Type Of Organic Modifier Research Articles

Determination of Enantiomeric Impurity in Tegoprazan Drug Substance by HPLC

ABSTRACTTegoprazan is a novel potassium‐competitive acid blocker used for gastroesophageal reflux disease. It is administered as the (S)‐ and (R)‐enantiomers are considered impurities that should be controlled. The objective of this work was to establish a chiral analytical method for the determination of the enantiomeric impurity of tegoprazan in the drug substance by high‐performance liquid chromatography (HPLC). Enantioselective separation was performed on a Chiralpak alpha1‐acid glycoprotein (AGP) column (4.6 mm × 250 mm, 5.0 µm) at 30°C utilizing a mobile phase consisting of 5 mmol L−1 ammonium acetate buffer (pH 6.0) and 2‐propanol (93:7, v/v) at a flow rate of 0.7 mL min−1 with a detection wavelength of 220 nm. The effects of chromatographic conditions, including the type and concentration of organic modifiers, buffer pH, buffer concentration, flow rate, and column temperature, were thoroughly investigated. Under the optimized conditions, the resolution between (S)‐ and (R)‐tegoprazan was greater than 3.0. Moreover, the developed method was validated in terms of linearity, limits of detection (LOD) and quantitation (LOQ), accuracy, precision, and stability. Each enantiomer showed a good linear relationship over the concentration range of 1.0–100 µg mL−1, with the correlation coefficient of 0.9999. The LOD and LOQ were 0.1 and 0.3 µg mL−1, respectively. In addition, the recoveries ranged from 94.10% to 99.39% with a relative standard deviation (RSD) of 1.9%. Application of this proposed method to determine the enantiomeric impurity in tegoprazan drug substance proved satisfactory. The quantitative results were about 2.0%, demonstrating that enantiomeric impurity remained in the tegoprazan drug substance and should be controlled in the quality criteria.

Design of mucoadhesive thiomer/organically modified montmorillonite nanocomposites: Evaluation of controlled drug release

This present work introduces a novel thiomer/nanoclay nanocomposite material with mucoadhesive and controlled release properties that has been prepared and evaluated as a potential drug carrier system. This hybrid material is based on thiolated alginate and organically modified montmorillonite (MMT). Alginate thiomer was synthesized by immobilization of l-cysteine on alginate backbone via carbodiimide reaction. Thiol/disulfide groups were identified and quantified by FT-IR, 1H NMR and Ellman's method. Rheological assays as preliminary in vitro mucoadhesion test using mucin show that complex viscosity increases until ∼7-fold compared to unmodified alginate/mucin, and G’ > G″ is present in thiomers, compared with G” > G′ present in unmodified alginate, which indicate strong interactions between thiomer and mucin. Thiomer/nanoclay nanocomposites were prepared by film casting method and characterized by TGA, XRD, TEM and rheometry. Nanocomposites maintain rheological properties showed by thiolated alginate when they are tested with mucin, increasing complex viscosity until ∼8-fold respect a nanocomposite formulation based on unmodified alginate. The release of deltamethrin from nanocomposite films was studied and the impact of the amount of nanoclay (0–7%) and four types of organic modifiers in MMT were evaluated. Different kinetic models were evaluated in order to study the mechanism involved in drug release. Zero, first, Higuchi and Korsmeyer-Peppas model were evaluated, being the last two kinetic models the ones with better fitting and higher values of R2. The presence of nanoclay on the formulation influence significantly (P < 0.001) deltamethrin short-term release showing an anomalous and Case-II transport mechanism. Compared with a Fickian diffusion when nanoclay is absent in the formulation. The diffusion coefficient D could decrease until ∼7-fold compared to a formulation without nanoclay. Long-term release is significantly influenced (P < 0.0001) by the chemical nature of organic modifier used on nanoclay and its interaction with the drug. This thiomer/nanoclay nanocomposite material could be a useful prospect as a mucoadhesive material for drug carrier with controlled drug release properties.

Investigation on improvement of enantioseparation based on clindamycin phosphate by chiral deep eutectic solvents in capillary electrophoresis.

