Collision-induced Dissociation Reactions Research Articles

An approach to estimate the activation energies of fragmentation occurring in quadrupole collision cell of the mass spectrometer.

The classical semi-quantitative Rice-Ramsperger-Kassel (RRK) theory was used for the calculation of the internal energy dependent reaction rate coefficient of the collision-induced dissociation (CID) reaction in tandem mass spectrometry (MS/MS). The survival yield (SY) was determined by the reaction rate equation for the unimolecular dissociation of the precursor ion. The parameters of the rate equation and the RRK model were approximated based on the instrumental conditions. We used the RRK equation for the description of the basic behavior of the fragmentation reactions and for the estimation of the internal energy of the precursor ion. The critical energies for fragmentation (Eo ) of various molecules were estimated and compared with those reported in the literature. The model was extended by taking into account the initial internal energy distribution of the ions created in the ion source. It must be emphasized that our approach provides only a crude estimate for Eo .

ESI/MS investigation of routes to the formation of silver hydride nanocluster dications [AgxHx−2Ly]2+ and gas-phase unimolecular chemistry of [Ag10H8L6]2+

When the bis(diphenylphosphino)methane (dppm) ligated silver hydride nanocluster salt [Ag3(L)3(μ3-H)](BF4)2 is allowed to react with NaBH4 in a methanol/chloroform solution for 5mins., and then diluted with acetonitrile and subjected to electrospray ionization mass spectrometry (ESI/MS), a range of silver hydride nanocluster dications are observed including: [Ag8H6L5]2+ and [AgxHx−2L6]2+, where x=9–15 and L=dppm. All of these clusters are no longer present in the ESI mass spectrum at 40 mins after mixing. Multistage mass spectrometry (MSn) experiments were carried out to determine the fragmentation chemistry of [Ag10H8L6]2+ under conditions of collision-induced dissociation (CID). The initial CID reactions involve sequential loss of two ligands (L) to produce [Ag10H8L4]2+. Further isolation and CID of [Ag10H8L4]2+ resulted in a rich series of product ions which arise from three classes of fragmentation reactions: (i) cluster fission to yield complementary ion pairs [Ag10−xH8-(x−1)L4−y] + and [AgxHx−1Ly]+ (x=1, 2 and 4); (ii) ligand loss associated with cluster fission to yield pairs of singly charged clusters [Ag10−xH8-(x−1)L4−y]+ and [AgxHx−1Ly−1]+ (x=1–4); (iii) ligand loss with concomitant loss of all the hydrides, presumably as four molecules of hydrogen to give the ligated silver cluster, [Ag10L3]2+. The subsequent fragmentation reactions of the product ions were also examined. Most of the singly charged ligated silver hydride clusters fragment to form [AgxHx−1Ly]+. The exceptions are [Ag9H8L2]+ and [Ag7H6L2]+ which, upon ligand loss also release all of the hydrides to form the ligated silver clusters, [Ag9L]+ and [Ag7L]+ respectively. DFT calculations were carried out to examine how the cluster geometry changes for the following processes: [Ag10H8L6]2+→[Ag10H8L4]2++2L→[Ag10H8L3]2++L→[Ag10L3]2++4H2. Losses of 2L from [Ag10H8L6]2+ and L from [Ag10H8L4]2+ were calculated to be endothermic by 2.9 and 1.9eV respectively, but the subsequent loss of 4H2 from [Ag10H8L3]2+ is exothermic by 0.2eV.

Effect of structural parameters on the electron capture dissociation and collision-induced dissociation pathways of copper(II)-peptide complexes.

The gas-phase dissociation pathways of proteins/peptides are usually affected by the nature of the charge carrier and the sequence of amino acid residues. The effects of peptide structural parameters, including peptide composition, chain length and amide hydrogen, on the gas-phase dissociation of Cu(II)-model peptide complexes were explored in this study. Polyglycine peptides with flexible frames were used as probes to reduce the complexity of the system and illustrate the mechanism. Results revealed that the types of fragment ions generated in the electron capture dissociation (ECD) of Cu(II)-adducted peptides changed according to the basic amino acid residue composition. Charged or neutral tryptophan side-chain losses were observed in the collision-induced dissociation (CID) of Cu(II)-peptide complexes. Internal electron transfer between tryptophan and metal ion within the complex occurred during the CID reaction, leaving the charge-reduced Cu(+) as a closed d-shell stable electron configuration. The choice of the reaction channel was then determined by the gas-phase basicity of the peptide. Amide hydrogen was critical in the formation of metalated b-/y-ions in the ECD process as determined through mutation of the backbone amide group. Increasing the chain length suppressed the ECD of Cu-metalated peptide species. Our results indicate that the structural parameters of peptides play important roles in the gas-phase dissociation processes of Cu-peptide complexes.

