Mechanistic investigation of ionization suppression in electrospray ionization

We show results from experiments designed to determine the relative importance of gas phase processes and solution phase processes into ionization suppression observed in biological sample extracts. The data indicate that gas phase reactions leading to the loss of net charge on the analyte is not likely to be the most important process involved in ionization suppression. The results point to changes in the droplet solution properties caused by the presence of nonvolatile solutes as the main cause of ionization suppression in electrospray ionization of biological extracts.     

Femtosecond laser ionization of organic amines with very low ionization potentials: relatively small suppressed ionization features

We examined the femtosecond nonresonant ionization of organic amines with vertical ionization potentials as low as 5.95 eV. The quantitative evaluation of suppressed ionization relative to the single active electron approximation model was done by comparing the saturation intensity, I(sat), in experiments and theory. ADK theory was found to be useful in predicting the ionization yield in the I(sat) scale within a factor of 2, even for molecules with very low ionization potentials. The degree of suppression was, however, smaller than that of benzene. The localization of electrons on the nitrogen atom was found to affect the ionization behavior under the strong laser field. The delocalized pi electrons in benzene could not follow the laser field adiabatically, while those in localized molecular orbitals could. In addition, the growth of a tunneling barrier due to the screening effect in amines may be relatively smaller than that in benzene.     

Triboelectric spray ionization

Triboelectric spray ionization (TESI) is a variation of electrospray ionization (ESI) using common instrumental components, including gas flow, solvent flow rate and heat, the only difference being the use of a high‐voltage power supply for ESI or a static charge for TESI. The ionization of solvent or analyte is due to the electrostatic potential difference formed between the spray electrode and counter electrode. The ion source contains a pneumatic spray operated over a range of flow rates (0.15–1.5 µl/min) and gas pressures (0–100). This new design contains a standalone spray assembly and an optional metal mesh in front of the spray. There are several parameters that affect the performance during ionization of molecules including the flow rate of solvent, gas pressure, temperature, solvent acidity, distance and potential difference between emitter and counter electrode. A variable electrostatic potential can be applied for higher ionization efficiency. The new ionization method was successfully applied to solutions of various proteins under different conditions. The same charge‐state distributions compared to other ESI techniques are observed for all the protein samples. The unique feature of TESI is very efficient spraying by using a natural electrostatic potential even at the potential that a human body can produce. This provides very gentle ionization efficiency of peptides and proteins in different solvents. Copyright © 2013 John Wiley & Sons, Ltd.     

Two-photon ionization thresholds of matrix-assisted laser desorption/ionization matrix clusters

Direct two-photon ionization of the matrix has been considered a likely primary ionization mechanism in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. This mechanism requires that the vertical ionization threshold of matrix materials be below twice the laser photon energy. Because dimers and larger aggregates may be numerous in the early stages of the MALDI plume expansion, their ionization thresholds are important as well. We have used two-color two-photon ionization to determine the ionization thresholds of jet cooled clusters of an important matrix, 2,5-dihydroxy benzoic acid (DHB), and mixed clusters with the thermal decomposition product of DHB, hydroquinone. The thresholds of the clusters were reduced by only a few tenths of an eV compared to the monomers, to an apparent limit of 7.82 eV for pure DHB clusters. None of the investigated clusters can be directly ionized by two nitrogen laser photons (7.36 eV), and the ionization efficiency at the thresholds is low.     

Photofragmentation study of hexamethyldisiloxane following core ionization and direct double ionization

X-ray photoelectron spectroscopy and Auger spectroscopy studies of gas-phase hexamethyldisiloxane (HMDSO) are presented. The photodissociation of this molecule is studied using various experimental coincidence techniques. We compare the fragmentation pathways observed after core ionization followed by Auger decay and after valence double photoionization of the molecule. A strongly selective production of the doubly charged tetramethyldisiloxane ion is observed in the low binding-energy regions. Theoretical calculations are carried out to tentatively explain the stability of the produced dication.     

Enhancement of ionization efficiency of mass spectrometric analysis from non-electrospray ionization friendly solvents with conventional and novel ionization techniques

Electrospray ionization mass spectrometry (ESI-MS) has significantly impacted the analysis of complex biological and petroleum samples. However ESI-MS has limited ionization efficiency for samples in low dielectric and low polarity solvents. Addition of a make-up solvent through a T union or electrospray solvent through continuous flow extractive desorption electrospray ionization (CF-EDESI) enable ionization of analytes in non-ESI friendly solvents. A conventional make-up solvent addition setup was used and a CF-EDESI source was built for ionization of nitrogen-containing standards in hexane or hexane/isopropanol. Factors affecting the performance of both sources have been investigated and optimized. Both the make-up solvent addition and CF-EDESI improve the ionization efficiency for heteroatom compounds in non-ESI friendly solvents. Make-up solvent addition provides higher ionization efficiency than CF-EDESI. Neither the make-up solvent addition nor the CF-EDESI eliminates ionization suppression of nitrogen-containing compounds caused by compounds of the same chemical class.     

