Differentiation between Isomeric 4,5-Functionalized 1,2,3-Thiadiazoles and 1,2,3-Triazoles by ESI-HRMS and IR Ion Spectroscopy.

A large variety of 1,2,3-thiadiazoles and 1,2,3-triazoles are used extensively in modern pure and applied organic chemistry as important structural blocks of numerous valuable products. Creation of new methods of synthesis of these isomeric compounds requires the development of reliable analytical tools to reveal the structural characteristics of these novel compounds, which are able to distinguish between isomers. Mass spectrometry (MS) is a clear choice for this task due to its selectivity, sensitivity, informational capacity, and reliability.

Ion-molecule reactions of mass-selected ions.

Gas-phase reactions of mass-selected ions with neutrals covers a very broad area of fundamental and applied mass spectrometry (MS). Oftentimes, ion-molecule reactions (IMR) can serve as a viable alternative to collision-induced dissociation and other ion dissociation techniques when using tandem MS. This review focuses on the literature pertaining applications of IMR since 2013.

Generation, Characterization, and Dissociation of Radical Cations Derived from Prolyl-glycyl-glycine.

Radical cations of an aliphatic tripeptide prolyl-glycyl-glycine (PGG) and its sequence ions [a + H] and [b - H] have been generated by collision-induced dissociation of the [Cu(Phen)(PGG)] complex, where Phen = 1,10-phenanthroline. Infrared multiple photon dissociation spectroscopy, ion-molecule reaction experiments, and theoretical calculations have been used to investigate the structures of these ions. The unpaired electron in these three radical cations is located at different α-carbons.

Role of Ligand in the Selective Production of Hydrogen from Formic Acid Catalysed by the Mononuclear Cationic Zinc Complexes [(L)Zn(H)] (L=tpy, phen, and bpy).

A series of zinc-based catalysts was evaluated for their efficiency in decomposing formic acid into molecular hydrogen and carbon dioxide in the gas phase using quadrupole ion trap mass spectrometry experiments. The effectiveness of the catalysts in the series [(L)Zn(H)] , where L=2,2':6',2''-terpyridine (tpy), 1,10-phenanthroline (phen) or 2,2'-bipyrydine (bpy), was found to depend on the ligand used, which turned out to be fundamental in tuning the catalytic properties of the zinc complex. Specifically, [(tpy)Zn(H)] displayed the fastest reaction with formic acid proceeding by dehydrogenation to produce the zinc formate complex [(tpy)Zn(O CH)] and H .

Gas-phase functionalized carbon-carbon coupling reactions catalyzed by Ni (II) complexes.

Gas-phase C-C coupling reactions mediated by Ni (II) complexes were studied using a linear quadrupole ion trap mass spectrometer. Ternary nickel cationic carboxylate complexes, [(phen)Ni (OOCR )] (where phen = 1,10-phenanthroline), were formed by electrospray ionization. Upon collision-induced dissociation (CID), they extrude CO forming the organometallic cation [(phen)Ni(R )] , which undergoes gas-phase ion-molecule reactions (IMR) with acetate esters CH COOR to yield the acetate complex [(phen)Ni (OOCCH )] and a C-C coupling product R -R .

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-NH] , was observed from the copper complex.

Near-UV Water Splitting by Cu, Ni, and Co Complexes in the Gas Phase.

(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)M(NO)] 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 + HO] 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.

Ligand-induced decarbonylation in diphosphine-ligated palladium acetates [CHCOPd((PR)CH)] (R = Me and Ph).

A new decarbonylation reaction is observed for [(K-acetate)Pd(K-diphosphine)] complexes. Gas-phase IR experiments identify the product as [CHPd(OP(Ph)CHPPh)]. DFT calculations uncovered a plausible mechanism involving O atom abstraction by the diphosphine ligand within the coordination sphere to yield the acetyl complex, [CHCOPd(OP(Ph)CHPPh)], which then undergoes decarbonylation.

Experimental Evidence for Noncanonical Thymine Cation Radicals in the Gas Phase.