Mobile Proton Triggered Radical Fragmentation of Nitroarginine Containing Peptides

Protonated nitroarginine, [R(NO2) + H](+), which contains the nitroguanidine 'explosophore,' undergoes homolytic N - N nitro-imine bond cleavage to expel NO2(•) and form a radical cation of arginine in high yield (100% relative abundance) upon low-energy collision-induced dissociation (CID). Other ionization states of nitroarginine, including [R(NO2) - H](-), and a fixed-charge derivative of nitroarginine do not expel NO2(•) (<1%), but instead dissociate via heterolytic bond cleavage with abundant losses of small molecules (N2O and H2N2O2) from the nitroguanidine group. The effects of proton mobility on the CID reactions of nitroarginine containing peptides was investigated for peptide derivatives of leucine enkephalin, including XYGGFLR(NO2), X = D, G, K, and R, by examining the different protonation states: [M - H](-); [M + H](+); and [M + 2H](2+). For [M + H](+) containing the less basic N-terminal residues (X = D, G) and all [M + 2H](2+), mobile proton fragmentation reactions that result in peptide sequence ions dominate. In contrast, for peptides containing the basic N-terminal residues (R and K), the CID spectra of both the [M - H](-) and [M + H](+) are dominated by the losses of small even-electron neutrals from the nitroarginine side-chain. The fraction of nitroguanidine directed fragmentation of the nitroarginine side chain that results in bond homolysis to form [XYGGFLR](+•) by expulsion of NO2(•) increases by more than 10 times as the protonation state changes from [M - H](-) (<10%) to [M + 2H](2+) (ca. 90%) and by about four times as the acidity of the [M + H](+) N-terminal residue increases from R (19.0%) to D (76.5%). These results indicate that protonated peptides containing nitroarginine can undergo non-canonical mobile proton triggered radical fragmentation.

Formation of radical anions of radiosensitizers and related model compounds via electrospray ionization

Radiosensitizers are used in radiotherapy to enhance tumour control of radioresistant hypoxic tumours. While the detailed mechanism of radiosensitization is still unknown, the formation of radical anions is believed to be a key step. Thus understanding the ionization reactions of radiosensitizers is crucial in evaluating the radiosensitization potential and in developing new and more effective drugs. The present work investigates the negative and positive electrospray ionization and subsequent collision-induced dissociation and electron-induced dissociation reactions of ions derived from nimorazole, misonidazole and related compounds using a hybrid linear ion trap – Fourier Transform Ion Cyclotron Resonance mass spectrometer (Finnigan-LTQ-FT). A key finding is that negative electrospray ionization of these radiosensitizers leads to the formation of radical anions, allowing their fragmentation reactions to be probed for the first time.

Combined collision-induced dissociation and photo-selected reaction monitoring mass spectrometry modes for simultaneous analysis of coagulation factors and estrogens

Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis of both coagulation proteins and estrogens, would be a very informative tool. In the present study, the merit of photo-selected reaction monitoring (SRM), a new analytical tool, was evaluated towards estrogens detection in plasma. Then, SRM and photo-SRM detection modes were combined for the simultaneous analysis of estrogen molecules together with heparin co-factor and factor XIIa, two proteins involved in the coagulation cascade. This study shows that photo-SRM could open new multiplexed analytical routes.

Detailed dynamics of three-body recombination of ions in central collisions

The potential energy surface describing quantitatively the dynamics of the collision induced dissociation reactions CsBr + Xe → Cs + + Br − + Xe, CsXe + + Br − is used to explore detailed dynamics of the reverse process of direct three-body recombination of the Cs + and Br − ions undergoing a central collision. For a stepwise analysis of the course of the elementary process, visualization of the trajectory and of the energy state of each pair of the particles is employed. Several different mechanisms of the reaction are found. Their occurrence depends on the impact parameter of the collision of the third body with the recombining pair and on the angles determining the spatial orientation of the ion velocities. The major role in stabilization of the recombination products is played by the repulsion potentials between the ions and the third body, but the amount of energy transferred depends not only on the repulsion interaction strength. Recombination is shown to be able to happen for very low energies of repulsion between the third body and the ions and even in the complete absence of repulsion. In all the cases, the particular recombination mechanism is determined by the dynamical features of the collision. The relation between the kinematic parameters of a collision of the three particles and the recombination mechanism is considered.

