Co-reporter:Choyce A. Weatherly, Siqi Du, Curran Parpia, Polan T. Santos, Adam L. Hartman, and Daniel W. Armstrong
ACS Chemical Neuroscience June 21, 2017 Volume 8(Issue 6) pp:1251-1251
Publication Date(Web):February 16, 2017
DOI:10.1021/acschemneuro.6b00398
The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be “unnatural”, have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (l- plus d-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured d-amino acid levels in brain tissue are typically ∼10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured d-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its d-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its d-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this d-amino acid is yet unknown. However, results suggest that d-glutamate metabolism is likely a unidirectional process and not a cycle, as per the l-glutamate/glutamine cycle. The results suggest that there might be unreported d-amino acid racemases in mammalian brains. The regulation and function of specific other d-amino acids are discussed.Keywords: blood; cortex; d-Amino acid levels; d-amino acid regulation; hippocampus; perfused brain tissue;
Co-reporter:M. Farooq Wahab, Darshan C. Patel, Rasangi M. Wimalasinghe, and Daniel W. Armstrong
Analytical Chemistry August 15, 2017 Volume 89(Issue 16) pp:8177-8177
Publication Date(Web):July 12, 2017
DOI:10.1021/acs.analchem.7b00931
New stationary phases are continuously developed for achieving higher efficiencies and unique selectivities. The performance of any new phase can only be assessed when the columns are effectively packed under high pressure to achieve a stable bed. The science of packing columns with stationary phases is one of the most crucial steps to achieve consistent and reproducible high-resolution separations. A poorly packed column can produce non-Gaussian peak shapes and lower detection sensitivities. Given the ever larger number of stationary phases, it is impossible to arrive at a single successful approach. The column packing process can be treated as science whose unified principles remain true regardless of the stationary phase chemistry. Phenomenologically, the column packing process can be considered as a constant pressure or constant flow high-pressure filtration of a suspension inside a column with a frit at the end. This process is dependent on the non-Newtonian suspension rheology of the slurry in which the particles are dispersed. This perspective lays out the basic principles and presents examples for researchers engaged in stationary phase development. This perspective provides an extensive set of slurry solvents, hardware designs, and a flowchart, a logical approach to optimal column packing, thus eliminating the trial and error approach commonly practiced today. In general, nonaggregating but high slurry concentrations of stationary phases tend to produce well packed analytical columns with small particles. Conversely, C18 packed capillary columns are best packed using agglomerating solvents.
Co-reporter:Mohsen Talebi;Lillian A. Frink;Rahul A. Patil
Food Analytical Methods 2017 Volume 10( Issue 12) pp:4062-4067
Publication Date(Web):29 June 2017
DOI:10.1007/s12161-017-0980-5
Kombucha is a fermented beverage made by mixing tea and sugar with bacteria and yeast. When kombucha products contain higher than 0.5% (v/v) alcohol, the legal limit for non-alcoholic drinks, they are classified as alcoholic beverages and are subject to relevant federal and state regulations. An efficient headspace gas chromatography technique utilizing an ionic liquid stationary phase is developed to accurately determine the ethanol content in 18 commercial kombucha samples. The range of ethanol in these products was 1.12–2.00% (v/v). The ethanol concentration of two batches of kombucha was analyzed over a period of 60 days under two different conditions. A significant increase in ethanol content of these samples was observed at 4 and 22 °C. The method accuracy was validated by analyzing 3 NIST ethanol-water standard reference solutions.
Co-reporter:Darshan C. Patel, Zachary S. Breitbach, JeongJae Yu, Kate A. Nguyen, Daniel W. Armstrong
Analytica Chimica Acta 2017 Volume 963(Volume 963) pp:
Publication Date(Web):22 April 2017
DOI:10.1016/j.aca.2017.02.005
•High-efficiency 2.7 μm superficially porous particles (SPPs).•High-throughput chiral separations in UHPLC and SFC on short quinine based columns.•Extensive characterization and comparison shown in LC and SFC.•Intrinsic column performances compared using geometry-independent kinetic plots.Two new anion-exchange columns were prepared by bonding tert-butyl carbamoylated quinine to 2.7 μm superficially porous particle (SPP) silica to create chiral stationary phases for high-efficiency and ultrafast chromatography. Performance and retention parameters of these new columns are compared with an analogous 5 μm fully porous particle (FPP) based Chiralpak QNAX column and a 3–4 fold increase in efficiency was observed. Ultrafast separations ranging from 12 s down to sub-second are shown using 2.7 μm SPPs bonded via hydrosilation to the selector. Potential benefits of 2.7 μm SPP based columns for increased LC-MS compatibility were investigated. A van Deemter plot comparison showed 2.7 μm SPP based columns provided a lower reduced plate height and a higher optimal linear velocity compared to the 5 μm FPP based column. With geometry-independent kinetic plots, 2.7 μm SPP and 5 μm FPP based columns were assessed for their kinetic performance and the maximal number of plates each column can generate in a given analysis time. The 2.7 μm SPP based column showed remarkable performance improvements in speed and efficiency as indicated by the kinetic plots.Download high-res image (287KB)Download full-size image
Co-reporter:Rasangi M. Wimalasinghe;Zachary S. Breitbach
Analytical and Bioanalytical Chemistry 2017 Volume 409( Issue 9) pp:2437-2447
Publication Date(Web):2017 March
DOI:10.1007/s00216-017-0190-4
Macrocyclic glycopeptide based liquid chromatography stationary phases are known for their highly selective peptide separations. Fast and ultrafast (tR < 1 min) high-efficiency separations were achieved with superficially porous particle (SPP)-based stationary phases. Separations of pharmaceutically important classes of peptides such as enkephalins and bradykinins have been achieved in less than 5 min in isocratic elution modes. Selectivity for peptides structurally similar to one another was increased with use of teicoplanin-based stationary phases compared with commercial C18 stationary phases. Ultrafast isocratic separations of structurally related peptides were achieved with teicoplanin- and vancomycin-based short SPP columns. Acidic mobile phases produced better separations. Ammonium formate was the optimal mobile phase buffer additive. Use of an appropriate combination of a macrocyclic glycopeptide stationary phase and a mobile phase permits faster and more electrospray ionization mass spectrometry compatible isocratic separations than previous gradient approaches. The tryptic peptide separation characteristics of the teicoplanin stationary phase are demonstrated. Additionally, compared with commercial C18 stationary phases, teicoplanin showed tryptic peptide separations with different selectivities.
Co-reporter:Rahul A. Patil;Mohsen Talebi;Leonard M. Sidisky
Chromatographia 2017 Volume 80( Issue 10) pp:1563-1574
Publication Date(Web):05 August 2017
DOI:10.1007/s10337-017-3372-5
Dicationic ionic liquids (ILs) are widely used as gas chromatography (GC) stationary phases as they show higher thermal stabilities, variety of polarities, and unique selectivities towards certain compounds. An important aspect contributing to them is that they show multiple solvation interactions compared to the traditional GC stationary phases. Dicationic ILs are considered as combination of three structural moieties: (1) cationic head groups; (2) a linkage chain; and (3) the counter anions. Modifications in these structural moieties can alter the chromatographic properties of IL stationary phases. In this study, a series of nine thermally stable IL stationary phases were synthesized by the combination of five different cations, two different linkage chains, and two different anions. Different test mixtures composed of a variety of compounds having different functional groups and polarities were analyzed on these columns. A comparison of the separation patterns of these different compounds on nine different IL columns provided some insights about the effects of structural modifications on the selectivities and polarities of dicationic ILs.
Co-reporter:Darshan C. Patel, Ross M. Woods, Zachary S. Breitbach, Alain Berthod, Daniel W. Armstrong
Tetrahedron: Asymmetry 2017 Volume 28, Issue 11(Issue 11) pp:
Publication Date(Web):15 November 2017
DOI:10.1016/j.tetasy.2017.09.006
Many biaryl compounds possess atropisomerism due to the steric hindrance of substituents at the ortho-position of the two aromatic moieties. Upon heating, atropisomers may have enough energy to surpass the rotational energy barrier and racemize. The thermal stability of five atropisomers was studied using chiral chromatography by following the change in enantiomeric excess ratio at different temperatures. The first order racemization reaction rate was obtained at a given temperature as the slope of the change in enantiomeric excess ratio versus time. For each atropisomer, the racemization rates at different temperatures led to the value of the rotational energy barrier for racemization, ΔG‡, and to the racemization half lifetime, t1/2, indicating the atropisomer thermal stability. Binaphthol started to racemize significantly at temperature of 190 °C and above while binaphthyldiamine was much more stable showing little or very minor racemization up to 210 °C. A chloro-substituted phenylamino-naphthol was very sensitive to thermal racemization starting at a low 40 °C.Download high-res image (78KB)Download full-size image
Co-reporter:M. Farooq Wahab, Darshan C. Patel, Daniel W. Armstrong
Journal of Chromatography A 2017 Volume 1509(Volume 1509) pp:
Publication Date(Web):4 August 2017
DOI:10.1016/j.chroma.2017.06.031
•Real peaks can concurrently front and tail for various reasons.•USP tailing factor is insufficient for total peak shape analysis.•Derivative test is a sensitive measure of peak asymmetry.•Gaussian test quantifies contribution from fronting and tailing.•Real peaks are analyzed with automated template in Excel.Most peak shapes obtained in separation science depart from linearity for various reasons such as thermodynamic, kinetic, or flow based effects. An indication of the nature of asymmetry often helps in problem solving e.g. in column overloading, slurry packing, buffer mismatch, and extra-column band broadening. However, existing tests for symmetry/asymmetry only indicate the skewness in excess (tail or front) and not the presence of both. Two simple graphical approaches are presented to analyze peak shapes typically observed in gas, liquid, and supercritical fluid chromatography as well as capillary electrophoresis. The derivative test relies on the symmetry of the inflection points and the maximum and minimum values of the derivative. The Gaussian test is a constrained curve fitting approach and determines the residuals. The residual pattern graphically allows the user to assess the problematic regions in a given peak, e.g., concurrent tailing or fronting, something which cannot be easily done with other current methods. The template provided in MS Excel automates this process. The total peak shape analysis extracts the peak parameters from the upper sections (> 80% height) of the peak rather than the half height as is done conventionally. A number of situations are presented and the utility of this approach in solving practical problems is demonstrated.
Co-reporter:Rahul A. Patil, Mohsen Talebi, Chengdong Xu, Sumit S. Bhawal, and Daniel W. Armstrong
Chemistry of Materials 2016 Volume 28(Issue 12) pp:4315
Publication Date(Web):June 8, 2016
DOI:10.1021/acs.chemmater.6b01247
Geminal dicationic ionic liquids (ILs) often display higher thermal stabilities, viscosities, and densities compared to traditional monocationic ILs. Also, dicationic ILs have advantages in terms of tuning of their physicochemical properties by different structural modifications. They can be considered as a combination of three structural moieties: (1) cationic head groups, (2) an alkane linker chain, and (3) the associated anions. Two types of each imidazolium, pyrrolidinium, and phosphonium cations were joined by different alkane linkages (C6, C9, and C12) to develop 18 different dications. These dications were paired with two different anions (NTf2– and PFOS–) to synthesize 36 different dicationic ILs. The effect of variations in the structural moieties of these related ILs on their physicochemical properties, including melting points, densities, viscosities, solubilities, and thermal stabilities, were evaluated. ILs synthesized in this study displayed TGA thermal stabilities in the range 330–467 °C. Also, nine ILs with high TGA stability and low melting points were tested with inverse gas chromatography, and some of them displayed stabilities up to 400 °C.
Co-reporter:Lillian A. Frink and Daniel W. Armstrong
Analytical Chemistry 2016 Volume 88(Issue 16) pp:8194
Publication Date(Web):July 27, 2016
DOI:10.1021/acs.analchem.6b02006
Measurement of water in petroleum and petroleum-based products is of industrial and economic importance; however, the varied and complex matrixes make the analyses difficult. These samples tend to have low amounts of water and contain many compounds which react with iodine, causing Karl Fischer titration (KFT) to give inaccurate, typically higher, results. A simple, rapid, automated headspace gas chromatography (HSGC) method which requires modified instrumentation and ionic liquid stationary phases was developed. Measurement of water in 12 petroleum products along with 3 National Institute of Standards and Technology reference materials was performed with the developed method. The range of water found in these samples was ∼12–3300 ppm. This approach appeared to be unaffected by complicated matrixes. The solvent-free nature of the HSGC method also negates the solubility limitations which are common with KFT.
Co-reporter:M. Farooq Wahab, Rasangi M. Wimalasinghe, Yadi Wang, Chandan L. Barhate, Darshan C. Patel, and Daniel W. Armstrong
Analytical Chemistry 2016 Volume 88(Issue 17) pp:8821
Publication Date(Web):August 16, 2016
DOI:10.1021/acs.analchem.6b02260
Sub-second liquid chromatography in very short packed beds is demonstrated as a broad proof of concept for chiral, achiral, and HILIC separations of biologically important molecules. Superficially porous particles (SPP, 2.7 μm) of different surface chemistries, namely, teicoplanin, cyclofructan, silica, and quinine, were packed in 0.5-cm-long columns for separating different classes of compounds. Several issues must be addressed to obtain the maximum performance of 0.5 cm columns with reduced plate heights of 2.6 to 3.0. Modified UHPLC hardware can be used to obtain sub-second separations provided extra-column dispersion is minimized and sufficient data acquisition rates are used. Further, hardware improvements will be needed to take full advantage of faster separations. The utility of power transform, which is already employed in certain chromatography detectors, is shown to be advantageous for sub-second chromatography. This approach could prove to be beneficial in fast screening and two-dimensional liquid chromatography.
Co-reporter:Chandan L. Barhate, M. Farooq Wahab, D. J. Tognarelli, Terry A. Berger, and Daniel W. Armstrong
Analytical Chemistry 2016 Volume 88(Issue 17) pp:8664
Publication Date(Web):August 8, 2016
DOI:10.1021/acs.analchem.6b01898
It is widely accepted that column technology is ahead of existing chromatographic instruments. The chromatographic output may not reflect the true picture of the peak profile inside the column. The instrumental optimization parameters become far more important when peaks elute in a few seconds. In this work, the low viscosity advantage of the supercritical/subcritical CO2 is coupled with the high efficiency of narrow particle size distribution silica. Using short efficient columns and high flow rates (up to 19 mL/min), separations on the order of a few seconds are demonstrated. In the domain of ultrafast supercritical fluid chromatography (SFC), unexpected results are seen which are absent in ultrafast liquid chromatography. These effects arise due to the compressible nature of the mobile phase and detector idiosyncrasies to eliminate back-pressure regulator noise. We demonstrate unusual connection tubing effects with 50, 75, 127, 254, and 500 μm tubings and show the complex relation of dead time, retention time, efficiency, and optimum velocity with the tubing diameter (via column outlet pressure). Fourier analysis at different back-pressure regulator (BPR) settings shows that some instruments have very specific noise frequencies originating from the BPR, and those specific frequencies vanish under certain conditions. The performance of embedded digital filters, namely, moving average, numerically simulated low pass RC, and Gaussian kernels, is compared. This work also demonstrates, using a simple derivative test, that some instruments employ interpolation techniques while sampling at “true” low frequencies to avoid picking up high frequency noise. Researchers engaged in ultrafast chromatography need to be aware of the instrumental nuances and optimization procedures for achieving ultrafast chiral or achiral separations in SFC mode.
