Tandem mass spectra of transition-metal ion adducts of glycosyl dithioacetals; distinction among stereoisomers

Electrospray ionization mass spectra of some glycosyl dithioacetals recorded in the presence of transition-metal chlorides, XCl2 (where X = Co, Mn and Zn), give abundant adduct ions such as [M+XCl]+ and [2M-H+X]+ and minor ions such as [M-H+X]+ and [2M+XCl]+. The tandem mass spectra of these adducts show characteristic elimination of neutral molecules such as H2O, HCl, EtSH, CH2O, C2H4O2/C2H4O. [M+XCl]+ ions fragment readily and the fragmentation appears to be stereochemically controlled as the relative abundances of the fragments are different for three stereoisomers. The added metal is lost as neutral molecules in the form of XCl(OH) and XCl(SEt). This is a predominant pathway in the ZnCl+ adducts. [2M+XCl]+ ions fragment preferentially by elimination of HCl, indicating strong metal interactions in the resulting dimeric [2M-H+X]+ ion. As there are several electron-rich centers in the molecule, the dimeric complex [2M-H+X]+ can have several structures and the observed fragmentations may reflect the sum of those of all these structures. The dimeric complexes fragment by elimination of neutral molecules leaving the dimeric interactions intact. The extent of fragmentation varies for the stereoisomers, leading to stereochemical differentiation.     

Li+- and Ag+-cationized per-O-acetyl- and Per-O-benzyl-α-D-thioglycosides: a collision-induced decomposition study

The collision-induced decompositions of the [M + Li]⁺ and [M + Ag]⁺ ions of per-O-acetyl- and per-O-benzyl-α-D -thioglycosides having phenyl sulphide, phenyl sulphoxide and phenyl sulphone as the aglycone moieties were studied. The [M + Li]⁺ ion of the acetyl derivative of the phenylthioglucoside shows loss of AcOLi, whereas its [M + Ag]⁺ ion shows elimination of PhSAg. Their sulphoxide and sulphone derivatives lose the C(1) and C(2) substituents to form the glucal under both Li⁺ and Ag⁺ cationization conditions. The corresponding benzyl derivatives do not show the loss of metal. The formation of glucal leads to ring fragmentation by retro-Diels-Alder reaction in the ring-activated benzyl derivatives.     

Tandem mass spectra of ammonium ion,metal ion and ligated metal ion adducts of acyclic sugar derivatives

The tandem mass (MS/MS) spectra of ammonium ion, metal ion and ligated metal ion adducts of chain-extended acyclic nitro-containing deoxyglucose and deoxygalactose derivatives have been studied. The ammonium adducts fragment primarily by elimination of ammonia followed by acetic acid, thus not giving much structural information. In contrast, cationization of these compounds by metal ions and ligated metal ions gave structurally informative and useful fragment ions on MS/MS. The metal ions and ligated metal ions play an important role in controlling and directing fragmentation. Retro-aldol fragmentation is facilitated by metal ions such as Li(+), Na(+), Ag(+) and Cu(+), whereas the adducts with higher alkali metal ions such as Rb(+) and Cs(+) fragment to give only the corresponding metal ions. The divalent metal ions such as Cu(2+) and Ba(2+) also induce retro-aldol fragmentation. However, the charge is carried by the aldehyde fragment in the case of Cu(2+) adducts, whereas the nitroalkane fragment carries the charge in the case of Ba(2+) adducts. Ligated metal ions such as ZnCl(+), CuCl(+), InCl(2) (+) and BaCl(+) also behave similarly and induce retro-aldol fragmentation in these acyclic sugars. Both the metal ion and ligated metal ion adducts can fragment by elimination of metal-containing neutral molecules.     