Collision-induced dissociation of MO + and MO 2+ (M = Ta and W): Metal oxide and dioxide cation bond energies

The collision-induced dissociation (CID) of TaO +, WO +, TaO 2 +, and WO 2 + with Xe along with reactions of TaO + and WO + with O 2 are studied as a function of kinetic energy using guided ion beam tandem mass spectrometry in order to elucidate the thermochemistry of the MO 2 + species. The kinetic energy dependences for the CID reactions show endothermic behavior, whereas the MO ++O 2 → MO 2 + + O reactions proceed near the collision limit indicating exothermic processes. Analyses of the endothermic CID reaction cross sections yield 0 K threshold energies in eV of E 0(Ta +–O) = 7.01 ± 0.12, E 0(W +–O) = 6.72 ± 0.10, E 0(OTa +–O) = 6.08 ± 0.12, and E 0(OW +–O) = 5.49 ± 0.09. The nature of the bonding in MO + and MO 2 + is discussed and compared for Ta and W and analyzed using theoretical calculations at the B3LYP/HW+/6-311 + G(3df) level of theory. Bond energies for all MO + and MO 2 + species are calculated using geometries calculated at this level as well as BHLYP and CCSD(T) levels and the Stuttgart–Dresden (SDD) and the Def2TZVPP basis sets. Reasonable agreement between the theoretical bond energies and experimental CID threshold energies for TaO +, WO +, TaO 2 +, and WO 2 + is found. Potential energy surfaces for the reaction of the metal cations with O 2 are also calculated at the B3LYP level of theory and reveal additional information about the reaction mechanisms.

Statistical Rate Theory and Kinetic Energy-Resolved Ion Chemistry: Theory and Applications

Ion chemistry, first discovered 100 years ago, has profitably been coupled with statistical rate theories, developed about 80 years ago and refined since. In this overview, the application of statistical rate theory to the analysis of kinetic-energy-dependent collision-induced dissociation (CID) reactions is reviewed. This procedure accounts for and quantifies the kinetic shifts that are observed as systems increase in size. The statistical approach developed allows straightforward extension to systems undergoing competitive or sequential dissociations. Such methods can also be applied to the reverse of the CID process, association reactions, as well as to quantitative analysis of ligand exchange processes. Examples of each of these types of reactions are provided and the literature surveyed for successful applications of this statistical approach to provide quantitative thermochemical information. Such applications include metal-ligand complexes, metal clusters, proton-bound complexes, organic intermediates, biological systems, saturated organometallic complexes, and hydrated and solvated species.

Halogenated silanes, radicals, and cations: Theoretical predictions on ionization energies, structures and potential energy surfaces of cations, proton affinities, and enthalpies of formation

Quantum chemistry study has been carried out on the structure and energetics of halogenated silanes, radicals, and cations (SiH x X y 0,+1, X = F, Cl, Br; x + y = 1–4). The geometries are optimized at B3LYP/6-31+G(2df,p) level. The adiabatic ionization energiess (IE as), relative energetics of cations, proton affinities (PAs) of silanes, and the enthalpies of formation are predicted using G3(CC) model chemistry. Non-classical ion complex structures are found for hydrogenated cations and transition states connecting classical and non-classical structures are also located. The most stable cations for silylene and silyl radicals have their classical divalent and trivalent structures, and those for silanes have non-classical structures except for SiH 3Br + and SiH 2Br 2 +. The non-classical structures for halosilane cations imply difficulty in experimentally measurement of the adiabatic ionization energies using photoionization or photoelectron studies. For SiH 3X, SiH 2X 2, and SiHX 3, the G3(CC) adiabatic IE as to classical ionic structures closest to their neutrals agree better with the photoelectron spectroscopic measurements. The transition states between classical and non-classical structures also hamper the photoionization determination of the appearance energies for silylene cations from silanes. The G3(CC) results for SiH x 0,+1 agree excellently with the photoionization mass spectrometric study, and the results for fluorinated and chlorinated species also agree with the previous theoretical predictions at correlation levels from BAC-MP4 to CCSD(T)/CBS. The predicted enthalpy differences between SiH 2Cl +, SiHCl 2 +, and SiCl 3 + are also in accordance with previous kinetics study. The G3(CC) results show large discrepancies to the collision-induced charge transfer and/or dissociation reactions involving SiF x + and SiCl x + ions, for which the G3(CC) enthalpies of formation are also significantly differed from the previous theoretical predictions, especially on SiF x + ( x = 2–4). The G3(CC) IE a and PA of SiF 4 are significantly different from previous experimental and theoretical studies; however, they are supported by current benchmark calculations at level of CCSD(T)/CBS + core-valence correction.