In this work, the potential synergetic effect between deep eutectic solvents and an antibiotic chiral selector (clindamycin phosphate) for enantioseparation was investigated in capillary electrophoresis. We synthesized a series of deep eutectic solvents with choline chloride as hydrogen bond acceptor and three α-hydroxyl acids (l-lactic acid, l-malic acid, and l-tartaric acid) as hydrogen bond donors. Compared to the single clindamycin phosphate separation system, significantly improved separations of model drugs were observed in several synergetic systems. Compared to deep eutectic solvents with a single hydrogen bond donor, deep eutectic solvents with mixed-type hydrogen bond donors were superior. The influences of several key parameters including the type and proportion of organic modifier, clindamycin phosphate concentrations, deep eutectic solvents concentrations, and buffer pH were investigated in detail. The mechanism of the enhanced separations in deep eutectic solvents systems was investigated by means of electroosmotic flow analysis, nuclear magnetic resonance analysis, and molecular modeling. It was the first time that the synergetic systems between deep eutectic solvents and antibiotic chiral selector were established in capillary electrophoresis, and these deep eutectic solvents were demonstrated to have a good synergetic effect with clindamycin phosphate for enantioseparation.

Short-term changes of soil physicochemical properties affected by organic modifier type and its application method

ABSTRACT Managing soil modifier application is important to improve the soil properties. The purpose of the experiment was to study the short-term (0, 60, 120, 180 days) changes of the soil properties affected by the organic modifier types (barberry biochar, poultry manure, vermicompost, wheat straw), and their application methods (mixing and mulching). This study was carried out in a laboratory scale where organic modifiers were used at 5% ratio (by weight) with four replicates. The factorial experiment was performed based on a totally random design using variance analysis, mean comparison and the least significant difference (LSD) test (p < 0.05). The soil characteristics were enhanced by all organic modifiers. The highest amounts of nitrogen, phosphorus, and potassium were obtained from the poultry manure. The highest amounts of calcium and magnesium were related to the barberry biochar at 120 and 180 days, and led to increasing up to 1.33, and 2.5 times, respectively, compared to the control. Promising results were observed in soil physicochemical properties when barberry biochar was applied as mixed with the soil for 180 days. The mixed application of the poultry manure and barberry biochar for 180 days was the best treatment.

Enantioselective separation and simulation studies of five flavanone glycosides on a cellulose tris-(3,5-dichlorophenylcarbamate) chiral stationary phase

In this study, the chiral separation of five flavanone glycosides was first examined on the cellulose tris-(3,5-dichlorophenylcarbamate) (CDCPC) chiral stationary phase (CSP) in the normal phase mode. The influence of acid additives, the type and proportion of organic modifiers, and column temperature were systematically evaluated and optimized. Under the optimum chromatographic conditions, hesperidin, eriocitrin, neohesperidin, naringin and narirutin enantiomers were completely or partially separated with resolutions of 2.56, 2.28, 1.84, 2.94 and 0.85. Moreover, to gain a better understanding of the chiral recognition mechanism, detailed computational simulations of CDCPC interacting with five pairs of enantiomers were carried out using molecular docking. The docking result demonstrated that the chiral recognition of analytes on CDCPC was an exothermic process which governed hydrogen bond, hydrophobic and unfavorable interaction. This work hoped to provide some guidance for the subsequent analysis of flavanone glycosides.

Study of Different Chiral Columns for the Enantiomeric Separation of Azoles Using Supercritical Fluid Chromatography

The enantiomeric separation of antifungal compounds is an arduous task in pharmaceutical and biomedical fields due to the different properties that each diastereoisomer presents. The enantioseparation of a group of fungicides (sulconazole, bifonazole, triadimefon and triadimenol) using supercritical fluid chromatography was achieved in this work. For this goal, four different chiral columns based on polysaccharide derivatives, as well as the effect of different chromatographic parameters such as temperature, type and percentage of organic modifier (methanol, ethanol and isopropanol), were thoroughly investigated. The inversion of the elution order of enantiomers as a result of a change in the stationary phase or organic modifier was also evaluated by employing a circular dichroism detector. The best separation conditions, in terms of the enantioresolution and analysis time, were obtained with the Lux® Cellulose-2 column using isopropanol as the organic modifier.

Toward the General Mechanistic Model of Liquid Chromatographic Retention.

