Dissociative electron transfer of copper(ii) complexes of glycyl(glycyl/alanyl)tryptophan in vacuo: IRMPD action spectroscopy provides evidence of transition from zwitterionic to non-zwitterionic peptide structures.

We report herein the first detailed study of the mechanism of redox reactions occurring during the gas-phase dissociative electron transfer of prototypical ternary [CuII(dien)M]˙2+ complexes (M, peptide). The two final products are (i) the oxidized non-zwitterionic π-centered [M]˙+ species with both the charge and spin densities delocalized over the indole ring of the tryptophan residue and with a C-terminal COOH group intact, and (ii) the complementary ion [CuI(dien)]+. Infrared multiple photon dissociation (IRMPD) action spectroscopy and low-energy collision-induced dissociation (CID) experiments, in conjunction with density functional theory (DFT) calculations, revealed the structural details of the mass-isolated precursor and product cations. Our experimental and theoretical results indicate that the doubly positively charged precursor [CuII(dien)M]˙2+ features electrostatic coordination through the anionic carboxylate end of the zwitterionic M moiety. An additional interaction exists between the indole ring of the tryptophan residue and one of the primary amino groups of the dien ligand; the DFT calculations provided the structures of the precursor ion, intermediates, and products, and enabled us to keep track of the locations of the charge and unpaired electron. The dissociative one-electron transfer reaction is initiated by a gradual transition of the M tripeptide from the zwitterionic form in [CuII(dien)M]˙2+ to the non-zwitterionic M intermediate, through a cascade of conformational changes and proton transfers. In the next step, the highest energy intermediate is formed; here, the copper center is 5-coordinate with coordination from both the carboxylic acid group and the indole ring. A subsequent switch back to 4-coordination to an intermediate IM1, where attachment to GGW occurs through the indole ring only, creates the structure that ultimately undergoes dissociation.

Hydrogen atom transfer in the radical cations of tryptophan-containing peptides AW and WA studied by mass spectrometry, infrared multiple-photon dissociation spectroscopy, and theoretical calculations.

Two types of radical cations of tryptophan-the π-radical cation and the protonated tryptophan-N radical-have been studied in dipeptides AW and WA. The π-radical cation produced by removal of an electron during collision-induced dissociation of a ternary Cu(II) complex was only observed for the AW peptide. In the case of WA, only the ion corresponding to the loss of ammonia, [WA-NH3] •+, was observed from the copper complex. Both protonated tryptophan-N radicals were produced by N-nitrosylation of the neutral peptides followed by transfer to the gas phase via electrospray ionization and subsequent collision-induced dissociation. The regiospecifically formed N• species were characterized by infrared multiple-photon dissociation spectroscopy which revealed that the WA tryptophan-N• radical remains the nitrogen radical, while the AW nitrogen radical rearranges into the π-radical cation. These findings are supported by the density functional theory calculations that suggest a relatively high barrier for the radical rearrangement (N• to π) in WA (156.3 kJ mol-1) and a very low barrier in AW (6.1 kJ mol-1). The facile hydrogen atom migration in the AW system is also supported by the collision-induced dissociation of the tryptophan-N radical species that produces fragments characteristic of the tryptophan π-radical cation. Gas-phase ion-molecule reactions with n-propyl thiol have also been used to differentiate between the π-radical cations (react by hydrogen abstraction) and the tryptophan-N• species (unreactive) of AW.

Loss of water from protonated polyglycines: interconversion and dissociation of the product imidazolone ions.