Gas phase synthesis, structure and unimolecular reactivity of silver iodide cluster cations, AgnIm+ (n = 2–5, 0 &lt; m &lt; n)

Multistage mass spectrometry (MS(n)) experiments reveal that gas phase silver iodide cluster cations, Ag(n)I(m)(+), are readily built up in a stepwise fashion via ion-molecule reactions between mass selected silver (Ag(3)(+) and Ag(5)(+)) or silver hydride (Ag(2)H(+) and Ag(4)H(+)) cluster cations and allyl iodide, in contrast to their reactions with methyl iodide, which solely result in ligation of the clusters. The stoichiometries of these clusters range from 1 < or = n < or = 5 and 1 < or = m < or = 4, indicating the formation of several new subvalent silver iodide clusters. Collision induced dissociation (CID) experiments were carried out on each of these clusters to shed some light on their possible structures. The products arising from CID of the Ag(n)I(m)(+) clusters are highly dependent on the stoichiometry of the cluster. Thus the odd-electron clusters Ag(4)I(2)(+) and Ag(5)I(+) fragment via loss of a silver atom. In contrast, the even-electron cluster ions all fragment via loss of AgI. In addition, Ag(2)I(2) loss is observed for the Ag(4)I(3)(+) and Ag(5)I(2)(+) clusters, while loss of Ag(3)I(3) occurs for the stoichiometric Ag(5)I(4)(+) cluster. DFT calculations were carried out on these Ag(n)I(m)(+) clusters as well as the neutrals associated with the ion-molecule and CID reactions. A range of different isomeric structures were calculated and their structures are described. A noteworthy aspect is that ligation of these silver clusters by I can have a profound effect on the geometry of the silver cluster. For example, D(3h) Ag(3)(+) becomes C(2v) Ag(3)I(+), which in turn becomes C(2h) Ag(3)I(2)(+). Finally, the DFT predicted thermochemistry supports the different types of reaction channels observed in the ion-molecule reactions and CID experiments.

Comparison of collision-induced dissociation and electron-induced dissociation of singly protonated aromatic amino acids, cystine and related simple peptides using a hybrid linear ion trap–FT-ICR mass spectrometer

The gas-phase fragmentation reactions of singly protonated aromatic amino acids, their simple peptides as well as simple models for intermolecular disulfide bonds have been examined using a commercially available hybrid linear ion trap-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Low-energy collision-induced dissociation (CID) reactions within the linear ion trap are compared with electron-induced dissociation (EID) reactions within the FT-ICR cell. Dramatic differences are observed between low-energy CID (which occurs via vibrational excitation) and EID. For example, the aromatic amino acids mainly fragment via competitive losses of NH(3) and (H(2)O+CO) under CID conditions, while side-chain benzyl cations are major fragment ions under EID conditions. EID also appears to be superior in cleaving the S-S and S-C bonds of models of peptides containing an intermolecular disulfide bond. Systematic studies involving fragmentation as a function of electron energy reveal that the fragmentation efficiency for EID occurs at high electron energy (more than 10 eV) compared with the low-electron energy (less than 0.2 eV) typically observed for electron capture dissociation fragmentation. Finally, owing to similarities between the types of fragment ions observed under EID conditions and those previously reported in ultraviolet photodissociation experiments and the electron-ionization mass spectra, we propose that EID results in fragmentation via electronic excitation and vibrational excitation. EID may find applications in analyzing singly charged molecular ions formed by matrix-assisted laser desorption ionization.