Large datasets of chromatographic retention times are relatively easy to collect. This statement is particularly true when mixtures of compounds are analyzed under a series of gradient conditions using chromatographic techniques coupled with mass spectrometry detection. Such datasets carry much information about chromatographic retention that, if extracted, can provide useful predictive information. In this work, we proposed a mechanistic model that jointly explains the relationship between pH, organic modifier type, temperature, gradient duration, and analyte retention based on liquid chromatography retention data collected for 187 small molecules. The model was built utilizing a Bayesian multilevel framework. The model assumes (i) a deterministic Neue equation that describes the relationship between retention time and analyte-specific and instrument-specific parameters, (ii) the relationship between analyte-specific descriptors (log P, pKa, and functional groups) and analyte-specific chromatographic parameters, and (iii) stochastic components of between-analyte and residual variability. The model utilizes prior knowledge about model parameters to regularize predictions which is important as there is ample information about the retention behavior of analytes in various stationary phases in the literature. The usefulness of the proposed model in providing interpretable summaries of complex data and in decision making is discussed.

Studies on the Effects of Process Conditions on Separation of B1, B2 and B3 Vitamin Mixture Using HILIC and RPLC Chromatography

In this work, a series of experiments on the retention of B1 (riboflavin), B2 (thiamine) and B3 (nicotinic acid) vitamins in the HILIC and RPLC conditions have been performed involving the effects of organic modifier type and content, pH of the eluent and buffering salt (ammonium acetate) concentration in the mobile phase as well as temperature of the system. For the needs of this study, three columns of different features have been chosen: Acclaim™ Mixed–Mode HILIC–1 (Dionex, Sunnyvale, CA, USA), Eurospher II 100–5 HILIC (Knauer, Berlin, Germany) and the RPLC column Nucleodur® C18 Gravity-SB (Macherey-Nagel, Duren, Germany). The influence of acetonitrile and methanol content in the eluent and process temperature have been tested and, based on that, the most promising systems have been selected regarding the possible separation of the vitamin mixture. Both the pH and buffering salt concentrations in the eluent have been adjusted in order to indicate the most effective system, which turned out to be the one involving the Nucleodur column and the eluent with 90% methanol, at pH 6 and Cbuff = 20 mmol/dm3, which enables separation of the mixture within a time as short as 2.5 min at a 1.0 mL/s flowrate in isocratic conditions.

Establishment and Molecular Modeling Study of Cyclodextrin-Based Synergistic Enantioseparation Systems with Three New Amino Acid Chiral Ionic Liquids as Additives in Capillary Electrophoresis.

Chiral ionic liquids (CILs) have attracted more and more attention due to their superior performance as chiral additives in capillary electrophoresis. In this work, based on the cyclodextrin (CD) derivatives and three new amino acid CILs (trifluoroacetate-L-Hydroxyproline, nitric acid-L-Hydroxyproline and trifluoroacetate-L-threonine), the new synergistic systems were established for chiral drug separation. In contrast to the traditional single glucosyl-β-CD (Glu-β-CD) separation system, the CIL/Glu-β-CD synergistic systems achieved improved resolution of three model drug racemates. Some experimental variables, such as CIL concentration, Glu-β-CD concentration, buffer pH, applied voltage, and the type and proportion of organic modifier, were optimized in the trifluoroacetate-L-Hydroxyproline/Glu-β-CD synergistic system. In addition, the recognition process in the synergistic system was studied through the molecular modeling method.

Optical Behavior of Curcuminoid Hybrid Systems as Coatings Deposited on Polyester Fibers

The recent development of the “eco-friendly” current has brought to the attention of researchers natural dyes that are biodegradable, do not cause allergies and generally have anti-UV protection, and antioxidant and antibacterial properties. In this study, we aimed to obtain hybrid materials of the dye–host matrix type, by using the sol–gel process. The silica network was generated by tetraethylorthosilicates and modified with organic siloxane derivatives: phenyltriethoxysilane, 3-glycidoxypropyltriethoxysilane, dimethoxydimethylsilane and dimethoxydiphenylsilane. The nanocomposites obtained by embedding curcumin in siloxane matrices were deposited on polyester fabric and evaluated for their properties, relative to the type of organic network modifier used. Fabrics covered with curcuminoid hybrid systems provide a hydrophobic surface, have fluorescent properties and a UPF +50, and, therefore, they can be used in various fields where it is necessary for textiles to provide signaling, self-cleaning or protection properties against ultraviolet radiation. The coated textile materials have very good resistance properties after several repeated washing cycles, and maintain the original UV protection factor at high values even after washing or during rubbing tests.

