Conformational studies of Zn-Ligand-Hexose diastereomers using ion mobility measurements and density functional theory calculations

Abstract

Ion mobility studies and density functional theory calculations were used to study the structures of [Zn/diethylenetriamine/Hexose/Cl] ϩ complexes in an effort to probe differences in the three-dimensional conformations. This information allows us to gain insight into the structure of these complexes before collisional activation, which is the first step in understanding the stereoselective dissociations observed under collisionally activated conditions. The collision cross sections obtained from the ion mobility measurements showed that the mannose structure is more compact than the galactose and glucose complexes, respectively. Using density functional theory, candidate structures for each of the experimentally observed complexes were generated. Two criteria were used to determine the most likely structures of these complexes before activation: (1) The allowed relative energies of the molecules (between 0 -90 kJ/mol) and (2) collision cross section agreement (within 2%) between the theoretically determined structures and the experimentally determined cross section. It was found that the identity of the monosaccharide made a difference in the overall conformation of the metal-ligand-monosaccharide complex. For glucose and galactose, metal coordination to O(6) was found to be favorable, with the monosaccharide occupying the 4 C 1 chair conformation, while for mannose, O(2) metal coordination was found with the monosaccharide in a B 3,0 conformation. Coordination numbers varied between four and six for the Zn(II) metal centers. Given these results, it appears that the stereochemistry of the monosaccharide influences the conformation and metal coordination sites of the Zn(II)/monosaccharide/dien complex. These differences may influence the dissociation products observed under collisionally activated conditions. (J Am Soc Mass Spectrom 2002, 13, 284 -293) © 2002 American Society for Mass Spectrometry T he use of ion mobility mass spectrometry (IMMS), in combination with theoretical methods to gain insight into the gas phase 3-dimensional structure of biomolecules, is now a well established technique [1][2][3][4][5][6][7]. Numerous examples of these types of studies can be found in the literature. For example, the conformation of peptide ions has been examined to determine how the gas phase structure mimics the solution phase structure [3], or how the substitution of different metal ions for protons affects the overall conformation of peptide chains [4]. Simple amino acids have been investigated by IMMS to determine if they are zwitterions in the gas phase as in solution [5]. IMMS has also been used as a technique to separate opiates and opiate metabolites [6] or even peptide mixtures [7].In this study, the gas phase structures of the three biologically relevant monosaccharides complexed with Zn(II)/diethylenetriamine are explored in an effort to probe the conformational differences among the complexes. The information gained aids the understanding of the coordination sites of metal ions to monosaccharides, and help...

Distinction of sialyl anomers on ESI- and FAB-MS/MS: Stereo-specific fragmentations

“…It is generally considered that sugar conformations prefer to have functional groups in the equatorial orientation, that is, C1-conformation for hexopyranose 1 ThermoFinnigan Product Support Bulletin # 104. 2 Here B designates the fragment ion containing the nonreducing end sugar unit on the nonreducing end side of the glycosidic oxygen as indicated by Domon and Costello [12].…”

“…We also acknowledge that other research groups have successfully distinguished anomers by mass spectrometry [13][14][15][16][17][18][19][20]. Among them, we are particularly interested in the report by Leavell et al [1] because they studied conformations of metal complexes of sugars.…”

“…The MS n fragmentation was induced by He, optimized by the normalized collision energy method based on the MRFA (methionyl-arginyl-phenylalanylalanine) fragmentation efficiency. 1 Precursor isolation width was 2 . Samples were introduced to the capillary by infusion at a rate of 5 L/min.…”

“…T he necessity for distinguishing sugar anomers has led to many new methodologies on simple sugars like mono-or disaccharides [1][2][3][4]. We report here the differences on the electrospray ionization (ESI) MS 2 and MS 3 product-ion spectra of lysoglyceroganglioside anomers and seek to elucidate the differences based on stereochemical considerations.…”

Separation of sodiated isobaric disaccharides and trisaccharides using electrospray ionization-atmospheric pressure ion mobility-time of flight mass spectrometry

“…These studies indicated that small differences in drift times of individual precursor ions could be obtained both in the positive and negative ion modes, although full resolution of isomers from mixtures was not demonstrated. Using a different approach, Leavell et al combined computational methods and ion mobility mass spectrometry (IMMS) to examine the gas-phase ion structure of diethylenetriamine-derivatized sugars as zinc-ligand-hexose diastereomers [29]. Their studies were performed with derivatized reducing sugars hence multiple peaks were observed for individual sugars representing different configurations of complexes.…”