Statistical modeling of sequential collision-induced dissociation thresholds

Thermochemistry determined from careful analysis of the energy dependence of cross sections for collision-induced dissociation (CID) reactions has primarily come from the primary dissociation channel. Higher order dissociations generally have thresholds measured to be higher than the thermodynamic limit because of the unknown internal and kinetic energy distributions of the primary products. A model that utilizes statistical theories for energy-dependent unimolecular decomposition to estimate these energy distributions is proposed in this paper. This permits a straightforward modeling of the cross sections for both primary and secondary dissociation channels. The model developed here is used to analyze data for K+(NH3)x, x=2-5, complexes, chosen because the thermochemistry previously determined by threshold CID studies agrees well with values from theory and equilibrium high pressure mass spectrometry. The model is found to reproduce the cross sections with high fidelity and the threshold values for secondary processes are found to be in excellent agreement with literature values. Furthermore, relative thresholds for higher order dissociation processes appear to provide accurate thermodynamic information as well.

Size matters! Fragmentation chemistry of [Cu(L)n]2+ complexes of diacylglycerophosphocholines as a function of coordination number (n = 2–7)

[Cu(L)(n)](2+) complexes of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (L = D6PC) are formed upon electrospray ionization mass spectrometry (ESI-MS) of an 8 mM solution of D6PC with 4 mM CuCl(2) in 10 mM ammonium acetate buffer, pH 6.1. The collision-induced dissociation (CID) reactions of the [Cu(L)(n)](2+) complexes were examined in a linear ion trap mass spectrometer. A rich fragmentation chemistry was observed, including: loss of a neutral ligand; intermolecular ligand-ligand S(N)2 methylation; metal ion induced ligand fragmentation via carboxylate abstraction; and phosphate abstraction. The dominant reaction channel depends on the size (n) of the complex. Thus loss of neutral ligand(s) is the sole reaction channel for n = 5-7. At n = 4, S(N)2 methylation and carboxylate abstraction start to compete with neutral ligand loss. At n = 2 the carboxylate abstraction and phosphate abstraction reactions dominate the CID spectrum. The carboxylate abstraction and phosphate abstraction reactions are likely to be driven via neighboring group pathways. PM3 calculations, carried out to compare competing neighboring pathways based on the relative stabilities of the product ions, suggest a preference for five-membered ring formation for ligand fragmentation involving both carboxylate and phosphate abstraction.

A computational study of structure–reactivity relationships in Na-adduct oligosaccharides in collision-induced dissociation reactions

Elucidating the fragmentation mechanisms in oligosaccharides using theoretical calculations is useful in analyzing the experimentally obtained mass spectra. Semi-empirical and ab initio quantum mechanics calculations were used to study the relationship between the structure and reactivity and the chemical properties of oligosaccharides. In these calculations, sodium-cationized oligosaccharides were investigated to determine Na + ion affinity at several binding positions; in addition, the dependence of the glycosidic bond cleavage on the Na + position was examined. The calculated structures reported in this study are directed at interpreting experimentally observed fragment ions, resulting from the cleavage of the glycosidic bonds. The calculated results for oligosaccharides containing between three and five monosaccharide units (27 oligosaccharides) were compared with experimental data generated by matrix-assisted laser-desorption/ionization (MALDI) using a quadrupole ion trap (QIT) with a time-of-flight (TOF) mass spectrometer (MS).

‘Top-down’ characterization of site-directed mutagenesis products of Staphylococcus aureus dihydroneopterin aldolase by multistage tandem mass spectrometry in a linear quadrupole ion trap

The gas-phase fragmentation reactions of a series of site-directed mutagenesis products of Staphylococcus aureus dihydroneopterin aldolase have been examined by multistage tandem mass spectrometry (MS/MS and MS(3)) in a linear quadrupole ion trap in order to explore the utility of this instrumentation for routine 'top-down' recombinant protein characterization. Following a rapid low resolution survey of the fragmentation behavior of the precursor ions from the wild type (WT) protein, selected charge states were subjected to detailed structural characterization by using high resolution 'zoom' and 'ultrazoom' resonance ejection MS/MS product ion scans. Dissociation of the [M + 18H](18+) charge state yielded a range of product ions from which extensive sequence information could be derived. In contrast, dissociation of the [M + 20H](20+) charge state resulted in a single dominant y(96) product ion formed by fragmentation between adjacent Ile/Gly residues, with only limited sequence coverage. Further extensive sequence information was readily obtained however, by MS(3) dissociation of this initial product. From the combined MS/MS and MS(3) spectra an overall sequence coverage of 66.9%, with fragmentation of 85 of the 127 amide bonds within the WT protein, was obtained. MS/MS and MS(3) of three of the four site-directed mutagenesis products (E29A), (Y61F) and (E81A) were found to yield essentially identical product ion spectra to the WT protein, indicating that these modifications had no significant influence on the fragmentation behavior. The specific site of modification could be unambiguously determined in each case by characterization of product ions resulting from fragmentation of amide bonds on either side of the mutation site. In contrast, MS/MS and MS(3) of the K107A mutant led to significantly different product ion spectra dominated by cleavages occurring N-terminal to proline, which restricted the ability to localize the modification site to within only an 8 amino acid region of the sequence. This work highlights the need for further studies to characterize the charge state, sequence and structural dependence to the low energy collision induced dissociation reactions of multiply protonated intact protein ions.

