Gas-phase proton-transport self-catalysed isomerisation of glutamine radical cation: The important role of the side-chain

The gas-phase isomerisation reaction of glutamine radical cation from [NH₂CH (CH₂CH₂CONH₂) COOH ]^+• to [ NH₂C (CH₂CH₂CONH₂) C (OH)₂]^+• has been studied theoretically using the MPWB1K functional approach. The [ NH₂ C (CH₂CH₂CONH₂) C (OH)₂]^+• diol species has been found to be the most stable isomer for glutamine radical cation. Moreover, it has been observed that glutamine has a long enough side-chain with basic groups that acts as a solvent molecule favouring the proton-transfer from C _α to COOH group. This fact reduces dramatically the isomerisation energy barriers compared to the same process for glycine radical cation in gas phase. Thus, this reaction can be considered as an example of gas-phase proton-transport catalysed reaction in which the proton-transport is carried out by the reactant molecule itself instead of any solvent. Contribution to the Serafin Fraga Memorial Issue.     

Mobile protons versus mobile radicals: Gas-phase unimolecular chemistry of radical cations of cysteine-containing peptides

A combination of electrospray ionization (ESI), multistage, and high-resolution mass spectrometry experiments are used to examine the gas-phase fragmentation reactions of radical cations of cysteine containing di- and tripeptides. Two different chemical methods were used to form initial populations of radical cations in which the radical sites were located at different positions: (1) sulfur-centered cysteinyl radicals via bond homolysis of protonated S-nitrosocysteine containing peptides; and (2) α-carbon backbone-centered radicals via Siu’s sequence of reactions (J. Am. Chem. Soc. 2008, 130, 7862). Comparison of the fragmentation reactions of these regiospecifically generated radicals suggests that hydrogen atom transfer (HAT) between the α C-H of adjacent residues and the cysteinyl radical can occur. In addition, using accurate mass measurements, deuterium labeling, and comparison with an authentic sample, a novel loss of part of the N-terminal cysteine residue was shown to give rise to the protonated, truncated N-formyl peptide (an even-electron x_n ion). DFT calculations were performed on the radical cation [GCG]^.+ to examine: the relative stabilities of isomers with different radical and protonation sites; the barriers associated with radical migration between four possible radical sites, [G.CG]⁺, [GC.G]⁺, [GCG.]⁺, and [GC(S.)G]⁺; and for dissociation from these sites to yield b₂-type ions.     

α-Glycyl cation, radical, and anion (H2NCH+/·/−COOH): Generation and characterization in the gas phase

The title species are synthesized in the gas phase and their unimolecular chemistry is determined by a combination of tandem mass spectrometry methods. Dissociative electron ionization of the α-amino acids valine, leucine, isoleucine, or serine produces the α-glycyl cation, H₂NCH⁺COOH, in high yield and purity. At threshold, this ion dissociates by CO loss to form the proton-bound complex HCNH⁺OH₂ via a tight 1,4-H migration that is associated with a high reverse barrier. After collisional activation, additional channels open, most notably the formation of the complementary and structure-characteristic fragments H₂NCH^+· (ionized aminocarbene) and ⁺COOH and the elimination of OH^·. Charge reversal and neutralization–reionization of H₂NCH⁺COOH conclusively show that α-glycyl anion, H₂NCH⁻COOH, and α-glycyl radical, H₂NCH^·COOH, are stable species residing in deep potential energy wells. In the microsecond time window of the experiments, a small fraction of the α-glycyl radical decomposes by sequential elimination of H₂O and CO. The α-glycyl anions arising by charge reversal of the cation or reionization of the radical partly undergo rearrangement losses of H₂ and H₂O, direct cleavages to ⁻COOH, OH⁻, and H₂N⁻, and consecutive fragmentation of these primary product anions.     

Photoinduced electron transfer reactions in the 10-methylacridinium cation–benzyltrimethylsilane system: steady-state and flash photolysis studies

