Linda Feketeová

Letter: intercluster chemistry of protonated and sodiated betaine dimers upon collision induced dissociation and electron induced dissociation.

The collision induced dissociation and electron induced dissociation spectra of the [2M + H]+ and [2M + Na]+ clusters of the zwitterionic amino acid, betaine (M), have been examined in a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer. Intercluster reactions are observed in the collision induced dissociation spectra of [2M + H]+ and [2M + Na]+ and in the electron induced dissociation spectrum of [2M + H]+.

Reactions in Nitroimidazole Triggered by Low-Energy (0–2 eV) Electrons: Methylation at N1-H Completely Blocks Reactivity†

Low-energy electrons (LEEs) at energies of less than 2 eV effectively decompose 4-nitroimidazole (4NI) by dissociative electron attachment (DEA). The reactions include simple bond cleavages but also complex reactions involving multiple bond cleavages and formation of new molecules. Both simple and complex reactions are associated with pronounced sharp features in the anionic yields, which are interpreted as vibrational Feshbach resonances acting as effective doorways for DEA. The remarkably rich chemistry of 4NI is completely blocked in 1-methyl-4-nitroimidazole (Me4NI), that is, upon methylation of 4NI at the N1 site. These remarkable results have also implications for the development of nitroimidazole based radiosensitizers in tumor radiation therapy.

Electron-induced dissociation of doubly protonated betaine clusters: controlling fragmentation chemistry through electron energy.

The [M21+2H]2+ cluster of the zwitterion betaine, M = (CH3)3NCH2CO2, formed via electrospray ionisation (ESI), has been allowed to interact with electrons with energies ranging from >0 to 50 eV in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The types of gas-phase electron-induced dissociation (EID) reactions observed are dependent on the energy of the electrons. In the low-energy region up to 10 eV, electrons are mainly captured, forming the charge-reduced species, {[M21+2H]+*}*, in an excited state, which stabilises via the ejection of an H atom and one or more neutral betaines. In the higher energy region, above 12 eV, a Coulomb explosion of the multiply charged clusters is observed in highly asymmetric fission with singly charged fragments carrying away more than 70% of the parent mass. Neutral betaine evaporation is also observed in this energy region. In addition, a series of singly charged fragments appears which arise from C-X bond cleavage reactions, including decarboxylation and CH3 group transfer. These latter reactions may arise from access of electronic excited states of the precursor ions.

Fragmentation of the tryptophan cluster [Trp9–2H]2− induced by different activation methods

Electrospray ionization (ESI) of tryptophan gives rise to multiply charged, non-covalent tryptophan cluster anions, [Trp(n)-xH](x-), in a linear ion trap mass spectrometer, as confirmed by high-resolution experiments performed on a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The smallest multiply charged clusters that can be formed in the linear ion trap as a function of charge state are: x = 2, n = 7; x = 3, n = 16; x = 4, n = 31. The fragmentation of the dianionic cluster [Trp(9)-2H](2-) was examined via low-energy collision-induced dissociation (CID), ultraviolet photodissociation (UVPD) at 266  nm and electron-induced dissociation (EID) at electron energies ranging from >0 to 30  eV. CID proceeds mostly via charge separation and evaporation of neutral tryptophan. The smallest doubly charged cluster that can be formed via evaporation of neutral tryptophans is [Trp(7)-2H](2-), consistent with the observation of this cluster in the ESI mass spectrum. UVPD gives singly charged tryptophan clusters ranging from n = 2 to n = 9. The latter ion arises from ejection of an electron to give the radical anion cluster, [Trp(9)-2H](-·). The types of gas-phase EID reactions observed are dependent on the energy of the electrons. Loss of neutral tryptophan is an important channel at lower energies, with the smallest doubly charged ion, [Trp(7)-2H](2-), being observed at 19.8  eV. Coulomb explosion starts to occur at 19.8  eV to form the singly charged cluster ions [Trp(x)-H](-) (x = 1-8) via highly asymmetric fission. At 21.8  eV a small amount of [Trp(2)-H-NH(3)](-) is observed. Thus CID, UVPD and EID are complementary techniques for the study of the fragmentation reactions of cluster ions.

