John C. Poutsma

IRMPD spectroscopy shows that AGG forms an oxazolone b2+ ion.

Infrared multiple photon dissociation (IRMPD) spectroscopy combined with theoretical vibrational spectra provides a powerful tool for probing structure. This technique has been used to probe the structure of protonated cyclic AG and the b(2)(+) ion from AGG. The experimental spectrum for protonated cyclo AG compares very well with the theoretical spectra for a diketopiperazine. The spectrum corresponds best to a combination of two structures protonation at the alanine and glycine amide oxygens. The experimental spectrum for the b(2)(+) ion from protonated AGG matches best to the theoretical spectrum for an oxazolone structure protonated on the ring nitrogen. In particular, the carbonyl stretching band at 1970 cm(-1) is blue-shifted by approximately 200 cm(-1) compared to the experimental spectrum for protonated cAG, indicating that these two structures are distinct. This is the first time that an IRPD spectrum of a b(2)(+) ion has been obtained and, for this ion, the oxazolone structure proposed based on prior calculations and experiments is confirmed by the spectroscopic method.

A tandem selected ion flow tube—triple quadrupole instrument

Abstract The design, operation and calibration of a selected ion flow tube (SIFT)—triple quadrupole instrument are described. A detailed examination of the gas-phase reaction between ClCH+2 and CH3Cl has been carried out in order to demonstrate some of the unique experimental capabilities of the new instrument. The primary reactions at room temperature and 0.6 Torr total pressure are thermoneutral Cl-isotope exchange and termolecular association to yield [ClCH2ClCH3]+, with apparent bimolecular rate coefficients of 6.6 x 10−11 and 4.1 x 10−11 cm3 s−1, respectively. Double-labelling experiments with ClCD+2 as the reactant ion identify hydride transfer as the mechanism for the observed Cl-isotope exchange. Collision-induced dissociation (CID) of the addition product yields ClCH+2 with a threshold energy of 31.1 ± 3.0 kcal mol−1. The relative yields of the35ClCH+2 and37ClCH2+ product ions produced by CID of the mass-selected (35Cl,37Cl) isotopomeric adduct have been measured as a function of the CH3Cl concentration in the flow reactor. Analysis of these data with a simple kinetic model indicates that approximately one third of the adduct-forming collisions are accompanied by Cl-exchange via hydride transfer within the collision complex. When the [ClCH2ClCH3]+ ions are formed in the flow tube by a “switching” reaction between ClCH+2(SCO) and CH3Cl, Cl-exchange does not occur, as shown by the complete retention of the original Cl-isotope in the ClCH+2 fragment ion produced by CID.

The proton affinity of proline analogs using the kinetic method with full entropy analysis

The proton affinity of proline analogs, L-azetidine-2-carboxylic acid (Aze), L-proline (Pro), and L-pipecolic acid (Pip), have been measured using the Armentrout modification of the extended kinetic method in a quadrupole ion trap instrument. Experimental values of 223.0 ± 1.5, 224.9 ± 1.6, and 225.6 ± 1.6 kcal/mol have been determined for the 298K proton affinities of Aze, Pro, and Pip respectively. High level theoretical calculations using both MP2 and B3LYP methods at a variety of basis sets were carried out in order to give theoretical predictions for the 298 K proton affinity and gas phase basicity of all three analogs. Recommended values for the gas phase basicity and proton affinity for proline based on our work and other recent determinations are 216 ± 2 and 224 ± 2 kcal/mol.