Thymine cation radicals were generated in the gas phase by collision-induced intramolecular electron transfer in [Cu(2,2':6,2″-terpyridine)(thymine)] complexes and characterized by ion-molecule reactions, UV-vis photodissociation action spectroscopy, and ab initio and density functional theory calculations. The experimental results indicated the formation of a tautomer mixture consisting chiefly (77%) of noncanonical tautomers with a C-7-H group. The canonical 2,4-dioxo-N-1,N-3-H isomer was formed as a minor component at ca.

Cytosine Radical Cations: A Gas-Phase Study Combining IRMPD Spectroscopy, UVPD Spectroscopy, Ion-Molecule Reactions, and Theoretical Calculations.

The radical cation of cytosine (Cyt ) is generated by dissociative oxidation from a ternary Cu complex in the gas phase. The radical cation is characterized by infrared multiple photon dissociation (IRMPD) spectroscopy in the fingerprint region, UV/Vis photodissociation (UVPD) spectroscopy, ion-molecule reactions, and theoretical calculations (density functional theory and ab initio). The experimental IRMPD spectrum features diagnostic bands for two enol-amino and two keto-amino tautomers of Cyt that are calculated to be among the lowest energy isomers, in agreement with a previous study.

Role of Hydrogen Bonding on the Reactivity of Thiyl Radicals: A Mass Spectrometric and Computational Study Using the Distonic Radical Ion Approach.

Experimental and computational quantum chemistry investigations of the gas-phase ion-molecule reactions between the distonic ions HN(CH)S (n = 2-4) and the reagents dimethyl disulfide, allyl bromide, and allyl iodide demonstrate that intramolecular hydrogen bonding can modulate the reactivity of thiyl radicals. Thus, the 3-ammonium-1-propanethiyl radical (n = 3) exhibits the lowest reactivity of these distonic ions toward all substrates. Theoretical calculations on this distonic ion highlight that its most stable conformation involves a six-membered ring configuration, and that it has the strongest intramolecular hydrogen bond.

Cysteine Radical/Metal Ion Adducts: A Gas-Phase Structural Elucidation and Reactivity Study.

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 C -based radicals, but they are not observed experimentally owing to the barriers associated with the hydrogen-atom transfer.

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.

Gas-phase tyrosine-to-cysteine radical migration in model systems.

Radical migration, both intramolecular and intermolecular, from the tyrosine phenoxyl radical Tyr(O(∙)) to the cysteine radical Cys(S(∙)) in model peptide systems was observed in the gas phase. Ion-molecule reactions (IMRs) between the radical cation of homotyrosine and propyl thiol resulted in a fast hydrogen atom transfer. In addition, radical cations of the peptide LysTyrCys were formed via two different methods, affording regiospecific production of Tyr(O(∙)) or Cys(S(∙)) radicals.

Investigation of Fragmentation of Tryptophan Nitrogen Radical Cation.

This work describes investigation of the fragmentation mechanism of tryptophan N-indolyl radical cation, H3N(+)-TrpN(•) (m/z 204) studied via DFT calculations and several gas-phase experimental techniques. The main fragment ion at m/z 131, shown to be a mixture of up to four isomers including 3-methylindole (3MI) π-radical cation, was found to undergo further loss of an H atom to yield one of the two isomeric m/z 130 ions. 3-Methylindole radical cation generated independently (via CID of [Cu(II)(terpy)3MI](•2+)) displayed gas-phase reactivity partially similar to that of the m/z 131 fragment, further confirming our proposed mechanism.

Evaluation of various silicon-and boron-containing compounds for the detection of phosphorylation in peptides via gas-phase ion-molecule reactions.

Gas-phase ion-molecule reactions [IMR] of various boron- and silicon-containing neutrals were investigated as a potential route for detecting phosphorylation within peptides in the negative ion mode. Trimethyl borate (TMB), triethyl borate (TEB) and N,O- Bis(trimethylsilyl)acetamide (TMSA), unlike diethylmethoxyborane (DEMB), diisopropoxymethylborane [DiPMB] and chlorotrimethylsi- Lane (TMSCIL], reacted differently if a phosphate moiety was present and thus are suitable to detect phosphorylation. During multistage collision-induced dissociation experiments of the reaction products of IMR with TMB and TEB, the [LSsF - 4H + B]- ion formed a modified y2 fragment allowing the phosphorylation site to be assigned, unlike reaction products of DEMB and DiPMB which lost both the phos- phoric acid and the boron-containing moiety.