Lithium and transition metal ions enable low energy collision-induced dissociation of polyglycols in electrospray ionization mass spectrometry

Electrospray ionization tandem mass spectrometry has the potential to be widely used as a tool for polymer structural characterization. However, the backbones or molecular chains of many industrial polymers including functional polyglycols are often difficult to dissociate in tandem mass spectrometers using low energy collision-induced dissociation (CID). We present a method that uses Li+ and transition metal ions such as Ag+ as the cationization reagents for electrospray ionization in an ion trap mass spectrometer. It is shown that lithium and transition metal polyglycol adduct ions can be readily fragmented with low energy CID. Comparative results from different cationization reagents in their abilities of producing both MS spectra and CID spectra are shown. This method opens the possibility of using conventional and readily available low energy CID tandem MS to study polyglycol structures.     

Characterization of iridoids by fast atom bombardment mass spectrometry followed by collision-induced dissociation of

Fast atom bombardment mass spectra of a series of naturally occurring and synthetically modified iridoid glycosides were studied using lithium cationization and collision-induced dissociation of the resulting [M+Li]+ ions. Lithium cationization leads to the unambiguous determination of the molecular masses of these compounds. Collision-induced dissociation of the lithiated molecular ions give valuable structural information regarding the nature of the substituent on both the aglycone and the sugar moieties. The characteristic fragmentation pathways identified are (1) elimination of neutral molecules comprising the substituents on either the aglycone or sugar moieties, (2) formation of lithiated aglycone and their fragment ions, (3) formation of lithiated sugar and their fragment ions, (4) fragmentation corresponding to the cleavage of the aglycone or sugar ring and (5) fragmentation characteristic of the substituents present in either the aglycone or sugar parts of the molecule. Elimination of two acyloxy radicals from the lithiated molecular ion is a characteristic fragmentation in the case of acyloxy derivatives.     

Metal ion adducts in the structural analysis of ginsenosides by electrospray ionization with multi-stage mass spectrometry

The effect of metal (Li+, Na+, K+, Ag+) cationization on collision-induced dissociation of ginsenosides was investigated by electrospray ionization mass spectrometry combined with multi-stage mass spectrometry (ESI-MS(n)). The fragments of sodiated and lithiated molecules give valuable structural information regarding the nature of the aglycone and the sequence and linkage information of sugar moieties. However, the number and relative abundances of fragment ions from lithiated ginsenosides are significantly greater than for the sodiated species. The K+ adducts undergo glycosidic cleavages and very limited cross-ring reactions. The silver ion adducts fragment mainly through glycosidic cleavages.     

Elimination of 118 Da: a characteristic fragmentation in the tandem mass spectra of 11(15 --> 1)-abeo-taxanes

The mechanism of the elimination of 118 Da from 11(15-->1)-abeo-taxanes was elucidated with the help of the tandem mass spectra of [M + NH(4)](+) and [M + Li](+) ions and the corresponding D-exchanged species. The fragmentation is triggered by the initial loss of the C-10 substituent. Evidence was also obtained for the stepwise elimination of acetone and acetic acid. Acetone is eliminated from the C-1 hydroxyisopropyl group and acetic acid from either the C-9 or C-7 acetoxy groups. The presence of an additional acetoxy group at C-13 leads to the direct elimination of 118 Da from [M + NH(4)](+) and [M + Li](+) ions involving the C-13 acetoxy group.     

Effect of metal cationization on the low-energy collision-induced dissociation of loganin, epi-loganin and ketologanin studied by electrospray ionization tandem mass spectrometry