Generation of α-acetolactone and the acetoxyl diradical •CH2COO• in the gas phase

Abstract The formation of neutral [C 2 ,H 2 ,O 2 ] has been investigated by tandem mass spectrometry in a sector instrument and by energy-resolved collision-induced dissociation in a flowing afterglow-triple quadrupole apparatus. The neutral species are generated by two different methods: (i) neutralization of the distonic anion radical • CH 2 COO − by collisional electron detachment and (ii) collision-induced loss of halides X − concomitant with formation of [C 2 ,H 2 ,O 2 ] from α-haloacetate ions XCH 2 COO − . The tandem mass spectrometry results suggest that neutralization of • CH 2 COO − and high-energy collisional activation of α-haloacetate ions lead to a mixture of α-acetolactone, c -(CH 2 C(O)O), and the acetoxyl diradical, • CH 2 COO • . Low-energy collisions with α-chloroacetate ions in the triple quadrupole analyzer produce α-acetolactone exclusively at the dissociation threshold. From the dissociation threshold measured for the appearance of Cl − from ClCH 2 COO − the heat of formation of acetolactone is determined to be ΔH f,298 = −47.3 ± 4.7 kcal/mol.

The Curtin−Hammett Principle in Mass Spectrometry

The Curtin-Hammett principle (CHP) is an important concept in physical organic chemistry and is often utilized in the investigation of reaction mechanisms. Two reactants, A and B, in rapid equilibrium, react to form products P(A) and P(B) with rates k(A) and k(B), respectively. If the reaction is under kinetic control and the rate of equilibration between the two reactants is much faster than the reactions to form products, then the branching ratio of products P(A) and P(B) depends solely on the difference in barrier heights for the two product channels. The CHP is based on the fact that the ratio of products formed is not determined by the reactant population ratio. However, the CHP also applies to studies in other areas of chemistry, including mass spectrometry. This Account describes work from our groups in which the results must be interpreted in light of the CHP. These studies illustrate two important implications of the CHP. First, they demonstrate how product distributions cannot be used to assess reactant structure in mechanistic studies in Curtin-Hammett systems. A recent investigation of the structure of hydroxysiliconate anions demonstrated that it was not possible to distinguish between the possible reactant ion structures. A second important implication of the CHP is that the structure of the reactant does not affect the product branching ratio and therefore does not need to be a consideration if the CHP applies. We address this aspect of the discussion through kinetic method studies of the acidities of amino acids and proton affinities of bifunctional compounds. Recently reported mass spectrometric studies illustrate how the CHP puts limitations on what conclusions can be drawn from product distribution studies but also allows experimental methods, such as the kinetic method, to be carried out for complicated systems without having to know all the details of the reactant ion structures. These studies show that although the CHP is most commonly applied in mechanistic studies in physical organic chemistry, it also applies to other areas of chemistry, including mass spectrometry. Although the CHP in some cases limits the conclusions that can be drawn from an experimental study, its proper application can often be used to greatly simplify very complicated chemical systems. Therefore, it is important in mass spectrometry, and indeed, in all areas of chemistry, to recognize those systems in which the CHP should and should not apply.

Investigations of the Mechanism of the “Proline Effect” in Tandem Mass Spectrometry Experiments: The “Pipecolic Acid Effect”

AbstractThe fragmentation behavior of a set of model peptides containing proline, its four-membered ring analog azetidine-2-carboxylic acid (Aze), its six-membered ring analog pipecolic acid (Pip), an acyclic secondary amine residue N-methyl-alanine (NMeA), and the D stereoisomers of Pro and Pip has been determined using collision-induced dissociation in ESI-tandem mass spectrometers. Experimental results for AAXAA, AVXLG, AAAXA, AGXGA, and AXPAA peptides are presented, where X represents Pro, Aze, Pip, or NMeA. Aze- and Pro-containing peptides fragment according to the well-established “proline effect” through selective cleavage of the amide bond N-terminal to the Aze/Pro residue to give yn+ ions. In contrast, Pip- and NMA-fragment through a different mechanism, the “pipecolic acid effect,” selectively at the amide bond C-terminal to the Pip/NMA residue to give bn+ ions. Calculations of the relative basicities of various sites in model peptide molecules containing Aze, Pro, Pip, or NMeA indicate that whereas the “proline effect’ can in part be rationalized by the increased basicity of the prolyl-amide site, the “pipecolic acid effect” cannot be justified through the basicity of the residue. Rather, the increased flexibility of the Pip and NMeA residues allow for conformations of the peptide for which transfer of the mobile proton to the amide site C-terminal to the Pip/NMeA becomes energetically favorable. This argument is supported by the differing results obtained for AAPAA versus AA(D-Pro)AA, a result that can best be explained by steric effects. Fragmentation of pentapeptides containing both Pro and Pip indicate that the “pipecolic acid effect” is stronger than the “proline effect.” Figureᅟ