Development of Proton-Transfer Ion Trap-Mass Spectrometry: On-line Detection and Identification of Volatile Organic Compounds in Air

We present a newly developed instrument that uses proton-transfer ion trap-mass spectrometry (PIT-MS) for on-line trace gas analysis of volatile organic compounds (VOCs). The instrument is based on the principle of proton-transfer reaction-mass spectrometry (PTR-MS): VOCs are ionized using PTRs and detected with a mass spectrometer. As opposed to a quadrupole mass filter in a PTR-MS, the PIT-MS instrument uses an IT-MS, which has the following advantages: (1) the ability to acquire a full mass spectrum in the same time as one mass with a quadrupole and (2) extended analytical capabilities of identifying VOCs by performing collision-induced dissociation (CID) and ion molecule reactions in the IT. The instrument described has, at its current status, limits of detection between 0.05 and 0.5 pbbv for 1-min measurements for all tested VOCs. The PIT-MS was tested in an ambient air measurement in the urban area of Boulder, Colorado, and intercompared with PTR-MS. For all measured compounds the degree of correlation between the two measurements was high (r2 > 0.85), except for acetonitrile (CH3CN), which was close to the limit of detection of the PIT-MS instrument. The two measurements agreed within less than 25%, which was within the combined measurement uncertainties. Automated CID measurements on m/z 59 during the intercomparison were used to determine the contributions of acetone and propanal to the measured signal; both are detected at m/z 59 and thus are indistinguishable in PTR-MS. It was determined that m/z 59 was mainly composed of acetone. An influence of propanal was detected only during a high pollution event. The advantages and future developments of PIT-MS are discussed.

Can radical cations of the constituents of nucleic acids be formed in the gas phase using ternary transition metal complexes?

Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) of ternary transition metal complexes of [M(L(3))(N)](2+) (where M = copper(II) or platinum(II); L(3) = diethylenetriamine (dien) or 2,2':6',2''-terpyridine (tpy); N = the nucleobases: adenine, guanine, thymine and cytosine; the nucleosides: 2'deoxyadenosine, 2'deoxyguanosine, 2'deoxythymine, 2'deoxycytidine; the nucleotides: 2'deoxyadenosine 5'-monophosphate, 2'deoxyguanosine 5'-monophosphate, 2'deoxythymine 5'-monophosphate, 2'deoxycytidine 5'-monophosphate) was examined as a means of forming radical cations of the constituents of nucleic acids in the gas phase. In general, sufficient quantities of the ternary complexes [M(L(3))(N)](2+) could be formed for MS/MS studies by subjecting methanolic solutions of mixtures of a metal salt [M(L(3))X(2)] (where M = Cu(II) or Pt(II); L(3) = dien or tpy; X = Cl or NO(3)) and N to ESI. The only exceptions were thymine and its derivatives, which failed to form sufficient abundances of [M(L(3))(N)](2+) ions when: (a) M = Pt(II) and L(3) = dien or tpy; (b) M = Cu(II) and L(3) = dien. In some instances higher oligomeric complexes were formed; e.g., [Pt(tpy)(dG)(n)](2+) (n = 1-13). Each of the ternary complexes [M(L(3))(N)](2+) was mass-selected and then subjected to collision-induced dissociation (CID) in a quadrupole ion trap. The types of fragmentation reactions observed for these complexes depend on the nature of all three components (metal, auxiliary ligand and nucleic acid constituent) and can be classified into: (i) a redox reaction which results in the formation of the radical cation of the nucleic acid constituent, N(+.); (ii) loss of the nucleic acid constituent in its protonated form; and (iii) fragmentation of the nucleic acid constituent. Only the copper complexes yielded radical cations of the nucleic acid constituent, with [Cu(tpy)(N)](2+) being the preferred complex due to suppression, in this case, of the loss of the nucleobase in its protonated form. The yields of the radical cations of the nucleobases from the copper complexes follow the order of their ionization potentials (IPs): G (lowest IP) > A > C > T (highest IP). Sufficient yields of the radical cations of each of the nucleobases allowed their CID reactions (in MS(3) experiments) to be compared to their even-electron counterparts.

