Search

Multistage mass spectrometry experiments, isotope labelling and DFT calculations were used to explore whether selective decarbonylation of formic acid could be mediated by molybdate anions [(MoO3)x(OH)]- (x = 1 and 2) via a formal catalytic cycle involving two steps. In step 1, both molybdate anions undergo gas-phase ion-molecule reactions (IMR) with formic acid to produce the coordinated formates [(MoO3)x(O2CH)]- and H2O. In step 2, both coordinated formates [(MoO3)x(O2CH)]- undergo decarbonylation under collision-induced dissociation (CID) conditions to reform the molybdate anions [(MoO3)x(OH)]- (x = 1 and 2), thus closing a formal catalytic cycle. In the case of [MoO3(O2CH)]- an additional decarboxylation channel also occurs to yield [MoO3(H)]-, which is unreactive towards formic acid. The reaction between [Mo18O3(18OH)]- and formic acid gives rise to [Mo18O3(O2CH)]- highlighting that ligand substitution occurs without 18O/16O exchange between the coordinated 18OH ligand and HC16O2H. The reaction between [(MoO3)x(OD)]- (x = 1 and 2) and DCO2H initially produces [(MoO3)x(OH)]- (x = 1 and 2), indicating that D/H exchange occurs. DFT calculations were carried out to investigate the reaction mechanisms and energetics associated with both steps of the formal catalytic cycle and to better understand the competition between decarbonylation and decarboxylation, which is crucial in developing a selective catalyst. The CO and CO2 loss channels from the monomolybdate anion [MoO3(O2CH)]- have similar barrier heights which is in agreement with experimental results where both fragmentation channels are observed. In contrast, the dimolybdate anion is more selective, since the decarbonylation pathway of [(MoO3)2(O2CH)]- is both kinetically and thermodynamically favoured, which agrees with experimental observations where the CO loss channel is solely observed.

A near thermal two-step catalytic cycle for the selective release of hydrogen from formic acid by mononuclear cuprate anions was revealed using multistage mass spectrometry experiments, deuterium labelling and DFT calculations. In gas-phase ion-molecule reactions, mononuclear copper hydride anions [(L)Cu(H)]- (where L = H-, O2CH-, BH4- and CN-) were found to react with formic acid (HCO2H) to yield [(L)Cu(O2CH)]- and H2. The copper formate anions [(L)Cu(O2CH)]- can decarboxylate via collision-induced dissociation (CID) to reform the copper hydride [(L)Cu(H)]-, thereby closing the two-step catalytic cycle. Analogous labelling experiments with d1-formic acid (DCO2H) reveal that the decarboxylation process also occurs spontaneously. A kinetic study was carried out to provide further insights into the species involved in this reaction. Energetics from density functional theory (DFT) calculations show that the key decarboxylation step can occur without CID, thus in support of experimental observations.

The wide availability, ease of handling and structural and functional diversity make carboxylic acids prized building blocks in organic synthesis. The past two decades has seen an explosion of interest in the development of new modes of reactivity of carboxylic acids and their derivatives. Of these, metal‐mediated decarboxylation reactions are attractive as they produce organometallic intermediates that can subsequently be used in C−X (where X=C, N, S etc) bond coupling reactions. Here the results of mechanistic studies integrating both gas‐ and condensed‐phase work are described for development of new extrusion‐insertion (ExIn) classes of reactions for the synthesis of amides, thioamides, amidines, alkenes and ketones from arylcarboxylic acids and suitable (hetero)cumulenes.

High-valent tetraalkylcuprates(iii) and -argentates(iii) are key intermediates of copper- and silver-mediated C-C coupling reactions. Here, we investigate the previously reported contrasting reactivity of [RMiii Me3 ]- complexes (M=Cu, Ag and R=allyl) with energy-dependent collision-induced dissociation experiments, advanced quantum-chemical calculations and kinetic computations. The gas-phase fragmentation experiments confirmed the preferred formation of the [RCuMe]- anion upon collisional activation of the cuprate(iii) species, consistent with a homo-coupling reaction, whereas the silver analogue primarily yielded [AgMe2 ]- , consistent with a cross-coupling reaction. For both complexes, density functional theory calculations identified one mechanism for homo coupling and four different ones for cross coupling. Of these pathways, an unprecedented concerted outer-sphere cross coupling is of particular interest, because it can explain the formation of [AgMe2 ]- from the argentate(iii) species. Remarkably, the different C-C coupling propensities of the two [RMiii Me3 ]- complexes become only apparent when properly accounting for the multi-configurational character of the wave function for the key transition state of [RAgMe3 ]- . Backed by the obtained detailed mechanistic insight for the gas-phase reactions, we propose that the previously observed cross-coupling reaction of the silver complex in solution proceeds via the outer-sphere mechanism.