Utilisation of gas-phase ion-molecule reactions for differentiation between phospho- and sulfocarbohydrates.

Gas-phase ion-molecule reactions of four boron-containing neutrals were explored as a means for differentiation between isobaric phospho- and sulfocarbohydrates. Phosphorylation and sulfation impose an addition of 80 Da to the molecular mass, so for low-resolution mass spectrometers compounds that have such modifications will appear at the same nominal mass-to-charge (m/z) ratio. However, the ions of these isobaric species behave differently in ion-molecule reactions.

MS/MS fragmentation behavior study of meso-phenylporphyrinoids containing nonpyrrolic heterocycles and meso-thienyl-substituted porphyrins.

Free base and cobalt(II) complexes of six meso-tetraphenylporphyrinoids containing nonpyrrolic heterocycles and of three meso-thienylporphyrins were investigated using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Their fragmentation was studied in a quadrupole ion trap as a function of the porphyrinoid macrocycle structure and compared with the fragmentation behavior of the benchmark compound meso-tetraphenylporphyrin. In situ oxidation of the neutral cobalt(II) complexes under ESI conditions produced singly charged cobalt(III) porphyrinoid ions; the free bases were ionized by protonation.

Structure and Reactivity of the Glutathione Radical Cation: Radical Rearrangement from the Cysteine Sulfur to the Glutamic Acid α-Carbon Atom.

A gas-phase radical rearrangement through intramolecular hydrogen-atom transfer (HAT) was studied in the glutathione radical cation, [γ-ECG] , which was generated by a homolytic cleavage of the protonated S-nitrosoglutathione. Ion-molecule reactions suggested that the radical migrates from the original sulfur position to one of the α-carbon atoms. Experiments on the radical cations of dipeptides derived from the glutathione sequence, [γ-EC] and [CG] , pointed to the glutamic acid α-carbon atom as the most likely site of the radical migration.

Structure and reactivity of the distonic and aromatic radical cations of tryptophan.

In this work, we regiospecifically generate and compare the gas-phase properties of two isomeric forms of tryptophan radical cations-a distonic indolyl N-radical (H3N(+) - TrpN(•)) and a canonical aromatic π (Trp(•+)) radical cation. The distonic radical cation was generated by nitrosylating the indole nitrogen of tryptophan in solution followed by collision-induced dissociation (CID) of the resulting protonated N-nitroso tryptophan. The π-radical cation was produced via CID of the ternary [Cu(II)(terpy)(Trp)](•2+) complex.

Structure and reactivity of homocysteine radical cation in the gas phase studied by ion-molecule reactions and infrared multiple photon dissociation.

The reactivity of the cysteine (Cys) and homocysteine (Hcy) radical cation was studied using ion-molecule reactions. The radical cations were generated via collision-induced dissociation (CID) of their S-nitrosylated precursors. Cleavage of the S-NO bond led to the formation of the radical initially positioned on the sulfur atom.

Erratum to: Axial imidazole binding strengths in porphyrinoid cobalt(III) complexes as studied by tandem mass spectrometry.

The Co(II) complexes of twelve meso-tetraaryl-porphyrins, -chlorins, and chlorin analogues containing non-pyrrolic heterocycles were synthesized and converted in situ to the corresponding Co(III) complexes coordinated to one or two imidazoles. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) in conjunction with the energy-variable collision-induced dissociation (CID) technique was used to compare the relative gas-phase binding strength of the axially coordinated imidazoles to the octahedral and square planar Co(III) porphyrinoid complex ions. The observed binding energies of these ligands were rationalized in terms of the effects of porphyrinoid core structure and meso-substitution on the electron density on the central Co(III) centers.