Collision-induced dissociation of isotopically labelled protonated pentaglycine produced two abundant [b5]+ ions, the products of the loss of water from the first and second amide groups, labelled [b5]+I and [b5]+II. IRMPD spectroscopy and DFT calculations show that these two [b5]+ ions feature N1-protonated 3,5-dihydro-4H-imidazol-4-one structures. 15N-Labelling established that some interconversion occurs between these two ions but dissociations are preferred. For both ions, DFT calculations show that the barrier to interconversion is slightly higher than those to dissociation. Dehydration of protonated hexaglycine produced three imidazolone ions. Ions [b6]+I and [b6]+II exhibit analogous CID spectra to those from [b5]+I and [b5]+II; however, the spectrum of the [b6]+III ion was dramatically different, showing losses predominantly of a further water molecule or cleavage of the second amide bond to give the glycyloxazolone (a deprotonated [b2]+ ion, labelled GlyGlyox (114 Da)) from the N-terminus. Protonated polyglycines [Glyn + H]+, where n = 7-9, all readily lose at least one water molecule. The corresponding [bn]+ ions lose either a further water molecule, an oxazolone from the N-terminus or a truncated peptide from the C-terminus. The number of amino acid residues in the latter two eliminated neutral molecules provides insight into the location of the imidazolone in the peptide chain and which oxygen was lost in the initial dehydration reaction. From this analysis, it appears that water loss from the longer protonated polyglycines is predominantly from the central residues.

Isomerization versus dissociation of phenylalanylglycyltryptophan radical cations.

Four isomers of the radical cation of tripeptide phenylalanylglycyltryptophan, in which the initial location of the radical center is well defined, have been isolated and their collision-induced dissociation (CID) spectra examined. These ions, the π-centered [FGWπ˙]+, α-carbon- [FGα˙W]+, N-centered [FGWN˙]+ and ζ-carbon- [Fζ˙GW]+ radical cations, were generated via collision-induced dissociation (CID) of transition metal-ligand-peptide complexes, side chain fragmentation of a π-centered radical cation, homolytic cleavage of a labile nitrogen-nitrogen single bond, and laser induced dissociation of an iodinated peptide, respectively. The π-centered and tryptophan N-centered peptide radical cations produced almost identical CID spectra, despite the different locations of their initial radical sites, which indicated that interconversion between the π-centered and tryptophan N-centered radical cations is facile. By contrast, the α-carbon-glycyl radical [FGα˙W]+, and ζ-phenyl radical [Fζ˙GW]+, featured different dissociation product ions, suggesting that the interconversions among α-carbon, π-centered (or tryptophan N-centered) and ζ-carbon-radical cations have higher barriers than those to dissociation. Density functional theory calculations have been used to perform systematic mechanistic investigations on the interconversions between these isomers and to study selected fragmentation pathways for these isomeric peptide radical cations. The results showed that the energy barrier for interconversion between [FGWπ˙]+ and [FGWN˙]+ is only 31.1 kcal mol-1, much lower than the barriers to their dissociation (40.3 kcal mol-1). For the [FGWπ˙]+, [FGα˙W]+, and [Fζ˙GW]+, the barriers to interconversion are higher than those to dissociation, suggesting that interconversions among these isomers are not competitive with dissociations. The [z3 - H]˙+ ions isolated from [FGα˙W]+ and [Fζ˙GW]+ show distinctly different fragmentation patterns, indicating that the structures of these ions are different and this result is supported by the DFT calculations.

Alkali-Metal-Ion-Assisted Hydrogen Atom Transfer in the Homocysteine Radical.

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.

Transnitrosylation products of the dipeptide cysteinyl-cysteine: an examination by tandem mass spectrometry and density functional theory.

The fragmentation pathways of protonated mono- and di-nitrosylated derivatives from the dipeptide Cys-Cys obtained by electrospray were examined. Protonated mononitrosylated dipeptide upon loss of ˙NO formed a radical cation, which in turn shows two fragment ions, one from the loss of HS˙ and the other from a neutral loss giving a radical cation of formula C2H5NS˙(+). Protonated dinitrosylated dipeptide dissociated by losing both ˙NO molecules, forming a cyclic structure with a vicinal disulfide bridge whose major dissociation channel was the loss of CO. After CO loss, two pathways were observed (loss of NH3 and C2H3NS) which were preceded by proton exchange occurring between one ß-carbon and the nitrogen atom. DFT calculations did not show significant differences in the energies involved for the loss of the NO radical from either of the cysteine residues of the protonated di-nitrosylated dipeptide. Upon loss of the first NO radical, the thiyl radical afforded the vicinal disulfide product with a small barrier through radical substitution of the remaining NO moiety. The calculated relative energy barriers for the different channels are in good agreement with experimental observations. Structures of the ions obtained after dissociation are suggested on the basis of the proposed mechanisms.