The gas-phase extrusion–insertion (ExIn) reactions of the palladium complexes [(phen)nPd (O2SC6H5)]+ (phen = 1,10-phenanthroline, n = 1 or 2), were investigated in the gas phase by multistage mass spectrometry (MSn) experiments consisting of electrospray ionisation and a linear ion trap combined with density functional theory (DFT) calculations. Desulfination of palladium sulfinate cations under collision-induced dissociation (CID) generates the organopalladium intermediates [(phen)nPd(C6H5)]+. Of these two organometallic cations, only [(phen)Pd(C6H5)]+ reacts with phenyl isocyanate via insertion to yield [(phen)Pd(NPhC(O)C6H5)]+. The formation of a coordinated amidate anion is supported by DFT calculations. In exploring this reactivity in the solution phase, we found that heating a mixture of benzenesulfinic acid, phenylisocyanate and palladium trifluoroacetate under a range of different conditions (ligand free versus with ligand, different solvents, addition of acid or base) failed to lead to the formation N-phenyl-benzamide in all cases. Instead, biphenyl was formed and could be isolated in a yield of 46%. DFT calculations using a solvent continuum reveal that the barrier associated with the insertion reaction lies above the competing sequential reactions of desulfination of a second phenyl sulfinate followed by reductive elimination of biphenyl.

Copper(I) borohydride ate complexes of the type Cat+[XCu(BH4)]- have been previously postulated as intermediates in the reactions of copper salts with borohydride. Negative ion electrospray ionization of an acetonitrile solution of copper(I) phenylacetylide with a 10-fold excess of sodium borohydride (NaBH4) revealed the formation of a diverse range of mononuclear, dinuclear and trinuclear cuprates with different numbers of BH4-, H- and CN- ligands, the latter likely being formed by abstraction of CN- from the acetonitrile solvent. Collision-induced dissociation was used to examine the fragmentation reactions of the following borohydride containing cuprates: [Cu(H)(BH4)]-, [Cu(BH4)2]-, [Cu(BH4)(CN)]-, [Cu2(H)(BH4)2]-, [Cu2(H)2(BH4)]-, [Cu2(BH4)2(CN)]-, [Cu2(H)(BH4)(CN)]-, [Cu3(H)(BH4)3]-, [Cu3(H)2(BH4)2]-, [Cu3(H)3(BH4)]-, [Cu3(BH4)2(CN)2]-, and [Cu3(H)(BH4)2(CN)]-. In all cases, BH3 loss is observed. For many of the dinuclear and trinuclear complexes cluster fragmentation by loss of CuH was also observed. In the case of [Cu2(H)2(BH4)]- and [Cu3(H)3(BH4)]-, loss of H2 was also observed. DFT calculations were used to explore potential structures of the various borohydride-containing cuprates and to predict the overall reaction energetics for the various fragmentation channels.

Gas-phase ion-ion reactions between tris-1,10-phenantholine metal dications, [(phen)3M]2+ (where M = Ni and Mg), and the tetraphenylborate anion yield the ion-pairs {[(phen)3M]2+[BPh4]-}+. The ion-pairs undergo transmetalation upon loss of a phen ligand to give the organometallic complexes [(phen)2M(Ph)]+. DFT calculations, used to determine the energy barriers for the transmetalation reactions and the hydrolysis reactions, are entirely consistent with the experimental results.

The metastable trilacunary heteropolyoxomolybdate [PMo9O31(py)3]3- - {PMo9}; py = pyridine) and the ditopic pyridyl bearing diarylethene (DAE) (C25H16N2F6S2) self-assemble via a facile ligand replacement methodology to yield the photo-active molecular capsule [(PMo9O31)2(DAE)3]6-. The spatial arrangement and conformation of the three DAE ligands are directed by the surface chemistry of the molecular metal oxide precursor with exclusive ligation of the photo-active antiparallel rotamer to the polyoxometalate (POM) while the integrity of the assembly in solution has been verified by a suite of spectroscopic techniques. Electrocyclisation of the three DAEs occurs sequentially and has been investigated using a combination of steady-state and time-resolved spectroscopies with the discovery of a photochemical cascade whereby rapid photoinduced ring closure is followed by electron transfer from the ring-closed DAE to the POM in the latent donor-acceptor system on subsequent excitation. This interpretation is also supported by computational and detailed spectroelectrochemical analysis. Ring-closing quantum yields were also determined using a custom quantum yield determination setup (QYDS), providing insight into the impact of POM coordination on these processes.

Deoxygenation and subsequent cracking of fatty acids are key steps in production of biodiesel fuels from renewable plant sources. Despite the fact that multiple catalysts, including those containing group 10 metals (Ni, Pd, and Pt), are employed for these purposes, little is known about the mechanisms by which they operate. In this work, we utilized tandem mass spectrometry experiments (MSn) to show that multiple types of fatty acids (saturated, mono-, and poly-unsaturated) can be catalytically deoxygenated and converted to smaller hydrocarbons using the ternary metal complexes [(phen)M(O2CR)]+], where phen = 1,10-phenanthroline and M = Ni, Pd, and Pt. The mechanistic description of deoxygenation/cracking processes builds on our recent works describing simple model systems for deoxygenation and cracking, where the latter comes from the ability of group 10 metal ions to undergo chain-walking with very low activation barriers. This article extends our previous work to a number of fatty acids commonly found in renewable plant sources. We found that in many unsaturated acids cracking can occur prior to deoxygenation and show that mechanisms involving group 10 metals differ from long-known charge-remote fragmentation reactions.