The effect of alkali metal and silver cationization on the collision-induced dissociation (CID) of loganin (1), epi-loganin (2) and ketologanin (3) is discussed. Their protonated molecular ions fragment mainly by glycosidic cleavages. The epimeric pairs (1 and 2) show differences in the abundances of the resulting fragment ions. Lithium cationization induces new dissociation pathways such as the retro-Diels-Alder (RDA) fragmentation followed by rearrangement. Unlike the dissociation of protonated molecular ions, the dissociation of lithiated molecules also provides lithiated sugar fragments. The CID of dilithiated molecules is substantially different from that of the monolithiated precursors. RDA reaction appears to be favoured by the presence of the additional lithium atom in the molecule. In addition, other ring cleavages are also induced. The abundances of the various fragment ions are different in the CID spectra of the epimeric pairs. Extensive D labelling and (6)Li labelling experiments confirmed many of the ion structures proposed. The CID spectra of the sodiated ions are generally weaker, although similar to those of the corresponding lithiated species. Higher alkali metal ion (K(+), Rb(+) and Cs(+)) adducts generated only the corresponding metal ions as products of CID. Similar fragmentations were also observed in the CID of the [M + Ag](+) ions of these compounds, the epimeric pairs showing characteristic differences in their CID behaviour. Copyright 2000 John Wiley & Sons, Ltd.     

Effects of ionization, metal cationization and protonation on 2'-deoxyguanosine: changes on sugar puckering and stability of the N-glycosidic bond

The influence of oxidation, protonation, and metal cationization with Cu(+) and Cu(2+) on the strength of the N-glycosidic bond in 2'-deoxyguanosine has been studied by means of quantum chemical calculations. In all cases, the N9-C1' bond distance increases (0.03-0.06 A) upon introducing positive charge in the guanine moiety, the observed variations being more important for the dicationic systems. Binding energies show that the effect of X(n)(+) in guanine hinders the homolytic dissociation, whereas it largely favors the heterolytic process. With respect to the deoxyribose ring, it has been found that metal binding, oxidation, and protonation do not significantly change the values of the phase angle of pseudorotation P. However, the glycosyl torsion angle chi varies considerably (from 242.0 degrees to 189.8 degrees) as a consequence of a stabilizing guanine-sugar (H8-O4') interaction due to the increase of acidity of guanine C8-H8 upon cationization.     

Collision-induced dissociation of MCl(+) adducts (M = Mg, Mn, Zn, Co, Ni and Cu) and Cu(+) and Ag(+) adducts of dithioalkyl ketene acetals

Electrospray ionization mass spectra of equimolar solutions of dithioalkyl ketene acetals 1 and 2 and metal chlorides (MgCl(2), MnCl(2), ZnCl(2), CoCl(2), NiCl(2) and CuCl(2)) produced abundant ligated metal ion adducts [1 + MCl](+) and [2 + MCl](+). In addition, CuCl(2) also gave rise to Cu(+) adducts. The ligated metal ion adducts upon collision-induced dissociation (CID) showed characteristic fragmentation pathways reflecting the favoured site of coordination. The results show that MgCl(+) prefers oxygen over sulfur, whereas the reverse is true for ZnCl(+) adducts, exemplified by the preferred fragmentation of [1 + MgCl](+) as elimination of MgCl(OH), while that of [1 + ZnCl](+) is expulsion of ZnCl(SCH(3)). Co and Ni chloride adducts tend to give stable metal coordinated species. Cleavage of the dithiolane ring followed by elimination of C(2)H(4)S is the preferred pathway during the CID of [2 + MCl](+) adducts. The CuCl(+) adducts of 1 and 2 showed reduction of Cu((I)) to Cu((0)) resulting in the M(+)(*)ions of 1 and 2. Abstraction of *CH(3) resulting in elimination of CuCH(3) was observed during CID of Cu(+) adducts of 1 and 2. A comparative study of the corresponding Ag(+) adducts revealed a similar behaviour.     

