Chiral 3D Open‐Framework Material Ni(D‐cam)(H2O)2 Used as GC Stationary Phase

Metal‐organic frameworks (MOFs) have been explored for analytical applications because of their outstanding properties such as high surface areas, flexibility and specific structure features, especially for chromatography application in recent years. In this work, a chiral MOF Ni(D‐cam)(H₂O)₂ with unusual integration of molecular chirality, absolute helicity, and 3‐D intrinsic chiral net was chosen as stationary phase to prepare Ni(D‐cam)(H₂O)₂‐coated open tubular columns for high‐resolution gas chromatographic (GC) separation. Two fused‐silica open tubular columns with different inner diameters and lengths, including column A (30 m × 250 µm i.d.) and column B (2 m × 75 µm i.d.), were prepared via a dynamic coating method. The chromatographic properties of the two columns were investigated using n‐dodecane as the analyte at 120 °C. The number of theoretical plates (plates/m) of the two metal–organic framework (MOF) columns was 1300 and 2750, respectively. The racemates, isomer and linear alkanes mixture were used as analytes for evaluating the separation properties of Ni(D‐cam)(H₂O)₂‐coated open tubular columns. The results showed that the columns offered good separations of isomer and linear alkanes mixture, especially racemates. Chirality 26:27–32, 2013. © 2013 Wiley Periodicals, Inc.     

Enantiomeric Separation of Bicyclo[2.2.2]octane‐Based 2‐Amino‐3‐Carboxylic Acids on Macrocyclic Glycopeptide Chiral Stationary Phases

Direct high‐performance liquid chromatographic (HPLC) separation of four bicyclo[2.2.2]octane based 2‐amino‐3‐carboxylic acid enantiomers were developed on chiral stationary phases (CSPs) containing different macrocyclic glycopeptide antibiotic selectors. The analyses were performed under reversed‐phase, polar organic and polar ionic mode on macrocyclic‐glycopeptide‐based Chirobiotic T, T2, TAG, and R columns. The effects of the mobile phase composition including the acid and base modifier, the structure of the analytes, and the temperature on the separations were investigated. Experiments were achieved at constant mobile phase compositions on different stationary phases in the temperature range 5–40°C. Thermodynamic parameters were calculated from plots of ln k or ln α versus 1/T. It was recognized that the enantioseparations in reversed‐phase and polar organic mode were enthalpically driven, but under polar‐ionic conditions entropically driven enantioseparation was observed as well. Baseline separation and determination of elution sequence were achieved in all cases. Chirality 26:200–208, 2014. © 2014 Wiley Periodicals, Inc.     

Separation of Ofloxacin and Its Six Related Substances Enantiomers by Chiral Ligand‐Exchange Chromatography

A chiral ligand‐exchange high‐performance liquid chromatography method was developed for the enantioseparation of ofloxacin and its six related substances termed impurities A, B, C, D, E, and F. The separation was performed on a conventional C₁₈ column. Different organic modifiers, copper salts, amino acids, the ratio of Cu²⁺ to amino acid, pH of aqueous phase, and column temperature were optimized. The optimal mobile phase conditions were methanol‐water systems consisting of 5 mmol/L copper sulfate and 10 mmol/L L‐isoleucine (L‐Ile). Under such conditions, good enantioseparation of ofloxacin and impurities A, C, E, and F could be observed with resolutions (R_S) of 3.54, 1.97, 3.21, 3.50, and 2.12, respectively. On the relationship between the thermodynamic parameters and structures of analytes, the mechanism of chiral recognition was investigated. It was concluded that ofloxacin and impurities A, C, E, and F were all enthalpically driven enantioseparation and that low column temperature was beneficial to enantioseparation. Furthermore, the structure–separation relationship of these analytes is also discussed. Chirality 27:843–849, 2015. © 2015 Wiley Periodicals, Inc.     