The mechanism of the photoinduced reaction of the lowest excited singlet state of the 10-methylacridinium (AcrMe⁺) cation with benzyltrimethylsilane (BTMSi) in acetonitrile has been investigated by means of steady-state and time-resolved methods. A variety of stable products was found after irradiation (365 nm) of the reaction mixture under aerobic and oxygen-free conditions. The stable products were identified and analyzed using UV–Vis spectrophotometry, high performance liquid chromatography (HPLC), and mass spectrometry (MS). Based on Stern–Volmer plots of the AcrMe⁺ fluorescence quenching by BTMSi (using fluorescence intensity and lifetime measurements), the rate constants were determined to be k _q = 1.24 (± 0.02) × 10¹⁰ M⁻¹ s⁻¹ and k _q = 1.23 (± 0.02) × 10¹⁰ M⁻¹ s⁻¹, i.e., close to the diffusion-controlled limit in acetonitrile, indicating the dynamic quenching mechanism. The quenching process was shown to occur via an electron-transfer reaction leading to the formation of acridinyl radicals (AcrMe^•) and C₆H₅CH₂Si(CH₃)₃ ^•+ radical cations. Based on stationary and flash photolysis experiments, a detailed mechanism of the secondary reactions is proposed and discussed. The AcrMe^• radical was shown to decay by two processes. The fast decay, observed on the nanosecond timescale, was attributed to the back-electron transfer occurring within the initial radical ion pair. The slow decay on the microsecond timescale was explained by recombination reactions of radicals which escaped from the radical pair, including benzyl radicals formed via C–Si bond cleavage in the C₆H₅CH₂Si(CH₃)₃ ^•+ radical cation.     

Ionization and Photofragmentation of Isolated Metalloporphyrin Cations Investigated by VUV Action Spectroscopy**

We investigated the photoionization and fragmentation of isolated metal protoporphyrin IX cations (MPPIX⁺ with M=Fe, Co, Zn) by means of vacuum-ultraviolet (VUV) action spectroscopy in the energy range of 8.5–35 eV. Experiments were carried out in the gas phase by interfacing an electrospray ionization tandem mass spectrometer with a synchrotron beamline. The mass spectra and partial ion yields show that photoexcitation of the precursor ions predominantly leads to ^.CH₂COOH radical side-chain losses of the macrocycle with additional methyl radical (^.CH₃) side-chain losses. Ionization, in contrast, leads to the formation of the intact ionized precursor and various doubly charged fragments which are mostly due to side-chain cleavages. Although statistical fragmentation dominates, we found evidence for non-statistical processes such as new fragments involving for example single and double H₂O losses, indicating that different relaxation mechanisms are at play upon photoionization compared to photoexcitation. The measured ionization energies were 9.6±0.2 eV, 9.4±0.2 eV and 9.6±0.2 eV for FePPIX⁺, CoPPIX⁺ and ZnPPIX⁺, respectively.     

Kinetics for tautomerizations and dissociations of triglycine radical cations

Fragmentations of tautomers of the α-centered radical triglycine radical cation, [GGG^•]⁺, [GG^•G]⁺, and [G^•GG]⁺, are charge-driven, giving b-type ions; these are processes that are facilitated by a mobile proton, as in the fragmentation of protonated triglycine (Rodriquez, C. F. et al. J. Am. Chem. Soc. 2001, 123, 3006–3012). By contrast, radical centers are less mobile. Two mechanisms have been examined theoretically utilizing density functional theory and Rice-Ramsperger-Kassel-Marcus modeling: (1) a direct hydrogen-atom migration between two α-carbons, and (2) a two-step proton migration involving canonical [GGG]^•+ as an intermediate. Predictions employing the latter mechanism are in good agreement with results of recent CID experiments (Chu, I. K. et al. J. Am. Chem. Soc. 2008, 130, 7862–7872).     

Density Functional Theory and Mass Spectrometry of Phthalate Fragmentations Mechanisms: Modeling Hyperconjugated Carbocation and Radical Cation Complexes with Neutral Molecules

This is the first ab initio study of the energetics of the fragmentation mechanisms of phthalate, by mass spectrometry, leading to protonated phthalic anhydride (m/z 149). Phthalates fragment by two major pathways; namely, the McLafferty + 1 rearrangement and the loss of alkoxy. Both pathways involve a carbonyl oxygen attack to the ortho-carbonyl carbon leading to structures with tetrahedral carbon intermediates that eventually give m/z 149. These pathways were studied by collision induced dissociation (CID) using triple quadrupole mass spectrometry. The proposed McLafferty + 1 pathway proceeds through a distonic M^•+, leading to the loss of an allylic-stabilized alkene radical. The McLafferty rearrangement step proceeds through a six-membered ring transition state with a small activation energy ranging 0.4–6.2 kcal/mol; the transfer of a second H from the distonic ion of the rearrangement step proceeds through a radical cation molecule complex. Based on quantum chemical modeling of the cation molecule complexes, two kinds of cation molecule complexes were identified as radical cation molecule complex and hyperconjugated cation molecule complex. This distinction is based on the cation and simplifies future modeling of similar complexes. Optimization of important fragments in these pathways showed cyclized and hydrogen-bonded structures to be favored. An exception was the optimized structure of the protonated phthalic anhydride (m/z 149) that showed a structure with an open anhydride ring.     