Distonic ions of the “ate” class

The gas phase synthesis, structure, and reactivity of distonic negative ions of the “ate” class are described. “Ate”-class negative ions are readily prepared in the gas phase by addition of neutral Lewis acids, such as BF3, BH3, and AlMe3, to molecular anions, carbene negative ions, and radical anions of biradicals. The ions contain either localized σ- or delocalized π-type radical moieties remote from relatively inert borate and aluminate charge sites. The free radical reactivity displayed by these ions appears to be independent of the charge site. As an example, the distonic alkynyl radical (·C≡CBF3−) is highly reactive and undergoes radical coupling reactions with NO2, NO, H2C=CH-CN, and H2C=CH-CH3. Radical-mediated group and atom transfers are observed with O2, CS2, and CH3SSCH3. Furthermore, H-atom abstraction reactions are observed, in accordance with the predicted high C-H bond strength of this species [DH298(H-C2BF3−)=130.8 kcal mol−1]. High level ab initio molecular orbital calculations on the prototype “ate”-class distonic ion · CH2BH3− and its conventional isomer CH3BH2·− reveal that CH3BH2·− is 3.2 kcal/mol more stable than the α-distonic form. However, the calculations also show that CH3BH2·− is unstable with respect to electron detachment, and only the α-distonic form ·CH2BH3− should be experimentally observed in the gas phase.

COMBINING ELECTROSPRAY IONIZATION AND THE FLOWING AFTERGLOW METHOD

The design and implementation of a simple electrospray ionization source for a flowing afterglow/triple quadrupole device are described. Ions can be electrosprayed directly into the room temperature flow tube through a heated capillary without the need for differential pumping or ion focusing. Detected ion currents at the detector sampling orifice as high as 3 pA have been achieved, and the mass spectra indicate little or no re-clustering of the desolvated ions with the background solvent vapor in the flow tube. Spatially and temporally resolved ion/molecule reactions of electrosprayed ions can be carried out in the flow reactor under thermal energy conditions. Sufficient ion densities can be achieved for tandem mass spectrometric experiments in the triple quadrupole analyzer, including energy-resolved collision-induced dissociation. Selected chemical applications illustrating these features are described, including proton transfer reactions with aromatic polysulfonate dianions and multiply protonated polypeptides and threshold CID of a doubly charged transition metal coordination complex.

A synthetic model of Hg(II) sequestration

Tridentate ligand N-(2-pyridylmethyl)-N-(2-(ethylthiolato)amine (L) forms the novel complex [Hg(5)(L)(6)](ClO(4))(4).toluene () with a bicyclo[3.3.3] Hg(5)S(6) core and 4-, 5- and 6-coordinate metal centers; characterization of a solution of by ESI-MS revealed elaborate speciation involving [Hg(n)L(n+1)(ClO(4))(n-2)](+), [Hg(n)L(n)(ClO(4))(n-1)](+) and [Hg(n)L(n-1)(ClO(4))(n)](+) ion families.

The heat of formation of (CH3O)2B

Abstract The proton affinity of trimethyl borate was determined to be 197 ± 3 kcal mol−1 by bracketing in both directions in a Fourier-transform ion cyclotron resonance mass spectrometer. This value was used to calculate a heat of formation of −46.3 ± 3.0 kcal mol−1 for CH3O(H)B(OCH3)+2. Collision-induced dissociation threshold energy measurements carried out in a flowing afterglow-triple quadrupole instrument yield an activation energy of 39.5 ± 3.5 kcal mol−1 for the dissociation of CH3O(H)B(OCH3)+2 to CH3OH and CH3O)2B+. This bond dissociation energy, together with the heat of formation of CH3O(H)B(OCH3)+2, was used to calculate a heat of formation of 41.4±4.6 kcal mol−1 for (CH3O)2B+.