Enantioseparation of chiral pharmaceuticals by vancomycin‐bonded stationary phase and analysis of chiral recognition mechanism

The drug chirality is attracting increasing attention because of different biological activities, metabolic pathways, and toxicities of chiral enantiomers. The chiral separation has been a great challenge. Optimized high‐performance liquid chromatography (HPLC) methods based on vancomycin chiral stationary phase (CSP) were developed for the enantioseparation of propranolol, atenolol, metoprolol, venlafaxine, fluoxetine, and amlodipine. The retention and enantioseparation properties of these analytes were investigated in the variety of mobile phase additives, flow rate, and column temperature. As a result, the optimal chromatographic condition was achieved using methanol as a main mobile phase with triethylamine (TEA) and glacial acetic acid (HOAc) added as modifiers in a volume ratio of 0.01% at a flow rate of 0.3 mL/minute and at a column temperature of 5°C. The thermodynamic parameters (eg, ΔH, ΔΔH, and ΔΔS) from linear van 't Hoff plots revealed that the retention of investigated pharmaceuticals on vancomycin CSP was an exothermic process. The nonlinear behavior of lnk′ against 1/T for propranolol, atenolol, and metoprolol suggested the presence of multiple binding mechanisms for these analytes on CSP with variation of temperature. The simulated interaction processes between vancomycin and pharmaceutical enantiomers using molecular docking technique and binding energy calculations indicated that the calculated magnitudes of steady combination energy (ΔG) coincided with experimental elution order for most of these enantiomers.     

Substituent effects on chiral resolutions of derivatized 1‐phenylalkylamines by heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin GC stationary phase

Chiral resolutions of trifluoroacetyl‐derivatized 1‐phenylalkylamines with different type and position of substituent were investigated by capillary gas chromatography by using heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin diluted in OV‐1701 as a chiral stationary phase. The influence of column temperature on retention and enantioselectivity was examined. All enantiomers of meta‐substituted analytes as well as fluoro‐substituted analytes could be resolved. Temperature had a favorable influence on enantioselectivity for small amines with substituents at the ortho‐position. The type of substituent at the stereogenic center of amines also had a crucial effect as the ethyl group led to poor enantioseparation. Among all analytes studied, trifluoroacetyl‐derivatized 1‐(2′‐fluorophenyl)ethylamine exhibited baseline resolution with the shortest analysis time.     

Comparative HPLC Enantioseparation of Thirty‐Six Aromatic Compounds on Four Columns of the Lux® Series: Impact of Substituents,Shapes and Electronic Properties

With the aim to define a combined computational/chromatographic empirical approach useful for the high‐performance liquid chromatography (HPLC) method development of new chiral compounds, 36 racemic aromatic compounds with different chemical structures were used as test probes on four polysaccharide‐based chiral stationary phases (CSPs) of the Lux series, namely Lux Cellulose‐1, Lux Cellulose‐2, Lux Cellulose‐4, and Lux Amylose‐2, using classical n‐hexane/2‐propanol mixtures as mobile phase. Electrostatic potential surfaces (EPSs) determined using Density Functional Theory (DFT) calculations were used to derive size, shape, and electronic properties of each analyte. Then a comparative HPLC screening was carried out in order to evaluate the impact of substituents, shapes, and electronic properties of the analytes on the chromatographic behavior as the column changes. The four CSPs showed good complementary recognition ability. The elution sequence was determined in 30 cases out of 36. The success rate to afford baseline separations (R_s ≥ 1.5) was estimated: 29 compounds out of 36 showed baseline enantioseparation on at least one of the four selected CSPs. The combined computational‐chromatographic screening furnished useful collective structure‐chromatographic behavior relationships and a map of the chiral discrimination abilities of the considered CSPs towards the analytes. On this basis, the chromatographic behavior of new analytes on a set of polysaccharide‐based CSPs can be mapped through the qualitative correlation of chromatographic parameters (k, α, R_s) to computed molecular properties of the analytes. Chirality 25:709–718, 2013. © 2013 Wiley Periodicals, Inc.     

