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Isomerization of the glutathione thiyl radical via hydrogen atom transfer (HAT) in its complexes with various singly and doubly charged metal ions was studied both experimentally and computationally. The glutathione thiyl radical/metal ion complexes were generated in a quadrupole ion trap mass spectrometer via collision-induced dissociation of S-nitrosoglutathione cationized by the metal ion of interest. The degree of HAT was monitored by gas-phase ion-molecule reactions of these complexes with nitric oxide – the initially formed thiyl radical species were shown previously to be reactive toward NO while the α-carbon (C α ) radicals were not. It was found that group IA metal ions facilitate HAT in the order K + > Na + > Li + > H + . This correlates well with the order of relative stability of the resulting C α species determined by density functional theory (DFT) calculations. Conversely, the glutathione thiyl radicals complexed by three different doubly-charged metal ions (Mg 2+ , Zn 2+ or Ni 2+ ) did not undergo HAT, thereby remaining the S-based radical species. This was rationalized in terms of the substantially smaller thermodynamic benefit of HAT in the case of Mg 2+ and Zn 2+ and even the endothermicity of this process for Ni 2+ , as predicted by the DFT calculations. Additionally, for the glutathione radical/Ni 2+ complex a possibility of iminol-type binding (as opposed to the “classical” keto form) to the metal ion was investigated computationally. It was found that the iminol structures are lower in energy than the keto ones, similar to the situation in the even-electron peptide/Ni 2+ complexes. [ABSTRACT FROM AUTHOR]

A new decarbonylation reaction is observed for [(K2-acetate)Pd(K2-diphosphine)]+ complexes. Gas-phase IR experiments identify the product as [CH3Pd(OP(Ph2)CH2PPh2)]+. DFT calculations uncovered a plausible mechanism involving O atom abstraction by the diphosphine ligand within the coordination sphere to yield the acetyl complex, [CH3COPd(OP(Ph2)CH2PPh2)]+, which then undergoes decarbonylation. [ABSTRACT FROM AUTHOR]

The formation and investigation of sulfur-based cysteine radicals cationized by a group 1A metal ion or Ag+ in the gas phase are reported. Gas-phase ion-molecule reactions (IMR) and infrared multiple-photon dissociation (IRMPD) spectroscopy revealed that the Li+, Na+, and K+ adducts of the cysteine radical remain S-based radicals as initially formed. Theoretical calculations for the three alkali metal ions found that the lowest-energy isomers are Cα-based radicals, but they are not observed experimentally owing to the barriers associated with the hydrogen-atom transfer. A mechanism for the S-to-Cα radical rearrangement in the metal ion complexes was proposed, and the relative energies of the associated energy barriers were found to be Li+>Na+>K+ at all levels of theory. Relative to the B3LYP functional, other levels of calculation gave significantly higher barriers (by 35-40 kJ mol−1 at MP2 and 44-47 kJ mol−1 at the CCSD level) using the same basis set. Unlike the alkali metal adducts, the cysteine radical/Ag+ complex rearranged from the S-based radical to an unreactive species as indicated by IMRs and IRMPD spectroscopy. This is consistent with the Ag+/cysteine radical complex having a lower S-to-Cα radical conversion barrier, as predicted by the MP2 and CCSD levels of theory. [ABSTRACT FROM AUTHOR]

Intramolecular hydrogen atom transfer (HAT) was examined in homocysteine (Hcy) thiyl radical/alkali metal ion complexes in the gas phase by combination of experimental techniques (ion-molecule reactions and infrared multiple photon dissociation spectroscopy) and theoretical calculations. The experimental results unequivocally show that metal ion complexation (as opposed to protonation) of the regiospecifically generated Hcy thiyl radical promotes its rapid isomerisation into an α-carbon radical via HAT. Theoretical calculations were employed to calculate the most probable HAT pathway and found that in alkali metal ion complexes the activation barrier is significantly lower, in full agreement with the experimental data. This is, to our knowledge, the first example of a gas-phase thiyl radical thermal rearrangement into an α-carbon species within the same amino acid residue and is consistent with the solution phase behaviour of Hcy radical. [ABSTRACT FROM AUTHOR]

The effects of hydrogen bonding and spin density at the oxygen atom on the gas-phase reactivity of phenoxyl radicals were investigated experimentally and theoretically in model systems and the dipeptide LysTyr. Gas-phase ion-molecule reactions were carried out between radical cations of several aromatic nitrogen bases with the neutrals nitric oxide and n -propyl thiol. Reactivity of radical cations 4–6 correlated with the spin density. The possibility of hydrogen bonding was explored in compounds which allowed four-, five-, and six-membered rings to be formed between the protonated nitrogen and the phenoxyl oxygen, while possessing similar spin density at the oxygen atom. The N + -H⋯O bond length was calculated to decrease in the series ( 1–3 ), consistent with the theoretical calculations finding weak hydrogen bonding in 2 and strong hydrogen bonding in 3 . This coincided with the decrease in reaction rates of 1–3 with both nitric oxide and n -propyl thiol. DFT calculations found that the lowest energy structure of the distonic radical cation of the dipeptide [LysTyr(O )] + has a short hydrogen bond between the protonated Lys side chain and the phenoxyl oxygen, 1.70 Å, which is consistent with its low reactivity. [ABSTRACT FROM AUTHOR]