Co-reporter:Hongyue Guo, Zachary S. Breitbach, Daniel W. Armstrong
Analytica Chimica Acta 2016 Volume 912() pp:74-84
Publication Date(Web):17 March 2016
DOI:10.1016/j.aca.2016.01.038
•Reduced matrix effects in groundwater and urine with PIESI-MS of anionic compounds.•Applicable to both a linear ion trap and a triple quadrupole mass spectrometer for reduction of matrix effects.•With PIESI-MS, matrix effects were minimized in groundwater or urine matrices.•In high levels of matrices, samples required less dilution to eliminate matrix effects.It is well-known that matrix effects in high performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) can seriously compromise quantitative analysis and affect method reproducibility. Paired ion electrospray ionization (PIESI) mass spectrometry is an approach for analyzing ultra-low levels of anions in the positive ion mode. This approach uses a structurally optimized ion pairing reagent to post-column associate with the anionic analyte, subsequently forming positively charged complexes. These newly formed complex ions are often more surface-active as compared to either the native anion or the ion pairing reagent. No studies have examined whether or not the PIESI approach mitigates matrix effects. Consequently, a controlled study was done using five analytes in highly controlled and reproducible synthetic groundwater and urine matrices. In addition, two different mass spectrometers (linear ion trap and triple quadrupole) were used. Compared to the negative ion mode, the PIESI-MS approach was less susceptible to matrix effects when performed on two different MS platforms. Using PIESI-MS, less dilution of the sample is needed to eliminate ionization suppression which, in turn, permits lower limits of detection and quantitation.
Co-reporter:M. Farooq Wahab, Purnendu K. Dasgupta, Akinde F. Kadjo, Daniel W. Armstrong
Analytica Chimica Acta 2016 Volume 907() pp:31-44
Publication Date(Web):11 February 2016
DOI:10.1016/j.aca.2015.11.043
•Concept of sampling frequency relevant to chromatographic peaks is revisited.•Association of response time with digital filters is described.•Qualitative identification of embedded filters with pulsed LED experiments.•Practical considerations for choosing sampling frequency and response times.•Effect of coupled sampling frequency and response time is shown.With increasingly efficient columns, eluite peaks are increasingly narrower. To take full advantage of this, choice of the detector response time and the data acquisition rate a.k.a. detector sampling frequency, have become increasingly important. In this work, we revisit the concept of data sampling from the theorem variously attributed to Whittaker, Nyquist, Kotelnikov, and Shannon. Focusing on time scales relevant to the current practice of high performance liquid chromatography (HPLC) and optical absorbance detection (the most commonly used method), even for very narrow simulated peaks Fourier transformation shows that theoretical minimum sampling frequency is still relatively low (<10 Hz). However, this consideration alone may not be adequate for real chromatograms when an appreciable amount of noise is present. Further, depending on the instrument, the manufacturer's choice of a particular data bunching/integration/response time condition may be integrally coupled to the sampling frequency. In any case, the exact nature of signal filtration often occurs in a manner neither transparent to nor controllable by the user. Using fast chromatography on a state-of-the-art column (38,000 plates), we evaluate the responses produced by different present generation instruments, each with their unique black box digital filters. We show that the common wisdom of sampling 20 points per peak can be inadequate for high efficiency columns and that the sampling frequency and response choices do affect the peak shape. If the sampling frequency is too low or response time is too large, the observed peak shapes will not remain as narrow as they really are – this is especially true for high efficiency and high speed separations. It is shown that both sampling frequency and digital filtering affect the retention time, noise amplitude, peak shape and width in a complex fashion. We show how a square-wave driven light emitting diode source can reveal the nature of the embedded filter. We discuss time uncertainties related to the choice of sampling frequency. Finally, we suggest steps to obtain optimum results from a given system.
Co-reporter:Hongyue Guo, Leah S. Riter, Chad E. Wujcik, Daniel W. Armstrong
Journal of Chromatography A 2016 Volume 1443() pp:93-100
Publication Date(Web):22 April 2016
DOI:10.1016/j.chroma.2016.03.020
•The analysis avoids derivatization and complex sample preparation steps.•Only 150 μL of samples were needed for various types of water analysis.•Both primary and secondary quantitative limits of glyphosate and AMPA are 0.1 ppb.•This method meets requirements for EU standards.A novel method based on high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was developed for the sensitive determination of glyphosate and its major degradation product, AMPA in environmental water samples. The method involves the use of MS compatible mobile phases (0.1% formic acid in water and acetonitrile) for HPLC and direct analysis of water samples without sample derivatization. The method has been validated in different types of water matrices (drinking, surface and groundwater) by accuracy and precision studies with samples spiked at 0.1, 7.5 and 90 ppb. All mean accuracy values ranged from 85% to 112% for glyphosate and AMPA using both primary and secondary quantitative ion transitions (RSD ≤ 10%). Moreover, both primary and secondary ion transitions for glyphosate and AMPA can achieve the quantitation limits at 0.1 ppb. The linear dynamic range of the calibration curves were from 0.1 to 100 ppb for each analyte at each ion transitions with correlation coefficient higher than 0.997.
Co-reporter:Choyce A. Weatherly, Ying Zhang, Jonathan P. Smuts, Hui Fan, Chengdong Xu, Kevin A. Schug, John C. Lang, and Daniel W. Armstrong
Journal of Agricultural and Food Chemistry 2016 Volume 64(Issue 6) pp:1422-1432
Publication Date(Web):February 8, 2016
DOI:10.1021/acs.jafc.5b05988
Four ionic liquid (IL) columns, SLB-IL59, SLB-IL60, SLB-IL65, and SLB-IL111, were evaluated for more rapid analysis or improved resolution of long-chain methyl and ethyl esters of omega-3, omega-6, and additional positional isomeric and stereoisomeric blends of fatty acids found in fish oil, flaxseed oil, and potentially more complicated compositions. The three structurally distinct IL columns provided shorter retention times and more symmetric peak shapes for the fatty acid methyl or ethyl esters than a conventional polyethylene glycol column (PEG), resolving cis- and trans-fatty acid isomers that coeluted on the PEG column. The potential for improved resolution of fatty acid esters is important for complex food and supplement applications, where different forms of fatty acid can be incorporated. Vacuum ultraviolet detection contributed to further resolution for intricate mixtures containing cis- and trans-isomers, as exemplified in a fatty acid blend of shorter chain C18:1 esters with longer chain polyunsaturated fatty acid (PUFA) esters.
Co-reporter:Yadi Wang, M. Farooq Wahab, Zachary S. Breitbach and Daniel W. Armstrong
Analytical Methods 2016 vol. 8(Issue 31) pp:6038-6045
Publication Date(Web):27 Jul 2016
DOI:10.1039/C6AY01246A
Stationary phases composed of native cyclofructan 6 (CF6) and benzoic acid modified CF6 were synthesized and evaluated for hydrophilic interaction liquid chromatography (HILIC). The ligands were bonded onto 2.7 μm core–shell silica using multipoint attachment technology. These cyclofructan 6 based columns exhibited excellent hydrolytic stability and efficiency (205000 N m−1). The new column chemistry was compared for stability with core–shell silica (the starting material) using neutral, positive and a negatively charged probes. Additionally, the advantage of the use of a pre-saturating column in HILIC mode is shown. The HILIC selectivity chart shows that the benzoic acid modified cyclofructan-6 column shows strong hydrophilicity as well as cation exchange property. A variety of hydrophilic/ionizable compounds were examined, and based on the selectivity chart, it was found that the new column chemistry is different from 33 commercial columns. The benzoic acid CF6 column can simultaneously separate acidic, neutral and basic drugs and produced considerably different retention and selectivity patterns for various classes of compounds including nucleic acid bases, β-blockers, salicylic acid and its analogues. The newly developed column chemistry also shows a potential to work in the reverse phase mode.
Co-reporter:Darshan C. Patel, Zachary S. Breitbach, Ross M. Woods, Yeeun Lim, Andy Wang, Frank W. Foss Jr., and Daniel W. Armstrong
The Journal of Organic Chemistry 2016 Volume 81(Issue 3) pp:1295-1299
Publication Date(Web):January 7, 2016
DOI:10.1021/acs.joc.5b02663
A mild, operationally simple, and single-step transition-metal-free protocol for the synthesis of enantiomerically pure (R)-(+)-2′-amino-1,1′-binaphthalen-2-ol (R-NOBIN) from (R)-(+)-1,1′-binaphthyl-2,2′-diamine (R-BINAM) is reported. The one-pot conversion proceeds with good yield and shows no racemization. The hydroxyl on the R-NOBIN product was shown to have come from water in the reaction medium via an H218O study. The correct value of the specific rotation of R-NOBIN was reported.
Co-reporter:Darshan C. Patel, Zachary S. Breitbach, M. Farooq Wahab, Chandan L. Barhate, and Daniel W. Armstrong
Analytical Chemistry 2015 Volume 87(Issue 18) pp:9137
Publication Date(Web):May 6, 2015
DOI:10.1021/acs.analchem.5b00715
A variety of brush-type chiral stationary phases (CSPs) were developed using superficially porous particles (SPPs). Given their high efficiencies and relatively low back pressures, columns containing these particles were particularly advantageous for ultrafast “chiral” separations in the 4–40 s range. Further, they were used in all mobile phase modes and with high flow rates and pressures to separate over 60 pairs of enantiomers. When operating under these conditions, both instrumentation and column packing must be modified or optimized so as not to limit separation performance and quality. Further, frictional heating results in axial thermal gradients of up to 16 °C and radial temperature gradients up to 8 °C, which can produce interesting secondary effects in enantiomeric separations. It is shown that the kinetic behavior of various CSPs can differ from one another as much as they differ from the well-studied C18 reversed phase media. Three additional interesting aspects of this work are (a) the first kinetic evidence of two different chiral recognition mechanisms, (b) a demonstration of increased efficiencies at higher flow rates for specific separations, and (c) the lowest reduced plate height yet reported for a CSP.
Co-reporter:Chandan L. Barhate, M. Farooq Wahab, Zachary S. Breitbach, David S. Bell, Daniel W. Armstrong
Analytica Chimica Acta 2015 Volume 898() pp:128-137
Publication Date(Web):22 October 2015
DOI:10.1016/j.aca.2015.09.048
•Chiral macrocyclic glycopeptides were bonded on sub-2 μm silica for high efficiency.•High efficiency chiral stationary phases and short columns allowed ultrafast separations.•Columns are compatible with normal phase, reversed phase, and polar organic mobile phases.•Rapid separations in SFC are also demonstrated.State of the art chiral chromatography still employs 3–5 μm bonded or immobilized chiral selectors in 10–25 cm columns. With the availability of 1.9 μm narrow particle size distribution (NPSD) silica, it is now possible to make ever shorter, high efficiency columns practical for sub-minute chiral separations. Three macrocyclic glycopeptides (teicoplanin, teicoplanin aglycone, and vancomycin) were bonded onto 1.9 μm NPSD particles. Such packed columns had ∼80% lower backpressure as compared to polydisperse (PD) 1.7 μm silica materials when using the same mobile phase. The decreased backpressure allowed for diminution of frictional heating and allowed for the use of the 1.9 μm NPSD particle based columns at high flow rates. The 1.9 μm NPSD particle based columns showed up to 190,000 plates m−1 for chiral molecules and 210,000 plates m−1 for achiral probes. Representative enantiomeric separations are shown for wide classes of compounds, including different types of amino acids, β-blockers, and pharmaceutically important heterocyclic compounds such as oxazolidinones. Applications in three liquid chromatography modes, namely, reversed phase, polar organic mode and normal phase chiral separations were shown with resolution values ranging from 1.5 to 5.7. Additionally, the same columns were used with supercritical fluid chromatography (SFC) for ultrafast separations.
Co-reporter:Chandan L. Barhate, Zachary S. Breitbach, Eduardo Costa Pinto, Erik L. Regalado, Christopher J. Welch, Daniel W. Armstrong
Journal of Chromatography A 2015 Volume 1426() pp:241-247
Publication Date(Web):24 December 2015
DOI:10.1016/j.chroma.2015.11.056
•Ultrafast separations of fluorinated drugs from corresponding desfluoro impurities.•Macrocyclic chiral selectors bonded to superficially porous particles were tested.•The chiral phases showed enhanced selectivity compared to other achiral phases.•HPLC-ESI-MS compatibility was demonstrated.•All separations are carried out under isocratic conditions.The separation of fluorinated active pharmaceutical ingredients (APIs) from their desfluoro analogs is a challenging analytical task due to their structural similarity. In this work, fluorine containing APIs and their corresponding desfluorinated impurities were separated on five new 2.7 μm superficially porous particles (SPPs) functionalized with bonded chiral selectors. The unique shape selectivity of bonded macrocyclic glycopeptides and oligosaccharides was utilized to separate seven pairs of fluoro/desfluoro APIs resulting in some unprecedented selectivity values. For example, SPP bonded isopropyl cyclofructan 6 yielded a selectivity of 2.73 for voriconazole and desfluoro voriconazole. Further, the SPP based columns allowed for rapid separations ranging from 9 to 55 s with very high efficiencies ranging from 45,000 to 70,000 plates/m (at high flow rates) in both reversed phase and polar organic modes. Chromatographic separation and detection by HPLC-ESI-MS was demonstrated using ezetimibe and voriconazole and their desfluorinated impurities. Among the tested phases, SPP hydroxypropyl-β-cyclodextrin separated the most fluorinated and desfluorinated analogs with baseline resolution.
Co-reporter:Sumit S. Bhawal, Rahul A. Patil and Daniel W. Armstrong
RSC Advances 2015 vol. 5(Issue 116) pp:95854-95856
Publication Date(Web):09 Nov 2015
DOI:10.1039/C5RA21279K
A method for high temperature Boc deprotection of amino acids and peptides in a phosphonium ionic liquid is described. The ionic liquid had low viscosity, high thermal stability and demonstrated a beneficial effect. The study extended the possibility for extraction of water soluble polar organic molecules using ionic liquids. Trace water significantly improved product purity and yield, while only 2 equiv. TFA led to deprotection within 10 min. The trityl group was also deprotected.