Electrospray ionization-mass spectrometry (ESI-MS) of mixtures of AgBF4 or AgNO3 with the capping ligand bis(diphenylarsino)methane ((Ph2 As)2 CH2 = dpam) in a solution of acetonitrile revealed the formation of the following cations: [Ag(CH3 CN)(dpam)]+ , [Ag(dpam)2 ]+ , [Ag2 (Cl)(dpam)2 ]+ , and [Ag3 (Cl)2 (dpam)3 ]+ . Addition of NaBH4 to these solutions results in the formation of the cluster cations [Ag2 (BH4 )(dpam)2 ]+ , [Ag2 (BH4 )(dpam)3 ]+ , [Ag3 (H)(BH4 )(dpam)3 ]+ , [Ag3 (BH4 )2 (dpam)3 ]+ , [Ag3 (H)(Cl)(dpam)3 ]+ , and [Ag3 (I)(BH4 )(dpam)3 ]+ , as established by ESI-MS. Use of NaBD4 confirmed that borohydride is the source of the hydride in these clusters. An Orbitrap Fusion LUMOS mass spectrometer was used to explore the gas-phase unimolecular chemistry of selected clusters via multistage mass spectrometry (MSn ) experiments employing low-energy collision-induced dissociation (CID) and high-energy collision-induced dissociation (HCD) experiments. The borohydride containing clusters fragment via two competing pathways: (i) ligand loss and (ii) B-H bond activation involving BH3 loss. Density functional theory (DFT) calculations were used to calculate the energetics of the optimized structures for all precursor ions, fragment ions, and neutrals and to estimate the reaction endothermicities. Generally, there is reasonable agreement between the most abundant product ion formed and the predicted endothermicity of the associated reaction channel. The DFT calculations predicted that the novel dimer [Ag2 (BH4 )(dpam)2 ]+ has a paddlewheel structure in which the dpam and BH4 - ligands bridge both silver centers.

The gas-phase extrusion-insertion reactions of the copper complex [bathophenanthroline (Bphen)CuI (O2 CC6 H5 )]2- , generated via electrospray ionization, was studied in a linear ion trap mass spectrometer with the combination of collision-induced dissociation (CID) and ion-molecule reaction (IMR) events. Multistage mass spectrometry (MSn ) experiments and density functional theory (DFT) demonstrated that extrusion of carbon dioxide from [(Bphen)Cu(O2 CC6 H5 )]2- (CID) gives the organometallic intermediate [(Bphen)Cu(C6 H5 )]2- , which subsequently reacts with carbon disulfide (IMR) via insertion to yield [(Bphen)Cu (SC(S)C6 H5 )]2- . The fragmentation of the product ion resulted in the formation of [Bphen]2- , [(Bphen)Cu]- and C6 H5 CS2 - under CID conditions. The formation of the latter two charge separation products thus provides evidence of C-C bond formation in the IMR step. Although analogous studies with isocyanate, which is isoelectronic with CS2 , showed a poor reactivity in the gas phase, the mechanistic understanding obtained from these model studies encourages future development of a solution phase protocol for the synthesis of amides from carboxylic acids and isocyanates mediated by copper(I) complexes.

Using fatty acids as renewable sources of biofuels requires deoxygenation. While a number of promising catalysts have been developed to achieve this, their operating mechanisms are poorly understood. Here, model molecular systems are studied in the gas phase using mass spectrometry experiments and DFT calculations. The coordinated metal complexes [(phen)M(O2CR)]+ (where phen=1,10‐phenanthroline; M=Ni or Pd; R=CnH2n+1, n≥2) are formed via electrospray ionization. Their collision‐induced dissociation (CID) initiates deoxygenation via loss of CO2 and [C,H2,O2]. The CID spectrum of the stearate complexes (R=C17H35) also shows a series of cations [(phen)M(R’)]+ (where R’ < C17) separated by 14 Da (CH2) corresponding to losses of C2H4‐C16H32 (cracking products). Sequential CID of [(phen)M(R’)]+ ultimately leads to [(phen)M(H)]+ and [(phen)M(CH3)]+, both of which react with volatile carboxylic acids, RCO2H, (acetic, propionic, and butyric) to reform the coordinated carboxylate complexes [(phen)M(O2CR)]+. In contrast, cracking products with longer carbon chains, [(phen)M(R)]+ (R>C2), were unreactive towards these carboxylic acids. DFT calculations are consistent with these results and reveal that the approach of the carboxylic acid to the “free” coordination site is blocked by agostic interactions for R > CH3.

Porphyromonas gingivalis and Tannerella forsythia use the type IX secretion system to secrete cargo proteins to the cell surface where they are anchored via glycolipids. In P. gingivalis, the glycolipid is anionic lipopolysaccharide (A-LPS), of partially known structure. Modified cargo proteins were deglycosylated using trifluoromethanesulfonic acid and digested with trypsin or proteinase K. The residual modifications were then extensively analyzed by tandem mass spectrometry. The C terminus of each cargo protein was amide-bonded to a linking sugar whose structure was deduced to be 2-N-seryl, 3-N-acetylglucuronamide in P. gingivalis and 2-N-glycyl, 3-N-acetylmannuronic acid in T. forsythia The structures indicated the involvement of the Wbp pathway to produce 2,3-di-N-acetylglucuronic acid and a WbpS amidotransferase to produce the uronamide form of this sugar in P. gingivalis The wbpS gene was identified as PGN_1234 as its deletion resulted in the inability to produce the uronamide. In addition, the P. gingivalisvimA mutant which lacks A-LPS was successfully complemented by the T. forsythiavimA gene; however, the linking sugar was altered to include glycine rather than serine. After removal of the acetyl group at C-2 by the putative deacetylase, VimE, VimA presumably transfers the amino acid to complete the biosynthesis. The data explain all the enzyme activities required for the biosynthesis of the linking sugar accounting for six A-LPS-specific genes. The linking sugar is therefore the key compound that enables the attachment of cargo proteins in P. gingivalis and T. forsythia We propose to designate this novel linking sugar biosynthetic pathway the Wbp/Vim pathway.IMPORTANCEPorphyromonas gingivalis and Tannerella forsythia, two pathogens associated with severe gum disease, use the type IX secretion system (T9SS) to secrete and attach toxic arrays of virulence factor proteins to their cell surfaces. The proteins are tethered to the outer membrane via glycolipid a

