Ákos Kuki

Size effect on fragmentation in tandem mass spectrometry

The collision energy or collision voltage necessary to obtain 50% fragmentation (characteristic collision energy/voltage, CCE or CCV) has been systematically determined for different types of molecules [poly(ethylene glycols) (PEG), poly(tetrahydrofuran) (PTHF), and peptides] over a wide mass (degrees of freedom) range. In the case of lithium-cationized PEGs a clear linear correlation (R(2) > 0.996) has been found between CCE and precursor ion mass on various instrument types up to 4.5 kDa. A similar linear correlation was observed between CCV and the mass-to-charge ratio. For singly and multiply charged polymers studied under a variety of experimental conditions and on several instruments, all data were plotted together and showed correlation coefficient R(2) = 0.991. A prerequisite to observe such a good linear correlation is that the energy and entropy of activation in a class of polymers is likely to remain constant. When compounds of different structure are compared, the CCV will depend not only on the molecular mass but the activation energy and entropy as well. This finding has both theoretical and practical importance. From a theoretical point of view it suggests fast energy randomization up to at least 4.5 kDa so that statistical rate theories are applicable in this range. These results also suggest an easy method for instrument tuning for high-throughput structural characterization through tandem MS: after a standard compound is measured, the optimum excitation voltage is in a simple proportion with the mass of any structurally similar analyte at constant experimental conditions.

Identification of silymarin constituents: An improved HPLC-MS method

A high-performance liquid chromatographic/tandem mass spectrometric method was developed for the determination of the major bioactive flavonolignans in silymarin, a herbal remedy extracted from the milk thistle Silybum marianum. In this study, eight active components of silymarin with the same elemental composition, including silychristins A and B, silydianin, silybin A and B, isosilybin A and B and an unknown compound were completely separated. Furthermore, three additional components were detected and partly separated; presumably two silybin stereoisomers and one isosilybin stereoisomer. The collision-induced dissociation (CID) MS/MS spectra of these silymarin constituents were studied: the spectral similarity values of the component pairs were determined, and simple criteria were found for distinguishing the components.

Energy-dependent collision-induced dissociation of lithiated polytetrahydrofuran: Effect of the size on the fragmentation properties

The fragmentation properties of singly and doubly lithiated polytetrahydrofuran (PTHF) were studied using energy-dependent collision-induced dissociation. The product ion spectrum of [PTHF + Li]+ showed the formation of three different series corresponding to product ions with hydroxyl, aldehyde and vinyl end-groups. Interestingly, besides these series, two additional, non-lithiated product ions C4H9O+ and C4H7+ were identified in the MS/MS spectra. The MS/MS of the doubly lithiated PTHF ([PTHF + 2Li]2+) with a number of repeat units ranging from 8 to 27 showed the formation of product ions similar to those of the singly lithiated series, however, doubly lithiated product ions and product ions formed by the loss of one Li+-ion from the precursor ion also appeared with significant abundances. Analysis of the breakdown curves for the singly and doubly charged PTHF indicated that the series A ions are formed most probably together with the series B ions, while members of the series C ions appeared at significantly higher collision energies. The fragmentation properties of [PTHF + Li]+ and [PTHF + 2Li]2+ were also interpreted using the survival yield method. It was found that the collision energy/voltage necessary to obtain 50% fragmentation (CV50) was dependent linearly on the number of the repeat units, i.e., on the size, or the number of degrees of freedom (DOF).

Estimation of Activation Energy from the Survival Yields: Fragmentation Study of Leucine Enkephalin and Polyethers by Tandem Mass Spectrometry

AbstractA simple collision model for multiple collisions occurring in quadrupole type mass spectrometers was derived and tested with leucine enkaphalin a common mass spectrometric standard with well-characterized properties. Implementation of the collision model and Rice-Ramsperger-Kassel-Marcus (RRKM) algorithm into a spreadsheet software allowed a good fitting of the calculated data to the experimental survival yield (SY) versus collision energy curve. In addition, fitting also ensured to estimate the efficiencies of the kinetic to internal energy conversion for Leucine enkephalin in quadrupole-time-of-flight and triple quadrupole instruments. It was observed that the experimental SY versus collision energy curves for the leucine enkephalin can be described by the Rice-Ramsperger-Kassel (RRK) formalism by reducing the total degrees of freedom (DOF) to about one-fifth. Furthermore, this collision model with the RRK formalism was used to estimate the critical energy (Eo) of lithiated polyethers, including polyethylene glycol (PEG), polypropylene glycol (PPG), and polytetrahydrofurane (PTHF) with degrees of freedom similar to that of leucine enkephalin. Applying polyethers with similar DOF provided the elimination of the effect of DOF on the unimolecular reaction rate constant. The estimated value of Eo for PEG showed a relatively good agreement with the value calculated by high-level quantum chemical calculations reported in the literature. Interestingly, it was also found that the Eo values for the studied polyethers were similar. Figureᅟ