Preparation and characterization of a new open‐tubular capillary column for enantioseparation by capillary electrochromatography

In order to use the enantioseparation capability of cationic cyclodextrin and to combine the advantages of capillary electrochromatography (CEC) with open‐tubular (OT) column, in this study, a new OT‐CEC, coated with cationic cyclodextrin (1‐allylimidazolium‐β‐cyclodextrin [AI‐β‐CD]) as chiral stationary phase (CSP), was prepared and applied for enantioseparation. Synthesized AI‐β‐CD was characterized by infrared (IR) spectrometry and mass spectrometry (MS). The preparation conditions for the AI‐β‐CD‐coated column were optimized with the orthogonal experiment design L₉(3⁴). The column prepared was characterized by scanning electron microscopy (SEM) and elemental analysis (EA). The results showed that the thickness of stationary phase in the inner surface of the AI‐β‐CD‐coated columns was about 0.2 to 0.5 μm. The AI‐β‐CD content in stationary phase based on the EA was approximately 2.77 mmol·m^?2. The AI‐β‐CD‐coated columns could separate all 14 chiral compounds (histidine, lysine, arginine, glutamate, aspartic acid, cysteine, serine, valine, isoleucine, phenylalanine, salbutamol, atenolol, ibuprofen, and napropamide) successfully in the study and exhibit excellent reproducibility and stability. We propose that the column, coated with AI‐β‐CD, has a great potential for enantioseparation in OT‐CEC.     

Nanocellulose 3, 5‐Dimethylphenylcarbamate Derivative Coated Chiral Stationary Phase: Preparation and Enantioseparation Performance

Nanocrystalline cellulose (NCC) with high surface area and high ordered crystalline structure was prepared from microcrystalline cellulose (MCC) under the hydrolysis of sodium hypochlorite. NCC was further reacted with 3,5‐dimethylphenyl isocyanate to obtain the nanocellulose derivative, and then coated successfully on the surface of silica gel to a prepared NCC‐coated chiral stationary phase (CSP) as a new kind of chiral separation material. Similarly, MCC derivative‐coated CSP was also prepared as contrast. The chiral separation performance of NCC‐based CSP was evaluated and compared with MCC‐based CSP by high‐performance liquid chromatography. Moreover, the effects of the alcohol modifiers, mobile phase additives, and flow rates on chiral separations were investigated in detail. The results showed that 10 chiral compounds were separated on NCC‐based CSP with better peak shape and higher column efficiency than MCC‐based CSP, which confirmed that NCC‐based CSP was a promising packing material for the resolution of chiral compounds.Chirality 28:376–381, 2016. © 2016 Wiley Periodicals, Inc.     

Resolution of Rac‐Bambuterol via Diastereoisomeric Salt Formation with o‐Chloromandelic Acid and Differences in the Enantiomers' Pharmacodynamical Effects in Guinea Pigs and Beagles

In this study an enantioseparation method for rac‐bambuterol (5‐(2‐(tert‐butylamino)‐1‐hydroxyethyl)‐1,3‐phenylene bis(dimethylcarbamate)) via diastereoisomeric salt formation with o‐chloromandelic acid was developed. The enantiomeric excess (ee) values and chemical purities of the desired products were confirmed by high‐performance liquid chromatography (HPLC) using chiral stationary phase and reverse‐phase HPLC analyses, respectively. The ee values and the chemical purities both exceeded 99%. Animal experiments showed that (R)‐bambuterol was a potent inhibitor for histamine‐induced asthma reactions. (S)‐bambuterol was ineffective in relaxing the airways. Both enantiomers increased heart rates in beagles. Therefore, replacing rac‐bambuterol with (R)‐bambuterol could be beneficial for asthma patients. Chirality 28:306–312, 2016. © 2016 Wiley Periodicals, Inc.     

Chiral separation and determination of amino acid enantiomers in fruit juice by open‐tubular nano liquid chromatography

A novel chiral porous‐layer stationary phase was developed for use in open‐tubular nano liquid chromatography. The stationary phase was prepared by an in‐situ polymerization of 3‐chloro‐2‐hydroxypropylmethacrylate (HPMA‐Cl) and ethylene dimethacrylate (EDMA). The reactive chloro groups at the surface of the porous stationary phase were reacted with β‐Cyclodextrin (β‐CD). The resulting morphology was characterized by using scanning electron microscopy (SEM) and Fourier‐transform infrared spectroscopy (FT‐IR). The chromatographic performance of the column was evaluated by hydrophilic interaction chromatography (HILIC). Amino acids were used as test solutes. The running buffer conditions for the enantioseparation were found to be 85% acetonitrile (ACN):10%MeOH: 5% H₂O at 0.1% v/v trifluoro acetic acid (TFA) (flow rate: 800 nL/min). The enantioseparation provided high theoretical plate numbers up to 26 000 platesm^?1. A good retention capacity within satisfactory retention times was also achieved. Real sample applicability of this column to the separation of amino acid enantiomers in fruit juice sample was demonstrated.     