Comparison of collision- versus electron-induced dissociation of Pt(II) ternary complexes of histidine- and methionine-containing peptides.

Incubation of the histidine-containing peptides (GH, HG, GGH, GHG, HGG) and methionine-containing peptides (GM, MG, GGM, GMG, MGG) with the platinum complexes [Pt(terpy)Cl](+) (A) and [Pt(dien)Cl](+) (B) followed by electrospray ionisation (ESI) led to a number of singly and doubly charged ternary platinum peptide complexes, including [Pt(L)M](2+) and [Pt(L)M-H](+) (where L = the ligand terpy or dien; M is a peptide). Each of the [Pt(L)M](2+) complexes was subjected to electron capture dissociation (ECD), collision-induced dissociation (CID) and electron-induced dissociation (EID), while each of the [Pt(L)M-H](+) complexes was subjected to CID and EID. Results from ECD suggest that the free electron is captured by the metal ion thus weakening the bonds to its ligands. In the case of the ligand terpy, which binds more strongly than dien, this weakening leads to the loss of the peptide. The minor products in the ECD spectra of [Pt(terpy)M](2+) complexes do show fragmentation along the peptide backbone, but the ions observed are of the a-, b-, and y-type. For the complexes with methionine-containing peptides, a marker ion, [Pt(L)SCH(3)](+), was found which is indicative of binding of Pt to the methionine side chain. For the histidine-containing peptides, an ion containing platinum, the auxiliary ligand, and the histidine imine was observed in many instances, thus indicating the binding of the histidine side chain to the metal, but other modes of Pt coordination (N-terminus) were also found to be competitive. These findings are consistent with a recent finding (Sze et al. J. Biol. Inorg. Chem. 2009; 14: 163) that Pt occupies the methionine-rich copper(I)-binding site rather than histidine-rich copper(II)-binding site in the CopC protein.

Comparison of collision- versus electron-induced dissociation of sodium chloride cluster cations

The collision-induced dissociation (CID) and electron-induced dissociation (EID) spectra of the [(NaCl)(m)(Na)(n)](n+) clusters of sodium chloride have been examined in a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer. For singly charged cluster ions (n = 1), mass spectra for CID and EID of the precursor exhibit clear differences, which become more pronounced for the larger cluster ions. Whereas CID yields fewer product ions, EID produces all possible [(NaCl)(x)Na](+) product ions. In the case of doubly charged cluster ions, EID again leads to a larger variety of product ions. In addition, doubly charged product ions have been observed due to loss of neutral NaCl unit(s). For example, EID of [(NaCl)(11)(Na)(2)](2+) leads to formation of [(NaCl)(10)(Na)(2)](2+), which appears to be the smallest doubly charged cluster of sodium chloride observed experimentally to date. The most abundant product ions in EID spectra are predominantly magic number cluster ions. Finally, [(NaCl)(m)(Na)(2)](+*) radical cations, formed via capture of low-energy electrons, fragment via the loss of [(NaCl)(n)(Na)](*) radical neutrals.

Gas-phase infrared spectrum and acidity of the radical cation of 9-methylguanine

Oxidative damage to DNA yields guanine radical cations. Their gas-phase IR spectroscopic signature and acidity have been modelled by the radical cation of 9-methylguanine. Comparisons with quantum chemistry calculations suggest that radical cation formation produces the ground-state keto tautomer, which has an N-H acidity enhanced by ~470 kJ mol(-1).