Characterization of polyethylenimine by electrospray ionization and matrix-assisted laser desorption/ionization

Branched polyethylenimines (PEIs) with lower average molecular weights (600, 1200 and 1800 Da) have been studied by Electrospray Ionization (ESI) and Matrix‐Assisted Laser Desorption/Ionization (MALDI) mass spectrometry. In both, ESI and MALDI mass spectra, the main distribution arises from protonated PEI oligomers with NH₂ end groups, [PEI + H]⁺, which are observed at m/z 43n + 18. A trace of sodium contamination in the PEI samples results in the presence of a series that appears at m/z 43n + 40 [PEI + Na]⁺. However, only the MALDI mass spectra show a [PEI + K]⁺ series at m/z 43n + 56, because of matrix contamination with potassium, and a series generated by condensation of the matrix with PEI at m/z 43n + 30. Collisionally activated dissociation tandem mass spectrometry (CAD (MS/MS)) of protonated PEI oligomers is shown to yield three fragment ion series b_n, and K_n. The experiments have demonstrated the capabilities of these mass spectrometry techniques, along with CAD MS/MS to detect and characterize such polar synthetic polymers. Copyright © 2011 John Wiley & Sons, Ltd.     

Electron ionization and chemical ionization mass spectra of pyridinium and isoquinolinium ylides

Electron ionization (EI) spectra and both positive and negative chemical ionization (CI) spectra have been obtained for four isoquinolinium ylides and two pyridinium ylides. Electron transfer reactions dominate the CI mass specra. The base peak in negative chemical ionization is the [M]^?· ion, formed by electron capture. In the positive methane CI spectra the molecular ion, [M]^+·, is relatively more intense than [MH]⁺ showing electron transfer to be the main positive ionization process. In the positive ammonia CI spectra, proton transfer to give [MH]⁺ is the main ionization process, but electron transfer is also observed. The EI spectra show fragmentations in which the aromatic nitrogen moiety retains the charge and fragmentation is by loss of radicals or small neutral molecules from the side-chains. Radical driven reactions are proposed to explain these spectra.     

Gas spherical ionization chamber

A pressurized ionization chamber detector able to measure radioactive sources in internal 2π or 4π geometry was built in order to characterize alpha and beta radioactive sources, i.e. to calibrate these sources by a relative method, and to test the behavior of gas mixtures in pressurized-gas radiation detectors. The detector we made is of spherical shape and works by collecting in a quasi-uniform electric field the ionization charges resulting from the interaction of ionizing radiation with gas in the sensitive volume of the chamber. An ionizing current proportional to the activity of the radioactive source to be measured is obtained. Pressure inside the detector in standard conditions is maximum 6 × 10⁵ Pa at 22 °C and the maximum allowed voltage is 3000 V. It is presented as a spherical ionization chamber with gas under pressure, geometrical shape, dimensions and structural characteristics, functional and technical parameters and preliminary experimental results obtained from radiation measurements in the laboratory SALMROM of the IFIN-HH.     

Ultrasound ionization of biomolecules

To date, mass spectrometric analysis of biomolecules has been primarily performed with either matrix‐assisted laser desorption/ionization (MALDI) or electrospray ionization (ESI). In this work, ultrasound produced by a simple piezoelectric device is shown as an alternative method for soft ionization of biomolecules. Precursor ions of proteins, saccharides and fatty acids showed little fragmentation. Cavitation is considered as a primary mechanism for the ionization of biomolecules. Copyright © 2010 John Wiley & Sons, Ltd.     

Molecule/radical reactions prior to ionization under negative chemical ionization conditions

It is shown that alkyl radical species present in CH₄ or iso-C₄H₁₀ plasma can react with substrate molecules to give [M+C_nH_2n] species. These species become evident especially in negative chemical ionization as [M+C_nH_2n]^?˙ and, less obviously, in positive chemical ionization as [M+C_nH_2n+1]⁺ ions which, for example in natural products chemistry, may be mistaken for a series of homologous compounds present in the sample.     

Reactions between substrate molecules and chemical ionization reagent gases prior to ionization

A survey of side reactions such as oxidation, hydrogenation, reductive removal of substituents and radical processes is presented, and the implications for mass spectroscopic analysis are pointed out.     

