Chiral Recognition Is Observed in the Deprotonation Reaction of Cytochrome c by (2 R )- and (2 S )-2-Butylamine

172

199

The effects of solvent composition on both the maximum charge states and charge state distributions of analyte ions formed by electrospray ionization were investigated using a quadrupole mass spectrometer. The charge state distributions of cytochrome c and myoglobin, formed from 47%/50%/ 3% water/solvent/acetic acid solutions, shift to lower charge (higher m/z) when the 50% solvent fraction is changed from water to methanol, to acetonitrile, to isopropanol. This is also the order of increasing gas-phase basicities of these solvents, although other physical properties of these solvents may also play a role. The effect is relatively small for these solvents, possibly due to their limited concentration inside the electrospray interface. In contrast, the addition of even small amounts of diethylamine (<0.4%) results in dramatic shifts to lower charge, presumably due to preferential proton transfer from the higher charge state ions to diethylamine. These results clearly show that the maximum charge states and charge state distributions of ions formed by electrospray ionization are influenced by solvents that are more volatile than water. Addition of even small amounts of two solvents that are less volatile than water, ethylene glycol and 2-methoxyethanol, also results in preferential deprotonation of higher charge state ions of small peptides, but these solvents actually produce an enhancement in the higher charge state ions for both cytochrome c and myoglobin. For instruments that have capabilities that improve with lower m/z, this effect could be taken advantage of to improve the performance of an analysis.Electrospray ionization (ESI) [1] is well recognized as a soft ionization method for producing gas-phase ions of large biopolymers, such as oligonucleotides, proteins, and even noncovalent biomolecular complexes [2]. In combination with mass spectrometry, molecular masses of large molecules can be measured with unprecedented accuracy [3]. The multiple charging of large analyte ions that occurs with ESI has the advantage that the masses of very large molecules can be measured using mass spectrometers with upper mass-to-charge limits. One outstanding challenge in ESI mass spectrometry is to accurately predict the observed charge state distribution of a large molecule, given its primary structure, the composition of the solvent system from which the ions are formed, instrumental conditions, etc. Several factors have been shown to influence the observed charge state distribution, including molecular conformation [4][5][6], acid-base chemistry both in solution and in the gas phase [7][8][9][10][11], solvent composition [8], instrumental factors, etc. Several models have been proposed to qualitatively account for some of these effects [12][13][14][15]. A general conclusion from several studies is that the electrospray charge state distributions of proteins formed from denaturing solution conditions are shifted to higher charge states (lower m/z) than those formed from solutions in which the protein has signific...

Section: Solvent Evaporation Versus Gas-phase Collisionsmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of solvent on the maximum charge state and charge state distribution of protein ions produced by electrospray ionization

Iavarone

Jurchen

Williams

2000

172

199

“…Other reports in the literature also assert the importance of pH on enantioselective solution phase separations [27][28][29]. With regard to mass spectrometry, these findings may prompt further evaluation of previous work using antimony(III)-tartrates in ESI-based enantioselective association experiments [14,15] [30], but to our knowledge, this is the first report of such behavior for small molecule enantioselective binding systems, recorded in both solution-phase targeting ESI-MS and gas-phase MS/MS dissociation experiments. This study sheds new light on the dynamic nature of antimony(III)-tartrate chiral selectors and prompts further investigation into a system that could indeed still be found quite useful for analytical separations (and therapeutic indications) if it can be controlled to a greater extent.…”

Section: Th Values (mentioning

confidence: 80%

Antimony(III)-D, L-tartrates exhibit proton-assisted enantioselective binding in solution and in the gas phase

Wijeratne

Miko

Gracia

et al. 2009

The negative ion mode ESI mass spectral analysis of antimony(III)-D-and -L-tartrate ("tartar emetic"), in association with leucine enantiomeric isotopomers, revealed remarkable protonassisted enantioselective molecular recognition phenomena. The current study infers that recognition of amino acids by antimony(III)-D,L-tartrate complexes requires that the chiral selector associate a proton to become enantioselective. The dianionic selector itself failed to show enantiomeric discrimination capacity. This observation was shown to be consistent both in solution-phase targeting full scan and gas-phase targeting collision threshold dissociation (CTD) experiments. Importantly, this disparity in enantioselective binding capacity between the dianionic and the protonated monoanionic representatives of antimony(III)-D-and -L-tartrates could only be clearly revealed by ESI-MS and tandem mass spectrometry experiments as described herein. This finding urges a more in-depth study of mechanisms associated with exhibited enantiomeric resolving capacity of antimony tartrates in HPLC and CE applications, as well as in former ESI-MS association studies. (J Am Soc Mass Spectrom 2009, 20, 2100 -2105

“…These differences can be exploited (i.e., by comparison to data for known standards) and used to determine the enantiomeric purity of a sample. Cooks [3][4][5][6][7][8][9][10][11][12][13][14][15][16], Dearden , Lebrilla [21][22][23][24][25][26], Speranza [27][28][29][30][31][32][33][34][35], and others have provided useful examples of this approach to stereochemical analysis.…”

mentioning

confidence: 99%

Stereoselectivity in the collision-activated reactions of gas phase salt complexes

Gronert

Fagin

Okamoto

2004

The collision-activated dissociations (CAD) of gas phase salt complexes composed of chiral ions were studied in a quadrupole ion trap mass spectrometer. Because both partners in the salt are chiral, diastereomeric complexes can be formed (e.g., RR, RS). Two general types of complexes were investigated. In the first, the complex was composed of deprotonated binaphthol and a chiral bis-tetraalkylammonium dication. CAD of these complexes leads to the transfer of a proton or an alkyl cation to the binaphtholate leading to a singly-charged tetraalkylammonium cation. During CAD, diastereomeric complexes give significantly different product distributions indicating reasonable stereoselectivity in the process. In the second system, the complexes involved a peptide dianion and a chiral tetraalkylammonium cation. These systems may be viewed as very simple models for the interactions of peptides/proteins with small chiral molecules. Again, stereoselectivity was evident during CAD, but the extent was dependent on the nature of the peptide and not observable in some cases. To better understand the structural features needed to achieve stereoselectivity in gas phase salt complexes, representative transition states were modeled computationally. The results suggest that it is critical for the asymmetry of the nucleophile (i.e., anion) to be well represented in the vicinity of its reactive center. T he high sensitivity and rapid analysis capabilities of mass spectrometry make it an attractive methodology for solving a wide range of analytical problems. However, stereochemical issues are a challenge because a mass-to-charge ratio provides no direct information with regards to the stereochemistry of a species. Nonetheless, many workers have developed novel approaches for gaining stereochemical information from mass spectrometric data [1,2]. Much of this work has focused on the development of methods that could be used to determine the enantiomeric purity of a product mixture . Like many condensed phase approaches to enantiomeric analysis, the methods rely on complexing the analyte with a substrate of known chirality. This leads to the formation of a pair of diastereomers (assuming that the analyte is not enantiomerically pure). The diastereomers are not equivalent and as a result have different stabilities, kinetic reactivities, and dissociation patterns. These differences can be exploited (i.e., by comparison to data for known standards) and used to determine the enantiomeric purity of a sample. Cooks [3][4][5][6][7][8][9][10][11][12][13][14][15][16], Dearden , , Speranza [27][28][29][30][31][32][33][34][35], and others have provided useful examples of this approach to stereochemical analysis.Along with methods for analyzing the enantiomeric purity of products, there is a growing need for the development of new reaction processes that are stereoselective. In general, these processes have been probed in the condensed phase, but there is no reason why mass spectrometry could not also be used to screen gas phase reactions for stereo...