Effect of alkali metal cationization on the collision-induced decomposition of alkyl per-O-acetyl-2-deoxy-2-halo-α-O-mannopyranosides

The effect of alkali metal cationization on the collision-induced decomposition of alkyl per-O-acetyl-2-deoxy-2-bromo-and-iodo-α-O-mannopyranosides was studied. The bromo sugars gave fairly abundant MH⁺, whereas for the iodo sugars the MH⁺ ions were insignificant. However, both the bromo and the iodo derivatives gave abundant M + alkali metal ion complexes. In contrast to the behaviour of the MH⁺ ion, the [M + Li]⁺, [M + Na]⁺ and [M + K]⁺ ions of these compounds do not decompose by loss of the C(1) substituent. Elimination of AcOH is the preferred fragmentation pathway of [M + Cat]⁺. Elimination of HX occurs only after loss of AcOH and CH₂CO from MH⁺, whereas [M + Cat]⁺ directly loses HX. The elimination of HX is more pronounced from [M + Na]⁺ and [M + K]⁺ than from [M + Li]⁺. Loss of AcOLi is an additional fragmentation route observed in the case of the decomposition of [M + Li]⁺ ion.     

Octahedral and tetrahedral coinage metal clusters: is three-dimensional d-orbital aromaticity viable?

The first quantitative evidence for the viability of three-dimensional aromatic clusters involving d-orbitals in pseudo-octahedral coinage metal cages M(6)Li(2) (M = Cu, Ag, Au) as well as in tetrahedral coinage metal cages M'(4)Li(4) (M' = Cu, Ag) was obtained computationally. These cages exhibit many features similar to those of their square planar M(4)Li(2) analogues. The large negative nucleus-independent chemical shifts (NICS) at the cage centers indicate three-dimensional delocalization. This diatropic character arises mostly from d-orbital delocalization combined with substantial contributions from the lowest-valence orbitals. The bonding molecular orbitals of the pseudo-octahedral clusters M(6)Li(2) (M = Cu, Ag, Au) are analogous to those in similar octahedral clusters involving p-orbital delocalization (e.g., B(6)H(6)(2-)). The M'(4)Li(4) clusters exhibit two isomeric forms: metal tetrahedral cages tetracapped by lithium cations on the outside [(M'(4)).4Li] and lithium tetrahedra on the inside capped by coinage metal atoms on each of the four faces [(Li(4)).4M]. Whereas the (M'(4)).4Li type structure is preferred for copper, gold and silver favor the (Li(4)).4M arrangement. NBO-NICS analysis shows that the large diatropic character in (M'(4)).4Li structures is due to the favorable contribution from both s- and d-orbitals, whereas the small NICS values in the center of (Li(4)).4M are due only to the diatropic contributions from the s-orbitals.     

Influence of "alternative" C-terminal amino acids on the formation of [b3 + 17 + Cat]+ products from metal cationized synthetic tetrapeptides

The aim of this study was to investigate the dissociation patterns, and in particular the relative abundance of [b(3) + 17 + Cat](+), for peptides with C-termini designed to allow transfer of the -OH required to generate the product ion, but not necessarily as the most favored pathway. Working with the hypothesis that formation of a five-membered ring intermediate, including intramolecular nucleophilic attack by a carbonyl oxygen atom, is an important mechanistic step, several model peptides with general sequence AcFGGX were synthesized, metal cationized by electrospray ionization and subjected to collision-induced dissociation (CID). The amino acid at position X was one that either required a larger ring intermediate (beta-alanine, gamma-aminobutyric acid and epsilon-amino-n-caproic acid to generate six-, seven- or nine- membered rings, respectively) to transfer -OH, lacked a structural element required for nucleophilic attack (aminoethanol) or prohibited cyclization because of the inclusion of a rigid ring (p- and m-aminobenzoic acid). For Ag(+), Li(+) and Na(+) cationized peptides, our results show that amino acids requiring the adoption of larger ring intermediates suppressed the formation of [b(3) + 17 + Cat](+), while amino acids that prohibit cyclization eliminated the reaction pathway completely. Formation of [b(3) - 1 + Cat](+) from the alkali metal cationized versions was not a favorable process upon suppression or elimination of the [b(3) + 17 + Cat](+) pathway: the loss of H(2)O to form [M - H(2)O + Cat](+) was instead the dominant dissociation reaction observed. Multiple-stage dissociation experiments suggest that [M - H(2)O + Cat](+) is not [b(4) - 1 + Cat](+) arising from the loss of H(2)O from the C-terminus, but may instead be a species that forms via a mechanism involving the elimination of an oxygen atom from an amide group.     

