G. van der Rest

Catalyzed keto-enol tautomerism of ionized acetone: a Fourier transform ion cyclotron resonance mass spectrometry study of proton transport isomerization

Abstract The unimolecular isomerization of CH3COCH3+· 1 into its more stable enol counterpart CH3C(OH)CH2+· 2 is known not to occur, as a significant energy barrier separates these ions. However, it is shown in this work that this isomerization can be catalyzed within a 1 : 1 ion-neutral complex. For instance, a Fourier transform ion cyclotron resonance mass spectrometry study shows that one, and only one, molecule of isobutyronitrile catalyzes the isomerization of 1 into 2. The rather low efficiency of the reaction (12%), as well as the strong isotope effect observed when CD3COCD3+· is used as the reactant ion, suggest that the catalyzed isomerization implicates a substantial intermediate energy barrier. This was confirmed by ab initio calculations that allow us to propose an isomerization mechanism in agreement with this experiment. The efficiency of different catalysts was studied. To be efficient, the catalyst must be basic enough to abstract a proton from the methyl group of ionized acetone but not too basic to give back this proton to oxygen. In other words, the proton affinity (PA) of an efficient catalyst must lie, in a first approximation, between the PA of the radical CH3COCH2· at the carbon site (PAC) and its PA at the oxygen site (PAO), which have been determined to be, respectively, 185.5 and 195.0 kcal mol−1. Most of the neutral compounds studied follow this PA rule. The inefficiency of alcohols in the catalytic process, although their PAs lie in the right area, is discussed. Keywords: Catalyzed keto-enol tautomerism; gas-phase proton transport; isomerization kinetics; proton affinity rule; FT-ICR mass spectrometry

“Proton-transport” catalysis in the gas phase. Keto-enol isomerization of ionized acetaldehyde

Abstract Fourier transform ion cyclotron resonance experiments show that a variety of molecules catalyze the hydrogen transfer which converts ionized acetaldehyde CH 3 CHO ·+ 1 to its vinyl alcohol counterpart CH 2 CHOH ·+ 2 . Each of these ions has been characterized by its specific bimolecular reactions with selected reactants. Calculations show that two pathways, for which the rate determining barriers have almost the same energy, are feasible. The first transition state involves a direct catalyzed 1,3-H transfer, while the second involves two successive 1,2-H transfers. A detailed experimental study, using methanol as a catalyst as well as labeled reactants, indicates that only the first pathway operates in the isomerization process. The different steps of these two independent pathways were elucidated. The first begins with the formation of a highly stabilized complex 3 , involving a two-center-three-electron interaction between the two oxygen atoms and an interaction between a hydrogen of the methyl group of 1 and the oxygen of methanol. This complex isomerizes into a complex 4 , which in turn gives the complex 5 , via a transition state located 6.3 kcal mol −1 below the energy of the reactants. This complex 5 corresponds to ionized vinyl alcohol hydrogen bonded to the oxygen of methanol, which dissociates to yield ion 2 . The second pathway begins with the interaction between the hydrogen of the CHO group and the oxygen of methanol and gives the complexes 6 and then 7 , which correspond to protonated methanol hydrogen bonded to a CH 3 CO · radical. Dissociation of 7 to give protonated methanol is favoured with respect to further isomerization leading to ionized vinyl alcohol. Compared to the unimolecular conversion between energetic ions 1 and 2 , which can occur either by a direct 1,3-H transfer or by a double 1,2-H transfer, the reaction of 1 with methanol catalyzes the first pathway while inhibiting the second one. In the case studied, catalysis is perhaps better described as a hydrogen atom transport.

Two different pathways for unimolecular and for catalyzed keto-enol isomerization of ionized acetophenone

Abstract Studies of the unimolecular reactions in the gas phase of the C 6 H 5 COCH 3 +· ( 1 ) and C 6 H 5 C(OH)CH 2 +· ( 2 ) ions have shown (1) that ion 1 does not convert to ion 2 prior to methyl radical loss, (2) that ion 2 isomerizes into ion 1 prior methyl radical loss, and (3) that this keto-enol isomerization does not occur by a direct 1,3-H transfer but by two successive 1,4-H transfers. Fourier transform ion cyclotron resonance experiments show that acetone catalyses the isomerization 1 → 2 . Further, by using labeled reactants, it is demonstrated that this isomerization occurs by a direct catalyzed 1,3-H transfer whereas the less energy demanding pathway connecting bare ions 1 and 2 is a double 1,4-H transfer. This represents the first description of a system for which the pathways connecting two isomeric ions are different for the unimolecular and for the catalyzed isomerizations.