Nucleophilic substitution by amide nitrogen in the aromatic rings of [zn - H]˙⁺ ions; the structures of the [b2 - H - 17]˙⁺ and [c1 - 17]⁺ ions.

Peptide radical cations that contain an aromatic amino acid residue cleave to give [zn - H]˙⁺ ions with [b2 - H - 17]˙⁺ and [c1 - 17](+) ions, the dominant products in the dissociation of [zn - H]˙⁺, also present in lower abundance in the CID spectra. Isotopic labeling in the aromatic ring of [Yπ˙GG](+) establishes that in the formation of [b2 - H - 17]˙⁺ ions a hydrogen from the δ-position of the Y residue is lost, indicating that nucleophilic substitution on the aromatic ring has occurred. A preliminary DFT investigation of nine plausible structures for the [c1 - 17](+) ion derived from [Y(π)˙GG](+) shows that two structures resulting from attack on the aromatic ring by oxygen and nitrogen atoms from the peptide backbone have significantly better energies than other isomers. A detailed study of [Y(π)˙GG](+) using two density functionals, B3LYP and M06-2X, with a 6-31++G(d,p) basis set gives a higher barrier for attack on the aromatic ring of the [zn - H]˙⁺ ion by nitrogen than by the carbonyl oxygen. However, subsequent rearrangements involving proton transfers are much higher in energy for the oxygen-substituted isomer leading to the conclusion that the [c1 - 17](+) ions are the products of nucleophilic attack by nitrogen, protonated 2,7-dihydroxyquinoline ions. The [b2 - H - 17]˙⁺ ions are formed by loss of glycine from the same intermediates involved in the formation of the [c1 - 17](+) ions.

Radical-induced dissociation leading to the loss of CO2 from the oxazolone ring of [b5- H]˙(+) ions.

Macrocyclization is commonly observed in large bn(+) (n≥ 4) ions and as a consequence can lead to incorrect protein identification due to sequence scrambling. In this work, the analogous [b5- H]˙(+) radical cations derived from aliphatic hexapeptides (GA5˙(+)) also showed evidence of macrocyclization under CID conditions. However, the major fragmentation for [b5- H]˙(+) ions is the loss of CO2 and not CO loss, which is commonly observed in closed-shell bn(+) ions. Isotopic labeling using CD3 and (18)O revealed that more than one common structure underwent dissociations. Theoretical studies found that the loss of CO2 is radical-driven and is facilitated by the radical being located at the Cα atom immediately adjacent to the oxazolone ring. Comparable energy barriers against macrocyclization, hydrogen-atom transfer, and fragmentations are found by DFT calculations and the results are consistent with the experimental observations that a variety of dissociation products are observed in the CID spectra.

Radical-induced, proton-transfer-driven fragmentations in [b(5)-H]˙(+) ions derived from pentaalanyl tryptophan.

The collision-induced dissociation (CID) of [b5 - H]˙(+) ions containing four alanine residues and one tryptophan give identical spectra regardless of the initial location of the tryptophan indicating that, as proposed for b5(+) ions, sequence scrambling occurs prior to dissociation. Cleavage occurs predominantly at the peptide bonds and at the N-Cα bond of the alanine residue that is attached to the N-terminus of the tryptophan residue. The product of the latter pathway, an ion at m/z 240, is the base peak in all the mass spectra. With the exception of one minor channel giving a b3(+) ion, the product ions retain both the tryptophan residue and the radical. Experiments with one trideuterated alanine established the sequences of loss of alanine residues. Formation of identical products implies a common intermediate, a [b5 - H]˙(+) ion that has a 'linear' structure in which the tryptophan residue is present as an α-radical located in the oxazolone ring, structure Ie. Density functional theory calculations show this structure to be at the global minimum, 14.6 kcal mol(-1) below the macrocyclic structure, ion II. Loss of CO from the [b5 - H]˙(+) ions is inhibited by the presence of the radical centre in the oxazolone ring and migration of the proton from the oxazolone ring onto the peptide backbone induces cleavage of an N-Cα or peptide bond. Three calculated structures for the ion at m/z 240 all have an oxazolone ring. Two of these structures may be formed from Ie, depending upon which proton migrates onto the peptide chain prior to the dissociation. The barrier to interconversion between these two structures requires a 1,3-hydrogen atom shift and is high (51.0 kcal mol(-1)), but both can convert into a third isomer that readily loses CO2 (barrier 38.7 kcal mol(-1)). The lowest barrier to the loss of CO, the usual fragmentation path observed for protonated oxazolones, is 47.0 kcal mol(-1).