Hybrid Reaction Systems for the Synthesis of Alkylated Compounds Based upon Cu‐Catalyzed Coupling of Radicals and Organometallic Species

A transition metal catalyzed alkylation with an alkyl halide is one of the most difficult reactions to achieve, because of the difficult oxidative addition of an alkyl‐halogen bond to a metal, and the tendency of the resulting alkylmetal intermediate to undergo a β‐hydride elimination reaction to give an olefin. In this review, we discuss hybrid reaction systems involving Cu catalyzed combination of radicals and organometallic species, which enable facile alkylation reactions to construct C?C and C‐heteroatom bonds. This paper highlights recent progress in arylation, alkenylation, alkynylation, cyclization, addition and introduction of heteroatoms via these hybrid reaction systems.     

Effect of stereochemistry on the electrospray ionization tandem mass spectra of transition metal chloride complexes of monosaccharides

The effect of stereochemistry on the complexation of aldohexoses (glucose, mannose, galactose, allose and talose) and ketohexoses (fructose, tagitose and sorbose) with transition metal chlorides (CoCl(2), NiCl(2), MnCl(2) and ZnCl(2)) has been investigated by electrospray ionization tandem mass spectrometry. Electrospray ionization of methanolic solutions of hexoses containing metal chlorides gave abundant ions corresponding to [M + MetCl](+) and [2M + MetCl](+) which on collision-induced dissociation gave characteristic fragment ions. The fragmentation pathways have been confirmed by examining methyl glucoside and several isotopically labeled glucoses. Eliminations of H(2)O and HCl, C-C cleavages and elimination of metalhydroxychloride are the competing fragmentation pathways observed. All these pathways seem to be influenced by the stereochemistry of the molecule. The fragmentation of the dimeric complexes, [2M + MetCl](+), is also controlled by the stereochemistry of the molecule. The abundance of the product ions corresponding to elimination of HCl is found to increase with increasing number of axial hydroxyl groups in aldohexoses. [2M + MetCl](+) dissociates by elimination of HCl followed by C(2)H(4)O(2) in aldohexose complexes and by elimination of HCl followed by C(3)H(6)O(3) in ketohexose complexes.     

Cationization of simple organic molecules by singly-charged Ag<Stack><Subscript>3</Subscript><Superscript>+</Superscript></Stack> cluster ions in matrix-assisted laser desorption/ionization mass spectrometry: Metal cluster-molecule interactions

It was found earlier that under matrix-assisted laser desorption/ionization (MALDI) conditions several organic compounds which produce adduct with silver ions, are also capable of forming adducts with Ag(3)(+) cluster ions under appropriate conditions. The Ag(3)(+) cluster ion can be in situ generated under the MALDI analysis conditions from silver trifluoroacetate cationization agent in the presence of organic MALDI matrices. In this article the fragmentation of a commercial plasticizer, a peracetylated isoflavone glycoside and a pyrazolylphenyl disulfide derivative cationized with silver ions and Ag(3)(+) cluster ions are compared. It was observed that the complexes of Ag(3)(+) are less fragmented than the corresponding adduct ions with Ag(+). The presumable fragmentation channel of [M + Ag(3)(+)] is the elimination of Ag(2) units from these complexes. No significant dissociation of [M + Ag(3)(+)], into M and Ag(3)(+) takes place, indicating a tight connection between the corresponding molecule and Ag(3)(+) cluster ion. However, with a compound carrying very labile groups, such as the pyrazolylphenyl disulfide derivative, intramolecular cleavages can occur prior to significant dissociation of the Ag(3)(+) cluster ion.     