Co-reporter:M. Farooq Wahab, Zachary S. Breitbach, Daniel W. Armstrong, Rick Strattan, and Alain Berthod
Journal of Agricultural and Food Chemistry 2015 Volume 63(Issue 40) pp:8966-8973
Publication Date(Web):October 2, 2015
DOI:10.1021/acs.jafc.5b03120
α-[(6-O-β-d-Glucopyranosyl-β-d-glucopyranosyl)oxy]-(αR)-benzeneacetonitrile, or R-amygdalin, is the most common cyanogenic glycoside found in seeds and kernels of the Rosaceae family and other plant genera such as Passiflora. Many commercially important seeds are analyzed for amygdalin content. In “alternative medicine”, amygdalin has been sold as a treatment for cancer for several decades without any rigorous scientific support for its efficacy. We have found that there are some inconsistencies and possible problems in the published analytical chemistry of amygdalin. It is shown that some analytical approaches do not account for the presence of the S-isomer; therefore, a fast reliable method was developed using a chiral stationary phase and HPLC. This approach allows “real-time” monitoring and complete and highly efficient separations. It is found that the S-amygdalin continuously forms in aqueous solutions. A striking result is that the conversion of amygdalin is glassware dependent. “Clean” vials from various vendors can show drastically different reaction rates of the conversion to the isomer (S-amygdalin, also called neo-amygdalin). The epimerization kinetics are dependent on the solvent, temperature, pH, and the nature of the container. For example, epimerization in water was complete in <15 min in a new glass vial taken from the box, whereas it can take >1 h in specially cleaned glassware. Conversely, epimerization can be significantly delayed at high temperature if high-density polyethylene is used as the container. Hence, inert plastic containers are recommended for storage of aqueous amygdalin solutions. Commercial preparations of R-amygdalin actually contain greater quantities of S-amygdalin and ∼ 5% of other degradation products.
Co-reporter:Hongyue Guo, Maressa D. Dolzan, Daniel A. Spudeit, Chengdong Xu, Zachary S. Breitbach, Uma Sreenivasan, Daniel W. Armstrong
International Journal of Mass Spectrometry 2015 Volume 389() pp:14-25
Publication Date(Web):15 October 2015
DOI:10.1016/j.ijms.2015.08.005
•Detection of the anionic drug metabolites in positive ion mode by using the paired ion electrospray ionization (PIESI) technique.•The detection sensitivity for the drug metabolites has been improved by 3 to 48 folds, as compared to the results obtained from the negative ion mode.•A method based on solid phase extraction and HPLC–MS was developed for simultaneous determination of drug metabolites in urine.The detection window for drugs of abuse, including performance-enhancing drugs, is limited by the sensitivity of analytical methodologies. Herein, paired ion electrospray ionization mass spectrometry (PIESI-MS) was employed for sensitive analysis of performance-enhancing drugs and drugs of abuse by detecting their glucuronide and sulfate conjugates. The proposed approach provides enhanced sensitivity for these drug metabolites, and overcomes the drawbacks of the less sensitive negative ion mode ESI-MS by detecting the anionic metabolites in the positive ion mode at higher m/z where the background noise is less. Absolute LODs down to sub-pg levels were obtained with the use of the optimal symmetrical or unsymmetrical ion pairing reagents. One to three orders of magnitude improvement were obtained compared to other reported methods performed in the negative ion mode. Structurally similar steroid conjugates were chromatographically separated and detected by HPLC coupled with PIESI-MS. Finally, an off-line solid phase extraction (SPE) protocol was successfully developed to eliminate any matrix effects in the analysis of human urine samples.
Co-reporter:Lin Wang, Chang Li, Qiuhong Yin, Su Zeng, Cuirong Sun, Yuanjiang Pan, Daniel W. Armstrong
Tetrahedron 2015 Volume 71(Issue 21) pp:3447-3452
Publication Date(Web):27 May 2015
DOI:10.1016/j.tet.2015.03.075
A binding pattern of cyclofructan 6 and p-aminobenzoic acid was disclosed using electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. The complex with stoichiometric composition 1:1 was formed as a result of intermolecular hydrogen bond interaction and ion dipole interaction. Spectrophotometic studies demonstrated that their binding properties could be actuated by modulating the pH from 2.0 to 10.0. This is the first demonstration of development of ‘switching’ binding pattern for cyclofructan 6.
Co-reporter:Yang Shu, John C. Lang, Zachary S. Breitbach, Haixiao Qiu, Jonathan P. Smuts, Mayumi Kiyono-Shimobe, Mari Yasuda, Daniel W. Armstrong
Journal of Chromatography A 2015 1390() pp: 50-61
Publication Date(Web):
DOI:10.1016/j.chroma.2015.02.018
Co-reporter:Yang Shu;Zachary S. Breitbach;Milan K. Dissanayake;Sirantha Perera;Joseph M. Aslan;Nagham Alatrash;Frederick M. MacDonnell
Chirality 2015 Volume 27( Issue 1) pp:64-70
Publication Date(Web):
DOI:10.1002/chir.22389
Abstract
The enantiomeric separation of 21 ruthenium (II) polypyridyl complexes was achieved with a novel class of cyclofructan-based chiral stationary phases (CSPs) in the polar organic mode. Aromatic derivatives on the chiral selectors proved to be essential for enantioselectivity. The R-napthylethyl carbamate functionalized cyclofructan 6 (LARIHC CF6-RN) column proved to be the most effective overall, while the dimethylphenyl carbamate cyclofructan 7 (LARIHC CF7-DMP) showed complementary selectivity. A combination of acid and base additives was necessary for optimal separations. The retention factor vs. acetonitrile/methanol ratio plot showed a U-shaped retention curve, indicating that different interactions take place at different polar organic solvent compositions. The separation results indicated that π–π interactions, steric effects, and hydrogen bonding contribute to the enantiomeric separation of ruthenium (II) polypyridyl complexes with cyclofructan chiral stationary phases in the polar organic mode. Chirality 27:64–70, 2015. © 2014 Wiley Periodicals, Inc.
Co-reporter:Daniel A. Spudeit;Zachary S. Breitbach;Maressa D. Dolzan;Gustavo A. Micke
Chirality 2015 Volume 27( Issue 11) pp:788-794
Publication Date(Web):
DOI:10.1002/chir.22526
Abstract
A superficially porous particle (SPP)-based hydroxypropyl-β-cyclodextrin (HPBCD) chiral stationary phase (CSP) was produced and its chromatographic performance was compared to both 5 µm and 3 µm fully porous particle (FPP)-based CSPs. The relative surface coverage of the HPBCD chiral selector on each particle was approximately equal, which resulted in equivalent enantiomeric selectivity (α) values on each phase when constant mobile phase conditions were used. Under such conditions, the SPP column resulted in greatly reduced analysis times and three times greater efficiencies compared to the FPP columns. When higher flow rates were used, efficiency gains per analysis times were five times greater for the SPP column compared to the FPP-based columns. When the mobile phases were altered to give similar analysis times on each column, resolution values were doubled for the SPP column. Finally, the novel SPP based HPBCD column proved to be stable for 500 injections under high flow rate (4.5 mL/min) and high pressure (400 bar) conditions used for an ultrafast (~45 sec) enantiomeric separation. Chirality 27:788–794, 2015. © 2015 Wiley Periodicals, Inc.
Co-reporter:Jonathan P. Smuts, Xin-Qi Hao, Zhaobin Han, Curran Parpia, Michael J. Krische, and Daniel W. Armstrong
Analytical Chemistry 2014 Volume 86(Issue 2) pp:1282
Publication Date(Web):December 27, 2013
DOI:10.1021/ac403686a
New cyclofructan-6 (CF6)-based chiral stationary phases (CSPs) bind barium cations. As a result, the barium-complexed CSPs exhibit enantioselectivity toward 16 chiral phosphoric and sulfonic acids in the polar organic mode (e.g., methanol or ethanol mobile phase containing a barium salt additive). Retention is predominantly governed by a strong ionic interaction between the analyte and the complexed barium cation as well as hydrogen bonding with the cyclofructan macrocycle. The log k versus log [X], where [X] = the concentration of the barium counteranion, plots for LARIHC–CF6-P were linear with negative slopes demonstrating typical anion exchange behavior. The nature of the barium counteranion also was investigated (acetate, methanesulfonate, trifluoroacetate, and perchlorate), and the apparent elution strength was found to be acetate > methanesulfonate > trifluoroacetate > perchlorate. A theory based upon a double layer model was proposed wherein kosmotropic anions are selectively adsorbed to the cyclofructan macrocycle and attenuate the effect of the barium cation. van’t Hoff studies for two analytes were conducted on the LARIHC–CF6-P for three of the barium salts (acetate, trifluoroacetate, and perchlorate), and the thermodynamic parameters governing retention and enantioselectivity are discussed. Interestingly, for the entropically driven separations, enantiomeric selectivity can increase at higher temperatures, even with decreasing retention.
Co-reporter:Chengdong Xu, Hongyue Guo, Zachary S. Breitbach, and Daniel W. Armstrong
Analytical Chemistry 2014 Volume 86(Issue 5) pp:2665
Publication Date(Web):February 7, 2014
DOI:10.1021/ac404005v
Paired ion electrospray ionization (PIESI) mass spectrometry was developed as a useful technique that provides sensitive detection for anions in the positive ion mode. The ion-pairing reagent (IPR) utilized plays an essential role affecting the detection limits. This work describes the design and synthesis of two novel dications with unsymmetrical structures and their utilization for anion detection and mechanistic insights. The performance of dications was evaluated for seven selected anions in both single ion monitoring (SIM) mode and selected reaction monitoring (SRM) mode. The unsymmetrical dications allowed sensitive detection for these anions with down to subpicogram limits of detection (LOD) and an improved sensitivity from 1.5 to 12 times compared to the corresponding symmetrical dications. The enhanced sensitivity could be attributed to the surface activity of the unsymmetrical dications, which results in a concurrent strong partitioning of the anion to the aerosol droplet surface. Surface activity measurements of the anion/IPR complex were conducted, and a correlation between the observed ESI responses and the surface activity of the complex was found. The mechanism was further explored and explained based on the concepts of the equilibrium partitioning model (EPM).
Co-reporter:Maressa D. Dolzan, Daniel A. Spudeit, Zachary S. Breitbach, William E. Barber, Gustavo A. Micke, Daniel W. Armstrong
Journal of Chromatography A 2014 Volume 1365() pp:124-130
Publication Date(Web):24 October 2014
DOI:10.1016/j.chroma.2014.09.010
•New HILIC column based on native CF6 bonded to superficially porous particles.•Efficiency up to 3.7 times higher than stationary phases with fully porous particles.•Analysis time up to 85% faster than using columns made with fully porous particles.A new HILIC stationary phase comprised of native cyclofructan-6 (CF6) bonded to superficially porous silica particles (2.7 μm) was developed. Its performance was evaluated and compared to fully porous silica particles with 5 μm (commercially available as FRULIC-N) and 3 μm diameters. Faster and more efficient chromatography was achieved with the superficially porous particles (SPPs). The columns were also evaluated in the normal phase mode. The peak efficiency, analysis time, resolution, and overall separation capabilities in both HILIC and normal phase modes were compared. The analysis times using the superficially porous based column in HILIC mode were shorter and the theoretical plates/min were higher over the entire range of flow rates studied. The column containing the superficially porous particles demonstrated higher optimum flow rates than the fully porous particle packed columns. At higher flow rates, the advantages of the superficially porous particles was more pronounced in normal phase separations than in HILIC, clearly demonstrating the influence that the mode of chromatography has on band broadening. However, the minimum reduced plate heights (hmin) were typically lower in HILIC than in the normal phase mode. Overall, the superficially porous particle based CF6 column showed clear advantages over the fully porous particle columns, in terms of high throughput and efficient separations of polar compounds in the HILIC mode.
Co-reporter:Daniel A. Spudeit, Maressa D. Dolzan, Zachary S. Breitbach, William E. Barber, Gustavo A. Micke, Daniel W. Armstrong
Journal of Chromatography A 2014 Volume 1363() pp:89-95
Publication Date(Web):10 October 2014
DOI:10.1016/j.chroma.2014.08.022
•First paper reporting the use of CSP chemically bonded to core–shell material.•The advantages of core–shell material for fast separation of enantiomers are shown.•Comparison between CSP based on fully and superficially porous material is shown.This work reports a comparison of HPLC separations of enantiomers with chiral stationary phases (CSPs) prepared by chemically bonding cyclofructan-6, functionalized with isopropyl carbamate groups on fully and superficially porous particles (SPPs). The chromatographic performance of the superficially porous CSP based column was compared with columns packed with 5 μm and 3 μm fully porous particles (FPPs). At a flow rate of 3.0 mL/min the number of plates on column afforded by the SPP column was ∼7× greater than the number of plates on column (same length) obtained when using the 5 μm FPP based column. The flow rate providing the highest efficiency separation was ∼1.0 mL/min for the SPP column while it was ∼0.5 mL/min for both FPP columns. It was found that the selectivity and resolution of the separations were comparable between fully porous and superficially porous based columns (under constant mobile phase conditions), even though the SPP column contained lower absolute amounts of chiral selector. When tested under constant retention conditions, the SPP based CSP greatly improved resolution compared to the FPP based columns. At high flow rates the efficiency gained by using superficially porous CSP was accentuated. The advantages of columns based on SPPs become more obvious from the viewpoint of plate numbers and resolution per analysis time.
Co-reporter:Ross M. Woods, Darshan C. Patel, Yeeun Lim, Zachary S. Breitbach, Hongyin Gao, Craig Keene, Gongqiang Li, László Kürti, Daniel W. Armstrong
Journal of Chromatography A 2014 Volume 1357() pp:172-181
Publication Date(Web):29 August 2014
DOI:10.1016/j.chroma.2014.04.080
•First chiral HPLC methods for recently synthesized biaryl atropisomers.•Preparative scale HPLC methods presented.•Thermodynamic parameters for enantiomeric separations determined.•Insights into forces driving retention and chiral recognition presented.Normal phase chiral HPLC methods are presented for the enantiomeric separation of 30 biaryl atropisomers including 18 new compounds recently produced via a novel synthetic approach. Three new cyclofructan based chiral stationary phases were evaluated. Separations were achieved for all but six analytes and the LARIHC™ CF6-P alone provided 15 baseline separations. Effects of polar modifiers and temperature effects also were studied. Apparent thermodynamic parameters were determined by van’t Hoff plots. Preparative scale methods were developed and employed resulting in the first ever isolation of these novel atropisomers in their pure enantiomeric form. Insights into the mechanism of retention and chiral discrimination are presented.
