A Mass Spectrometry Method for the Determination of Enantiomeric Excess in Mixtures of d , l -Amino Acids

Self Cite

Gas-phase zwitterionic amino acids were formed in complexes of underivatized ␤-cyclodextrin through reactions with a neutral base, n-propylamine. The reaction was performed in the analyzer cell of an electrospray ionization-Fourier transform mass spectrometer. Most of the natural amino acids were studied with three cyclodextrin hosts including ␣-, ␤-, and ␥-cyclodextrin to understand better the structural features that lead to the stabilization of the zwitterionic complexes. Molecular dynamics calculations were performed to provide insight into the structural features of the complexes. The rate constants of the reactions were obtained through kinetic plots. Examination of both L-and D-enantiomers of the amino acid showed that the reaction was enantioselective. The reaction was then employed to analyze mixtures of Glu enantiomers naturally occurring in the bacteria Bacillus licheniformis. (J Am Soc Mass Spectrom 2006, 17, 442-452)

mentioning

confidence: 99%

Structural relationships in small molecule interactions governing gas-phase enantioselectivity and zwitterionic formation

Cong

Czerwieniec

McJimpsey

et al. 2006

Self Cite

“…This approach [26] comprises the use of the Relative intensity I r of the complex as a response of the complexed concentration of G. I r is defined as follows: I r ϭ I c /I tot , where I tot ϭ I c ϩ I G . As Figure 6 indicates, the repeatability of the measurements is excellent for all samples.…”

Section: Resultsmentioning

confidence: 99%

“…These results suggest that "false positives" inclusion complexes should be precluded by applying other techniques to prove the complex formation. Since then, different studies have been reported that evidenced the existence of gas-phase inclusion complexes involving methods such as collision-induced dissociation [15,18,22], blackbody induced radiation dissociation [23], heated capillary dissociation [24], and mainly by guest-exchange reactions in gas phase with a CD host sensitive to the chirality of the amino acid guest [20,25,26].…”

mentioning

confidence: 99%

Efficient determination and evaluation of model cyclodextrin complex binding constants by electrospray mass spectrometry

Dotsikas

Loukas

2003

Electrospray ionization mass spectrometry (ESI-MS) is now routinely used for the detection of cyclodextrin noncovalent complexes, complementing previously established methods. Hostguest complexes formed in solution are also stable for characterization by ESI in the gas phase. This paper reports the first investigations to characterize the stability of three inclusion complexes between ␤-cyclodextrin (␤-CD) and three model "guest" molecules, by determining the cyclodextrin compound complex stability constant (K st ) with the use of mass spectrometric studies. The relative signal intensity of the complexes were monitored in the positive ion mode by mixing each "guest" molecule with an up to 50-fold molar excess of ␤CD. A novel linear equation, similar to Benesi-Hildebrand, was derived allowing the determination of K st for 1:1 stoichiometry in all complexes. These values were compared with the K st obtained by spectrophotometric experiments and they were evaluated to be slightly different, indicating the validity of the described method. (J

“…For example, chiral recognition based on gasphase ion/molecule reactions has been investigated by several research groups [18 -25]. In work by Dearden et al [18,23,24] and Lebrilla et al [19,22,25], a chiral host was used to form diastereometric adducts with a chiral ligand in the solution phase. The adduct ions were then electrosprayed into the gas phase, and allowed to exchange the chiral ligand through ion/molecule reaction with a neutral gas.…”

mentioning

confidence: 99%

“…Chiral distinction was achieved based on the variation of the exchange rate with the chirality of the analyte incorporated into the adduct ion. Quantification of the amount of each enantiomer was accomplished through the utilization of a calibration curve of the apparent exchange equilibrium constant versus enantiomeric excess [24] or by generating a calibration curve after a constant reaction time between the abundance of the unexchanged reactant and the mole fraction of one enantiomer [25]. In addition, ion/ molecule reactions have also been successively used in the differentiation of diasteromeric species [26 -28].…”

mentioning

confidence: 99%

Investigation of ion/molecule reactions as a quantification method for phosphorylated positional isomers: An FT-ICR approach

Gao

Kim

Leavell

et al. 2003

A rapid and accurate method of quantifying positional isomeric mixtures of phosphorylated hexose and N-acetylhexosamine monosacchrides by using gas-phase ion/molecule reactions coupled with FT-ICR mass spectrometry is described. Trimethyl borate, the reagent gas, reacts readily with the singly charged negative ions of phosphorylated monosaccharides to form two stable product ions corresponding to the loss of one or two neutral molecules of methanol from the original adduct. Product distribution in the ion/molecule reaction spectra differs significantly for isomers phosphorylated in either the 1-or the 6-position. As a result, the percents of total ion current of these product ions for a mixture of the two isomers vary with its composition. In order to determine the percentage of each isomer in an unknown mixture, a multicomponent quantification method is utilized in which the percents of total ion current of the two product ions for each pure monosaccharide phosphate and the mixture are used in a two-equation, two-unknown system. The applicability of this method is demonstrated by successfully quantifying mock mixtures of four different isomeric pairs: Glucose-1-phosphate and glucose-6-phosphate; mannose-1-phosphate and mannose-6-phosphate; galactose-1-phosphate and galactose-6-phosphate; N-acetylglucosamine-1-phosphate and N-acetylglucosamine-6-phosphate. The effects of mixture concentrations and ion/molecule reaction conditions on the quantification are also discussed. Our results demonstrate that this assay is a fast, sensitive, and robust method to quantify isomeric mixtures of phosphorylated monosaccharides. . In particular, the phosphate linkage position of carbohydrates is important to regulate biological function. For example, the conversion between the 6-phosphate and the 1-phosphate isomers of several monosaccharides, which is regulated by the corresponding phosphate mutases, plays an important role in the glycosylation of glycoproteins [5,6]. Specifically, the deficiency of the enzyme phosphomannomutase, which catalyzes the conversion of mannose-6-phosphate to mannose-1-phosphate in the early step of biosynthesis of lipid-linked oligosaccharides, is responsible for a disease called CDG-1a [1], in which glycoproteins with truncated N-linked carbohydrates are formed.Despite their importance, analysis of phosphorylated carbohydrates by traditional methods has been problematic due to their structural variety and non-characteristic UV absorbance. As a result, traditional enzyme kinetic measurements of the phosphate mutases mentioned above require up to three coupling enzymes [7][8][9]. Recently, Turecek et al. [10] reported an affinity capture and elution/electrospray ionization mass spectrometry assay of phosphomannomutase and phosphomannose isomerase. In their method, the product isomer was subjected to another enzymatic reaction that altered its mass in order to be detected by mass spectrometry. Direct quantitative analysis of phosphorylated glucose has been reported using anion-exchange chromatography ...