Efficiency of nano-electrospray ionization

The efficiency of nano-electrospray ionization, defined as the flux of ions reaching the detector of a triple-quadrupole mass spectrometer divided by the flux of analyte ions leaving the needle, has been measured in a series of controlled experiments with dodecyltrimethyl ammonium (DDTMA) bromide, myoglobin, Glu- [1]-fibrinopeptide, and gramicidin S. By varying the flow rate from each needle, the optimum efficiency was determined. In general, the efficiency increased as the flow rate decreased. For DDTMA, efficiencies of up to 12% were measured, although efficiencies of approximately 1% were more common. Ion current measurements indicated efficient transfer of ions from the needle through to the detector. Significant needle-to-needle variations in efficiency were encountered and attributed to variations in ion-generation efficiency.     

Towards the electrospray ionization mass spectrometry ionization efficiency scale of organic compounds

An approach that allows setting up under predefined ionization conditions a rugged self-consistent quantitative experimental scale of electrospray ionization (ESI) efficiencies of organic compounds is presented. By ESI ionization efficiency (IE) we mean the efficiency of generating gas-phase ions from analyte molecules or ions in the ESI source. The approach is based on measurement of relative ionization efficiency (RIE) of two compounds (B1 and B2) by infusing a solution containing both compounds at known concentrations (C1 and C2) and measuring the mass-spectrometric responses of the protonated forms of the compounds (R1 and R2). The RIE of B1 and B2 is expressed as logRIE(B1, B2) = log[(R1 . C2)/(C1 . R2)]. The relative way of measurement leads to cancellation of many of the factors affecting IE (ESI source design, voltages in the source and ion transport system, solvent composition, flow rates and temperatures of the nebulizing and drying gases). Using this approach an ESI IE scale containing ten compounds (esters and aromatic amines) and spanning over 4 logRIE units has been compiled. The consistency of the scale (the consistency standard deviation of the scale is s = 0.16 logRIE units) was assured by making measurements using different concentration ratios (at least 6-fold concentration ratio range) of the compounds and by making circular validation measurements (the logRIE of any two compounds was checked by measuring both against a third compound).     

Electron ionization of acetylene

Relative partial ionization cross sections and precursor specific relative partial ionization cross sections for fragment ions formed by electron ionization of C2H2 have been measured using time-of-flight mass spectrometry coupled with a 2D ion-ion coincidence technique. We report data for the formation of H+, H+2, C2+, C+/C2+ 2, CH+/C2H+2, CH+2, C+2, and C2H+ relative to the formation of C2H+2, as a function of ionizing electron energy from 30-200 eV. While excellent agreement is found between our data and one set of previously published absolute partial ionization cross sections, some discrepancies exist between the results presented here and two other recent determinations of these absolute partial ionization cross sections. We attribute these differences to the loss of some translationally energetic fragment ions in these earlier studies. Our relative precursor-specific partial ionization cross sections enable us, for the first time, to quantify the contribution to the yield of each fragment ion from single, double, and triple ionization. Analysis shows that at 50 eV double ionization contributes 2% to the total ion yield, increasing to over 10% at an ionizing energy of 100 eV. From our ion-ion coincidence data, we have derived branching ratios for charge separating dissociations of the acetylene dication. Comparison of our data to recent ab initio/RRKM calculations suggest that close to the double ionization potential C2H2+2 dissociates predominantly on the ground triplet potential energy surface (3Sigma*g) with a much smaller contribution from dissociation via the lowest singlet potential energy surface (1Delta g). Measurements of the kinetic energy released in the fragmentation reactions of C2H2+2 have been used to obtain precursor state energies for the formation of product ion pairs, and are shown to be in good agreement with available experimental data and with theory.     

Differentiation of diastereomeric N-aryltetrahydropyrano/tetrahydrofuranochromenylamines under electron ionization and chemical ionization conditions

A series of diastereomeric 4S,5S,6R/S-tetrahydropyrano- and 3S,4S,5R/S-tetrahydrofuranochromenylamine derivatives (a/b isomers; 1-26) has been studied under electron ionization (EI) and chemical ionization (CI) conditions. The EI mass spectra of all diastereomeric compounds show two characteristic fragment ions, of which one is formed by retro-Diels-Alder (RDA) reaction from the molecular ion, retaining the charge on the diene fragment, and the other [M-(HNAr)]+ ion by a simple radical loss. The RDA process is more favorable in all b isomers, whereas the radical loss is dominant in all a isomers; based on these two ions it is easy to differentiate the two diastereomers. The collision-induced dissociation (CID) spectra of all the molecular ions also show the same trend, which reflects the stereoselectivity in the formation of the two characteristic fragment ions. The results of theoretical calculations performed are in accordance with the experimental observations. The CI experiments (methane and isobutane) on all the diastereomeric compounds also enabled the differentiation of the isomers.