Co-reporter:Chengdong Xu, Eduardo Costa Pinto and Daniel W. Armstrong
Analyst 2014 vol. 139(Issue 17) pp:4169-4175
Publication Date(Web):08 Jul 2014
DOI:10.1039/C4AN00775A
A highly sensitive paired ion electrospray ionization mass spectrometry (PIESI-MS) approach was developed for the trace determination of sphingolipids. Apart from their structure role, specific sphingolipids can play a role in cell signaling and as disease markers. With the optimal pairing reagents, detection limits ranged from low femtomole to picomole levels for 14 selected sphingolipids. This improved the detection sensitivity of ESI-MS for many of these analytes up to ∼4000 times.
Co-reporter:Zachary S. Breitbach;Choyce A. Weatherly;Ross M. Woods;Chengdong Xu;Glenda Vale;Alain Berthod
Journal of Separation Science 2014 Volume 37( Issue 5) pp:558-565
Publication Date(Web):
DOI:10.1002/jssc.201301265
In contrast to the plethora of publications on the separation of fatty acids, analogous studies involving fatty amines are scarce. A recently introduced ionic-liquid-based capillary column for GC was used to separate trifluoroacetylated fatty amines focusing on the analysis of a commercial sample. Using the ionic liquid column (isothermal mode at 200°C) it was possible to separate linear primary fatty amines from C12 to C22 chain length in less 25 min with MS identification. The log of the amine retention factors are linearly related to the alkyl chain length with a methylene selectivity of 0.117 kcal/mol for the saturated amines and 0.128 kcal/mol for the mono-unsaturated amines. The sp2 selectivity for unsaturated fatty amines also could be calculated as 0.107 kcal/mol for the ionic liquid column. The commercial sample was quantified by GC with flame ionization detection (FID). An LC method also was developed with a reversed phase gradient separation using acetonitrile/formate buffer mobile phases and ESI-MS detection. Native amines could be detected and identified by their single ion monitoring chromatograms even when partial coelution was observed. The analysis of the commercial sample returned results coherent with those obtained by GC–FID and with the manufacturer's data.
Co-reporter:Choyce A. Weatherly, Ross M. Woods, and Daniel W. Armstrong
Journal of Agricultural and Food Chemistry 2014 Volume 62(Issue 8) pp:1832-1838
Publication Date(Web):February 17, 2014
DOI:10.1021/jf4050167
Analysis of ethanol and water in consumer products is important in a variety of processes and often is mandated by regulating agencies. A method for the simultaneous quantitation of ethanol and water that is simple, accurate, precise, rapid, and cost-effective is demonstrated. This approach requires no internal standard for the quantitation of both ethanol and water at any/all levels in commercial products. Ionic liquid based gas chromatography (GC) capillary columns are used to obtain a fast analysis with high selectivity and resolution of water and ethanol. Typical run times are just over 3 min. Examination of the response range of water and ethanol with GC, thermal conductivity detection (TCD), and barrier ionization detection (BID) is performed. Quantitation of both ethanol and water in consumer products is accomplished with both TCD and BID GC detectors using a nonlinear calibration. Validation of method accuracy is accomplished by using standard reference materials.
Co-reporter:Lillian A. Frink, Choyce A. Weatherly, Daniel W. Armstrong
Journal of Pharmaceutical and Biomedical Analysis 2014 Volume 94() pp:111-117
Publication Date(Web):June 2014
DOI:10.1016/j.jpba.2014.01.034
•Headspace GC with ionic liquids diluent could evaluate water content in 4 mg samples.•Water content was determined for 22 active pharmaceutical ingredients.•2 different highly efficient GC detectors, thermal conductivity detection and the new barrier ionization detector were utilized.A rapid, accurate, precise and versatile analytical method was developed for the detection and quantification of water in solid active pharmaceutical ingredients (APIs). The headspace gas chromatography (HSGC) method utilized an ionic liquid (IL) based open tubular capillary GC column to increase sensitivity and ruggedness of this method. ILs are also utilized as the headspace solvent because of their low vapor pressure, unique physiochemical properties and high thermal stability. This method is not affected by side reactions and solubility problems which are common with Karl Fischer Titration (KFT) methods. Nor is it as limited as weight loss on drying approaches. The ability to use either/both modern thermal conductivity or barrier ion discharge GC detection provides flexibility, different dynamic ranges and sensitivity. The developed method also was shown to be broadly applicable.
Co-reporter:Choyce A. Weatherly, Yun-Cheol Na, Yasith S. Nanayakkara, Ross M. Woods, Ankit Sharma, Jérôme Lacour, Daniel W. Armstrong
Journal of Chromatography B 2014 Volume 968() pp:40-48
Publication Date(Web):1 October 2014
DOI:10.1016/j.jchromb.2014.05.013
•Enantiomeric separation of 14 functionalized ethano-Tröger base racemates in HPLC and CE.•An example of γ-CD showing superior enantioselectivity for a class of compounds compared to β-CD.•Greater retention on the β-CD CSP shows strong inclusion is not necessary for chiral recognition.•PCA of RSP-CD, and LARIHC-RN showed that retention is governed by the size of the R1 substituent.•PCA of γ -CD, RSP-CD, and LARIHC-RN showed enantioresolution is not governed by retention.The enantiomeric separation of a series of racemic functionalized ethano-bridged Tröger base compounds was examined by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Using HPLC and CE the entire set of 14 derivatives was separated by chiral stationary phases (CSPs) and chiral additives composed of cyclodextrin (native and derivatized) and cyclofructan (derivatized). Baseline separations (Rs ≥ 1.5) in HPLC were achieved for 13 of the 14 compounds with resolution values as high as 5.0. CE produced 2 baseline separations. The separations on the cyclodextrin CSPs showed optimum results in the reversed phase mode, and the LARIHC™ cyclofructan CSPs separations showed optimum results in the normal phase mode. HPLC separation data of the compounds was analyzed using principal component analysis (PCA). The PCA biplot analysis showed that retention is governed by the size of the R1 substituent in the case of derivatized cyclofructan and cyclodextrin CSPs, and enantiomeric resolution closely correlated with the size of the R2 group in the case of non-derivatized γ-cyclodextrin CSP. It is clearly shown that chromatographic retention is necessary but not sufficient for the enantiomeric separations of these compounds.
Co-reporter:Choyce A. Weatherly, Yun-Cheol Na, Yasith S. Nanayakkara, Ross M. Woods, Ankit Sharma, Jérôme Lacour, Daniel W. Armstrong
Journal of Chromatography B 2014 Volumes 955–956() pp:72-80
Publication Date(Web):1 April 2014
DOI:10.1016/j.jchromb.2014.01.058
•Enantiomeric separation of 14 functionalized ethano-Tröger base racemates in HPLC and CE.•An example of γ-CD showing superior enantioselectivity for a class of compounds compared to β-CD.•Greater retention on the β-CD CSP shows strong inclusion is not necessary for chiral recognition.•PCA of RSP-CD, and LARIHC-RN showed that retention is governed by the size of the R1 substituent.•PCA of γ -CD, RSP-CD, and LARIHC-RN showed enantioresolution is not governed by retention.The enantiomeric separation of a series of racemic functionalized ethano-bridged Tröger base compounds was examined by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Using HPLC and CE the entire set of 14 derivatives was separated by chiral stationary phases (CSPs) and chiral additives composed of cyclodextrin (native and derivatized) and cyclofructan (derivatized). Baseline separations (Rs ≥ 1.5) in HPLC were achieved for 13 of the 14 compounds with resolution values as high as 5.0. CE produced 2 baseline separations. The separations on the cyclodextrin CSPs showed optimum results in the reversed phase mode, and the LARIHC™ cyclofructan CSPs separations showed optimum results in the normal phase mode. HPLC separation data of the compounds was analyzed using principal component analysis (PCA). The PCA biplot analysis showed that retention is governed by the size of the R1 substituent in the case of derivatized cyclofructan and cyclodextrin CSPs, and enantiomeric resolution closely correlated with the size of the R2 group in the case of non-derivatized γ-cyclodextrin CSP. It is clearly shown that chromatographic retention is necessary but not sufficient for the enantiomeric separations of these compounds.
Co-reporter:Lillian A. Frink;Muhammad A. Khan;Laszlo Kürti;John R. Falck
Chromatographia 2014 Volume 77( Issue 23-24) pp:1607-1612
Publication Date(Web):2014 December
DOI:10.1007/s10337-014-2776-8
High-performance liquid chromatographic (HPLC) and gas chromatographic (GC) methods were developed for the separation of enantiomers of 12 novel aziridines. The HPLC separations were performed on cyclodextrin, cyclofructan, amylose, cellulose and macrocyclic glycopeptide-based chiral stationary phases, whereas the GC separations were performed only on cyclodextrin-based chiral stationary phases. The amylose-based HPLC chiral stationary phases showed good selectivity toward the aziridines, while having low retention factors. It was shown that the HPLC generally provided better separations for most of the compounds as compared to GC. Effective enantiomeric separations for ten aziridines were developed.
Co-reporter:Chengdong Xu, Daniel W. Armstrong
Analytica Chimica Acta 2013 Volume 792() pp:1-9
Publication Date(Web):20 August 2013
DOI:10.1016/j.aca.2013.05.054
•A new HPLC–MS/MS method based on paired ion electrospray ionization (PIESI) has been developed to determine acidic pesticides at ultratrace levels.•This method provides orders of magnitude greater sensitivity than in the usual negative mode.•Sub-picogram level LODs were obtained using optimal ion-pairing reagent.•Trace amounts of pesticides in water samples were determined by using this method.A novel method based on the paired ion electrospray ionization (PIESI) mass spectrometry has been developed for determination of acidic pesticides at ultratrace levels in surface and ground waters. The proposed approach provides greatly enhanced sensitivity for acidic pesticides and overcomes the drawbacks of the less sensitive negative ion mode ESI-MS. The limits of detection (LODs) of 19 acidic pesticides were evaluated with four types of dicationic ion-pairing reagent (IPR) in both single ion monitoring (SIM) and selected reaction monitoring (SRM) mode. The LOD of 19 pesticides obtained with the use the optimal dicationic ion-pairing reagent ranged from 0.6 pg to 19 pg, indicating the superior sensitivity provided by this method. The transition pathways for different pesticide-IPR complexes during the collision induced dissociation (CID) were identified. To evaluate and eliminate any matrix effects and further decrease the detection limits, off-line solid-phase extraction (SPE) was performed for DI water and a river water matrix spiked with 2000 ng L−1 and 20 ng L−1 pesticides standards respectively, which showed an average percent recovery of 93%. The chromatographic separation of the acidic pesticides was conducted by high-performance liquid chromatography (HPLC) using a C18 column (250 mm × 2.1 mm) in the reversed phase mode using linear gradient elution. The optimized HPLC–PIESI-MS/MS method was utilized for determination of acidic pesticide at ng L−1 level in stream/pond water samples. This experimental approach is 1–3 orders of magnitude more sensitive for these analytes than other reported methods performed in the negative ion mode.
Co-reporter:Yasith S. Nanayakkara, Ross M. Woods, Zachary S. Breitbach, Sachin Handa, LeGrande M. Slaughter, Daniel W. Armstrong
Journal of Chromatography A 2013 Volume 1305() pp:94-101
Publication Date(Web):30 August 2013
DOI:10.1016/j.chroma.2013.06.044
•21 chiral isochromene derivatives were separated for the first time by chromatography.•Separation data and structural features of 35 chiral isochromenes were analyzed.•Principal component analysis was used for the study.•Some structural features increase retention while others enhance chiral resolution.Isochromene derivatives are very important precursors in the natural products industry. Hence the enantiomeric separations of chiral isochromenes are important in the pharmaceutical industry and for organic asymmetric synthesis. Here we report enantiomeric separations of 21 different chiral isochromene derivatives, which were synthesized using alkynylbenzaldehyde cyclization catalyzed by chiral gold(I) acyclic diaminocarbene complexes. All separations were achieved by high-performance liquid chromatography with cyclodextrin based (Cyclobond) chiral stationary phases. Retention data of 21 chiral compounds and 14 other previously separated isochromene derivatives were analyzed using principal component analysis. The effect of the structure of the substituents on the isochromene ring on enantiomeric resolution as well as the other separation properties was analyzed in detail. Using principal component analysis it can be shown that the structural features that contribute to increased retention are different from those that enhance enantiomeric resolution. In addition, principal component analysis is useful for eliminating redundant factors from consideration when analyzing the effect of various chromatographic parameters. It was found that the chiral recognition mechanism is different for the larger γ-cyclodextrin as compared to the smaller β-cyclodextrin derivatives. Finally this specific system of chiral analytes and cyclodextrin based chiral selectors provides an effective format to examine the application of principal component analysis to enantiomeric separations using basic retention data and structural features.
Co-reporter:Haixiao Qiu, Nilusha L.T. Padivitage, Lillian A. Frink, Daniel W. Armstrong
Tetrahedron: Asymmetry 2013 Volume 24(Issue 18) pp:1134-1141
Publication Date(Web):30 September 2013
DOI:10.1016/j.tetasy.2013.07.019
The enantiomeric purity of chiral reagents used in asymmetric syntheses directly affects the apparent reaction selectivity and the product’s enantiomeric excess. Herein, 46 recently available chiral compounds were evaluated in order to determine their actual enantiomeric compositions. They have not been assayed previously and/or have been introduced after 2006, when the last comprehensive evaluation of commercially available chiral compounds was reported. These compounds are widely used in asymmetric syntheses as chiral synthons, catalysts, and auxiliaries. The enantioselective analysis methods include HPLC approaches using Chirobiotic, Cyclobond and LARIHC series chiral stationary phases, and GC approaches using Chiraldex chiral stationary phases. Accurate, efficient assays for selected compounds are given. All enantiomeric test results were categorized within five impurity levels (i.e., <0.01%, 0.01–0.1%, 0.1–1%, 1–10% and >10%). Different batches of the same reagent from the same company can have different levels of enantiomeric impurities. Many of the reagents tested were found to have less than 0.1% enantiomeric impurities. Only one of the chiral compounds was found to have an enantiomeric impurity exceeding 10%.
Co-reporter:Sirantha Perera;Yun-Cheol Na;Thomas Doundoulakis;Victor J. Ngo;Qing Feng;Zachary S. Breitbach;Carl J. Lovely
Chirality 2013 Volume 25( Issue 2) pp:133-140
Publication Date(Web):
DOI:10.1002/chir.22127
ABSTRACT
High performance liquid chromatography (HPLC) and capillary electrophoresis (CE) were used to examine the enantiomeric separation of a series of 17 racemic tetrahydrobenzimidazole analytes. These compounds were prepared as part of a synthetic program directed towards a select group of pyrrole-imidazole alkaloids. This group of natural products has a unique framework of pyrrole- and guanidine-containing fused rings which can be constructed through the intermediacy of a tetrahydrobenzimidazole scaffold. Several bonded cyclodextrin- (both native and derivatized) and derivatized cyclofructan-based chiral stationary phases were evaluated for their ability to separate these racemates via HPLC. Similarly, several cyclodextrin derivatives and derivatized cyclofructan were evaluated for their ability to separate this set of chiral compounds via CE. Enantiomeric selectivity was observed for the entire set of racemic compounds using HPLC with resolution values up to 3.0. Among the 12 different CSPs, enantiomeric recognition was most frequently observed with the Cyclobond RN and LARIHC CF6-P, while the Cyclobond DMP yielded the greatest number of baseline separations. Fifteen of the analytes showed enantiomeric recognition in CE with resolution values as high as 5.0 and hydroxypropyl-γ-cyclodextrin was the most effective chiral additive. Chirality 25:133–140, 2013. © 2012 Wiley Periodicals, Inc.