Synthesis of dendrimer‐type chiral stationary phases based on the selector of (1S,2R)‐(+)‐2‐Amino‐1,2‐diphenylethanol derivate and their enantioseparation evaluation by HPLC

In our recent work, a series of dendritic chiral stationary phases (CSPs) were synthesized, in which the chiral selector was L‐2‐(p‐toluenesulfonamido)‐3‐phenylpropionyl chloride (selector I), and the CSP derived from three‐generation dendrimer showed the best separation ability. To further investigate the influence of the structures of dendrimer and chiral selector on enantioseparation ability, in this work, another series CSPs ( CSPs 1‐4 ) were prepared by immobilizing (1S,2R)‐1,2‐diphenyl‐2‐(3‐phenylureido)ethyl 4‐isocyanatophenylcarbamate (selector II) on one‐ to four‐generation dendrimers that were prepared in previous work. CSPs 1 and 4 demonstrated the equivalent enantioseparation ability. CSPs 2 and 3 showed the best and poorest enantioseparation ability respectively. Basically, these two series of CSPs exhibited the equivalent enantioseparation ability although the chiral selectors were different. Considering the enantioseparation ability of the CSP derived from aminated silica gel and selector II is much better than that of the one derived from aminated silica gel and selector I, it is believed that the dendrimer conformation essentially impacts enantioseparation. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Liquid chromatographic direct resolution of flecainide and its analogs on a chiral stationary phase based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

Flecainide, an antiarrythmic agent, and its analogs were resolved on a high performance liquid chromatographic chiral stationary phase (CSP) based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid with the use of a mobile phase consisting of methanol‐acetonitrile‐trifluoroacetic acid‐triethylamine (80/20/0.1/0.3, v/v/v/v). The chiral resolution was quite successful, the separation factors (α) and the resolutions (R_S) for 20 analytes including flecainide being in the range of 1.19–1.82 and 1.73–6.80, respectively. The ortho‐substituent of the benzoyl group of analytes was found to cause decrease in the retention times of analytes probably because of the conformational deformation of analytes originated from the steric hindrance exerted by the ortho‐substituent. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Enantioseparation and molecular modeling study of five β‐adrenergic blockers on Chiralpak IC column

A new high‐performance liquid chromatography (HPLC) method was developed for the enantiomeric resolution of five β‐adrenergic blockers on a Chiralpak IC column (250 mm × 4.6 mm, 5.0 μm particle size) in normal phase mode. The mobile phase used was n‐hexane‐ethanol‐diethylamine in different proportions at the flow rate of 1.0 mL/min with the column temperature of 25°C using a UV detector at 230 nm. The influences of base additives and alcohol modifiers were evaluated and optimized. The maximum resolution values for bevantolol, propranolol carteolol, esmolol, and metoprolol were 4.80, 2.77, 2.09, 2.30, and 1.11, respectively. To gain a better understanding of the interaction between chiral stationary phase and analyte enantiomers, the molecular docking of chiral stationary phase with five pairs of enantiomer was carried out using AutoDock molecular docking technique. By simulation studies, the mechanism of chiral recognition was determined. According to the results, hydrogen bond interactions and π‐π interactions were the chief interactions for the chiral recognition.     

Enantioselective potential of polysaccharide‐based chiral stationary phases in supercritical fluid chromatography