Characterizing the Intramolecular H-bond and Secondary Structure in Methylated GlyGlyH<Superscript>+</Superscript> with H<Subscript>2</Subscript> Predissociation Spectroscopy

We report vibrational predissociation spectra of the four protonated dipeptides derived from glycine and sarcosine, GlyGlyH⁺•(H₂)_1,2, GlySarH⁺•(D₂)₂, SarGlyH⁺•(H₂)₂, and SarSarH⁺•(D₂)₂, generated in a cryogenic ion trap. Sharp bands were recovered by monitoring photoevaporation of the weakly bound H₂ (D₂) molecules in a linear action regime throughout the 700–4200 cm^–1 range using a table-top laser system. The spectral patterns were analyzed in the context of the low energy structures obtained from electronic structure calculations. These results indicate that all four species are protonated on the N-terminus, and feature an intramolecular H-bond involving the amino group. The large blue-shift in the H-bonded N–H fundamental upon incorporation of a methyl group at the N-terminus indicates that this modification significantly lowers the strength of the intramolecular H-bond. Methylation at the amide nitrogen, on the other hand, induces a significant rotation (~110^o) about the peptide backbone.     

Reactions of the radial cattions of acetic acid and acetic anhydride in CFCl3

The ESR spectra of -irradiated, at –196 °C, solutions of acetic acid and acetic anhydride were studied depending on their concentrations in CFCl₃. The structure of thus produced radical cations is confirmed with the deuterium substituted analogues. It has been shown that the ion-molecular reaction of the radical cation CH₂COOH⁺ in the isolated dimer takes place for the dilute solutions of acetic acid in CFCl₃ resulting in the formation of CH₃COO follwed by its decomposition to CH₃+CO₂ while the radicals CH₂COOH are formed via secondary processes. The reactions of radical cations of acetic oxide have been also studied.     

Degradation processes in the cellulose/<Emphasis Type="Italic">N</Emphasis>-methylmorpholine-<Emphasis Type="Italic">N</Emphasis>-oxide system studied by HPLC and ESR. Radical formation/recombination kinetics under UV photolysis at 77 K

Degradation processes of N-methylmorpholine-N-oxide monohydrate (NMMO), cellulose and cellulose/NMMO solutions were studied by high performance liquid chromatography (HPLC) and electron spin resonance (ESR) spectroscopy. Kinetics of radical accumulation processes under UV (λ = 248 nm) excimer laser flash photolysis was investigated by ESR at 77 K. Beside radical products of cellulose generated and stabilized at low temperature, radicals in NMMO and cellulose/NMMO solutions were studied for the first time in those systems and attributed to nitroxide type radicals ∼CH₂–NO^•–CH₂∼ and/or ∼CH₂–NO^•–CH₃∼ at the first and methyl ^•CH₃ and formyl ^•CHO radicals at the second step of the photo-induced reaction. Kinetic study of radicals revealed that formation and recombination rates of radical reaction depend on cellulose concentration in cellulose/NMMO solutions and additional ingredients, e.g., Fe(II) and propyl gallate. HPLC measurements showed that the concentrations of ring degradation products, e.g., aminoethanol and acetaldehyde, are determined by the composition of the cellulose/NMMO solution. Results based on HPLC are mainly maintained by ESR that supports the assumption concerning a radical initiated ring-opening of NMMO.     

Chemical ionization desorption mass spectrometry of some quaternary ammonium salts

The ammonia chemical ionization desorption spectra of N,N-dimethyl quaternary ammonium iodides in addition to high protonated molecular ion [M + H]⁺ intensity, show signals for an ion radical composed of N-methyl abstracted salt cation and ammonia [C + NH₃? CH₃]^+˙. These ions corresponding to the cation +2 show increased importance in the chemical ionization mode, using the same reagent gas. The technique of chemical ionization desorption appears suitable for the analysis of salts, and thus for the determination of the molecular weight of both anion and cation.     