Co-reporter:Ying Zhang, Jonathan P. Smuts, Edra Dodbiba, Rekha Rangarajan, John C. Lang, and Daniel W. Armstrong
Journal of Agricultural and Food Chemistry 2012 Volume 60(Issue 36) pp:9305-9314
Publication Date(Web):August 11, 2012
DOI:10.1021/jf302179c
Rosemary, whose major caffeoyl-derived and diterpenoid ingredients are rosmarinic acid, carnosol, and carnosic acid, is an important source of natural antioxidants and is being recognized increasingly as a useful preservative, protectant, and even as a potential medicinal agent. Understanding the stability of these components and their mode of interaction in mixtures is important if they are to be utilized to greatest effect. A study of the degradation of rosmarinic acid, carnosol, carnosic acid, and a mixture of the three was conducted in ethanolic solutions at different temperatures and light exposure. As expected, degradation increased with temperature. Some unique degradation products were formed with exposure to light. Several degradation products were reported for the first time. The degradation products were identified by HPLC/MS/MS, UV, and NMR. The degradation of rosemary extract in fish oil also was investigated, and much slower rates of degradation were observed for carnosic acid. In the mixture of the three antioxidants, carnosic acid serves to maintain levels of carnosol, though it does so at least in part at the cost of its own degradation.
Co-reporter:Lin Wang, Yunfeng Chai, Cuirong Sun, Daniel W. Armstrong
International Journal of Mass Spectrometry 2012 Volumes 323–324() pp:21-27
Publication Date(Web):1 June 2012
DOI:10.1016/j.ijms.2012.06.003
Interactions between transition metal ions (Fe2+, Co2+, Ni2+, Cu2+ and Zn2+) and cyclofrunctans (CFs) in different solvents were investigated using positive electrospray ionization mass spectrometry (ESI-MS). ESI mass spectral analysis revealed that the 1:1 complexes were formed stably in ion trap and Fourier transform ion cyclotron resonance mass spectrometers (or in solution). The transition metal ion affinities of CFs were influenced by different solvents. In methanol and acetone, the complexation of CFs with transition metal ions was weak and the complexes of CFs with alkali metal ions were dominant. In contrast, the complexes of CFs with transition metal ions were the most abundant species in the presence of acetonitrile. The stability of inclusion complexes between cyclofructans and transition metal ions were tested by collision-induced dissociation through determining the CE50 values. The gas phase stability of cyclofructans in binding with transition metal cations was found to be in the order of Ni2+ > Fe2+ > Co2+ > Zn2+ > Cu2+, which did not follow the size of ionic radius. An experimental approach based on ESI-MS is therefore established to study the host–guest interactions between cyclofructans and transition metal ions.Graphical abstractHighlights► An experimental approach based on ESI-MS is established to study the host–guest interactions between cyclofructans and transition metal ions. ► The transition metal ion affinities of CFs were influenced by different solvents. ► We study the gas phase selectivity of cyclofructan for transition metal cations by CE50 method.
Co-reporter:Tharanga Payagala
Chirality 2012 Volume 24( Issue 1) pp:17-53
Publication Date(Web):
DOI:10.1002/chir.21975
Abstract
In recent years, the field of chiral ionic liquids (CILs) has undergone exponential growth. As the technology has advanced, new ways of synthesizing stable and structurally diverse ionic liquids have been established. This has led to heretofore unknown applications of CILs as well as in improving efficiency of previously identified applications. In this review article we have compiled a comprehensive database containing structures and physical properties of notable CILs that have been synthesized during the last 6 years. Their applications in the fields of asymmetric organic synthesis, spectroscopy, and chromatography are also illustrated. This is an expansion of our previous review, which covered the literature before 2005. Chirality, 2011. © 2011 Wiley Periodicals, Inc.
Co-reporter:Haixiao Qiu, Eranda Wanigasekara, Ying Zhang, Tran Tran, Daniel W. Armstrong
Journal of Chromatography A 2011 Volume 1218(Issue 44) pp:8075-8082
Publication Date(Web):4 November 2011
DOI:10.1016/j.chroma.2011.09.016
New zwitterionic stationary phases were synthesized by covalently bonding 3-P,P-diphenylphosphonium-propylsulfonate to silica gel. The resulting materials possess both a negatively charged sulfonate group and a positively charged quaternary phosphonium group, which means that there is no net charge over a wide pH range. The retention mechanism and chromatographic behavior of polar solutes under HILIC conditions were studied on these zwitterionic phases. Compared to the commercial ZIC-HILIC column and a bare silica gel stationary phase, the newly synthesized zwitterionic stationary phases provided greater retention, higher peak efficiency and better peak symmetry in the HILIC mode. The analytes examined included: β-blockers, nucleic acid bases and nucleosides, salicylic acid and its analogues, and water soluble vitamins. Factors, such as the type of organic modifiers, solvent composition, pH and the buffer concentration of the mobile phase, have been considered as potential variables for controlling the chromatographic retention of polar analytes.Highlights► Zwitterionic stationary phase. ► HILIC separation. ► Mobile phase effect.
Co-reporter:Haixiao Qiu, Lucie Loukotková, Ping Sun, Eva Tesařová, Zuzana Bosáková, Daniel W. Armstrong
Journal of Chromatography A 2011 Volume 1218(Issue 2) pp:270-279
Publication Date(Web):14 January 2011
DOI:10.1016/j.chroma.2010.11.027
New stationary phases for hydrophilic interaction liquid chromatography (HILIC) were synthesized by covalently attaching native cyclofructan 6 (CF6) to silica gel. The chromatographic characteristics of the new stationary phases were evaluated and compared to three different types of commercial HILIC columns. The CF6 columns produced considerably different retention and selectivity patterns for various classes of polar analytes, including nucleic acid compounds, xanthines, β-blockers, salicylic acid and its derivatives, and maltooligosaccharides. Univariate optimization approaches were examined including organic modifier (acetonitrile) contents and buffer pH and salt concentration. The thermodynamic characteristic of the CF6 stationary phase was investigated by considering the column temperature effect on retention and utilizing van’t Hoff plots. CF6 based stationary phases appear to have exceptionally broad applicability for HILIC mode separations.
Co-reporter:Edra Dodbiba, Chengdong Xu, Tharanga Payagala, Eranda Wanigasekara, Myeong Hee Moon and Daniel W. Armstrong
Analyst 2011 vol. 136(Issue 8) pp:1586-1593
Publication Date(Web):18 Feb 2011
DOI:10.1039/C0AN00848F
Phospholipids make up one of the more important classes of biological molecules. Because of their amphipathic nature and their charge state (e.g., negatively charged or zwitterionic) detection of trace levels of these compounds can be problematic. Electrospray ionization mass spectrometry (ESI-MS) is used in this study to detect very small amounts of these analytes by using the positive ion mode and pairing them with fifteen different cationic ion pairing reagents. The phospholipids used in this analysis were phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA), 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC), cardiolipin (CA) and sphingosyl phosphoethanolamine (SPE). The analysis of these molecules was carried out in the single ion monitoring (SIM) positive mode. In addition to their detection, a high performance liquid chromatography and mass spectrometry (HPLC-MS) method was developed in which the phospholipids were separated and detected simultaneously within a very short period of time. Separation of phospholipids was developed in the reverse phase mode and in the hydrophilic interaction liquid chromatography (HILIC) mode HPLC. Their differences and impact on the sensitivity of the analytes are compared and discussed further in the paper. With this technique, limits of detection (LODs) were very easily recorded at low ppt (ng L−1) levels with many of the cationic ion pairing reagents used in this study.
Co-reporter:Ping Sun, Chunlei Wang, Nilusha Lasanthi Thilakarathna Padivitage, Yasith S. Nanayakkara, Sirantha Perera, Haixiao Qiu, Ying Zhang and Daniel W. Armstrong
Analyst 2011 vol. 136(Issue 4) pp:787-800
Publication Date(Web):07 Dec 2010
DOI:10.1039/C0AN00653J
The two best aromatic-functionalized cyclofructan chiral stationary phases, R-naphthylethyl-carbamate cyclofructan 6 (RN-CF6) and dimethylphenyl-carbamate cyclofructan 7 (DMP-CF7), were synthesized and evaluated by injecting various classes of chiral analytes. They provided enantioselectivity toward a broad range of compounds, including chiral acids, amines, metal complexes, and neutral compounds. It is interesting that they exhibited complementary selectivities and the combination of two columns provided enantiomeric separations for 43% of the test analytes. These extensive chromatographic results provided useful information about method development of specific analytes, and also gave some insight as to the enantioseparation mechanism.
Co-reporter:Jonathan Smuts;Eranda Wanigasekara
Analytical and Bioanalytical Chemistry 2011 Volume 400( Issue 2) pp:435-447
Publication Date(Web):2011 April
DOI:10.1007/s00216-011-4767-z
A class of stationary phases for packed column supercritical fluid chromatography (SFC), referred to as immobilized ionic liquids (IILs), is evaluated with a two-part study: (1) a cation effect study and (2) an anion effect study. The former study compares six different IILs (tripropylphosphonium, tributylphosphonium, methyl-imidazolium, benzyl-imidazolium, triphenylphosphonium, and 4,4′-bipyridyl) on silica gel, evaluating their performance in SFC with all the counter anions as trifluoroacetate (TFA−). In the latter study, the stationary phase consisted of a bonded tributylphosphonium cation and varying counter anions (acetate, TFA−, chloride, NTf2−, and perchlorate). An order of retentivity was established for the cation effect study, and the favorable behavior of phosphonium-based stationary phases is reported for the first time in SFC. It was not possible to always assign a retentivity order for the anion effect study, but wide variations in selectivity are noted for different anions showing the tunable nature of this class of stationary phases.
Co-reporter:Tharanga Payagala;Eranda Wanigasekara
Analytical and Bioanalytical Chemistry 2011 Volume 399( Issue 7) pp:2445-2461
Publication Date(Web):2011 March
DOI:10.1007/s00216-010-4615-6
Three new polymeric chiral stationary phases were synthesized based on (1S,2S)-1,2-bis(2,4,6-trimethylphenyl)ethylenediamine, (1S,2S)-1,2-bis(2-chlorophenyl)ethylenediamine, and (1S,2S)-1,2-di-1-naphthylethylenediamine via a simple free-radical-initiated polymerization in solution. These monomers are structurally related to (1S,2S)-1,2-diphenylethylenediamine which is the chiral monomer used for the commercial P-CAP-DP polymeric chiral stationary phase (CSP). The performance of these three new chiral stationary phases were evaluated in normal phase high-performance liquid chromatography (HPLC) and supercritical fluid chromatography and the results were compared with those of the P-CAP-DP column. All three new phases showed enantioselectivity for a large number of racemates with a variety of functional groups, including amines, amides, alcohols, amino acids, esters, imines, thiols, and sulfoxides. In normal phase, 68 compounds were separated with 28 baseline separations (Rs ≥ 1.5) and in SFC, 65 compounds were separated with 24 baseline separations. In total 72 out of 100 racemates were separated by these CSPs with 37 baseline separations. Complimentary separation capabilities were observed for many analytes. The new polymeric CSPs showed similar or better enantioselectivities compared with the commercial column in both HPLC and SFC. However, faster separations were achieved on the new stationary phases. Also, it was shown that these polymeric stationary phases have good sample loading capacities while maintaining enantioselectivity.
Co-reporter:Yasith S. Nanayakkara, Hyejin Moon and Daniel W. Armstrong
ACS Applied Materials & Interfaces 2010 Volume 2(Issue 7) pp:1785
Publication Date(Web):June 29, 2010
DOI:10.1021/am100269d
RC filters are used to discriminate unwanted frequency elements of a specific signal. Here we report a new concept for a tunable RC filter. The concept was demonstrated by developing a tunable RC filter “consisting of an ionic liquid drop placed on a dielectric layer.” Cut-off frequency of the filter can be altered and controlled by changing the drop shape via electrowetting. The dielectric layer and the solid−liquid interface behave as serially connected capacitors, where the total capacitance is a function of drop shape (or contact angle). The drop shape and hence the total capacitance can be instantly controlled by electrowetting. The change in the capacitance will change the cutoff frequency of the filter. For a 5 μL ionic liquid drop, the achieved “tunability range” was 4.5−9.8 kHz. This demonstrates that the new concept is attainable. This RC filter system could potentially be used as a detecting technique.Keywords: critical frequency; cutoff frequency,; electrowetting; ionic liquids; RC filter; [bmim][NTf2]
Co-reporter:Yasith S. Nanayakkara, Sirantha Perera, Shreyas Bindiganavale, Eranda Wanigasekara, Hyejin Moon and Daniel W. Armstrong
Analytical Chemistry 2010 Volume 82(Issue 8) pp:3146
Publication Date(Web):March 29, 2010
DOI:10.1021/ac9021852
This paper presents a study of electrowetting of ionic liquids (ILs) under AC voltages, where nine different ILs (including mono-, di-, and tricationic varieties) with three different AC frequencies (60 Hz, 1 kHz, 10 kHz) were experimentally investigated. The main foci of this study are (i) an investigation of AC frequency dependence on the electrowetting of ILs; (ii) obtaining theoretical relationships between the relevant factors that explain the experimentally achieved frequency dependence; and (iii) a systematic comparison of electrowetting of ILs using AC vs DC voltage fields. The frequency of the AC voltage was found to be directly related to the apparent contact angle change (Δθ) of the ILs. This relationship was further analyzed and explained theoretically. The electrowetting properties of ILs under AC voltages were compared to that under DC voltages. All tested ILs showed greater apparent contact angle changes with AC voltage conditions than with DC voltage conditions. The effect of structure and charge density also was examined. Electrowetting reversibility under AC voltage conditions was studied for few ILs. Finally, the physical properties and AC electrowetting properties of ILs were measured and tabulated.
