Assigning structures to ions in the gas phase

The purpose of this short review is critically to assess the important experiments in gas phase ion chemistry whose correct interpretation can lead to the assigning of structures to organic positive ions. The methods fall into two main categories, (i) the measurement of ion enthalpies and transition state energies for their fragmentations and (ii) the detailed examination of the unimolecular and collision-induced fragmentation behaviour of cations, anions and neutral species. It is argued that in general, none of the above methods alone can suffice for an ion structure determination, but that in combination these techniques provide a powerful tool by means of which ion structures may confidently be assigned.     

Emission of M2X+ cluster ions in thermal ionization mass spectrometry in the presence of graphite.

The emission of M2X+ cluster ions in thermal ionization mass spectrometry when graphite is loaded on the heating filaments was studied. The emission model of non-reductive thermal ionization of graphite was preliminarily discussed and factors influencing the thermal emission of M2X+ ions were investigated. The results show that the intensities of M2X+ cluster ions are related to ionic radius and crystal lattice energy, and possibly also to the solvation energies of ions. The intensities of M2Cl+ (M stands for K, Rb, and Cs) cluster ions, the M2Cl+/M+ ratios, and the 37Cl/35Cl ratios determined from M2Cl+ ion measurement usually increase with measurement time. The variation of the 37Cl/35Cl ratios determined from Cs2Cl+ ion measurement is lower than those based on K2Cl+ and Rb2Cl+ ion measurement, indicating the lowest isotopic fractionation.     

Mass spectrometry of labile onium ions and carbocation salts. Study by desorption-ionization mass spectrometry: Fast atom bombardment,field desorption and 252Cf plasma desorption time-of-flight mass spectrometry

In contrast to the accepted notion that mass spectrometry is impractical as an analytical tool in condensed-phase preparative carbocation chemistry, it has been shown that desorption ionization techniques (fast atom bombard-ment, field desorption and²⁵²Cf plasma desorption time-of-flight mass spectrometry) provide rapid and reliable methods for relative molecular mass determination for a wide variety of highly unstable, fragile carbocation salts and onium ions. In addition, interesting fragment ions and cluster ions (two cations and one anion) are observed. Application of these methods to study several dication ether salts has also been demonstrated.     

SMART: A data reporting standard for mass spectrometry imaging By Ying Xi,Alexandria L. Sohn,Alena N. Joignant,Stephanie M. Cologna,Boone M. Prentice and David C. Muddiman

Mass spectrometry imaging (MSI) is an important analytical technique that simultaneously reports the spatial location and abundance of detected ions in biological, chemical, clinical, and pharmaceutical studies. As MSI grows in popularity, it has become evident that data reporting varies among different research groups and between techniques. The lack of consistency in data reporting inherently creates additional challenges in comparing intra- and inter-laboratory MSI data. In this tutorial, we propose a unified data reporting system, SMART, based on the common features shared between techniques. While there are limitations to any reporting system, SMART was decided upon after significant discussion to more easily understand and benchmark MSI data. SMART is not intended to be comprehensive but rather capture essential baseline information for a given MSI study; this could be within a study (e.g., effect of spot size on the measured ion signals) or between two studies (e.g., different MSI platform technologies applied to the same tissue type). This tutorial does not attempt to address the confidence with which annotations are made nor does it deny the importance of other parameters that are not included in the current SMART format. Ultimately, the goal of this tutorial is to discuss the necessity of establishing a uniform reporting system to communicate MSI data in publications and presentations in a simple format to readily interpret the parameters and baseline outcomes of the data.     

Selective isotopic exchange of polyfimctional ions in tandem mass spectrometry: Methodology,applications and mechanism

Isotopic exchange of mass-selected odd- and even-electron molecular ions of aromatic compounds upon collision with deuterated gases was investigated as a function of reagent gas, interaction time and collision energy. Use of ND₃ as reagent allows exchange of all active hydrogens for the compound types studied, providing a count of the total number of active hydrogens present in the analyte. CH₃OD exchanges specific types of active hydrogens, such as phenolic and carboxylic hydrogens, without exchanging amino hydrogens. This selectivity assists in the identification and enumeration of different types of active hydrogens present in polyfunctional compounds. The H–D exchange patterns serve to differentiate isomeric aromatic compounds containing methoxy, amino, hydroxy and carboxylic acid substituents. Trapping of mass-selected ions in the collision region of a triple quadrupole mass spectrometer greatly enhances the degree of H–D exchange, thereby facilitating determination of the number of active hydrogens in the analyte. Triple stage mass spectrometric experiments, performed in a pentaquadrupole mass spectrometer, help elucidate the exchange process. Isotopic exchange in the collision region of a tandem mass spectrometer also provides insights into the site of protonation in molecules containing several functional groups. The proximity of the functional groups and the proton affinity difference between the analyte and the reagent gas are important factors in site-specific H–D exchange in polyfunctional compounds. An investigation of the effects of collision energy reveals that cluster ion formation plays a major role in the exchange mechanism operating in the triple quadrupole and that H–D exchange, ion-molecule adduct formation and endothermic fragmentation are competitive reaction channels.     