Tribological performance of organic molybdenum in the presence of organic friction modifier.

The tribological performance of organic molybdenum in the present of organic friction modifier was investigated in this study. Three types of organic friction modifiers were selected, which are Glycerol monooleate, Pentaerythritol and N,N-Dimethylhexadecylamine. The organic molybdenum are MoDTC, MoDDP and molybdenum amide. Friction coefficient and wear were studied in block-on-ring test rig with steel test specimens. Experimental results indicate the Pentaerythritol shows synergistic effect with MoDTC in wide range temperature, while increased the friction coefficient of molybdenum amide in high temperature. N,N-Dimethylhexadecylamine shows synergistic effect with molybdenum amide, while hindered the friction reduction performance of MoDTC in low temperature. The presence of Glycerol monooleate reduced friction coefficient of MoDTC in low temperature, while increased the friction coefficient of molybdenum amide in most situations. All the tested organic friction modifiers improved the friction reduction performance of MoDDP. Most of the tested organic friction modifiers reduced the wear of organic molybdenum. The PT shows the best anti-wear performance with MoDTC. The tribo-chemical products in test specimens lubricated with different lubricant formulas indicate that the presences of Pentaerythritol promotes the production of MoS2 in MoDTC. N,N-Dimethylhexadecylamine promotes the production of MoS2 in molybdenum amide. The side products of MoO1.6S1.6 and Cr/MoS2 of MoDDP in high temperature lead to high friction coefficient.

Chiral separation and molecular simulation study of six antihistamine agents on a coated cellulose tri-(3,5-dimethylphenycarbamate) column (Chiralcel OD-RH) and its recognition mechanisms.

Enantiomeric separation of six antihistamine agents was first systematically investigated on a cellulose-based chiral stationary phase (CSP), that is, cellulose tris-(3,5-dimethyl phenyl carbamate) (Chiralcel OD-RH), under the reversed-phase mode. Orphenadrine, meclizine, terfenadine, dioxopromethazine, and carbinoxamine enantiomers were completely separated under the optimized mobile phase conditions with resolutions of 5.02, 1.93, 1.68, 1.67, and 1.54, respectively. Mequitazine was partially separated with a resolution of 0.77. The influences of type and concentration of buffer salt, the pH of buffer solution, and the type and ratio of organic modifier on the chiral separation were evaluated and optimized. For a better insight into the enantiorecognition mechanisms, molecular docking was carried out via the Autodock software. The lowest binding energy and the optimal conformations of the analytes/CSP complexes were supplied, and the mechanisms of chiral recognition were determined. According to the results, the key interactions for the chiral recognition of these six analytes on CDMPC were π-π interactions, hydrophobic interactions, hydrogen bond interactions, and some special interactions.

Tetraalkylammonium-l-tartrate ionic liquids as sole chiral selectors in capillary electrophoresis

In the field of separation science, the use of tartaric acid-based ionic liquids (TTILs) for chiral separation has not yet been reported. In this work, six novel mono- and di-tetraalkylammonium l-tartrate ILs (TAA-l-TTs) with different alkane chain length were evaluated for their potential as sole chiral selectors in capillary electrophoresis (CE). In comparison with conventional l-tartaric acid (l-TT) chiral selector, these IL-type chiral selectors exhibit remarkably improved enantioseparation performance, which is even better than most previously reported TT ester-type chiral selectors. Major factors influencing CE separation were investigated, including the background electrolyte (BGE) composition, ILs concentration, type and proportion of organic modifier, buffer pH, etc. The results show that the l-TT-based IL-type chiral selectors prefer a weak acid buffer (150 mM boric acid at pH 4.5) with a high proportion of methanol (80%-90%). The best resolutions (Rs) were obtained when the IL concentration was set at 60 mM. We further carried out a series of comparative experiments and a molecular simulation study to explore the enantiorecognition mechanism of TTILs. The result indicates that the TAA-l-TTs cannot be considered as a simple combination of TAA salt and l-TT. The dissociation degree of TTILs may be an important factor influencing the enantiorecognition process.

Application of achiral-chiral two-dimensional HPLC for separation of phenylalanine and tryptophan enantiomers in dietary supplement.