Formation, isomerization, and dissociation of ε- and α-carbon-centered tyrosylglycylglycine radical cations.

The fragmentation products of the ε-carbon-centered radical cations [Y(ε)˙LG](+) and [Y(ε)˙GL](+), made by 266 nm laser photolysis of protonated 3-iodotyrosine-containing peptides, are substantially different from those of their π-centered isomers [Y(π)˙LG](+) and [Y(π)˙GL](+), made by dissociative electron transfer from ternary metal-ligand-peptide complexes. For leucine-containing peptides the major pathway for the ε-carbon-centered radical cations is loss of the side chain of the leucine residue forming [YG(α)˙G](+) and [YGG(α)˙](+), whereas for the π-radicals it is the side chain of the tyrosine residue that is lost, giving [G(α)˙LG](+) and [G(α)˙GL](+). The fragmentations of the product ions [YG(α)˙G](+) and [YGG(α)˙](+) are compared with those of the isomeric [Y(ε)˙GG](+) and [Y(π)˙GG](+) ions. The collision-induced spectra of ions [Y(ε)˙GG](+) and [YGG(α)˙](+) are identical, showing that interconversion occurs prior to dissociation. For ions [Y(ε)˙GG](+), [Y(π)˙GG](+) and [YG(α)˙G](+) the dissociation products are all distinctly different, indicating that dissociation occurs more readily than isomerization. Density functional theory calculations at B3LYP/6-31++G(d,p) gave the relative enthalpies (in kcal mol(-1) at 0 K) of the five isomers to be [Y(ε)˙GG](+) 0, [Y(π)˙GG](+) -23.7, [YGG(α)˙](+) -28.7, [YG(α)˙G](+) -31.0 and [Y(α)˙GG](+) -38.5. Migration of an α-C-H atom from the terminal glycine residue to the ε-carbon-centered radical in the tyrosine residue, a 1-11 hydrogen atom shift, has a low barrier, 15.5 kcal mol(-1) above [Y(ε)˙GG](+). By comparison, isomerization of [Y(ε)˙GG](+) to [YG(α)˙G](+) by a 1-8 hydrogen atom migration from the α-C-H atom of the central glycine residue has a much higher barrier (50.6 kcal mol(-1)); similarly conversion of [Y(ε)˙GG](+) into [Y(π)˙GG](+) has a higher energy (24.4 kcal mol(-1)).

Phosphate Migration versus the Loss of Phosphoric Acid in Protonated Phosphopeptides: A Computational Study.