The enantioselective potential of two polysaccharide‐based chiral stationary phases for analysis of chiral structurally diverse biologically active compounds was evaluated in supercritical fluid chromatography using a set of 52 analytes. The chiral selectors immobilized on 2.5 μm silica particles were tris‐(3,5‐dimethylphenylcarmabate) derivatives of cellulose or amylose. The influence of the polysaccharide backbone, different organic modifiers, and different mobile phase additives on retention and enantioseparation was monitored. Conditions for fast baseline enantioseparation were found for the majority of the compounds. The success rate of baseline and partial enantioseparation with cellulose‐based chiral stationary phase was 51.9% and 15.4%, respectively. Using amylose‐based chiral stationary phase we obtained 76.9% of baseline enantioseparations and 9.6% of partial enantioseparations of the tested compounds. The best results on cellulose‐based chiral stationary phase were achieved particularly with propane‐2‐ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO₂, respectively. Methanol and basic additive isopropylamine were preferred on amylose‐based chiral stationary phase. The complementary enantioselectivity of the cellulose‐ and amylose‐based chiral stationary phases allows separation of the majority of the tested structurally different compounds. Separation systems were found to be directly applicable for analyses of biologically active compounds of interest.     

Synthesis and Application of C2 and C3 Symmetric (R)‐Phenylglycinol‐Derived Chiral Stationary Phases

A C3 symmetric (R)‐phenylglycinol N‐1,3,5‐benzenetricarboxylic acid‐derived chiral stationary phase (CSP) and three C2 symmetric (R)‐phenylglycinol CSPs were newly synthesized using o‐, m‐, and p‐phthaloyl dichlorides. © 2016 Wiley Periodicals, Inc. These CSPs were used to compare the resolution of 25 chiral samples using a previously reported 3,5‐dinitrobenzoyl (R)‐phenylglycinol‐derived CSP. Even though all CSPs have the same chiral moiety, the C3 symmetric CSP showed the best resolution. Chirality 28:186–191, 2016.© 2016 Wiley Periodicals, Inc.     

Enantioseparation of nine indanone and tetralone derivatives by HPLC using carboxymethyl‐β‐cyclodextrin as the mobile phase additive

High‐performance liquid chromatography (HPLC) is a powerful method in the area of chiral separation. In this study, a method of HPLC using carboxymethyl‐β‐cyclodextrin (CM‐β‐CD) as chiral selector was developed for enantioseparation of nine indanone and tetralone derivatives. The separation was performed on a conventional C₁₈ column. The optimal mobile phase was a mixture of methanol and 0.05 mol/L phosphate buffer at pH 1.8 (55:45, v /v) containing 22.9 mmol/L CM‐β‐CD. Under such conditions, the resolutions of all analytes were over 1.8 except for Compound F. The results of the study indicate the presence of a complex with 1:1 stoichiometry of the inclusion complex. In addition, it can be inferred from thermodynamic analysis that the behavior of formation of the inclusion complex and enantioseparation occurred simultaneously, while they were driven by different forces. The effect of analyte structure is also discussed.     

Development of a Validated LC Method for Separation of Process‐Related Impurities Including the R‐enantiomer of S‐Pramipexole on Polysaccharide Chiral Stationary Phases

Despite the availability of a few methods for individual separation of S‐pramipexole from its process‐related impurities, no common liquid chromatography (LC) method is reported so far in the literature. The present article describes the development of a single‐run LC method for simultaneous determination of S‐pramipexole and its enantiomeric and process‐related impurities on a Chiralpak AD‐H (150 x 4.6 mm, 5μm) column using n‐hexane/ethanol/n‐butylamine (75:25:0.1 v/v/v) as a mobile phase in an isocratic mode of elution at a flow rate of 1.2 ml/min at 30°C. The chromatographic eluents were monitored at a wavelength of 260 nm using a photodiode array detector. Excellent enantioseparation with good resolutions (Rs ≥ 2.88) and peak shapes (A_s ≤ 1.21) for all analytes was achieved. The proposed method was validated according to International Conference Harmonization (ICH) guidelines in terms of accuracy, precision, sensitivity, and linearity. Limits of quantification of impurities (0.25–0.55 μg/ml) indicate the highest sensitivity achievable by the proposed method. The method has an advantage of selectivity and suitability for routine determination of not only chiral impurity but also all possible related substances in active pharmaceutical ingredients of S‐pramipexole. Chirality 27:430–435, 2015. © 2015 Wiley Periodicals, Inc.     