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(O2 CH)]+ and H2 . The catalysts [(L)Zn(H)]+ are reformed by decarboxylating the zinc formate complexes [(L)Zn(O2 CH)]+ by collision-induced dissociation, which is the only reaction channel for each of the ligands used. The decarboxylation reaction was found to be reversible, since the zinc hydride complexes [(L)Zn(H)]+ react with carbon dioxide yielding the zinc formate complex. This reaction was again substantially faster for L=tpy than L=phen or bpy. The energetics and mechanisms of these processes were modelled using several levels of density functional theory (DFT) calculations. Experimental results are fully supported by the computational predictions.

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 (OOCR1 )]+ (where phen = 1,10-phenanthroline), were formed by electrospray ionization. Upon collision-induced dissociation (CID), they extrude CO2 forming the organometallic cation [(phen)Ni(R1 )]+ , which undergoes gas-phase ion-molecule reactions (IMR) with acetate esters CH3 COOR2 to yield the acetate complex [(phen)Ni (OOCCH3 )]+ and a C-C coupling product R1 -R2 . These Ni(II)/phenanthroline-mediated coupling reactions can be performed with a variety of carbon substituents R1 and R2 (sp3 , sp2 , or aromatic), some of them functionalized. Reaction rates do not seem to be strongly dependent on the nature of the substituents, as sp3 -sp3 or sp2 -sp2 coupling reactions proceed rapidly. Experimental results are supported by density functional theory calculations, which provide insights into the energetics associated with the C-C bond coupling step.

Here we describe a new conceptual approach for the design of a heterogeneous metal‐organic framework (MOF) catalyst based on UiO‐67 for the selective decarboxylation of formic acid, a reaction with important applications in hydrogen storage andin situgeneration of H2. Models for the {CuH} reactive catalytic site at the organic linker are assessed. In the first model system, gas‐phase mass spectrometry experiments and DFT calculations on a fixed charge bathophen ligated copper hydride complex, [(phen*)Cu(H)]2−, were used to demonstrate that it acts as a catalyst for the selective decomposition of formic acid into H2and CO2via a two‐step catalytic cycle. In the first step liberation of H2to form the carboxylate complex, [(phen*)Cu(O2CH)]2−occurs, which in the second step selectively decomposes via CO2extrusion to regenerate the hydride complex. DFT calculations on four other model systems showed that changing the catalyst to neutral [(LCu(H)] complexes or embedding it within a MOF results in mechanisms which are essentially identical. Thus catalytic active sites located on the organic linker of a MOF appear to be close to a gas‐phase environment, thereby benefitting from the favorable characteristics of gas‐phase reactions and validating the use of gas‐phase models to design new MOF based catalysts.

We report new structural motifs for Cu nanoclusters that conceptually represent seed crystals for large face-centred cubic (FCC) crystal growth. Kinetically controlled syntheses, high resolution mass spectrometry experiments for determination of the dication formulae and crystallographic characterisation were carried out for [Cu18 H16 (DPPE)6 ][BF4 ][Cl] (DPPE=bis(diphenylphosphino)ethane) and [Cu16 H14 (DPPA)6 ][(BF4 )2 ] (DPPA=bis(diphenylphosphino)amine) polyhydrido nanoclusters, which feature the unprecedented bifrustum and frustum metal-core architecture in metal nanoclusters. The Cu18 nanocluster contains two Cu9 frustum cupolae and the Cu16 nanocluster has one Cu9 frustum cupola and a Cu7 distorted hexagonal-shape base. Gas-phase experiments revealed that both Cu18 H16 and Cu16 H14 cores can spontaneously release H2 upon removal of one bisphosphine capping ligand.

RATIONALE: Potassium organotrifluoroborates (RBF3 K) are important reagents used in organic synthesis. Although mass spectrometry is commonly used to confirm their molecular formulae, the gas-phase fragmentation reactions of organotrifluoroborates and their alkali metal cluster ions have not been previously reported. METHODS: Negative-ion mode electrospray ionization (ESI) together with collision-induced dissociation (CID) using a triple quadrupole mass spectrometer were used to examine the fragmentation pathways for RBF3- (where R = CH3 , CH3 CH2 , CH3 (CH2 )3 , CH3 (CH2 )5 , c-C3 H5 , C6 H5 , C6 H5 CH2 , CH2 CHCH2 , CH2 CH, C6 H5 CO) and M(RBF3 )2- (M = Na, K), while density functional theory (DFT) calculations at the M06/def2-TZVP level were used to examine the structures and energies associated with fragmentation reactions for R = Me and Ph. RESULTS: Upon CID, preferentially elimination of HF occurs for RBF3- ions for systems where R = an alkyl anion, whereas R- formation is favoured when R = a stabilized anion. At higher collision energies loss of F- and additional HF losses are sometimes observed. Upon CID of M(RBF3 )2- , formation of RBF3- is the preferred pathway with some fluoride transfer observed only when M = Na. The DFT-calculated relative thermochemistry for competing fragmentation pathways is consistent with the experiments. CONCLUSIONS: The main fragmentation pathways of RBF3- are HF elimination and/or R- loss. This contrasts with the fragmentation reactions of other organometallate anions, where reductive elimination, beta hydride transfer and bond homolysis are often observed. The presence of fluoride transfer upon CID of Na(RBF3 )2- but not K(RBF3 )2- is in agreement with the known fluoride affinities of Na+ and K+ and can be rationalized by Pearson's HSAB theory.