Residue-specific phosphorylation is a protein post-translational modification that regulates cellular functions. Experimental determination of the exact sites of protein phosphorylation provides an understanding of the signaling and processes at work for a given cellular state. Any experimental artifact that involves migration of the phosphate group during measurement is a concern, as the outcome can lead to erroneous conclusions that may confound studies on cellular signal transduction. Herein, we examine computationally the mechanism by which a phosphate group migrates from one serine residue to another serine in monoprotonated pentapeptides [BA-pSer-Gly-Ser-BB + H]+ → [BA-Ser-Gly-pSer-BB + H]+ (where BA and BB are different combinations of the three basic amino acids, histidine, lysine, and arginine). In addition to moving the phosphate group, the overall mechanism involves transferring a proton from the N-terminal amino acid, BA, to the C-terminal amino acid, BB. This is not a synchronous process, and there is a key high-energy intermediate, structure C, that is zwitterionic with both the basic amino acids protonated and the phosphate group attached to both serine residues and carrying a negative charge. The barriers to moving the phosphate group are calculated to be in the range of 219-274 kJ mol-1 at the B3LYP/6-31G(d) level. These barriers are systematically slightly lower and in good agreement with single-point energy calculations at both M06-2X/6-311++G(d,p) and MP2/6-31++G(d,p) levels. The competitive reaction, loss of phosphoric acid from the protonated pentapeptides, has a barrier in the range of 176-202 kJ mol-1 at the B3LYP/6-31G(d) level. Extension of the theory to M06-2X/6-311++G(d,p)//B3LYP/6-31G(d) and MP2/6-31++G(d,p)// B3LYP/6-31G(d) gives higher values for the loss of phosphoric acid, falling in the range of 196-226 kJ mol-1; these are comparable to the barriers against phosphate migration at the same levels of theory. For larger peptides His-pSer-(Gly)n-Ser-His, where n has values from 2 to 5, the barriers against the loss of phosphoric acid are higher than those against the phosphate group migration. This difference is most pronounced and significant when n = 4 and 5 (the differences are approximately 80 kJ mol-1 under the single-point energy calculations at the M06-2X and MP2 levels). Energy differences using two more recent functionals, M08-HX and MN15, on His-pSer-(Gly)n-Ser-His, where n = 1 and 5, are in good agreement with the M06-2X and MP2 calculations. These results provide the mechanistic rationale for phosphate migration versus other competing reactions in the gas phase under tandem mass spectrometry conditions.

Metal ion complexes with HisGly: comparison with PhePhe and PheGly.

Gas-phase complexes of five metal ions with the dipeptide HisGly have been characterized by DFT computations and by infrared multiple photon dissociation spectroscopy (IRMPD) using the free electron laser FELIX. Fine agreement is found in all five cases between the predicted IR spectral features of the lowest energy structures and the observed IRMPD spectra in the diagnostic region 1500-1800 cm(-1), and the agreement is largely satisfactory at longer wavelengths from 1000 to 1500 cm(-1). Weak-binding metal ions (K(+), Ba(2+), and Ca(2+)) predominantly adopt the charge-solvated (CS) mode of chelation involving both carbonyl oxygens, an imidazole nitrogen of the histidine side chain, and possibly the amino nitrogen. Complexes with Mg(2+) and Ni(2+) are found to adopt iminol (Im) binding, involving the deprotonated amide nitrogen, with tetradentate chelation. This tetradentate coordination of Ni(II) is the preferred binding mode in the gas phase, against the expectation under condensed-phase conditions that such binding would be sterically unfavorable and overshadowed by other outcomes such as metal ion hydration and formation of dimeric complexes. The HisGly results are compared with corresponding results for the PheAla, PheGly, and PhePhe ligands, and parallel behavior is seen for the dipeptides with N-terminal Phe versus His residues. An exception is the different chelation pattern determined for PhePhe versus HisGly, reflecting the intercalation-type cation binding pocket of the PhePhe ligand. The complexes group into three well-defined spectroscopic patterns: nickel and magnesium, calcium and barium, and potassium. Factors leading to differentiation of these distinct spectroscopic categories are (1) differing propensities for choosing the iminol binding pattern, and (2) single versus double charge on the metal center. Nickel and magnesium ions show similar gas-phase binding behavior, contrasting with their quite different patterns of peptide interaction in condensed phases.

Amination with Pd-NHC complexes: rate and computational studies involving substituted aniline substrates.

The amination of aryl chlorides with various aniline derivatives using the N-heterocyclic carbene-based Pd complexes Pd-PEPPSI-IPr and Pd-PEPPSI-IPent (PEPPSI=pyridine, enhanced precatalyst, preparation, stabilization, and initiation; IPr=diisopropylphenylimidazolium derivative; IPent= diisopentylphenylimidazolium derivative) has been studied. Rate studies have shown a reliance on the aryl chloride to be electron poor, although oxidative addition is not rate limiting. Anilines couple best when they are electron rich, which would seem to discount deprotonation of the intermediate metal ammonium complex as being rate limiting in favour of reductive elimination. In previous studies with secondary amines using PEPPSI complexes, deprotonation was proposed to be the slow step in the cycle. These experimental findings relating to mechanism were corroborated by computation. Pd-PEPPSI-IPr and the more hindered Pd-PEPPSI-IPent catalysts were used to couple deactivated aryl chlorides with electron poor anilines; while the IPr catalysis was sluggish, the IPent catalyst performed extremely well, again showing the high reactivity of this broadly useful catalyst.