This study developed a two-dimensional heart-cutting LC method for the separation of amino acid enantiomers. Two approaches for achiral separation of amino acids, phenylalanine and tryptophan, were selected. Amino acids were separated on C18 or hydrophilic interaction liquid chromatography (HILIC) columns in first dimension after their enantiomer separation on a teicoplanin chiral column in second dimension. Mobile phases for both separation systems were optimized by testing different types of organic modifiers, concentrations of ion-pair agent (sodium 1-octanesulfonate), and ionic modifier (ammonium acetate). The resolution of enantiomers higher than 1.5 for both amino acids was achieved using a C18-teicoplanin coupled column separation system with mobile phases methanol/2 mM sodium 1-octanesulfonate (10:90 and 75:25, step gradient between achiral and chiral columns, respectively). The lower resolution of amino acid enantiomers (RS ˃ 0.9), but higher column efficiency, was achieved on a HILIC-teicoplanin separation system with mobile phases acetonitrile/50 mM ammonium acetate (90:10 and 80:20, step gradient between achiral and chiral columns, respectively). The developed heart-cutting 2D-LC methods were validated in terms of linearity, limit of detection, limit of quantification, precision, and accuracy. The results suggested that the developed methods were applicable for the simultaneous determination of amino acid enantiomers in the dietary supplement. The sample contained l-phenylalanine and l-tryptophan.

Effect of type of organic modifier on the clay layered-based nanocomposites flammability and toxic gases emission

Well dispersed polyethylene (PE) nanocomposites were developed. Montmorillonite (MMT) as aluminosilicate clay layers was modified using organic silanes of different side chains. The MMT was grafted using 3-(trimethoxysilyl)propylamine, N-[3-(trimethoxysilyl)propyl]ethylenediamine, and trimethoxyvinylsilane. The modification process of MMT using organic different silanes was elucidated using microscopic, thermogravimetric, spectroscopic, and X-ray diffraction tools. Then, the developed organoclays were dispersed uniformly in PE matrix producing well exfoliated and dispersed polymer nanocomposites. The mass loadings of dispersed organoclay were varied and the impact of organic silane structure was studied. Thermal stability and flammability properties of the developed polymer nanocomposites were evaluated. The peak heat release rate and average heat release rate were reduced by 48% and 61%, respectively compared to virgin polymer. Also, the average mass loss rate was significantly reduced by 50%. This is in addition to reduction in emission of carbon monoxide (CO) and carbon dioxide (CO2) by 45% and 56%, respectively. The effect of side chain of organosilane on the performance of modified clay layers was studied. The toxicity of gases evolved during combustion process of PE and their polymer nanocomposites were evaluated using Fourier transform infrared connected to cone calorimeter. Additionally, the influence of organic silane on the pyrolysis and toxic gases emission was further studied.

Enantioseparation of Eight Pairs of Tetralone Derivative Enantiomers on Cellulose Based Chiral Stationary Phase by HPLC

Background: Tetralone derivatives, important resources for the development of new drugs which can act in the treatment of central nervous system disorders or participate in synthesis reaction for the synthesis of various pharmaceuticals, have great research value and a bright prospect in exploitation. Methods: A novel chiral HPLC method for efficient enantioseparation of eight tetralone derivative enantiomers was developed on cellulose based CHIRALPAK IC chiral stationary phase under normal mode by investigating the effects of type and content of organic modifier, column temperature and flow rate on retention and enantioselectivity. Besides, the specificity, linearity, stability, precision, accuracy and robustness of this method were also validated. Results: Satisfactory enantioseparation was obtained for all enantiomers in n-hexane/2-propanol mobile phase system at ambient temperature. The thermodynamic study indicated that the solute transfer from the mobile to stationary phase was enthalpically favorable, and the process of enantioseparation was mainly enthalpy controlled. This method met the requirements for quantitative determination of tetralone derivative enantiomers. Conclusion: This study can provide great and important application value for enantioseparation of eight pairs of newly synthesized tetralone derivative enantiomers under normal mode using CHIRALPAK IC chiral column.