Translating a homogenous catalyst into a heterogeneous catalyst requires a fundamental understanding of how the catalyst “fits” into the zeolite and how the reaction is influenced. Previous studies of bimetallic catalyst design identified a potent copper homobinuclear catalyst, [(L)Cu2(H)]+for the selective decomposition of formic acid. Here, a close interplay between theory and experiment shows how to preserve this selective reactivity within zeolites. Gas‐phase experiments and DFT calculations showed that switching from 1,1‐bis(diphenylphosphino)‐methane ligand to the 1,8‐naphthyridine ligand produced an equally potent catalyst. DFT calculations show that this new catalyst neatly fits into a zeolite which does not perturb reactivity, thus providing a unique example on how “heterogenization” of a homogenous catalyst for the selective catalysed extrusion of carbon dioxide from formic acid can be achieved, with important application in hydrogen storage and in situ generation of H2.

We report a new approach for the synthesis of heterohexa‐ and heterodecametalates via the use of non‐aqueous, microwave‐assisted reaction conditions. The two novel molybdovanadates have been isolated and characterized in the solid and solution states using single‐crystal X‐ray diffraction, FT‐IR, UV/Vis, multinuclear NMR spectroscopy, and ESI‐MS. The relative stabilities of the possible structural isomers were probed using dispersion‐corrected DFT calculations for both polyoxometalate systems.

Resistance to insecticides through enhanced metabolism is a worldwide problem. The Cyp6g1 gene of the vinegar fly, Drosophila melanogaster, is a paradigm for the study of metabolic resistance. Constitutive overexpression of this gene confers resistance to several classes of insecticides, including the neonicotinoid imidacloprid (IMI). The metabolism of IMI in this species has been previously shown to yield oxidative and nitro-reduced metabolites. While levels of the oxidative metabolites are correlated with CYP6G1 expression, nitro-reduced metabolites are not, raising the question of how these metabolites are produced. Some IMI metabolites are known to be toxic, making their fate within the insect a second question of interest. These questions have been addressed by coupling the genetic tools of gene overexpression and CRISPR gene knock-out with the mass spectrometric technique, the Twin-Ion Method (TIM). Analysing axenic larvae indicated that microbes living within D. melanogaster are largely responsible for the production of the nitro-reduced metabolites. Knock-out of Cyp6g1 revealed functional redundancy, with some metabolites produced by CYP6G1 still detected. IMI metabolism was shown to produce toxic products that are not further metabolized but readily excreted, even when produced in the Central Nervous System (CNS), highlighting the significance of transport and excretion in metabolic resistance.

Ein neuer Ansatz zur Synthese von Heterohexa‐ und Heterodecametallaten unter nichtwässrigen, mikrowellengestützten Reaktionsbedingungen wurde entwickelt. Die zwei neuartigen Molybdovanadate wurden isoliert und im festen sowie gelösten Zustand mittels Einkristall‐Röntgenbeugung, FT‐IR‐, UV/Vis‐ und multinuklearer NMR‐Spektroskopie sowie ESI‐MS charakterisiert. Die relativen Stabilitäten der möglichen Strukturisomere beider Polyoxometallatsysteme wurden mithilfe von dispersionskorrigierten DFT‐Rechnungen untersucht.

Design of new bimetallic catalysts requires an understanding of how cooperative effects of the metal sites influences reactivity. Here we show how switching one or both of the silver atoms in binuclear silver hydride cations, [dppmAg2(H)]+ (dppm=1,1‐Bis(diphenylphosphino)‐methane), with all combinations of copper and/or gold maintains selective dehydrogenation of formic acid, enhancing reactivity by up to 2 orders of magnitude. This is a key step in the selective, catalyzed extrusion of carbon dioxide from formic acid, HO2CH, with important applications in hydrogen storage and in situ generation of H2. Decarboxylation of [dppmMM′(O2CH)]+ through collision induced dissociation regenerates [dppmMM′(H)]+. DFT calculations provide insights into these cooperative effects. The copper homobinuclear catalyst performs best overall.