Transient species and its properties of melatonin

Reactive oxygen species (ROS) are generated dur- ing radiation, respiratory burst, normal metabolic processes and so on. There are enzymatic and non-enzymatic antioxidants such as superoxide dis- mutase (SOD), glutathione peroxidase (GSH-Px), vi- tamin E (VE) and carotenoids that can either inhibit or repair the ROS-induced damage. ROS is essential to maintain physiological homeostasis. However, exces- sive ROS give rise to oxidative damage to proteins, lipids and DNA which related t…     

Analysis of selective androgen receptor modulators by gas chromatography-microchip atmospheric pressure photoionization-mass spectrometry

A gas chromatography-microchip atmospheric pressure photoionization-mass spectrometric (GC-μAPPI-MS) method was developed and used for the analysis of three 2-quinolinone-derived selective androgen receptor modulators (SARMs). SARMs were analyzed from spiked urine samples, which were hydrolyzed and derivatized with N-methyl-N-(trimethylsilyl)trifluoroacetamide before analysis. Trimethylsilyl derivatives of SARMs formed both radical cations (M^+•) and protonated molecules ([M + H]⁺) in photoionization. Better signal-to-noise ratios (S/N) were obtained in MS/MS analysis using the M^+• ions as precursor ions than using the [M + H]⁺ ions, and therefore the M^+• ions were selected for the precursor ions in selected reaction monitoring (SRM) analysis. Limits of detection (LODs) with the method ranged from 0.01 to 1 ng/mL, which correspond to instrumental LODs of 0.2–20 pg. Limits of quantitation ranged from 0.03 to 3 ng/mL. The mass spectrometric response to the analytes was linear (R ≥ 0.995) from the LOQ concentration level up to 100 ng/mL concentration, and intra-day repeatabilities were 5%–9%. In addition to the GC-μAPPI-MS study, the proof-of-principle of gas chromatography-microchip atmospheric pressure chemical ionization-Orbitrap MS (GC-μAPCI-Orbitrap MS) was demonstrated.     

The protonated betaine/ammonia complex: how stable is the gas-phase zwitterion structure?

The ammonium ion stabilizes a betaine zwitterion in the gas phase forming a salt-bridge structure, [(CH₃)₃N⁺CH₂COO^–NH₄⁺] that is 3.7 kcal/mol less stable than the ion/molecule complex between protonated betaine and neutral ammonia, (CH₃)₃N⁺CH₂COOH/NH₃. DFT calculations have reversed the previously determined relative stability based on PM3 calculations and are in agreement with black-body infrared radiative dissociation experiments. A double-well potential energy surface is formed with a rather low central barrier separating the two complexes. This is conducive to efficient hydrogen/deuterium exchange in agreement with experiment. It prevents the existence of the salt-bridge complex as a distinct species under thermal conditions.     

Enthalpies of addition of radicals to aldehydes, ketones, acids and esters

Enthalpies of the addition of radicals HO^•, HO₂ ^•, CH₃ ^•, CH₃O^•, CH₃O₂ ^• to the C=0 bond of model aldehydes, ketones, acids and esters have been calculated by thermodynamic and quantum chemical methods. It has been shown that the exothermic effect of these reactions decreases in the row HO^•>CH₃O^•>CH₃ ^•>HOO^•>CH₃OO^•.     

Effect of electron-withdrawing power of the substituted group on?OH radical reaction with substituted aryl sulphides: A pulse radiolysis study

In neutral aqueous solution of (phenylthio)acetic acid, hydroxyl radical is observed to react with a bimolecular rate constant of 7.2 × 10^-1 dm³ mol⁻s⁻ and the transient absorption bands are assigned to^•OH radical addition to benzene and sulphur with a rough estimated values of 50 and 40% respectively. The reaction of the^•OH radical with diphenyl sulphide (k = 4.3 × 10⁸ dm³ mol⁻¹ s⁻¹) is observed to take place with formation of solute radical cation, OH-adduct at sulphur and benzene with estimated values of about 12, 28 and 60% respectively. The transient absorption bands observed on reaction of^•OH radical, in neutral aqueous solution of 4-(methylthio)phenyl acetic acid, are assigned to solute radical cation (λ_max = 550 and 730 nm), OH-adduct at sulphur (λ_max = 360 nm) and addition at benzene ring (λ_max = 320 nm). The fraction of^•OH radical reacting to form solute radical cation is observed to depend on the electron-withdrawing power of substituted group. In acidic solutions, depending on the concentration of acid and electron-withdrawing power, solute radical cation is the only transient species formed on reaction of^•OH radical with the sulphides studied.     