Solvation in Electrospray Mass Spectrometry: Effects on the Reaction Kinetics of Fragmentation Mediated by Ion-Neutral Complexes

In electrospray ionization (ESI) on a triple quadrupole mass spectrometer, benzydamine, a molecule with an N,N-dimethylaminopropoxyl side chain, showed a fragmentation pattern in Q1 scans that is dramatically different from the mass-selected collision-induced dissociation (CID) of its MH(+) ion. The N,N-dimethylimmonium ion, which dominates in Q1 scans at higher energies, is only a minor product in all CID spectra. By using a smaller model molecule, N,N,N',N'-tetramethyl-1,3-propanediamine, with the kinetic energy release measured for the corresponding reaction, we have demonstrated that an ion-neutral complex composed of the N,N-dimethylazetidine cation and a neutral counterpart is involved. When the ion-neutral complex intermediate evolves toward elimination to form the immonium ion, the transition state is stabilized by the neutral species. Solvation of the ion-neutral complex, which obstructs the separation of the two partners by the resulting tighter enclosure, facilitates the elimination by enhancing the stabilization of the transition state. Therefore, the prevalence of the immonium ion in Q1 scans was a result of solvation in the ESI source. In CID reactions, where the decomposing ions are mass-selected and thus solvation does not exist, the immonium ion was a minor product, and the separation of the ion-neutral complex became dominant.

Collision-induced dissociation tandem mass spectrometry of desferrioxamine siderophore complexes from electrospray ionization of UO2(2+), Fe3+ and Ca2+ solutions.

Desferrioxamine (DEF) is a trihydroxamate siderophore typical of those produced by bacteria and fungi for the purpose of scavenging Fe(3+) from environments where the element is in short supply. Since this class of molecules has excellent chelating properties, reaction with metal contaminants such as actinide species can also occur. The complexes that are formed can be mobile in the environment. Because the natural environment is extremely diverse, strategies are needed for the identification of metal complexes in aqueous matrices having a high degree of chemical heterogeneity, and electrospray ionization mass spectrometry (ESI-MS) has been highly effective for the characterization of siderophore-metal complexes. In this study, ESI-MS of solutions containing DEF and either UO(2)(2+), Fe(3+) or Ca(2+) resulted in generation of abundant singly charged ions corresponding to [UO(2)(DEF - H)](+), [Fe(DEF - 2H)](+) and [Ca(DEF - H)](+). In addition, less abundant doubly charged ions were produced. Mass spectrometry/mass spectrometry (MS/MS) studies of collision-induced dissociation (CID) reactions of protonated DEF and metal-DEF complexes were contrasted and rationalized in terms of ligand structure. In all cases, the most abundant fragmentation reactions involved cleavage of the hydroxamate moieties, consistent with the idea that they are most actively involved with metal complexation. Singly charged complexes tended to be dominated by cleavage of a single hydroxamate, while competitive fragmentation between two hydroxamate moieties increased when the doubly charged complexes were considered. Rupture of amide bonds was also observed, but these were in general less significant than the hydroxamate fragmentations. Several lower abundance fragmentations were unique to the metal examined: abundant loss of H(2)O occurred only for the singly charged UO(2)(2+) complex. Further, NH(3) was eliminated only from the singly charged Fe(3+) complex; this and fragmentation of C-C and C-N bonds derived from neither the hydroxamate nor the amide groups suggested that Fe(3+) insertion reactions were competing with ligand complexation. In no experiments were coordinating solvent molecules observed, attached either to the intact complexes or to the fragment ions, which indicated that both intact DEF and its fragments were occupying all of the coordination sites around the metal centers. This conclusion was based on previous experiments that showed that undercoordinated UO(2)(2+) and Fe(3+) readily added H(2)O and methanol in the ESI quadrupole ion trap mass spectrometer that was used in this study.