Investigation of fusidic acid as a chiral selector in capillary electrophoresis

In this short communication, we report the use of a steroid antibiotic, Fusidic Acid (Fus), as a novel chiral selector for enantioseparation in capillary electrophoresis (CE). Fus can be classified into the antibiotic chiral selector family but does not belong to any of the previously reported subfamilies. Factors influencing Fus in CE enantioseparations were systematically investigated including the composition of the background electrolyte (BGE), buffer pH, type and proportion of organic modifier, concentration of Fus, etc. The best separations were obtained with 50 mM phosphate buffer (pH 8.0) containing 60–70 mM Fus and 50% methanol. A preliminary analysis on the separation mechanism showed that Fus is especially suitable for the chiral analytes containing a rigid planar structure. The development of Fus as a novel chiral selector can be considered as a valuable work not only because of its unique enantioselectivity, but also because there are a number of steroids in nature that are structurally similar to Fus. This work indicates that the screening of high-efficient chiral selectors from these steroids is an attractive and promising research area.

Comparison of polysaccharide-based and protein-based chiral liquid chromatography columns for enantioseparation of drugs.

Two different columns-Lux Cellulose-1 and Chiralpak CBH-were evaluated for their chiral recognition abilities for eight drugs comprising three β-blockers, one antacid, and four cathinones in polar-organic elution mode and reversed-phase elution mode, respectively. The factors that affected the enantioseparation were tested and optimized to develop a suitable chiral separation method whose LC conditions are compatible with MS detection. In polar-organic elution mode with the Lux Cellulose-1 column, methanol and acetonitrile were tested as the main components of the mobile phase. In addition, the effects of adding isopropanol as organic modifier, acidic additives (formic acid), and basic additives (diethylamine) were evaluated. In reversed-phase elution mode with the Chiralpak CBH column, the effect of type and concentration of organic modifier (isopropanol, acetonitrile, and methanol), the mobile phase pH (6.4 and 5.0), and buffer concentration (1mM-20mM ammonium acetate) were evaluated. The best enantioseparation was achieved with the Chiralpak CBH column with a mobile phase composed of 5mM ammonium acetate aqueous (pH = 6.4)/methanol (95/5, v/v) at a flow rate of 0.1 mL/min and a temperature of 30°C. Under these conditions, six of eight chiral drugs were baseline separated.

Gold nanoparticles coated with a tetramethylammonium lactobionate ionic liquid for enhanced chiral differentiation in open tubular capillary electrochromatography: application to enantioseparation of β-blockers.

A new bilayer chiral stationary phase for use in open tubular capillary electrochromatography (OT-CEC) system is described. Gold nanoparticles were modified with L-cysteine, with a tetramethylammonium lactobionate ionic liquid that acts as the chiral selector. The gold nanoparticle-coated column provides good enantioseparation and favorable reproducibility. Compared with an uncoated separation system, the column developed displays improved separation of the racemic β-blockers propranolol, esmolol, bisoprolol and sotalol (resolutions of enotiomers are 6.29, 6.11, 6.12 and 6.02, respectively). The materials and coatings were characterized by scanning electron microscopy and transmission electron microscopy. The main driving forces (CEC and electro-osmotic flow) were studied to evaluate the variation of the immobilized columns. The effects of buffer pH value, concentration of chiral selector, type of organic modifier and applied voltage were optimized. Satisfactory relative standard deviations were achieved in run-to-run, day-to-day and column-to-column experiments. Graphical abstractSchematic preparation of a capillary column with bilayer chiral selectors coated gold nanoparticles. This novel OT-CEC system was applied for separation of four basic racemic β-blockers.

Synthesis and application of tetramethylammonium-carboxymethylated-β-cyclodextrin: A novel ionic liquid in capillary electrophoresis enantioseparation

In this study, a carboxymethylated-β-cyclodextrin-based chiral ionic liquid (CIL), tetramethylammonium-carboxymethylated-β-cyclodextrin (TMA-CM-β-CD) was successfully designed and synthesized. This cyclodextrin-based ionic liquids (ILs) was used as the sole chiral selector in capillary electrophoresis, and it is very interesting to find that the chiral separation capability can be remarkably improved when a conventional cyclodextrin chiral selector evolved into an IL chiral selector. The ionic liquid showed satisfactory separation performance towards twelve tested drugs. A series of parameters affecting the enantioseparation, such as the type and proportion of organic modifier, buffer pH, chiral selector concentration, as well as applied voltage were systematically investigated. Additionally, the molecular docking program Autodock was applied to further demonstrate the mechanism of chiral recognition and the enhanced enantioselectivity of TMA-CM-β-CD, which kept in agreement with our experimental results.