Assigning in vivo carbamylation and acetylation in human lens proteins using tandem mass spectrometry and database searching

In this paper, we show that ion trap mass spectrometers can differentiate acetylation and carbamylation modifications based on database search results for a lens protein sample. These types of modifications are difficult to distinguish on ion trap instruments because of their lower resolution and mass accuracy. The results were corroborated by using accurate mass information derived from MALDI TOF MS analysis of eluted peptides from a duplicate capillary RPLC separation. Tandem mass spectra of lysine carbamylated peptides were further verified by manual assignments of fragment ions and by the presence of characteristic fragment ions of carbamylated peptides. It was also observed that carbamylated peptides show a strong neutral loss of the carbamyl group in collision induced dissociation (CID), a feature that can be prognostic for carbamylation. In a lens tissue sample of a 67-year-old patient, 12 in vivo carbamylation sites were detected on 7 different lens proteins and 4 lysine acetylation sites were detected on 3 different lens proteins. Among the 12 in vivo carbamylation sites, 9 are novel in vivo carbamylation modification sites. Notably, in vivo carbamylation of γS crystallin, βA4 crystallin, βB1 crystallin, and βB2 crystallin observed in this study have never been reported before.     

Investigation of L/D-threonine substituted L-serine octamer ions by mass spectrometry and infrared photodissociation spectroscopy

Threonine-substituted serine octamer ions were generated by electrospray ionization(ESI) and investigated by mass spectrometry and infrared photodissociation(IRPD) spectroscopy. IRPD spectra of[L-Ser_7+ L/D-Thr_1]H~+and [L-Ser_6+ L/D-Thr_2]H~+were obtained in the range of 2700–3600 cm~(-1). Chiral differentiation was achieved by comparing their IRPD spectra. The main difference located in the range of 3300–3500 cm~(-1). And the results indicate the substitution of L-Ser by D-Thr could weaken the intermolecular H-bonds and loosen the original structures of serine octamers.     

Assigning product ions from complex MS/MS spectra: The importance of mass uncertainty and resolving power

This study offers a unique insight into the mass accuracy and resolving power requirements in MS/MS analyses of complex product ion spectra. In the examples presented here, accurate mass assignments were often difficult because of multiple isobaric interferences and centroid mass shifts. The question then arose whether the resolving power of a medium-resolution quadrupole time-of flight (QqTOF) is sufficient or high-resolution Fourier-transform ion cyclotron resonance (FT-ICR) is required for unambiguous assignments of elemental compositions. For the comparison, two paralytic shellfish poisons (PSP), saxitoxin (STX) and neosaxitoxin (NEO), with molecular weights of 299 and 315 g x mol(-1), respectively, were chosen because of the high peak density in their MS/MS spectra. The assessment of QqTOF collision-induced dissociation spectra and FT-ICR infrared multiphoton dissociation spectra revealed that several intrinsic dissociation pathways leading to isobaric fragment ions could not be resolved with the QqTOF instrument and required FT-ICR to distinguish very close mass differences. The second major source of interferences was M + 1 species originating from coactivated 13C12Cc-1 ion contributions of the protonated molecules of the PSPs. The problem in QqTOF MS results from internal mass calibration when the MH+ ions of analyte and mass calibrant are activated at the same time in the collision or trapping cell. Although FT-ICR MS readily resolved these interfering species, the QqTOF did not provide resolving power >20,000 (full width at half maximum) required to separate most isobaric species. We were able to develop a semi-internal QqTOF calibration technique that activated only the isolated 12C isotope species of the protonated molecules, thus reducing the M + 1 interferences significantly. In terms of overall automated elemental formulas assignment, FT-ICR MS achieved the first formula hit for 100% of the product ions, whereas the QqTOF MS hit rate was only 56 and 65% for STX and NEO product ions, respectively. External mass calibration from commercial FT-ICR and QqTOF instruments gave similar results.     

Heuristic programming as an ion generator in mass spectrometry. II—Generation of primary ions from simple cyclic structures

The Ion Generator computer program has now the ability to fragment cyclic structures Examples of mechanisms which are proposed by the program for the fragmentation of simple ring compounds are presented.