Metalloenzymes preorganize the reaction environment to steer substrate(s) along the required reaction coordinate. Here, we show that phosphine ligands selectively facilitate protonation of binuclear silver hydride cations, [LAg2(H)](+) by optimizing the geometry of the active site. This is a key step in the selective, catalysed extrusion of carbon dioxide from formic acid, HO2CH, with important applications (for example, hydrogen storage). Gas-phase ion-molecule reactions, collision-induced dissociation (CID), infrared and ultraviolet action spectroscopy and computational chemistry link structure to reactivity and mechanism. [Ag2(H)](+) and [Ph3PAg2(H)](+) react with formic acid yielding Lewis adducts, while [(Ph3P)2Ag2(H)](+) is unreactive. Using bis(diphenylphosphino)methane (dppm) reshapes the geometry of the binuclear Ag2(H)(+) scaffold, triggering reactivity towards formic acid, to produce [dppmAg2(O2CH)](+) and H2. Decarboxylation of [dppmAg2(O2CH)](+) via CID regenerates [dppmAg2(H)](+). These gas-phase insights inspired variable temperature NMR studies that show CO2 and H2 production at 70 °C from solutions containing dppm, AgBF4, NaO2CH and HO2CH.

The metabolic fate of a compound can often determine the success of a new drug lead. Thus, significant effort is directed toward identifying the metabolites formed from a given molecule. Here, an automated and nontargeted procedure is introduced for detecting drug metabolites without authentic metabolite standards via the use of stable isotope labeling, liquid chromatography mass spectrometry (LC/MS), and high-performance computing. LC/MS of blood plasma extracts from rats that were administered a 1:1 mixture of acetaminophen (APAP) and (13)C6-APAP resulted in mass spectra that contained "twin" ions for drug metabolites that were not detected in control spectra (i.e., no APAP administered). Because of the development of a program (high-resolution twin-ion metabolite extraction; HiTIME) that can identify twin-ions in high-resolution mass spectra without centroiding (i.e., reduction of mass spectral peaks to single data points), 9 doublets corresponding to APAP metabolites were identified. This is nearly twice that obtained by use of existing programs that make use of centroiding to reduce computational cost under these conditions with a quadrupole time-of-flight mass spectrometer. By a manual search for all reported APAP metabolite ions, no additional twin-ion signals were assigned. These data indicate that all the major metabolites of APAP and multiple low-abundance metabolites (e.g., acetaminophen hydroxy- and methoxysulfate) that are rarely reported were detected. This methodology can be used to detect drug metabolites without prior knowledge of their identity. HiTIME is freely available from https://github.com/bjpop/HiTIME .

RATIONALE: Non-covalent amino acid clusters are the subject of intense research in diverse areas including peptide bond formation studies or the determination of proton affinities or methylating abilities of amino acids. However, most of the research has focused on positive ions and little is known about anionic clusters. METHODS: Fragmentation reactions of deprotonated tryptophan (Trp), [Trp-H](-) and Trp singly deprotonated non-covalently bound clusters [Trp(n) -H](-), n = 2, 3, 4, were investigated using low-energy collision-induced dissociation (CID) with He atoms, high-energy CID with Na atoms, and electron-induced dissociation (EID) with 20-35 eV electrons. Fragmentation of the monomeric Trp anion, where all labile hydrogens were exchanged for deuterium [d(4) -Trp-D](-), was investigated using low-energy CID and EID, in order to shed light on the dissociation mechanisms. RESULTS: The main fragmentation channel for Trp cluster anions, [Trp(n) -H](-), n >1, is the loss of the neutral monomer. The fragmentation of the deprotonated Trp monomer induced by electrons resembles the fragmentation induced by high-energy collisions through electronic excitation of the parent. However, the excitation must precede in a different way, shown through only monomer loss from larger clusters, n >1, in case of EID, but intracluster chemistry in the case of high-energy CID. CONCLUSIONS: The anion of the indole ring C(8)H(6) N(-) has been identified in the product ion spectra of [Trp(n) -H](-) using all activation methods, thus providing a diagnostic marker ion. No evidence was found for formation of peptide bonds as a route to prebiotic peptides in the fragmentation reactions of these singly deprotonated Trp cluster ions.

The bis(diphenylphosphino)methane (L = Ph2PCH2PPh2) ligated silver deuteride nanocluster dication, [Ag10D8L6](2+), has been synthesised in the condensed phase via the reaction of bis(diphenylphosphino)methane, silver nitrate and sodium borodeuteride in the methanol : chloroform (1 : 1) mixed solvent system. The photoionisation and photofragmentation of this mass-selected cluster were studied using a linear ion trap coupled to the DESIRS VUV beamline of the SOLEIL Synchrotron. At 15.5 eV the main ionic products observed are [Ag10D8L5](2+), [Ag10D8L4](2+), [Ag10D8L6](3+)˙, [Ag9D8L4](2+)˙, and [AgL2](+). The later two products arise from fragmentation of [Ag10D8L6](3+)˙. An analysis of the yields of these product ions as a function of the photon energy reveals the onset for the formation of [AgL2](+) and [Ag9D8L4](2+)˙ is around 2 eV higher than that for ionisation to produce [Ag10D8L5](3+)˙. The onset of ionisation energy of [Ag10D8L6](2+) was determined to be 9.3 ± 0.3 eV from a fit of the yield of the product ion, [Ag10D8L6](3+)˙, as a function of the VUV photon energy. DFT calculations at the RI-PBE/RECP-def2-SVP level of theory were carried out to search for a possible structure of the cluster and to estimate its vertical and adiabatic ionisation energies. The calculated lowest energy structure of the [Ag10D8L6](2+) nanocluster contains a symmetrical bicapped square antiprism as a silver core in which hydrides are located as a mix of triangular faces and edges. Four of the bisphosphines bind to the edges of the cluster core as bidentate ligands, the remaining two bisphosphines bind via a single phosphorus donor atom to each of the apical silver atoms. The DFT calculated adiabatic ionisation energy for this structure is 8.54 eV, in satisfactory agreement with experiment.