Novel C<Subscript>β</Subscript>–C<Subscript>γ</Subscript> Bond Cleavages of Tryptophan-Containing Peptide Radical Cations

In this study, we observed unprecedented cleavages of the C_β–C_γ bonds of tryptophan residue side chains in a series of hydrogen-deficient tryptophan-containing peptide radical cations (M^•+) during low-energy collision-induced dissociation (CID). We used CID experiments and theoretical density functional theory (DFT) calculations to study the mechanism of this bond cleavage, which forms [M – 116]⁺ ions. The formation of an α-carbon radical intermediate at the tryptophan residue for the subsequent C_β–C_γ bond cleavage is analogous to that occurring at leucine residues, producing the same product ions; this hypothesis was supported by the identical product ion spectra of [LGGGH – 43]⁺ and [WGGGH – 116]⁺, obtained from the CID of [LGGGH]^•+ and [WGGGH]^•+, respectively. Elimination of the neutral 116-Da radical requires inevitable dehydrogenation of the indole nitrogen atom, leaving the radical centered formally on the indole nitrogen atom ([Ind]^•-2), in agreement with the CID data for [WGGGH]^•+ and [W_1-CH3GGGH]^•+; replacing the tryptophan residue with a 1-methyltryptophan residue results in a change of the base peak from that arising from a neutral radical loss (116 Da) to that arising from a molecule loss (131 Da), both originating from C_β–C_γ bond cleavage. Hydrogen atom transfer or proton transfer to the γ-carbon atom of the tryptophan residue weakens the C_β–C_γ bond and, therefore, decreases the dissociation energy barrier dramatically.     

The structure and dissociation pathways of protonated methanol: An ab initio molecular orbital study

Ab initio molecular orbital calculations with moderately large polarization basis sets and including valence-electron correlation have been used to examine the structure and dissociation mechanisms of protonated methanol [CH₃OH₂]⁺. Stable isomers and transition structures have been characterized using gradient techniques. Protonated methanol is found to be the only stable isomer in the [CH₅O]⁺ potential surface. There is no evidence for a tightly-bound complex, [HOCH₂]⁺…?H₂, analogous to the preferred structure [CH₃]⁺…?H₂ of [CH₅]⁺. Protonated methanol is found to possess a pyramidal arrangement of bonds at the oxygen atom with a barrier to inversion of 8kJ mol^?1. The lowest energy fragmentation pathways are dissociation into methyl cation and water (predicted to require 284 kJ mol^?1 with zero reverse activation energy) and loss of molecular hydrogen (endothermic by 138 kJ mol^?1 but with a reverse activation barrier of 149 kJ mol^?1). The results offer a possible explanation as to why production of [CH₂OH]⁺ from the reaction of methyl cation with water is not observed. Other dissociation processes examined include loss of a hydrogen atom to yield the methylenoxonium radical cation or methanol radical cation (requiring 441 and 490 kJ mol^?1, respectively) and loss of a proton to yield neutral methanol (requiring 784 kJ mol^?1).     

Kinetics of the ?OH-radical initiated reactions of acetic acid and its deuterated isomers

Kinetics of the ^•OH-initiated reactions of acetic acid and its deuterated isomers have been investigated performing simulation chamber experiments at T = 300 ± 2 K. The following rate constant values have been obtained (± 1σ, in cm³ molecule⁻¹ s⁻¹): k ₁(CH₃C(O)OH + ^•OH) = (6.3 ± 0.9) × 10⁻¹³, k ₂(CH₃C(O)OD + ^•OH) = (1.5 ± 0.3) × 10⁻¹³, k ₃(CD₃C(O)OH + ^•OH) = (6.3 ± 0.9) × 10⁻¹³, and k ₄(CD₃C(O)OD + ^•OH) = (0.90 ± 0.1) × 10⁻¹³. This study presents the first data on k ₂(CH₃C(O)OD + ^•OH). Glyoxylic acid has been detected among the products confirming the fate of the ^•CH₂C(O)OH radical as suggested by recent theoretical studies.     

Rate constant for the reaction CH3CO?+ HBr and the enthalpy of formation of the CH3CO?radical

Summary Pulsed laser photolysis coupled with time-resolved UV-absorption monitoring of CH₃CO^•radicals was applied to obtain the rate constant, k₁, for the reaction CH₃CO^•+ HBr → CH₃C(O)H + Br (1); k₁(298 K) = (3.59 ± 0.23 (2σ))x10^-12cm³molecule^-1s^-1. Utilization of k₁in a third law procedure has provided the standard enthalpy of formation value ofD_fH°₂₉₈(CH₃CO^•) = -10.04 ± 1.10 (2σ) kJ mol^-1in excellent agreement with a very recent IUPAC recommendation.