Gas phase catalyzed keto-enol isomerization of cations by proton transport☆

Abstract In the gas phase, the unimolecular isomerization of the H 3 COC(O)CH 2 CO + cation 1 ( m / z 101) into the H 3 CO(HO)CCHCO + enol ion 2 by a 1,3-H shift possesses a high energy barrier and is therefore not observed. In contrast, in the cell of a FT-ICR mass spectrometer, interaction with gaseous methanol catalyzes the isomerization of 1 into its more stable isomer 2 , which can be characterized by low energy collision with argon. This exothermic reaction is irreversible. Reaction with labeled methanol and ligand exchange experiments indicate the existence of two distinct reactions. By formation of a covalent bond, one reaction yields protonated dimethyl malonate while the second one leads to ion 2 by a 1,3-H transfer catalyzed by methanol. Conversely, loss of methanol from collisionally activated long-lived m / z 133 cations formed by protonation of dimethyl malonate yields some m / z 101 ions with structure 2 , which shows that methanol catalyzes the isomerization of ion 1 within a [ 1 , CH 3 OH] complex. The efficiency of different catalysts is studied in order to probe the mechanism of the isomerization processes.

Ter-Body Intermediates in the Gas Phase: Reaction of Ionized Enols with tert-Butanol

In the gas phase, the CH2CHOH.+ enol radical cation 1 as well as its higher homologues CH3CHCHOH.+2 and (CH3)2CCHOH.+3, undergo exactly the same sequence of reactions with tert-butanol, leading to the losses of isobutene, water and water plus alkene. Fourier transform ion cyclotron resonance (FT-ICR) experiments using labeled reactants as well as ab initio calculations show that independent pathways can be proposed to explain the observed reactivity. For ion 1, taken as the simplest model, the first step of the reaction is formation of a proton bound complex which gives, by a simple exothermic proton transfer, the ter-body intermediate [CH2CHO., H2O, C(CH3)3+]. This complex, which was shown to possess a significant lifetime, is the key intermediate which undergoes three reactions. First, it can collapse to yield tert-butylvinyl ether with elimination of water. Second, by a regiospecific proton transfer, this complex can isomerize into three different ter-body complexes formed of water, isobutene and ionized enol. Within one of these complexes, which does not interconvert with the others, elimination of isobutene leads to the formation of a solvated enol ion. Within the others, a cycloaddition—cycloreversion process can proceed to yield the ionized enol 3 (loss of water and ethylene channel).

The end product of transglutaminase crosslinking: Simultaneous quantitation of [Nε-(γ-glutamyl) lysine] and lysine by HPLC–MS3

Transglutaminases catalyze the formation of Nepsilon-(gamma-glutamyl) isodipeptide crosslinks between proteins. These enzymes are thought to participate in a number of diseases, including neurological disease and cancer. A method associating liquid chromatography and multiple stage mass spectrometry has been developed for the simultaneous quantitation of [Nepsilon-(gamma-glutamyl) lysine] isodipeptide and lysine on an ion trap mass spectrometer. Highly specific detection has been achieved in MS3 mode. The method includes a derivatization step consisting of butylation of carboxylic groups and acetylation of amide groups, a liquid-liquid extraction, and a 19-min separation on a 100x2.1-mm Beta-basic C18 column with an acetonitrile gradient elution. 13C6-(15)N2 isotopes of the isodipeptide and the lysine serve as internal standards. The assay was linear in the range of 50 pmol/ml to 75 nmol/ml for the isodipeptide and the range of 10 nmol/ml to 3.5 micromol/ml for the lysine, with correlation coefficients greater than 0.99 for both ions. Intra- and inter-day coefficients of variation ranged from 3.5 to 15.9%. The method was successfully applied to human biological samples known to be crosslinked by transglutaminase such as cornified envelopes of epidermis, fibrin, and normal and Huntington disease brain.

