enantiomers and TMβCD is probably a measure of chiral discrimination, which results in the separation of the enantiomers as observed in the experimental studies.
  2. Wan Ibrahim WA, Arsad SR, Maarof H, Sanagi MM, Aboul-Enein HY
    Chirality, 2015 Mar;27(3):223-7.
    PMID: 25523071 DOI: 10.1002/chir.22416
    This work aimed to develop a chiral separation method of ketoconazole enantiomers using electrokinetic chromatography. The separation was achieved using heptakis (2, 3, 6-tri-O-methyl)-β-cyclodextrin (TMβCD), a commonly used chiral selector (CS), as it is relatively inexpensive and has a low UV absorbance in addition to an anionic surfactant, sodium dodecyl sulfate (SDS). The influence of TMβCD concentration, phosphate buffer concentration, SDS concentration, buffer pH, and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 2.5 containing 20 mM TMβCD, 5 mM SDS, and 1.0% (v/v) methanol with an applied voltage of 25 kV at 25 °C with a 5-s injection time (hydrodynamic injection). The four ketoconazole stereoisomers were successfully resolved for the first time within 17 min (total analysis time was 28 min including capillary conditioning). The migration time precision of this method was examined to give repeatability and reproducibility with RSDs ≤5.80% (n =3) and RSDs ≤8.88% (n =9), respectively.
  3. Bayat S, Tejo BA, Salleh AB, Abdmalek E, Normi YM, Abdul Rahman MB
    Chirality, 2013 Nov;25(11):726-34.
    PMID: 23966316 DOI: 10.1002/chir.22205
    A series of tripeptide organocatalysts containing a secondary amine group and two amino acids with polar side chain units were developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4-nitrobenzaldehyde and cyclohexanone. The effectiveness of short polar peptides as asymmetric catalysts in aldol reactions to attain high yields of enantio- and diastereoselective isomers were investigated. In a comparison, glutamic acid and histidine produced higher % ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric aldol addition reaction in aqueous media.
  4. Wan Ibrahim WA, Abd Wahib SM, Hermawan D, Sanagi MM, Aboul-Enein HY
    Chirality, 2013 Jun;25(6):328-35.
    PMID: 23716264 DOI: 10.1002/chir.22156
    Cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) method was developed for simultaneous enantioseparation of three imidazole drugs namely tioconazole, isoconazole and fenticonazole. Three easily available and inexpensive cyclodextrins namely 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD) and heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) were evaluated to discriminate the six stereoisomers of the drugs. However, none of the three CDs gave a complete enantioseparation of the drugs. Effective enantioseparation of tioconazole, isoconazole and fenticonazole was achieved using a combination of 35 mM HP-γ-CD and 10 mM DM-β-CD as chiral selectors. The best separation using both HP-γ-CD and DM-β-CD (35 mM:10 mM) as chiral selectors were accomplished in background electrolyte (BGE) containing 35 mM phosphate buffer (pH 7.0), 50 mM sodium dodecyl sulfate (SDS) and 15% (v/v) acetonitrile at 27 kV and 30 °C with all peaks resolved in less than 15 min with resolutions, Rs 1.90-27.22 and peak efficiencies, N > 180 000. The developed method was linear over the concentration range of 25-200 mg l(-1) (r(2) > 0.998) and the detection limits (S/N = 3) of the three imidazole drugs were found to be 2.7-7.7 mg l(-1). The CD-MEKC method was successfully applied to the determination of the three imidazole drugs in spiked human urine sample and commercial cream formulation of tioconazole and isoconazole with good recovery (93.6-106.2%) and good RSDs ranging from 2.30-6.8%.
  5. Agustian J, Kamaruddin AH, Aboul-Enein HY
    Chirality, 2012 May;24(5):356-67.
    PMID: 22517322 DOI: 10.1002/chir.22019
    Because chiral liquid chromatography (LC) could become a powerful tool to estimate racemic atenolol quantity, excellent enantiomeric separation should be produced during data acquisition for satisfactory observation of atenolol concentrations throughout the racemic resolution processes. Selection of chiral LC column and analytical protocol that fulfill demands of the ultra fast LC analysis is essential. This article describes the characteristics of atenolol chromatographic separation that resulted from different resolution media and analytical protocols with the use of a Chiralcel® OD column. The chromatograms showed quite different characteristics of the separation process. The single enantiomer and racemic atenolol could be recognized by the Chiralcel® OD column in less than 20 min. Symmetrical peaks were obtained; however, several protocols produced peaks with wide bases and slanted baselines. Observations showed that efficient enantioresolution of racemic atenolol was obtained at slow mobile phase flow rate, decreased concentration of amine-type modifier but increased alcohol content in mobile phase and highest ultraviolet detection wavelength were required. The optimal ultra fast LC protocol enables to reduce and eliminate the peaks of either the atenolol solvent or the buffers and provided the highest peak intensities of both atenolol enantiomers.
  6. Wan Ibrahim WA, Abd Wahib SM, Hermawan D, Sanagi MM, Aboul-Enein HY
    Chirality, 2012 Mar;24(3):252-4.
    PMID: 22271616 DOI: 10.1002/chir.21990
    A cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) technique has been developed for enantioseparation of vinpocetine using an inexpensive 2-hydroxypropyl-β-CD (HP-β-CD) as the chiral selector (CS). The best chiral separation was achieved using 40 mM HP-β-CD as the CS in 50 mM phosphate buffer (pH 7.0) consisting of 40 mM sodium dodecyl sulfate (SDS) at a separation temperature and separation voltage of 25°C and 25 kV, respectively. To the author's best knowledge, this is the first CD-MEKC study able to successfully separate the four stereoisomer of vinpocetine in separation time of 9.5 min and resolution of 1.04-3.87.