Gas phase attachment of water and methanol to Ag(I) complexes with alpha-amino acids in an ion trap mass spectrometer

Electrospray ionization was used to generate gas phase complexes of Ag+ with selected alpha-amino acids. Following storage (isolation without collisional activation) in an ion trap mass spectrometer, the mass spectra produced from the complexes of Ag+ with alpha-amino acids such as alanine, valine and tert-leucine contained peaks consistent with the formation of water or methanol molecule adduct ions. The same adduct ions were not present, however, in the mass spectra generated from the Ag+ complexes with phenylalanine, tyrosine and tryptophan following isolation and storage under similar conditions. For those complexes that showed reactivity, the uptake of water and methanol increased with longer storage times in the ion trap. A preliminary molecular modeling study using phenylalanine demonstrated that the aromatic ring coordinates the Ag+ ion, and the interaction between the metal ion and pi-system, in part, is assumed to prohibit the binding of water or methanol during isolation in the gas phase. This conclusion is supported by a comparison of the adduct formation by the Ag+ complexes with phenylalanine, 4-fluorophenylalanine and alpha-aminocyclohexanepropionic acid. In addition, collision induced dissociation experiments involving the Ag+ complexes of phenylalanine, tyrosine and tryptophan suggest that limiting the coordination of the Ag ion by the complexing molecule (i.e. by loss of a coordinating functional group and/or change in structure due to dissociation) results in the binding of a water or methanol molecule during storage in the ion trap. Surprisingly, the bare Ag+ ion, when trapped and stored under identical experimental conditions, formed neither adduct species, suggesting that the attachment of water or methanol may be due to interactions with a molecular orbital within the Ag+/molecule complex.     

Metal ion complexes in the structural analysis of phospholipids by electrospray ionization tandem mass spectrometry

The effects of metal cationization on collisionally activated dissociation (CAD) of phospholipids were investigated by electrospray ionization with quadrupole ion trap tandem mass spectrometry. The metal ions include Li(+), Na(+), K(+), Sr(2+), Ba(2+), and the first transition series. CAD of the transition metal ion-bound lipid complexes gave significant yields of product ions that identify the positions of the two fatty acyl substituents on the glycerophospholipid backbone. The cobalt(II) ion, which has a single naturally occurring isotope, was expected to be a better cationization reagent as it produces simpler mass spectra than other transition metal ions. CAD of the cobalt(II) ion complexes of glycerophosphoethanolamines, glycerophosphoglycerols and glycerophosphoserines yielded product ions that revealed information regarding both the lipid classes and the regiospecific positions of the two fatty acyl substituents.     

Matrix-assisted laser desorption/ionization analysis of lipids and high molecular weight hydrocarbons with lithium 2,5-dihydroxybenzoate matrix

Lithium 2,5-dihydroxybenzoate (LiDHB) is shown to be a very effective matrix for matrix-assisted laser desorption/ionization (MALDI) analysis of nonpolar long-chain lipids, hydrocarbons and polymers. Under standard desorption and ionization conditions using a conventional nitrogen UV laser (337 nm), hydrocarbons (C(24)-C(40)), diverse lipids (triglycerides, diglycerides, wax esters from leaves) and saturated polymers are effectively lithiated providing [M+Li](+) ions. The formation of lithiated hydrocarbons is not accompanied by an elimination of hydrogen or other fragmentation reactions and, due to the relatively simple isotopic distribution of lithium, seems to be more useable for analysis of hydrocarbon mixtures than the previously used silver cationization agents. The mass calibration can be conveniently performed either externally or internally using poly(ethylene glycol) commercial standards.     

Complexes of cationic coinage metal clusters Mn (M=Cu, Ag, Au; n=1–4) and H2S: a theoretical study

Geometries and vibrational frequencies of complexes of cationic coinage metal clusters M_n⁺ (M=Cu, Ag, Au; n=1–4) and H₂S are computed using density functional theory. Thermochemical values for M_n⁺H₂S decomposition channels involving loss of an H atom, H₂ molecule, M atom, or M₂ molecule are also computed. Significantly different results are obtained for closed-shell (n odd) and open-shell (n even) complexes.