Co-reporter:Zachary S. Breitbach, Eranda Wanigasekara, Edra Dodbiba, Kevin A. Schug, and Daniel W. Armstrong
Analytical Chemistry 2010 Volume 82(Issue 21) pp:9066
Publication Date(Web):October 11, 2010
DOI:10.1021/ac102115w
Recently, we have shown that dilute multivalent cationic reagents can be paired with analyte anions in ESI-MS, thereby allowing them to be detected in the positive mode at very low limits of detection. However, there can be differences in the efficiency of this technique depending on the nature of the cationic pairing agent and the anion being analyzed. In this study, three dicationic ion-pairing agents and four singly charged anionic species were examined in a series of experiments to elucidate the mechanism of action that allows for such sensitive detection and the profound differences in the selectivity of this ion-pairing method. The binding constants for the dication/anion complexes were determined by NMR and ESI-MS. The results indicated that the binding of these species is greatly enhanced as they move from the solution phase to the gas phase. Furthermore, surface tension measurements for the complexes were performed. This test revealed that, as the dication pairs with the anion, it creates a surface-active species within the ESI droplet. This is determined to be one of the major factors that leads to the overall sensitivity enhancement. This has led to a better understanding of how this ion-pairing technique produces unprecedented limits of detection for anions and why there are selectivity differences in pairing agents of different structures.
Co-reporter:Ping Sun, Daniel W. Armstrong
Analytica Chimica Acta 2010 Volume 661(Issue 1) pp:1-16
Publication Date(Web):19 February 2010
DOI:10.1016/j.aca.2009.12.007
Ionic liquids (ILs) are composed entirely of ions and they possess fascinating properties, including low volatility, tunable viscosity and miscibility, and electrolytic conductivity, which make ILs unique and useful for many applications in chemical analysis. The dramatic increase in the number of publications on ILs is indicative of the tremendous interest in this field from analytical chemists. This review summarizes recent efforts in the major subdisciplines of analytical chemistry, including extractions, gas chromatography, liquid chromatography, capillary electrophoresis, mass spectrometry, electrochemistry, sensors, and spectroscopy.
Co-reporter:Ping Sun, Daniel W. Armstrong
Journal of Chromatography A 2010 Volume 1217(Issue 30) pp:4904-4918
Publication Date(Web):23 July 2010
DOI:10.1016/j.chroma.2010.04.079
A new chiral stationary phase (CSP) was developed by bonding isopropyl-carbamate functionalized cyclofructan6 (IP-CF6) to the silica gel. It was evaluated by injecting 119 racemic primary amine-containing compounds. This CSP showed pronounced enantioselectivity toward all types of primary amines, separating 93% of all tested compounds. Baseline separation was achieved even for some simple aliphatic racemic amines that contained no other functionality. The polar organic mode was shown to be the effective mobile phase owing to higher efficiency. This new chiral stationary phase showed great potential for preparative-scale separations. It is also interesting that the chiral selector, R-naphthylethyl-carbamate functionalized CF6 (RN-CF6), was found to provide complementary selectivity for the relatively few amine analytes that did not separate on IP-CF6. Thus between the two CSPs, 98% of attempted amine compounds were separated.
Co-reporter:Ke Huang, Xiaotong Zhang, Daniel W. Armstrong
Journal of Chromatography A 2010 Volume 1217(Issue 32) pp:5261-5273
Publication Date(Web):6 August 2010
DOI:10.1016/j.chroma.2010.06.025
Ionic liquids (ILs) are used to dissolve ionic cyclodextrin (CD) derivatives to produce a new type of gas chromatographic chiral stationary phase. Compared to a previous study with neutral cyclodextrin chiral selectors, the new ionic liquid-based stationary phase exhibits broader enantioselectivities, up to seven times higher efficiencies, and greater thermal stabilities. When compared to the analogous commercial column with polysiloxane matrix, it exhibits different enantioselectivities, more symmetric peak shapes and some complementary enantioseparations. The most profound separation enhancements are usually found for more polar analytes.
Co-reporter:Man-Yung Tong, Tharanga Payagala, Sirantha Perera, Frederick M. MacDonnell, Daniel W. Armstrong
Journal of Chromatography A 2010 Volume 1217(Issue 7) pp:1139-1148
Publication Date(Web):12 February 2010
DOI:10.1016/j.chroma.2009.09.003
Sodium arsenyl-(l)-(+) tartrate (Na2[As2(+)-tart2]·3H2O) was examined and evaluated as a chiral selector using capillary electrophoresis. This chiral selector showed enantioselective associations with many cationic analytes, including primary, secondary, and tertiary amines. Also, baseline separations of ruthenium(II) polypyridyl complexes were achieved within 10 min. The effect of buffer type, chiral selector concentration, voltage applied, buffer concentration, buffer pH and organic modifier concentration were examined and optimized.
Co-reporter:Ying Zhang, Zachary S. Breitbach, Chunlei Wang and Daniel W. Armstrong
Analyst 2010 vol. 135(Issue 5) pp:1076-1083
Publication Date(Web):16 Feb 2010
DOI:10.1039/B925945G
Cyclofructans cannot be used as chiral stationary phases for GLC in their native states. This is due to their high melting points and their inability to be solubilized in other liquid stationary phases. However, when cyclofructans are derivatized (via the 3-, 4-, or 6-hydroxyl groups) they can then be dissolved in an achiral matrix and the mixture is suitable as a GLC chiral stationary phase. In this study, per-O-methylated cycloinulohexaose (PM-CF6), per-O-methylated cycloinuloheptose (PM-CF7) and 4,6-di-O-pentyl cycloinulohexaose (DP-CF6) were tested as new chiral selectors for GLC. Enantiomeric separations of several different compounds were observed when using the derivatized cyclofructans as chiral selectors. The enantiomers separated include esters, β-lactams, alcohols, and amino acid derivatives. Differences in the enantiomeric separations obtained by using PM-CF6, PM-CF7 and DP-CF6 as the chiral selector were observed. These differences gave some insight as to the mechanism of enantioselectivity for permethylated cyclofructans as GLC chiral selectors.
Co-reporter:Chunlei Wang, Samuel H. Yang, Jianguang Wang, Peter Kroll, Kevin A. Schug, Daniel W. Armstrong
International Journal of Mass Spectrometry 2010 Volume 291(Issue 3) pp:118-124
Publication Date(Web):15 April 2010
DOI:10.1016/j.ijms.2010.01.014
Cyclofructans, cyclic fructofuranose oligomers, form complexes with a variety of metal cations in solution. ESI-MS was used to investigate both solution and gas phase selectivities of cyclofructans for alkali metal cations. In the gas phase, cyclofructans bind to alkali metal cations in the order of Li+ > Na+ > K+ > Rb+ > Cs+. The gas phase selectivity, obtained by competitive dissociation of ternary complexes between one cyclofructan and two different metal cations, was confirmed with density functional theory calculations. The calculated binding strength is from −99 to −383 kJ mol−1 for cyclofructan 6 and the alkali metal cations. The cyclofructan's 3-position oxygens are the most likely interaction points for the alkali metals. For the solution phase study, sodium and potassium complexes of cyclofructans were the most abundant species in the ESI-MS spectra. Compared with previous solution phase studies of cyclofructans, ESI-MS produced higher abundance of complexes with Li+ and lower abundance of complexes with larger metal cations. The relative intensities of different cyclofructan–metal cation complexes observed in the ESI-MS spectra was a reflection of both the solution phase and gas phase stability of different complex ions.We study the solution and gas phase selectivity of cyclofructan for alkali metal cations by ESI-MS and DFT calculations.
Co-reporter:Man-Yung Tong, Chunxia Jiang, Daniel W. Armstrong
Journal of Pharmaceutical and Biomedical Analysis 2010 53(1) pp: 75-80
Publication Date(Web):
DOI:10.1016/j.jpba.2010.03.010
Co-reporter:Xiaotong Zhang;Ye Bao;Ke Huang;Kimber L. Barnett-Rundlett
Chirality 2010 Volume 22( Issue 5) pp:495-513
Publication Date(Web):
DOI:10.1002/chir.20771
Abstract
Dalbavancin is a new compound of the macrocyclic glycopeptide family. It was covalently linked to 5 μm silica particles using two different binding chemistries. Approximately 250 racemates including (a) heterocyclic compounds, (b) chiral acids, (c) chiral amines, (d) chiral alcohols, (e) chiral sulfoxides and sulfilimines, (f) amino acids and amino acid derivatives, and (g) other chiral compounds were tested on the two new chiral stationary phases (CSPs) using three different mobile phases. As dalbavancin is structurally related to teicoplanin, the same set of chiral compounds was screened on two commercially available teicoplanin CSPs for comparison. The dalbavancin CSPs were able to separate some enantiomers that were not separated by the teicoplanin CSPs and also showed improved separations for many racemates. However, there were other compounds only separated or better separated on teicoplanin CSPs. Therefore, the dalbavancin CSPs are complementary to the teicoplanin CSPs. Chirality, 2010. © 2009 Wiley-Liss, Inc.
Co-reporter:Tharanga Payagala, Ying Zhang, Eranda Wanigasekara, Ke Huang, Zachary S. Breitbach, Pritesh S. Sharma, Leonard M. Sidisky and Daniel W. Armstrong
Analytical Chemistry 2009 Volume 81(Issue 1) pp:160
Publication Date(Web):December 9, 2008
DOI:10.1021/ac8016949
Trigonal tricationic ionic liquids (ILs) are a new class of ILs that appear to be unique when used as gas chromatographic stationary phases. They consist of four core structures; (1) A = mesitylene core, (2) B = benzene core, (3) C = triethylamine core, and (4) D = tri(2-hexanamido)ethylamine core; to which three identical imidazolium or phosphonium cationic moieties were attached. These were coated on fused silica capillaries, and their gas chromatographic properties were evaluated. They were characterized using a linear solvation parameter model and a number of test mixtures. On the basis of the literature, it is known that both monocationic and dicationic ILs possess almost identical polarities, solvation characteristics, and chromatographic selectivities. However, some of the trigonal tricationic ILs were quite different. The different solvation parameters and higher apparent polarities appear to generate from the more rigid trigonal geometry of these ILs, as well as their ability to retain the positive charges in relatively close proximity to one another in some cases. Their unique selectivities, retention behaviors, and separation efficiencies were demonstrated using the Grob mixture, a flavor and fragrance test mixture, alcohols/alkanes test, and FAME isomer separations. Two ILs C1 (methylimidazolium substitution) and C4 (2-hydroxyethylimidazolium substitution) had higher apparent polarities than any know IL (mono, di, and tricationic ILs) or commercial stationary phases. The tri(2-hexanamido)ethylamine core IL series proved to be very interesting in that it not only showed the highest separation efficiency for all test mixtures, but it also is the first IL stationary phase (containing NTf2− anions) that eliminates peak tailing for alcohols and other H-bonding analytes. The thermal stabilities were investigated using three methods: thermogravimetric analysis (TGA) method, temperature programmed gas chromatographic method (TPGC), and isothermal gas chromatographic method. The D core series had a high working temperature range, exceptional selectivities, and higher separation efficiencies than comparable polarity commercial columns. It appears that this specific type of multifunctional ILs may have the most promising future as a new generation of gas chromatographic stationary phases.
Co-reporter:Ping Sun, Chunlei Wang, Zachary S. Breitbach, Ying Zhang and Daniel W. Armstrong
Analytical Chemistry 2009 Volume 81(Issue 24) pp:10215
Publication Date(Web):December 14, 2009
DOI:10.1021/ac902257a
An unusual class of chiral selectors, cyclofructans, is introduced for the first time as bonded chiral stationary phases. Compared to native cyclofructans (CFs), which have rather limited capabilities as chiral selectors, aliphatic- and aromatic-functionalized CF6s possess unique and very different enantiomeric selectivities. Indeed, they are shown to separate a very broad range of racemic compounds. In particular, aliphatic-derivatized CF6s with a low substitution degree baseline separate all tested chiral primary amines. It appears that partial derivatization on the CF6 molecule disrupts the molecular internal hydrogen bonding, thereby making the core of the molecule more accessible. In contrast, highly aromatic-functionalized CF6 stationary phases lose most of the enantioselective capabilities toward primary amines, however they gain broad selectivity for most other types of analytes. This class of stationary phases also demonstrates high “loadability” and therefore has great potential for preparative separations. The variations in enantiomeric selectivity often can be correlated with distinct structural features of the selector. The separations occur predominantly in the presence of organic solvents.
Co-reporter:Molly M. Warnke, Zachary S. Breitbach, Edra Dodbiba, Jeffrey A. Crank, Tharanga Payagala, Pritesh Sharma, Eranda Wanigasekara, Xiaotong Zhang, Daniel W. Armstrong
Analytica Chimica Acta 2009 Volume 633(Issue 2) pp:232-237
Publication Date(Web):9 February 2009
DOI:10.1016/j.aca.2008.11.056
A general method for detecting bisphosphonate drugs by ESI-MS and LC–ESI-MS as positive ions has been developed. Bisphosphonates can have multiple negative charges in solution. Tricationic ion-pairing reagents were paired with bisphosphonates to form a positively charged complex. It was clear that this facile pairing method worked. However, an appreciable presence of −1 bisphosphonate species were observed in positive mode ESI-MS (i.e. as the +2 complex with tricationic reagents). This led to an extended investigation on the use of dicationic pairing agents. The use of dicationic reagents improved the detection sensitivity for all of the bisphosphonates. Tandem mass spectrometry also improved the limits of detection for most of the bisphosphonates using both the tricationic and dicationic pairing reagents. A tricationic reagent also was used as an ion-pairing reagent in chromatography experiments. Thus the addition of a single reagent produced benefits in that it increased chromatographic retention and enhanced the ESI-MS detection of bisphosphonates.
Co-reporter:Ke Huang, Daniel W. Armstrong
Organic Geochemistry 2009 Volume 40(Issue 2) pp:283-286
Publication Date(Web):February 2009
DOI:10.1016/j.orggeochem.2008.10.009
The detection and complete separation of crocetane (2,6,11,15-tetramethylhexadecane) and phytane (2,6,10,14-tetramethylhexadecane), two widely investigated hydrocarbon biomarkers for archaea in geological environments, are reported. The essential components of the analysis are a series of derivatized cyclodextrin capillary GC stationary phases. In addition, the further separation of stereoisomers of both compounds was observed on the highly selective permethyl-2-hydroxypropyl-β-cyclodextrin stationary phase. In Nature, as in the laboratory, the synthesis (diagenesis) of these biomarkers determines their structures and stereochemistry. Hence, methods that allow their characterization and quantitation provide useful geochemical information.