Infrared multiple-photon dissociation spectroscopy of tripositive ions: lanthanum-tryptophan complexes.

Collision-induced charge disproportionation limits the stability of triply charged metal ion complexes and has thus far prevented successful acquisition of their gas-phase IR spectra. This has curtailed our understanding of the structures of triply charged metal complexes in the gas phase and in biological environments. Herein we report the first gas-phase IR spectra of triply charged La(III) complexes with a derivative of tryptophan (N-acetyl tryptophan methyl ester), and an unusual dissociation product, a lanthanum amidate. These spectra are compared with those predicted using density functional theory. The best structures are those of the lowest energies that differ by details in the π-interaction between La(3+) and the indole rings. Other binding sites on the tryptophan derivative are the carbonyl oxygens. In the lanthanum amidate, La(3+) replaces an H(+) in the amide bond of the tryptophan derivative.

Intramolecular hydrogen atom migration along the backbone of cationic and neutral radical tripeptides and subsequent radical-induced dissociations.

Dissociation of peptide radical ions involves competition between charge-induced and radical-induced reactions that can be preceded by isomerization. The isomeric radical cations of the peptide methyl ester [G˙GR-OMe](+) and [GG˙R-OMe](+) provide very similar collision-induced dissociation (CID) spectra, suggesting that isomerization occurs prior to fragmentation. They undergo characteristic radical-induced bond cleavage of the peptide N-terminal amide bond resulting in the y2(+) ion, and of the arginine side-chain's Cα-Cß bond giving protonated allylguanidine {[CH2[double bond, length as m-dash]CHCH2NHC(NH2)2](+), m/z 100}. The absence of a y2(+) fragment ion in the CID of the radical cationic tripeptide [ACH3G˙R](+) and of an m/z 100 ion in the spectrum of [G˙ACH3R](+) (where ACH3 is an α-aminoisobutyric acid residue, which cannot form an α-carbon-centered radical through hydrogen atom transfer) establishes the importance of hydrogen atom migration along the peptide backbone prior to specific radical-induced fragmentations. Herein we use density functional theory (DFT) at the B3LYP/6-31++G(d,p) level to evaluate the barriers for interconversion between the α-carbon-centered radicals and for dissociation. The radical cations [G˙GR](+) and [GG˙R](+) have their radicals located on the α-carbon atoms of the peptide backbone and their charge densities largely sequestered on the guanidine groups of the side-chain of arginine residues. This is in contrast to the isomeric radical cations of [GGG]˙(+), in which the charge resides necessarily on the peptide backbone. The lower charge densities on the backbones of [G˙GR](+) and [GG˙R](+) result in greater structural flexibility, decreasing the barrier for interconversion between these α-carbon-centered radicals to 36.2 kcal mol(-1) (cf. 44.7 kcal mol(-1) for [GGG]˙(+)). The total absence of charge, assessed by examining intramolecular hydrogen atom transfers among the three α-carbon centers of the isomeric neutral α-carbon-centered triglycine radicals [GGG-H]˙, leads to an additional but slight reduction in enthalpy, to approximately 34 kcal mol(-1).

Amination with Pd-NHC complexes: rate and computational studies on the effects of the oxidative addition partner.

Pd-PEPPSI-IPent, a recently-developed N-heterocyclic carbene (NHC) complex, has been evaluated in amination reactions with secondary amines and it has shown superb reactivity under the most mildly basic reaction conditions. Rate and computational studies were conducted to provide insight into the mechanism of the transformation. The IPent catalyst coordinates to the amine much more strongly than the IPr variant, thus favouring deprotonation with comparatively weak bases. Indeed the reaction is first order in base and only slightly more than zeroth order in amine.

Glutathione radical cation in the gas phase; generation, structure and fragmentation.