Collisions of Slow Ions C3Hn+ and C3Dn+ (n = 2–8) with Room Temperature Carbon Surfaces: Mass Spectra of Product Ions and the Ion Survival Probability

Collisions of C3H n + (n = 2–8) ions and some of their per-deuterated analogs with room temperature carbon (HOPG) surfaces (hydrocarbon-covered) were investigated over the incident energy range 13–45 eV in beam scattering experiments. The mass spectra of product ions were measured and main fragmentation paths of the incident projectile ions, energized in the surface collision, were determined. The extent of fragmentation increased with increasing incident energy. Mass spectra of even-electron ions C3H7+ and C3H5+ showed only fragmentations, mass spectra of radical cations C3H8•+ and C3H6•+ showed both simple fragmentations of the projectile ion and formation of products of its surface chemical reaction (H-atom transfer between the projectile ion and hydrocarbons on the surface). No carbon-chain build-up reaction (formation of C4 hydrocarbons) was detected. The survival probability of the incident ions, Sa, was usually found to be about 1–2% for the radical cation projectile ions C3H8•+, C3H6•+, C3H4•+ and C3H2•+ and several percent up to about 20% for the even-electron projectile ions C3H7+, C3H5+, C3H3+. A plot of Sa values of C1, C2, C3, some C7 hydrocarbon ions, Ar+ and CO2+ on hydrocarbon-covered carbon surfaces as a function of the ionization energies (IE) of the projectile species showed a drop from about 10% to about 1% and less at IE 8.5–9.5 eV and further decrease with increasing IE. A strong correlation was found between log Sa and IE, a linear decrease over the entire range of IE investigated (7–16 eV), described by log Sa = (3.9 ± 0.5) – (0.39 ± 0.04) IE.

Unimolecular chemistry of doubly protonated zwitterionic clusters.

Electrospray ionization and tandem mass spectrometry experiments have been used to study the fragmentation and electron-ion interactions of doubly charged zwitterionic clusters, [M(15) + 2H](2+) (where M = Glycine Betaine (GB), (CH(3))(3)N(+)CH(2)CO(2)(-), and Dimethylsulfonioacetate (DMSA), (CH(3))(2)S(+)CH(2)CO(2)(-)) which are close to the stability limit, i.e., the Coulomb repulsion of the charge within the cluster competes with attractive forces. The intercluster chemistry was studied using collision-induced dissociation (CID) and electron-induced dissociation (EID) in which the energy of the electrons has been varied from >0 to 30 eV. Experimental results suggest that the zwitterionic binding energy in the clusters follow the order GB > DMSA, which is consistent with theoretical calculations that highlight that the lower dipole moment of DMSA leads to a binding energy of DMSA that is 0.86 times smaller than that for GB. Multiply protonated clusters of both GB and DMSA dissociate through Coulomb explosion, which is in competition with neutral evaporation for DMSA. Electronic excitation of the cluster under EID conditions at higher electron energies >12 eV can lead to new intercluster reactions associated with bond cleavages where differences between the sulfur and nitrogen betaines are minor.

Intercluster reactions show that (CH3)2S(+)CH2CO2H is a better methyl cation donor than (CH3)3N(+)CH2CO2H.

The intrinsic methylating abilities of the known biological methylating zwitterionic agents, dimethylsulfonioacetate (DMSA), (CH3)2S+CH2CO2− (1) and glycine betaine (GB), (CH3)3N+CH2CO2− (2), have been examined via a range of gas phase experiments involving collision-induced dissociation (CID) of their proton-bound homo- and heterodimers, including those containing the amino acid arginine. The relative yields of the products of methyl cation transfer are consistent in all cases and show that protonated DMSA is a more potent methylating agent than protonated GB. Since methylation can occur at more than one site in arginine, the [M + CH3]+ ion of arginine, formed from the heterocluster [DMSA + Arg + H]+, was subject to an additional stage of CID. The resultant CID spectrum is virtually identical to that of an authentic sample of protonated arginine-O-methyl ester but is significantly different to that of an authentic sample of protonated NG-methyl arginine. This suggests that methylation has occurred within a salt bridge complex of [DMSA + Arg + H]+, in which the arginine exists in the zwitterionic form. Finally, density functional theory calculations on the model salts, (CH3CO2−)[(CH3)3S+] and (CH3CO2−)[(CH3)4N+], show that methylation of CH3CO2− by (CH3)3S+ is both kinetically and thermodynamically preferred over methylation by (CH3)4N+.