Co-reporter:Molly M. Warnke, Zachary S. Breitbach, Edra Dodbiba, Eranda Wanigasekara, Xiaotong Zhang, Pritesh Sharma, Daniel W. Armstrong
Journal of the American Society for Mass Spectrometry 2009 Volume 20(Issue 3) pp:529-538
Publication Date(Web):March 2009
DOI:10.1016/j.jasms.2008.11.015
A general and sensitive method for detecting divalent anions by ESI-MS and LC/ESI-MS as positive ions has been developed. The anions are paired with tricationic reagents to form positively charged complexes. In this study, four tricationic reagents, 2 trigonal and 2 linear, were used to study a wide variety of anions, such as disulfonates, dicarboxylates, and inorganic anions. The limits of detection for many of the anions studied were often improved by tandem mass spectrometry. Tricationic pairing agents can also be used with chromatography to enhance the detection of anions. The tricationic reagents were also used to detect monovalent anions by monitoring the doubly charged positive complex. The limits of detection for some of the divalent anions by this method are substantially lower than by other current analytical techniques.Tricationic ion-pairing agents are used for the detection of divalent anions as singly charged complexes in positive ion mode ESI-MS.Figure optionsDownload full-size imageDownload high-quality image (95 K)Download as PowerPoint slide
Co-reporter:Jeffrey A. Crank
Journal of The American Society for Mass Spectrometry 2009 Volume 20( Issue 10) pp:1790-1800
Publication Date(Web):2009 October
DOI:10.1016/j.jasms.2009.05.020
Second generation ionic liquid matrices are developed, examined, and tested. They have shown a wide mass detection range (<1000 Da to >270,000 Da) for proteins and peptides with greater S/N ratios than solid matrices. These ionic liquid matrices also exhibit the ability to effectively ionize proteins of large mass without disrupting noncovalent interactions between monomers. Both the anionic and cationic moieties have been varied systematically to find an ionic liquid matrix with the best physical properties, analyte signal intensity, and widest mass detection range. It was determined that both the proton affinity and pKa of the cation have a large effect on the ionic liquid matrices’ ability to effectively ionize the analyte. The ionic liquid matrices can be used to detect polysaccharides with fewer degradation products than solid matrices. N,N-diisopropylethylammonium α-cyano-4-hydroxycinnamate and N-isopropyl-N-methyl-t-butylammonium α-cyano-4-hydroxycinnamate were the best matrices for proteins and peptides, while N,N-diisopropylethylammonium α-cyano-4-hydroxycinnamate and N,N-diisopropylethylammonium ferulate were the best matrices for carbohydrates.
Co-reporter:Chunxia Jiang;Man-Yung Tong;Sirantha Perera;Ye Bao ;Frederick M. MacDonnell
Chirality 2009 Volume 21( Issue 1) pp:208-217
Publication Date(Web):
DOI:10.1002/chir.20641
Abstract
Capillary zone electrophoresis (CZE) and micellar capillary electrophoresis (MCE) were applied for the enantiomeric separation of nine mononuclear tris(diimine)ruthenium(II) complexes as well as the separation of all stereoisomers of a dinuclear tris(diimine)ruthenium(II) complex. Nine cyclodextrin (CD) based chiral selectors were examined as run buffer additives to evaluate their effectiveness in the enantiomeric separation of tris(diimine)ruthenium(II) complexes. Seven showed enantioselectivity. Sulfated γ-cyclodextrin (SGC), with four baseline and three partial separations, was found to be the most useful chiral selector. In CZE mode, the derivatized γ-CDs were more effective than β-CDs while sulfated CDs work better than carboxymethyl CDs. In MCE mode, hydroxypropyl β-CD separated the greatest number of tris(diimine) ruthenium(II) complexes. The effects of chiral selector concentration, run buffer pH and concentration, the concentration ratio between chiral selector and other factors were investigated. Chirality, 2009. © 2008 Wiley-Liss, Inc.
Co-reporter:Ke Huang;Eniko Forro;Ferenc Fulop;Antal Peter
Chromatographia 2009 Volume 69( Issue 3-4) pp:331-337
Publication Date(Web):2009 February
DOI:10.1365/s10337-008-0888-8
Enantiomers of 19 racemic β-lactams, with 3 and 4-position substitutions, were separated using gas chromatography. Excellent results were achieved on derivatized cyclodextrin-based GC chiral stationary phases (CSPs). All 19 compounds were baseline separated, most with high resolution factors. The Chiraldex G-TA was found to be the most powerful CSP with the broadest enantioselectivity, while Chiraldex B-DM produced the fastest separations for most of the compounds assayed. Results obtained in this work suggest that GC can serve as a potential method for the enantiomeric separation of sufficiently volatile solid β-lactams.
Co-reporter:Pritesh S. Sharma, Tharanga Payagala, Eranda Wanigasekara, Aruna B. Wijeratne, Junmin Huang and Daniel W. Armstrong
Chemistry of Materials 2008 Volume 20(Issue 13) pp:4182
Publication Date(Web):June 3, 2008
DOI:10.1021/cm800830v
Co-reporter:Yasith S. Nanayakkara, Hyejin Moon, Tharanga Payagala, Aruna B. Wijeratne, Jeffrey A. Crank, Pritesh S. Sharma and Daniel W. Armstrong
Analytical Chemistry 2008 Volume 80(Issue 20) pp:7690
Publication Date(Web):September 25, 2008
DOI:10.1021/ac8009802
Water or aqueous electrolytes are the dominant components in electrowetting on dielectric (EWOD)-based microfluidic devices. Low thermal stability, evaporation, and a propensity to facilitate corrosion of the metal parts of integrated circuits or electronics are drawbacks of aqueous solutions. The alternative use of ionic liquids (ILs) as electrowetting agents in EWOD-based applications or devices could overcome these limitations. Efficient EWOD devices could be developed using task-specific ILs. In this regard, a fundamental study on the electrowetting properties of ILs is essential. Therefore electrowetting properties of 19 different ionic liquids, including mono-, di-, and tricationic, plus mono- and dianionic ILs were examined. All tested ILs showed electrowetting of various magnitudes on an amorphous flouropolymer layer. The effects of IL structure, functionality, and charge density on the electrowetting properties were studied. The enhanced stability of ILs in electrowetting on dielectric at higher voltages was studied in comparison with water. Deviations from classical electrowetting theory were confirmed. The physical properties of ILs and their electrowetting properties were tabulated. These data can be used as references to engineer task-specific electrowetting agents (ILs) for future electrowetting-based applications.
Co-reporter:Chunlei Wang, Daniel W. Armstrong, Chau-Dung Chang
Journal of Chromatography A 2008 Volume 1194(Issue 2) pp:172-177
Publication Date(Web):20 June 2008
DOI:10.1016/j.chroma.2008.04.063
Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) is widely used as important colorant in the aquaculture feed industry, and as nutraceuticals in human health products. Synthetic all-trans-astaxanthin consists of a mixture of a pair of enantiomers (3R,3′R and 3S,3′S) and a mesoform (3R,3′S). A high-performance liquid chromatography (HPLC) method for direct, rapid, and baseline separation of three stereoisomers of all-trans-astaxanthin is described for the first time on an immobilized cellulosic column (Chiralpak IC). Enantiomers of two important precursors in the biosynthetic pathway of astaxanthin, adonirubin and adonixanthin, were also directly separated. In addition, the major cis form of astaxanthin (13-cis-astaxanthin) resulted from isomerization was isolated with preparative C18 separation, and the separation of all four stereoisomers of 13-cis-astaxanthin is achieved. Finally, a stereoisomeric purity test of commercial astaxanthin supplements confirmed that they were from a natural source, although their levels were quite low.
Co-reporter:Chunlei Wang;Chunxia Jiang
Journal of Separation Science 2008 Volume 31( Issue 11) pp:1980-1990
Publication Date(Web):
DOI:10.1002/jssc.200800174
Abstract
There is a natural tendency in science to prefer straightforward, logical classification systems. The use of mobile phase–stationary phase combinations that do not fit neatly into the standard “normal phase” or “reversed-phase” categories has been going on for over 50 years. The term “hydrophilic interaction chromatography” (HILIC) is sometimes being used as a general category for these “other” separations. In some cases, it may be appropriate and in others, not. Indeed the mechanistic constrains used to define the method seem to be varying with time. Given the name HILIC, it is assumed that water is not only present in the mobile phase, but also plays an essential role in the retention mechanism. However, there is residual water present in all organic solvents. Regardless, the number of reported separations in this alternative mode has increased tremendously in the last two decades. This is due to the advent of new stationary phases and an emphasis on polar, biologically important molecules. We discuss the relationships between HILIC and other chromatographic modes. We then examine two classes of stationary phases that have played a major role in these separations. These particular stationary phases can be used to provide appreciable mechanistic information as well.
Co-reporter:Molly M. Warnke;Eranda Wanigasekara
Analytical and Bioanalytical Chemistry 2008 Volume 392( Issue 7-8) pp:1325-1333
Publication Date(Web):2008 December
DOI:10.1007/s00216-008-2383-3
Glutathione (GSH) conjugation of 4-hydroxy-2(E)-nonenal (HNE) is an efficient means of cellular detoxification. HNE is a byproduct of lipid peroxidation which has shown toxicity but also signaling roles. E-1-hydroxynon-2-en-4-one (HNO) is another byproduct of lipid peroxidation which has the same molecular weight as HNE. This study presents the LC-MS detection of GS-HNE, HNE, and HNO in tissue samples without derivatization and with minimal sample preparation. Tissue samples were taken from wild-type mice and knock-out mice, which have been bred without the RLIP76 transfer protein. Extraction procedures were developed to determine GS-HNE and HNE levels in the mouse liver tissue. A gradient elution LC–MS method was developed for GS-HNE analysis using electrospray ionization and selected ion monitoring (SIM). The HNE/HNO method involves isocratic elution due to instability issues. Higher levels of GSHNE, HNE, and HNO were found in the knock-out animals, due to the absence of the RLIP76 transport mechanism.
Co-reporter:Jeffrey W. Remsburg;Renee J. Soukup-Hein
Journal of The American Society for Mass Spectrometry 2008 Volume 19( Issue 2) pp:261-269
Publication Date(Web):2008 February
DOI:10.1016/j.jasms.2007.11.002
Twenty-three different dications were investigated for their effectiveness in pairing with singly charged anions, thereby allowing the electrospray ionization mass spectrometry (ESI-MS) detection of anions as positively charged complexes. Nitrate, iodide, cyanate, monochloroacetate, benzenesulfonate, and perfluoro-octanoate were chosen as representative test anions as they differ in mass, size-to-charge ratio, chaotropic nature, and overall complexity. Detection limits were found using direct injection of the anion into a carrier liquid containing the dication. Detection limits are given for all six anions with each of the 23 dications. Each anion was easily detected at the ppb (µg/L) and often the ppt (ng/L) levels using certain dicationic reagents. The ability of dicationic reagents to pair with anions and produce ESI-MS signals varied tremendously. Indeed, only a few dications can be considered broadly useful and able to produce sensitive results. Liquid chromatography (LC)-ESI-MS also was investigated and used to show how varying the dicationic reagent produced significantly different peak intensities. Also, the use of tandem mass spectrometry can lead to even greater sensitivity when using imidazolium based dications.
Co-reporter:Xinxin Han;Jeffrey W. Remsburg;Lingfeng He;Thomas E. Beesly
Chromatographia 2008 Volume 67( Issue 3-4) pp:199-210
Publication Date(Web):2008 February
DOI:10.1365/s10337-007-0490-5
Two new synthetic polymeric chiral stationary phases (CSPs) based on trans-(1S,2S)-cyclohexanedicarboxylic acid bis-4-vinylphenylamide (I) and trans-N,N′-(1R,2R)-cyclohexanediyl-bis-4-ethenylbenzamide (II) monomers were prepared and evaluated by normal phase high performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC). A variety of chiral compounds were separated on these two new CSPs. The different orientation of the amide groups in the two CSPs resulted in a striking difference in the enantioselectivity properties of these two CSPs. Their differences in enantioselectivity with HPLC and SFC were compared.
Co-reporter:Ye Bao;Junmin Huang;Tingyu Li
Chromatographia 2008 Volume 67( Issue 1 Supplement) pp:13-32
Publication Date(Web):2008 May
DOI:10.1365/s10337-007-0438-9
A pentaproline-based chiral stationary phase was prepared and the selectivity of the column was evaluated with 194 racemic compounds in three mobile phase modes: normal-phase mode, polar organic mode and reversed-phase mode. 94 racemates out of 194 were separated and the normal-phase mode proved to be the separation mode of broadest applicability. The column is stable in all common organic solvents and no degradation in column performance was observed in any mode even after more than 1,000 injections. A brief sample loading test was performed on the 250 mm × 4.6 mm column and 13.2 mg of α-methyl-9-anthracenemethanol was baseline separated. Retention behavior in the normal-phase mode and the effect of analyte structure on retention and enantioselectivity are discussed.
Co-reporter:Xinxin Han and Daniel W. Armstrong
Accounts of Chemical Research 2007 Volume 40(Issue 11) pp:1079
Publication Date(Web):October 3, 2007
DOI:10.1021/ar700044y
Ionic liquids are liquids composed completely of ions. In the past two decades, ionic liquids have been widely used as “green solvents” replacing traditional organic solvents for organic synthesis and catalysis. In addition, ionic liquids are playing an increasingly important role in separation science. In this Account, the application of ionic liquids in all areas of separation science including extractions, gas chromatography, and supported liquid membrane processes are highlighted.
Co-reporter:Tharanga Payagala, Junmin Huang, Zachary S. Breitbach, Pritesh S. Sharma and Daniel W. Armstrong
Chemistry of Materials 2007 Volume 19(Issue 24) pp:5848
Publication Date(Web):October 31, 2007
DOI:10.1021/cm702325a
Co-reporter:Clifford R. Mitchell, Daniel W. Armstrong, Alain Berthod
Journal of Chromatography A 2007 Volume 1166(1–2) pp:70-78
Publication Date(Web):28 September 2007
DOI:10.1016/j.chroma.2007.07.078
Five parameter linear solvation energy relationships (LSER) are known to have little or no shape recognition ability. However, it is proposed to use LSER studies to get insights into chiral recognition mechanisms. Since the two enantiomers have exactly the same five A–V solute descriptors being still separated by chiral stationary phases (CSPs), it can be considered that they form two different transient diastereoisomers with the CSP. It is then possible to perform LSER studies on the enantioselectivity factors taken as the two enantiomer retention factor ratios. In a first step, the five a –vv system parameters of four CSPs of the macrocyclic glycopeptide types were determined using a set of test solutes with known A–V descriptors, both in the reversed phase and the normal phase modes. In a second step, the A–V descriptors of 18 enantiomeric pairs were tentatively established using five achiral columns with known a –vv parameters. This was successful for the five molecular enantiomers only. It was found that the predicted retention factor for the molecular enantiomers separated on a given CSP corresponded either to retention factor of the first experimentally eluted enantiomer or to the second one or to none of them. Using the enantioselectivity factors it was possible to obtain the Δa –Δv parameters corresponding to the difference in CSP properties seen by the two enantiomers. For the five molecular enantiomeric pairs in the reversed phase mode with a teicoplanin CSP, it was found that there was an elevated contribution by the e coefficient that we interpret as a possible interaction between surface charges on the teicoplanin CSP and solute induced dipoles. Steric effects, seen on the vv parameter, are second in magnitude followed by H-bond and polar interactions. Only one solute could be studied in the normal phase mode showing a different mechanism with polar and steric major interactions.