Two different chemical methods have been used to form glutathione radical cations: (1) collision-induced dissociations (CIDs) of the ternary complex [Cu(II)(tpy)(M)]˙(2+) (M = GSH, tpy = 2,2':6',2''-terpyridine) and (2) homolysis of the S-NO bond in protonated S-nitrosoglutathione. The radical cations, M˙(+), were trapped and additional CIDs were performed. They gave virtually identical CID spectra, suggesting a facile interconversion between initial structures prior to fragmentation. DFT calculations at the B3LYP/6-31++G(d,p) level of theory have been used to study interconversion between different isomers of the glutathione radical cation and to examine mechanisms by which these ions fragment. The N-terminal α-carbon-centred radical cation, strongly stabilized by the captodative effect, is at the global minimum, which is 8.5 kcal mol(-1) lower in enthalpy than the lowest energy conformer of the S-centred radical cation. The barrier against interconversion is 18.1 kcal mol(-1) above the S-centred radical.

Doubly charged protonated a ions derived from small peptides.

Protonated a(2) and a(3) (therefore doubly charged) ions in which both charges lie on the peptide backbone are formed in collision-induced dissociations of [La(III)(peptide)(CH(3)CN)(m)](3+) complexes. Abundant (a(3)+H)(2+) ions are formed from triproline (PPP) and peptides with a proline residue at the N-terminus; these peptides are the most effective in producing ions of the type (a(2)+H)(2+) and (a(3)+H)(2+). A systematic study of the effect of the location of the proline residue and other residues of aliphatic amino acids on the generation of protonated a ions is reported. Density functional theory calculations at B3LYP/6-311++G(d,p) gave the proton affinity of the a(3) ion derived from PPP to be 167.6 kcal mol(-1), 2.6 kcal mol(-1) higher than that of water. The protonated a(2) ions of diglycine and diproline and a(3) ions of triglycine have lower proton affinities and are only observed in lower abundances, possibly due to proton transfer to water in ion-molecule reactions.

Structure of the [M + H - H2O]+ ion from tetraglycine: a revisit by means of density functional theory and isotope labeling.

Collision-induced dissociations of protonated (18)O-labeled tetraglycines labeled separately at either the first or the second amide bond established that water loss from the backbone occurs from the N-terminal residue. Density functional theory at B3LYP/6-311++G(d,p) predicted that the low-energy [G(4) + H - H(2)O](+) product ion is an N(1)-protonated 3,5-dihydro-4H-imidazol-4-one. The ion at the lowest energy, III, is 24.8 kcal mol(-1) lower than the protonated oxazole structure, II, proposed by Bythell et al. (J. Phys. Chem A2010, 114, 5076-5082). In addition, structure III has a predicted IR spectrum that provides a better match with the published experimental IRMPD spectrum than that of structure II.

Cations Derived from Fentanyls Generated by Atmospheric Pressure Photoionization in the Presence of Ammonia: An IMS-MS Study.

A set of fentanyl molecules when subjected to vacuum UV atmospheric pressure photoionization (VUV-APPI) in the presence of dopants (ammonia and anisole) shows two major bands in the ion mobility-mass spectrometry (IMS-MS) spectrum corresponding to (a) the protonated fentanyl, [M+H]+ and (b) a unique [M-74]+ ion. For the parent fentanyl, the [M-74]+ ion is at m/z 262 but, in the absence of ammonia, the product ion is shifted to m/z 245, corresponding to a difference of NH3. Collision-induced dissociations (CID) of the [M-74]+ ions for all the different fentanyls examined here show the same pattern of neutral losses, namely NH3 and HN=CH2, and the dominant product ion is at m/z 84 (shifted to m/z 98 for 3-methylfentanyl and m/z 142 and 231 for carfentanyl). Dissociation of the [M-74-NH3]+ ion derived from the fentanyls yields the same product ions as found in the electron impact (EI) ionization spectra of the fentanyls. The dissociation products of the [M-74-HN=CH2]+ ion are different, include the ion at m/z 84, and correspond to the fragmentation products of protonated norfentanyls. Theoretical modeling supports the opening of new fragmentation channels as a result of the reaction of the initially formed iminium cation with ammonia at atmospheric pressure.