Ambident reactivity and characterization of small ionized carbenes

Abstract The gas phase reactions of five ionized carbenes, HCOH + 1, HCNH2 + 2, CH3COH + 3, HOCOH + 4 and HOCNH2 + 5 with different molecules are studied by FT-ICR mass spectrometry. Interaction between an ionized carbene and a molecule can yield two kinds of stable adducts, as expected from the electronic structure of the carbene radical cations, explaining the ambident reactivity of these ions. The first kind of adduct corresponds to H-bonded species (hydrogen-bridged radical cations), the second to covalent structures. Since interconversion between these adducts is generally slow, each kind of adduct leads to a particular set of reactions. The H-bonded species can be involved in the protonation of the neutral as well as in the catalyzed interconversion between the carbene and its conventional radical cation counterpart. The covalent adducts, formed by reaction of ionized carbenes with methanal and alkenes, are β-distonic ions. Reactions with labeled propene show that the so formed distonic ions either dissociate by simple cleavage or undergo rearrangements and H-exchange after isomerization into conventional ions by 1,4-H transfers. Cyclopropane gives a characteristic reaction of the carbene structure: addition yields a γ-distonic ion which loses ethylene. Finally, H , I and SCH3 abstraction from appropriate neutrals confirms a radical reactivity of the carbenic carbon.

The gas-phase reactions of the methoxymethyl cation with aldehydes and ketones

The results of both mass-analysed ion kinetic energy spectroscopy and Fourier transform ion cyclotron resonance experiments involving reactions of the methoxymethyl cation CH3OCH2+ with a variety of aldehydes and ketones are reported. With ketones, the reaction yields a covalent complex whose dissociation either gives back the CH3OCH2+ cation or leads to a methyl cation transfer to the ketone. Except for CH2O, a third pathway is open with aldehydes. A hydride transfer to CH3OCH2+ yields a RCO+ acylium product ion. The branching ratio of these three pathways strongly depends on the structure of the aldehyde. Ab initio calculations confirm that the results can be explained by the interconversion of covalent structures and electrostatic complexes on the potential energy surface.

Reactions of CH(3)CHO(.+) and of CH(3)COH(.+) with water upon Fourier transform ion cyclotron resonance conditions.

The reactions of CH3CHO + and of CH3COH + with water yield the same products, at almost the same rate. It is shown, by using a characteristic reaction of the carbene structure, that a molecule of water converts CH3COH + into its more stable isomer CH3CHO +, which is a new example of catalyzed 1,2-H transfer. The dominant product is the proton-bound dimer of water which, in fact, comes from the [H2OH+…CH3] and [H2OH+…CO] primary products whose observed abundances are poor. In a related system, ionized formamide/water, a water molecule catalyzes the 1,3-transfer leading from the solvated carbene to the [H2O…H+…H2N–C=O] stable intermediate, which eliminates CO without back energy. In contrast, such a process does not take place in the studied system since the cleavage of the so formed [H2OH+…CH3CO] transient intermediate involves a high back energy; this is explained by the charge repartition within this intermediate. In fact, a different pathway takes place. The solvated acetaldehyde ion isomerizes into a terbody intermediate in which protonated water is bonded to a CO molecule on the one hand and to a methyl radical on the other hand. Simple cleavages of this complex yield the observed products.

Evidence for an alkene metathesis reaction during the unimolecular dissociation of (CH 3 ) 3 COCHCH 2

The unimolecular reaction of the metastable tert-butyl vinyl ether radical cation leads mainly to elimination of ethylene. From metastable ion studies as well as Fourier transform ion cyclotron resonance measurements and by using isotopic labeling, it is proposed that the fragmentation begins with the cleavage of the O–C(butyl) bond. This behavior, which contrasts with that of ionized alkylethers, is the consequence of the presence of a vinyl group that allows the formation of a neutral allylic radical. The key intermediate of the fragmentation is likely to be a [CH2CHOH, (CH3)2CCH2]•+ complex in which a cycloaddition–cycloreversion reaction occurs. This intermediate is the same as that produced by a McLafferty rearrangement in appropriate aldehyde radical cations.