Preparative Enantioseparation of β‐Substituted‐2‐Phenylpropionic Acids by Countercurrent Chromatography With Substituted β‐Cyclodextrin as Chiral Selectors

Preparative enantioseparation of four β‐substituted‐2‐phenylpropionic acids was performed by countercurrent chromatography with substituted β‐cyclodextrin as chiral selectors. The two‐phase solvent system was composed of n‐hexane‐ethyl acetate‐0.10 mol L‐1 of phosphate buffer solution at pH 2.67 containing 0.10 mol L^‐1 of hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) or sulfobutylether‐β‐cyclodextrin (SBE‐β‐CD). The influence factors, including the type of substituted β‐cyclodextrin, composition of organic phase, concentration of chiral selector, pH value of the aqueous phase, and equilibrium temperature were optimized by enantioselective liquid–liquid extraction. Under the optimum separation conditions, 100 mg of 2‐phenylbutyric acid, 100 mg of tropic acid, and 50 mg of 2,3‐diphenylpropionic acid were successfully enantioseparated by high‐speed countercurrent chromatography, and the recovery of the (±)‐enantiomers was in the range of 90–91% for (±)‐2‐phenylbutyric acid, 91–92% for (±)‐tropic acid, 85–87% for (±)‐2,3‐diphenylpropionic acid with purity of over 97%, 96%, and 98%, respectively. The formation of 1:1 stoichiometric inclusion complex of β‐substituted‐2‐phenylpropionic acids with HP‐β‐CD was determined by UV spectrophotometry and the inclusion constants were calculated by a modified Benesi‐Hildebrand equation. The results showed that different enantioselectivities among different racemates were mainly caused by different enantiorecognition between each enantiomer and HP‐β‐CD, while it might be partially caused by different inclusion capacity between racemic solutes and HP‐β‐CD. Chirality 27:795–801, 2015. © 2015 Wiley Periodicals, Inc.     

Enantioseparation and determination of flumequine enantiomers in multiple food matrices with chiral liquid chromatography coupled with tandem mass spectrometry

The present work firstly described the enantioseparation and determination of flumequine enantiomers in milk, yogurt, chicken, beef, egg, and honey samples by chiral liquid chromatography‐tandem mass spectrometry. The enantioseparation was performed under reversed‐phase conditions on a Chiralpak IC column at 20°C. The effects of chiral stationary phase, mobile phase components, and column temperature on the separation of flumequine enantiomers have been studied in detail. Target compounds were extracted from six different matrices with individual extraction procedure followed by cleanup using Cleanert C18 solid phase extraction cartridge. Good linearity (R²>0.9913) was obtained over the concentration range of 0.125 to 12.5 ng g^‐1 for each enantiomer in matrix‐matched standard calibration curves. The limits of detection and limits of quantification of two flumequine enantiomers were 0.015‐0.024 and 0.045‐0.063 ng g^‐1, respectively. The average recoveries of the targeted compounds varied from 82.3 to 110.5%, with relative standard deviation less than 11.7%. The method was successfully applied to the determination of flumequine enantiomers in multiple food matrices, providing a reliable method for evaluating the potential risk in animal productions.     

GC Separation of Enantiomers of Alkyl Esters of 2‐Bromo Substituted Carboxylic Acids Enantiomers on 6‐TBDMS‐2,3‐di‐alkyl‐ β‐ and γ‐Cyclodextrin Stationary Phases

The gas chromatographic separation of enantiomers of 2‐Br carboxylic acid derivatives was studied on four different 6‐TBDMS‐2,3‐di‐O‐alkyl‐ β‐ and ‐γ‐CD stationary phases. The differences in thermodynamic data {ΔH and –ΔS} for the 15 structurally related racemates were evaluated. The influence of structure differences in the alkyl substituents covalently attached to the stereogenic carbon atom, as well as in the ester group of the homologous analytes, and the selectivity of modified β‐ and γ‐ cyclodextrin derivatives was studied in detail. The cyclodextrin cavity size, as well as elongation of alkyl substituents in positions 2 and 3 of 6‐TBDMS‐β‐CD, also affected their selectivity. The quality of enantiomeric separations is influenced mainly by alkyl chains of the ester group of the molecule and this appears to be independent of the CD stationary phase used. In some cases the separations occur as the result of external adsorption rather than inclusion complexations with the chiral selector. It was found that the temperature dependencies of the selectivity factor were nonlinear. Chirality 26:279–285, 2014. © 2014 Wiley Periodicals, Inc.