Co-reporter:Junmin Huang Dr.;Xiaotong Zhang;Daniel W. Armstrong Dr.
Angewandte Chemie International Edition 2007 Volume 46(Issue 47) pp:
Publication Date(Web):24 OCT 2007
DOI:10.1002/anie.200703606
Hydrophobic pocket pleaser: A novel asymmetric catalytic system in water mediated by sulfated β-cyclodextrin (see picture) can bind the organocatalyst tert-butylphenoxyproline and associated hydrophobic reactants. Enantio- and diastereoselectivities up to >99 % and close to quantitative yields could be achieved for stoichiometric direct aldol reactions of cyclohexanone and aryl aldehydes with this system.
Co-reporter:Molly M. Warnke;F. Albert Cotton
Chirality 2007 Volume 19(Issue 3) pp:179-183
Publication Date(Web):27 DEC 2006
DOI:10.1002/chir.20355
Extended metal atom chains (EMACs) contain a linear metal chain wrapped by various ligands. Most complexes are of the form M3(dpa)4X2, where M = metal, dpa = 2,2′-dipyridylamide, and X = various anions. The ligands form helical coils about the metal chain, which results in chiral EMAC complexes. The EMACs containing the metals Co and Cu were partially separated in polar organic mode using a vancomycin-based chiral stationary phase. Under similar conditions, two EMACs with Ni metal and varying anions could be baseline separated. The polar organic mode was used because of the instability of the compounds in aqueous mobile phases. Also, these conditions are more conducive to preparative separations. Polarimetric measurements on the resolved enantiomers of Ni3(dpa)4Cl2 indicate that they have extraordinarily high specific rotations (on the order of 5000 deg cc/g dm). Chirality, 2007. © 2006 Wiley-Liss, Inc.
Co-reporter:Renee J. Soukup-Hein;Jeff Schneiderheinze;Paul Mehelic
Chromatographia 2007 Volume 66( Issue 7-8) pp:461-468
Publication Date(Web):2007 October
DOI:10.1365/s10337-007-0387-3
Previous work on the LC separation of peptides had shown that macrocyclic glycopeptide stationary phases to be selective for peptides of five to thirteen amino acids in length. In this work, the selectivity of the teicoplanin stationary phase is compared to that of a C18 stationary phase for seven diastereomeric enkephalin peptides. The teicoplanin stationary phase separated all seven diastereomeric enkephalin peptides in a single chromatographic run. The insertion of d-amino acids into the primary enkephalin sequence produced areas of hydrophobicity that influenced retention order on the C18 stationary phase. However, analogous trends are not observed on the teicoplanin stationary phase, which is more polar and structurally diverse. Optimization of the mobile phase and the use of a step-gradient for the enkephalin separation on the teicoplanin stationary phase is discussed. Also, the selectivity of macrocyclic glycopeptide stationary phases for peptides of 14, 28, 30, and 36 amino acids also is investigated and compared to separation on a C18 stationary phase. A method for eluting peptides with multiple basic amino acids, which tend to be strongly retained on the macrocyclic glycopeptide stationary phases, is presented.
Co-reporter:Xinxin Han;Chunlei Wang;Lingfeng He
Analytical and Bioanalytical Chemistry 2007 Volume 387( Issue 8) pp:2681-2697
Publication Date(Web):2007 April
DOI:10.1007/s00216-007-1154-x
A new synthetic polymeric chiral stationary phase for liquid chromatography was prepared via free-radical-initiated polymerization of trans-9,10-dihydro-9,10-ethanoanthracene-(11S,12S)-11,12-dicarboxylic acid bis-4-vinylphenylamide. The new polymeric chiral stationary phase (CSP) showed enantioselectivity for many chiral compounds in multiple mobile phases. High stability and sample capacities were observed on this polymeric chiral stationary phase. Mobile phase components and additives affected chiral separation greatly. This new synthetic chiral stationary phase is complementary to two other related commercially available CSPs: the P-CAP and P-CAP-DP columns. Interactions between the chiral stationary phase and analytes that lead to retention and chiral recognition include hydrogen bonding, dipolar, and π–π interactions. Repulsive (steric) interactions also contribute to chiral recognition.
Co-reporter:Junmin Huang Dr.;Xiaotong Zhang;Daniel W. Armstrong Dr.
Angewandte Chemie 2007 Volume 119(Issue 47) pp:
Publication Date(Web):24 OCT 2007
DOI:10.1002/ange.200703606
In die (hydrophobe) Tasche gesteckt: In einem neuartigen Katalysesystem für asymmetrische Umwandlungen in Wasser (siehe Bild) bindet ein sulfatiertes β-Cyclodextrin den Organokatalysator tert-Butylphenoxyprolin und die hydrophoben Reaktanten. Stöchiometrische direkte Aldolreaktionen von Cyclohexanon mit Arylaldehyden ergaben Enantio- und Diastereoselektivitäten über 99 % und nahezu quantitative Ausbeuten.
Co-reporter:Qiqing Zhong, Lingfeng He, Thomas E. Beesley, Walter S. Trahanovsky, Ping Sun, Chunlei Wang, Daniel W. Armstrong
Journal of Chromatography A 2006 Volume 1115(1–2) pp:19-45
Publication Date(Web):19 May 2006
DOI:10.1016/j.chroma.2006.02.065
The synthesis and evaluation of new dinitrophenyl (DNP) substituted β-cyclodextrin (β-CD) chiral stationary phases (CSPs) for the enantioseparation of various classes of chiral analytes by HPLC are presented. The dinitrophenyl substituted β-CD derivatives are synthesized and covalently bonded to functionalized 5 μm spherical porous silica gel. These are the first reported derivatized cyclodextrin which contains π-electron deficient substituents (i.e., π-acidic moieties). The column performance in terms of their ability to separate enantiomers is evaluated. A variety of different dinitro-substituted aryl groups are investigated and compared. The pH of the mobile phase buffers, the buffer composition, the number and position of the dinitro groups on the phenyl ring substituent, the degree of substitution, and the bonding strategy all greatly affect the performance of the CSPs. A large variety of racemic compounds have been separated successfully on these CSPs. The bonded dinitrophenyl-derivatized cyclodextrins are stable in all three mobile phase modes, namely, the reversed-phase, polar organic, and normal phase modes. No degradation in column performance was observed in any mode of operation even after more than 1000 injections. The analytical applicability of these types of CSPs for enantiomeric separations is discussed in detail.
Co-reporter:Tom Ling Xiao;Eva Tesarova;Jared L. Anderson;Matthew Egger
Journal of Separation Science 2006 Volume 29(Issue 3) pp:429-445
Publication Date(Web):17 FEB 2006
DOI:10.1002/jssc.200500332
HPLC enantiomeric separations of a wide variety of racemic analytes was evaluated using chiral stationary phases (CSPs) based on the macrocyclic glycopeptides teicoplanin (T), teicoplanin aglycone (TAG), and methylated teicoplanin aglycone (Me-TAG) in two different mobile phase modes, i. e., the RP mode and the polar organic (PO) mode. Comparison of the enantiomeric separations using Chirobiotic T, Chirobiotic TAG, and the methylated form of TAG were conducted in order to gain a better understanding of the roles of the polar functional groups on the CSP. Substantial effects due to the cleavage of saccharides and/or methylation on chiral separations were observed in both separation modes. Improved separation efficiencies for many acidic analytes were obtained by methylating the H-bonding groups of TAG. These groups were believed to be a contributing factor to band broadening on TAG due to their negative effect on mass transfer between the stationary phase and mobile phase. Ionic/dipolar interactions between the carboxylate group of the analytes and the amine groups on T, TAG, or Me-TAG are important for chiral discrimination. Therefore, analytes possessing a carboxyl group are good candidates for successful separations on these CSPs. Hydrophobic interactions are important for enantiomeric separations in the RP mode where the H-bonding interactions between analytes and the chiral selectors are relatively weak. Me-TAG offers higher hydrophobicity, which can accentuate the interactions of analytes with hydrophobic moieties, but these interactions are not necessarily stereoselective. In the PO mobile phase, electrostatic/dipolar interactions between polar functional groups are the dominating interactions in chiral recognition. Another important factor is steric fit, which could be changed with every modification of the T structure. Therefore, substantial changes of enantioseparations were obtained within this studied group of CSPs. The PO mode was shown to be the most powerful mobile phase mode for enantiomeric separations on T-based stationary phases, mainly due to the improved efficiency. Methylation of the TAG proved to be a very useful tool for investigating the chiral recognition mechanism for this group of chiral selectors.
Co-reporter:Ke Huang, Zachary S. Breitbach, Daniel W. Armstrong
Tetrahedron: Asymmetry 2006 Volume 17(Issue 19) pp:2821-2832
Publication Date(Web):27 October 2006
DOI:10.1016/j.tetasy.2006.10.014
The enantiomeric excess of chiral reagents used in asymmetric syntheses directly affects the reaction selectivity and product purity. In this work, 84 of the more recently available chiral compounds were evaluated to determine their actual enantiomeric composition. These compounds are widely used in asymmetric syntheses as chiral synthons, catalysts, and auxiliaries. These include chiral alcohols, amines, amino alcohols, amides, carboxylic acids, epoxides, esters, ketones, and oxolanes among other classes of compounds. All enantiomeric test results were categorized within five impurity levels (i.e., <0.01%, 0.01–0.1%, 0.1–1%, 1–10%, and >10%). The majority of the reagents tested were determined to have enantiomeric impurities over 0.01%, and two of them were found to contain enantiomeric impurities exceeding the 10% level. The most effective enantioselective analysis method was a GC approach using a Chiraldex GTA chiral stationary phase (CSP). This method worked exceedingly well with chiral amines and alcohols.Eighty-four commercially available chiral synthons, auxiliaries, and catalysts were evaluated to determine their actual enantiomeric composition.
Co-reporter:Lillian A. Frink, Daniel W. Armstrong
Journal of Pharmaceutical Sciences (August 2016) Volume 105(Issue 8) pp:2288-2292
Publication Date(Web):1 August 2016
DOI:10.1016/j.xphs.2016.05.014
A rapid, accurate, and precise headspace gas chromatographic (HSGC) analytical method was developed for the detection and quantification of water in drug products. The analysis is able to be performed in 10 min and automated. The HSGC method used an ionic liquid (IL) based open tubular capillary gas chromatographic column to increase the ruggedness of this method and provide improved peak shapes for water. Due to the ionic liquids low vapor pressure, unique physiochemical properties, and high thermal stability, they also make idea solvents for HSGC. Unlike Karl Fischer titration methods, this HSGC method is not affected by side reactions. The developed method was shown to be broadly applicable. The water content in 12 different samples was found to range from 1%-7% water. The use of HSGC was highly sensitive and only required 10 mg of sample. In addition, it was found to have greater precision and accuracy than Karl Fischer titration and greater precision and speed than loss on drying.
Co-reporter:Ping Sun, Arthi Krishnan, Abhishek Yadav, Frederick M. MacDonnell, Daniel W. Armstrong
Journal of Molecular Structure (12 November 2008) Volume 890(Issues 1–3) pp:75-80
Publication Date(Web):12 November 2008
DOI:10.1016/j.molstruc.2008.02.030
![Phosphonium, 1,1'-(1,12-dodecanediyl)bis[1,1,1-tripropyl-, salt with 1,1,1-trifluoro-N-[(trifluoromethyl)sulfonyl]methanesulfonamide (1:2)](/data/chemimg/3780300/1022962-06-6.png)
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![Phosphonium, tributyltetradecyl-, salt with 1,1,1-trifluoro-N-[(trifluoromethyl)sulfonyl]methanesulfonamide (1:1)](/data/chemimg/3780300/855788-71-5_b.png)
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![Piperidine,3-[(1,3-benzodioxol-5-yloxy)methyl]-4-phenyl-, (3S,4R)-](http://img.cochemist.com/ccimg/324100/324024-00-2.png)
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![1H-Pyrazole-3-carbonitrile,5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(R)-(trifluoromethyl)sulfinyl]-](http://img.cochemist.com/ccimg/302600/302578-97-8.png)
![1H-Pyrazole-3-carbonitrile,5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(R)-(trifluoromethyl)sulfinyl]-](http://img.cochemist.com/ccimg/302600/302578-97-8_b.png)
![1H-Pyrazole-3-carbonitrile,5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(S)-(trifluoromethyl)sulfinyl]-](http://img.cochemist.com/ccimg/302600/302578-96-7.png)
![1H-Pyrazole-3-carbonitrile,5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(S)-(trifluoromethyl)sulfinyl]-](http://img.cochemist.com/ccimg/302600/302578-96-7_b.png)
![[1,1'-Binaphthalene]-2,2'-diol,3,3'-dibromo-](http://img.cochemist.com/ccimg/149900/149821-06-7.png)
![[1,1'-Binaphthalene]-2,2'-diol,3,3'-dibromo-](http://img.cochemist.com/ccimg/149900/149821-06-7_b.png)
![[2,2'-Binaphthalene]-1,1'-diol,3,3'-diphenyl-, (2S)-](http://img.cochemist.com/ccimg/147800/147702-14-5.png)
![[2,2'-Binaphthalene]-1,1'-diol,3,3'-diphenyl-, (2S)-](http://img.cochemist.com/ccimg/147800/147702-14-5_b.png)
![[2,2'-Binaphthalene]-1,1'-diol,3,3'-diphenyl-, (2R)-](http://img.cochemist.com/ccimg/147800/147702-13-4.png)
![[2,2'-Binaphthalene]-1,1'-diol,3,3'-diphenyl-, (2R)-](http://img.cochemist.com/ccimg/147800/147702-13-4_b.png)
![[1,1'-Binaphthalene]-2,2'-diol,3,3'-dibromo-, (1S)-](http://img.cochemist.com/ccimg/119800/119707-74-3.png)
![[1,1'-Binaphthalene]-2,2'-diol,3,3'-dibromo-, (1S)-](http://img.cochemist.com/ccimg/119800/119707-74-3_b.png)
![[1,1'-Binaphthalene]-2,2'-diol,3,3'-dibromo-, (1R)-](http://img.cochemist.com/ccimg/111800/111795-43-8.png)
![[1,1'-Binaphthalene]-2,2'-diol,3,3'-dibromo-, (1R)-](http://img.cochemist.com/ccimg/111800/111795-43-8_b.png)
![[1,1'-Binaphthalene]-2,2'-diol, 3,3'-bis(triphenylsilyl)-, (1S)-](http://img.cochemist.com/ccimg/111800/111795-33-6.png)
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![[1,1'-Binaphthalen]-2-ol,2'-amino-](http://img.cochemist.com/ccimg/134600/134532-03-9.png)
![[1,1'-Binaphthalen]-2-ol,2'-amino-](http://img.cochemist.com/ccimg/134600/134532-03-9_b.png)