Acetaminophen (paracetamol, APAP) is a safe and widely used analgesic medication when taken at therapeutic doses. However, APAP can cause potentially fatal hepatotoxicity when taken in overdose or in patients with metabolic irregularities. The production of the electrophilic and putatively toxic compound N-acetyl-p-benzoquinone imine (NAPQI), which cannot be efficiently detoxicated at high doses, is implicated in APAP toxicity. Numerous studies have identified that excess NAPQI can form covalent linkages to the thiol side chains of cysteine residues in proteins; however, the reactivity of NAPQI toward other amino acid side chains is largely unexplored. Here, we report a survey of the reactivity of NAPQI toward 11 N-acetyl amino acid methyl esters and four peptides. (1)H NMR analysis reveals that NAPQI forms covalent bonds to the side-chain functional groups of cysteine, methionine, tyrosine, and tryptophan residues. Analogous reaction products were observed when NAPQI was reacted with synthetic model peptides GAIL-X-GAILR for X = Cys, Met, Tyr, and Trp. Tandem mass spectrometry peptide sequencing showed that the NAPQI modification sites are located on the "X" residue in each case. However, when APAP and the GAIL-X-GAILR peptide were incubated with rat liver microsomes that contain many metabolic enzymes, NAPQI formed by oxidative metabolism reacted with GAIL-C-GAILR exclusively. For the peptides where X = Met, Tyr, and Trp, competing reactions between NAPQI and alternative nucleophiles precluded arylation of the target peptide by NAPQI. Although Cys residues are favorably targeted under these conditions, these data suggest that NAPQI can, in principle, also damage proteins at Met, Tyr, and Trp residues.

Gas-phase experiments using collision-induced dissociation in an ion trap mass spectrometer have been used in combination with density functional theory (DFT) calculations (at the B3LYP/SDD6–31+G(d) level of theory) to examine the competition between decarboxylation and loss of a coordinated acetonitrile in the unimolecular fragmentation reactions of the silver acetate and silver propiolate complexes, [RCO2Ag2(CH3CN)n]+ (where R = CH3 and CH3C≡C; n = 1 and 2), introduced into the gas-phase via electrospray ionisation. When R = CH3, loss of acetonitrile is the sole reaction channel observed for both complexes (n = 1 and 2), consistent with DFT calculations, which highlight that the barriers for decarboxylation 2.18 eV (n = 2) and 1.96 eV (n = 1) are greater than the binding energies of the coordinated acetonitriles (1.60 eV for n = 2; 1.64 eV for n = 1). In contrast, when R = CH3C≡C, decarboxylation is the main fragmentation pathway observed for both complexes (n = 1 and 2), with loss of acetonitrile only being a minor product channel. This is consistent with DFT calculations, which reveal that the barriers for decarboxylation are 1.17 eV (n = 2) and 1.16 eV (n = 1), which are both below the binding energies of the coordinated acetonitriles (1.55 eV for n = 2; 1.56 eV for n = 1). The barrier for decarboxylation of [CH3C≡CCO2Ag2]+ is 1.22 eV, which is less than the 2.06 eV reported for decarboxylation of [CH3CO2Ag2]+ (Al Sharif et al. Organometallics, 2013, 32, 5416). The observed ease of decarboxylation of silver propiolate complexes in the gas-phase is consistent with the recently reported use of silver salts in metal catalysed decarboxylative C–C and C–X bond forming reactions of propiolic acids.

The ion-molecule reactions of the rhenium oxide anions, [ReOx](-) (x = 2 - 4) with the organic substrates methane, ethene, methanol and acetic acid have been examined in a linear ion trap mass spectrometer. The only reactivity observed was between [ReO(2)](-) and acetic acid. Isotope labelled experiments and high-resolution mass spectrometry measurements were used to assign the formulas of the ionic products. Collision-induced dissociation and ion-molecule reactions with acetic acid were used to probe the structures of the mass-selected primary product ions. Density functional theory calculations [PBE0/LanL2DZ6-311+G(d)] were used to suggest possible structures. The three primary product channels observed are likely to arise from the formation of: the metallalactone [ReO(2)(CH(2)CO(2))](-) (m/z 277) and H(2); [CH(3)ReO(2)(OH)](-) (m/z 251) and CO; and [ReO(3)](-) (m/z 235), H(2) and CH(2)CO.