  7. Kamaruddin AH, Uzir MH, Aboul-Enein HY, Halim HN
    Chirality, 2009 Apr;21(4):449-67.
    PMID: 18655180 DOI: 10.1002/chir.20619
    This review tracks a decade of dynamic kinetic resolution developments with a biocatalytic inclination using enzymatic/microbial means for the resolution part followed by the racemization reactions either by means of enzymatic or chemocatalyst. These fast developments are due to the ability of the biocatalysts to significantly reduce the number of synthetic steps which are common for conventional synthesis. Future developments in novel reactions and products of dynamic kinetic resolutions should consider factors that are needed to be extracted at the early synthetic stage to avoid inhibition at scale-up stage have been highlighted.
  8. Azhari NR, Yahaya N, Mohd Suah FBM, Prabu S, Yih Hui B, Shahriman MS, et al.
    Chirality, 2021 01;33(1):37-50.
    PMID: 33197086 DOI: 10.1002/chir.23285
    A chiral separation method coupled with capillary electrophoresis (CE) analysis for ketoconazole and miconazole enantiomers using chiral selectors such as β-cyclodextrin (β-CD) and hydroxypropyl-β-CD (HP-β-CD) was developed in this study, which included the optimisation, validation and application of the method on the antifungal cream samples. The formation of inclusion complex between the hosts (β-CD and HP-β-CD) and guests (ketoconazole and miconazole) were compared and analysed using ultraviolet-visible spectrophotometry, nuclear magnetic resonance (NMR) spectroscopy and molecular docking methods. Results from the study showed that in a concentration that ranged between 0.25 and 50 mg L-1 , the linear calibration curves of each enantiomer had a high coefficient of regression (R2 > 0.999), low limit of detection (0.075 mg L-1 ) and low limit of quantification (0.25 mg L-1 ). The relative standard deviation (RSD) of the intraday and interday analyses ranged from 0.79% to 8.01% and 3.30% to 11.43%, respectively, while the recoveries ranged from 82.0% to 105.7% (RSD < 7%, n = 3). The most probable structure of the inclusion complexes was proposed based on the findings from the molecular docking studies conducted using the PatchDock server.
  9. Agustian J, Kamaruddin AH, Aboul-Enein HY
    Chirality, 2017 Jul;29(7):376-385.
    PMID: 28439969 DOI: 10.1002/chir.22702
    As the (R)-enantiomer of racemic atenolol has no β-blocking activity and no lack of side effects, switching from the racemate to the (S)-atenolol is more favorable. Transesterification of racemic atenolol using free enzymes investigated as a resource to resolve the racemate via this method is limited. Screenings of enzyme, medium, and acetyl donor were conducted first to give Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate. A statistical design of the experiment was then developed using Central Composite Design on some operational factors, which resulted in the conversions of 11.70-61.91% and substrate enantiomeric excess (ee) of 7.31-100%. The quadratic models are acceptable with R2 of 95.13% (conversion) and 89.63% (ee). The predicted values match the observed values reasonably well. Temperature, agitation speed, and substrate molar ratio factor have low effects on conversion and ee, but enzyme loading affects the responses highly. The interaction of temperature-agitation speed and temperature-substrate molar ratio show significant effects on conversion, while temperature-agitation speed, temperature-substrate molar ratio, and agitation speed-substrate molar ratio affect ee highly. Optimum conditions for the use of Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate were found at 45°C, 175 rpm, 2000 U, and 1:3.6 substrate molar ratio.
  10. Obaid A, Mohd Jamil AK, Saharin SM, Mohamad S
    Chirality, 2021 11;33(11):810-823.
    PMID: 34486177 DOI: 10.1002/chir.23354
    A simple, inexpensive but effective approach for visual chiral recognition of ketoprofen enantiomers was developed using L-cysteine capped silver nanoparticles (L-Cys-AgNPs) as a colorimetric sensor. Upon the addition of R-ketoprofen to L-Cys-AgNPs, rapid aggregation occurred, and the solution changed color from yellow to green. However, the presence of S-ketoprofen did not induce any color change. The results were characterized using UV-Vis, FESEM, FT-IR, SERS, and zeta potential measurements. The chiral assay described in this work is easily distinguished with the naked eyes or using a UV-Vis spectrometer. The sensor revealed a good linear response to ketoprofen enantiomers in the concentration range of 8.33-33.3 μM with a detection limit of 4.52 μM and relative standard deviation of 3.73%. The proposed method was utilized for the determination of ketoprofen racemic mixtures in water samples and commercial tablets. The method excels by its simplicity, low cost, and good availability of materials.
  11. Agustian J, Kamaruddin AH, Aboul-Enein HY
    Chirality, 2017 Dec;29(12):847-853.
    PMID: 28963758 DOI: 10.1002/chir.22769
    Kinetic resolution of (R,S)-atenolol is a faster strategy to produce (S)-atenolol. Since this racemate is a less soluble compound, resolution of its ester offers high concentrations in the process. A good analytical method is required to observe the enantiomer concentrations. This paper described application of ultra-fast liquid chromatography on the atenolol ester separation using different resolution media and analytical procedures. Chiralcel OD column resolved the ester. The chromatograms indicated different characteristics of the process. The enantiomers could be recognized by the column in less than 1 (one) hour. Symmetrical peaks were obtained, but several procedures produced peaks with wide bases and slanted baselines. Efficient enantioresolution was obtained at high mobile phase flow rate, decreased concentration of amine-type modifier, but increased alcohol content in the mobile phase. High UV detection wavelength was required. At 1.0 mL/min, the (90/10/0.5) composition resulted α = 1.46 and RS  = 0.9998 that were good separation.
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