Gas-phase reactivity of several sulfur-based radical cations with various volatile neutrals was studied in a modified quadrupole ion trap mass spectrometer. The radical cations were formed by two methods. The first method (introduced by Siu and co-workers) involved electron transfer from the sulfur-containing ligand of interest (all with a C S double bond) to Cu 2+ ion in a ternary complex upon collision-induced dissociation. The second method utilized aromatic/heterocyclic thiol compounds which upon oxidation formed disulfides. Collision-induced dissociation of protonated disulfides lead to homolytic cleavage of S S bond (often among other products). The radical cations produced by these two methods displayed very similar reactivity toward the five neutrals used in this study. This was explained by the resonance stabilization of these species within the N C S motif leading to similar structures. Density functional theory calculations showed that in all of these systems independent of the method of production most of the spin density resided on the sulfur atom and the C S bond held a partially double character. [ABSTRACT FROM AUTHOR]

A highly sensitive, selective, and rugged quantification method was developed and validated for decitabine (5-aza-2′-deoxycytidine) in human plasma treated with 100 μg/mL of tetrahydrouridine (THU). Chromatographic separation was accomplished using hydrophilic interaction liquid chromatography (HILIC) and detection used electrospray ionization (ESI) tandem mass spectrometry (MS/MS) by monitoring lithiated adducts of the analytes as precursor ions. The method involves simple acetonitrile precipitation steps (in an ice bath) followed by injection of the supernatant onto a Thermo Betasil Silica-100, 100 × 3.0 mm, 5 μm LC column. Protonated ([M+H] + ), sodiated ([M+Na] + ), and lithiated ([M+Li] + ) adducts as precursor ions for MS/MS detection were evaluated for best sensitivity and assay performance. During initial method development abundant sodium [M+Na] + and potassium [M+K] + adducts were observed while the protonated species [M+H] + was present at a relative abundance of less than 5% in Q1. The alkali adducts were not be able to be minimized by the usual approach of increasing acid content in mobile phases. Significant analyte/internal standard (IS) co-suppression and inter-lot response differences were observed when using the sodium adduct as the precursor ion for quantification. By adding 2 mM lithium acetate in aqueous mobile phase component, the lithium adduct effectively replaced other cationic species and was successfully used as the precursor ion for selected reaction monitoring (SRM) detection. The method demonstrated the separation of anomers and from other endogenous interferences using a 3-min gradient elution. Decitabine stock, working solution stabilities were investigated during method development. Three different peaks, including one from anomerization, were observed in the SRM transition of the analyte when it was in neutral aqueous solution. The assay was validated over a concentration range of 0.5–500 ng/mL (or 0.44–440 pg injected on column) in 50 μL of human plasma. The accuracy and precision were within 8.6% relative error and 6.3% coefficient of variation, respectively. Decitabine was stable in THU treated human plasma for at least 68 days and after 5 freeze–thaw cycles when stored at −70 °C. Stability of decitabine in THU treated human whole blood, matrix factor and recovery were also evaluated during method validation. The method was successfully used for clinical sample analysis. [ABSTRACT FROM AUTHOR]

The article offers information on the roles of mixers in liquid chromatography (LC) systems. Topics discussed include information on the use of mixers in pumping systems to remove irregularities in mobile phase composition; discussions on the effect of diluent and eluent mismatch on hydrophilic interaction liquid chromatography separations; and the analyte recovery and plugging of LC components and columns.

(2,2′-Bipyridine)M═O+ ions (M = Cu, Ni, Co) were generated by collision-induced dissociation and near-UV photodissociation of readily available [(2,2′-bipyridine)MII(NO3)]+ ions in the gas phase, and their structure was confirmed by ion–molecule reactions combined with isotope labeling. Upon storage in a quadrupole ion trap, the (2,2′-bipyridine)M═O+ ions spontaneously added water, and the formed [(2,2′-bipyridine)M═O + H2O]+ complexes eliminated OH upon further near-UV photodissociation. This reaction sequence can be accomplished at a single laser wavelength in the range of 260–340 nm to achieve stoichiometric homolytic cleavage of gaseous water. Structures, spin states, and electronic excitations of the metal complexes were characterized by ion–molecule reactions using 2H and 18O labeling, photodissociation action spectroscopy, and density functional theory calculations. [ABSTRACT FROM AUTHOR]