Metal-catalyzed decarboxylative coupling reactions of esters offer new opportunities for formation of C–C bonds with CO2 as the only coproduct. Here I provide an overview of: key solution phase literature; thermochemical considerations for decarboxylation of esters and thermolysis of esters in the absence of a metal catalyst. Results from my laboratory on the use of multistage ion trap mass spectrometry experiments and DFT calculations to probe the gas-phase metal catalyzed decarboxylative cross-coupling reactions of allyl acetate and related esters are then reviewed. These studies have explored the role of the metal carboxylate complex in the gas phase decarboxylative coupling of allyl acetate proceeding via a simple two-step catalytic cycle. In Step 1, an organometallic ion, [CH3ML]+/– (where M is a group 10 or 11 metal and L is an auxillary ligand), is allowed to undergo ion-molecule reactions with allyl acetate to generate 1-butene and the metal acetate ion, [CH3CO2ML]+/–. In Step 2, the metal acetate ion is subjected to collision-induced dissociation to reform the organometallic ion and thereby close the catalytic cycle. DFT calculations have been used to explore the mechanisms of these reactions. The organometallic ions [CH3CuCH3]–, [CH3Cu2]+, [CH3AgCu]+ and [CH3M(phen)]+ (where M = Ni, Pd and Pt) all undergo C–C bond coupling reactions with allyl acetate (Step 1), although the reaction efficiencies and product branching ratios are highly dependant on the nature of the metal complex. For example, [CH3Ag2]+ does not undergo C–C bond coupling. Using DFT calculations, a diverse range of mechanisms have been explored for these C–C bond-coupling reactions including: oxidative-addition, followed by reductive elimination; insertion reactions and SN2-like reactions. Which of these mechanisms operate is dependant on the nature of the metal complex. A wide range of organometallic ions can be formed via decarboxylation (Step 2) although these reactions can be in

Nitroimidazoles are important compounds with chemotherapeutic applications as antibacterial drugs or as radiosensitizers in radiotherapy. Despite their use in biological applications, little is known about the fundamental properties of these compounds. Understanding the ionization reactions of these compounds is crucial in evaluating the radiosensitization potential and in developing new and more effective drugs. Thus, the present study investigates the decomposition of negative and positive ions of 2-nitroimidazole and 4(5)-nitroimidazole using low- and high-energy Collision-Induced Dissociation (CID) and Electron-Induced Dissociation (EID) by two different mass spectrometry techniques and is supported by quantum chemistry calculations. EID of [M+H](+) leads to more extensive fragmentation than CID and involves many radical cleavages including loss of H˙ leading to the formation of the radical cation, M˙(+). The stability (metastable decay) and the fragmentation (high-energy CID) of the radical cation M˙(+) have been probed in a crossed-beam experiment involving primary electron ionization of the neutral nitroimidazole. Thus, fragments in the EID spectra of [M+H](+) that come from further dissociation of radical cation M˙(+) have been highlighted. The loss of NO˙ radical from M˙(+) is associated with a high Kinetic Energy Release (KER) of 0.98 eV. EID of [M-H](-) also leads to additional fragments compared to CID, however, with much lower cross section. Only EID of [M+H](+) leads to a slight difference in the decomposition of 2-nitroimidazole and 4(5)-nitroimidazole.

Guanine radical cations are formed upon oxidation of DNA. Deoxyguanosine (dG) is used as a model, and the gas-phase infrared (IR) spectroscopic signature and gas-phase unimolecular and bimolecular chemistry of its radical cation, dG˙(+), A, which is formed via direct electrospray ionisation (ESI/MS) of a methanolic solution of Cu(NO3)2 and dG, are examined. Quantum chemistry calculations have been carried out on 28 isomers and comparisons between their calculated IR spectra and the experimentally-measured spectra suggest that A exists as the ground-state keto tautomer. Collision-induced dissociation (CID) of A proceeds via cleavage of the glycosidic bond, while its ion–molecule reactions with amine bases occur via a number of pathways including hydrogen-atom abstraction, proton transfer and adduct formation. A hidden channel, involving isomerisation of the radical cation via adduct formation, is revealed through the use of two stages of CID, with the final stage of CID showing the loss of CH2O as a major fragmentation pathway from the reformed radical cation, dG˙(+). Quantum chemistry calculations on the unimolecular and bimolecular reactivity are also consistent with A being present as a ground-state keto tautomer.

CONSPECTUS: Decarboxylation chemistry has a rich history, and in more recent times, it has been recruited in the quest to develop cheaper, cleaner, and more efficient bond-coupling reactions. Thus, over the past two decades, there has been intense investigation into new metal-catalyzed reactions of carboxylic substrates. Understanding the elementary steps of metal-mediated transformations is at the heart of inventing new reactions and improving the performance of existing ones. Fortunately, during the same time period, there has been a convergence in mass spectrometry (MS) techniques, which allows these catalytic processes to be examined efficiently in the gas phase. Thus, electrospray ionization (ESI) sources have been combined with ion-trap mass spectrometers, which in turn have been modified to either accept radiation from tunable OPO lasers for spectroscopy based structural assignment of ions or to allow the study of ion-molecule reactions (IMR). The resultant "complete" gas-phase chemical laboratories provide a platform to study the elementary steps of metal-catalyzed decarboxylation reactions in exquisite detail. In this Account, we illustrate how the powerful combination of ion trap mass spectrometry experiments and DFT calculations can be systematically used to examine the formation of organometallic ions and their chemical transformations. Specifically, ESI-MS allows the transfer of inorganic carboxylate complexes, [RCO2M(L)n](x), (x = charge) from the condensed to the gas phase. These mass selected ions serve as precursors to organometallic ions [RM(L)n](x) via neutral extrusion of CO2, accessible by slow heating in the ion trap using collision induced dissociation (CID). This approach provides access to an array of organometallic ions with well-defined stoichiometry. In terms of understanding the decarboxylation process, we highlight the role of the metal center (M), the organic group (R), and the auxiliary ligand (L), along with cluster nuclearity, in pr