Dopant-Assisted Atmospheric Pressure Photoionization Mass Spectrometry of Polyisobutylene Derivatives Initiated by Mono- and Bifunctional Initiators

Nine polyisobutylene (PIB) derivatives with different end groups (chlorine, vinyl, isobutenyl, 2,2-diphenylvinyl, and carboxyl) and molecular weights (1000 to 4500 g/mol), initiated by monofunctional and aromatic bifunctional initiators were studied by atmospheric pressure photoionization mass spectrometry (APPI-MS) in both negative and positive ion modes. Consistent with previous findings, negative ion APPI-MS revealed end-group identities through the formation of PIB adducts with chloride ions formed in situ from a chlorinated solvent (e.g., CCl4) in the presence of a dopant (toluene). In positive ion mode, considerable fragmentation of these PIB derivatives was observed, rendering end-group determinations very difficult. The Mn values obtained by APPI(−)-MS were considerably lower than those determined by SEC for PIB derivatives with Mn higher than 2000 g/mol. PIBs containing carboxyl termini can undergo collision-induced dissociation, yielding structurally important product ions. The resulting APPI-MS/MS intensities were found to reflect the “arm-length” distribution for PIBs with bifunctional aromatic moieties. In positive ion mode, [M+COCl]+ adducts were observed for PIBs with an aromatic initiator moiety. The origin of the COCl+ species is also discussed.

Rapid detection of hazardous chemicals in textiles by direct analysis in real-time mass spectrometry (DART-MS).

Residues of chemicals on clothing products were examined by direct analysis in real-time (DART) mass spectrometry. Our experiments have revealed the presence of more than 40 chemicals in 15 different clothing items. The identification was confirmed by DART tandem mass spectrometry (MS/MS) experiments for 14 compounds. The most commonly detected hazardous substances were nonylphenol ethoxylates (NPEs), phthalic acid esters (phthalates), amines released by azo dyes, and quinoline derivates. DART-MS was able to detect NPEs on the skin of the person wearing the clothing item contaminated by NPE residuals. Automated data acquisition and processing method was developed and tested for the recognition of NPE residues thereby reducing the analysis time.

Theoretical size distribution in linear step-growth polymerization for a small number of reacting species.

The size distributions for the linear step-growth polymerization containing a relatively small number of molecules (in the range of 20-10000) have been calculated using computer simulations. Contrary to the most probable distribution of Flory, which predicts a continuous linear increase of the polydispersity index (PDI) from the value of 1 to 2, it has been found that the PDI increases up to a certain maximum value followed by a decrease to unity as the extent of conversion (p) approaches unity. The maxima of the PDI versus p curves as well as the sharpness of the decrease of these curves to unity have been found to strongly depend on the number of reacting species. In addition, on the basis of a rigorous statistical treatment, the number and the weight-average size distributions have been derived, which are in perfect agreement with those obtained by computer simulation. Furthermore, the derived distributions can also be applied for the description of reaction products of depolymerization reactions.

A simple method to estimate relative stabilities of polyethers cationized by alkali metal ions

Dissociation of doubly cationized polyethers, namely [P + 2X](2+) into [P + X](+) and X(+), where P = polyethylene glycol (PEG), polypropylene glycol (PPG) and polytetrahydrofuran (PTHF) and X = Na, K and Cs, was studied by means of energy-dependent collision-induced dissociation tandem mass spectrometry. It was observed that the collision voltage necessary to obtain 50% fragmentation (CV(50)) determined for the doubly cationized polyethers of higher degree of polymerization varied linearly with the number of degrees of freedom (DOF) values. This observation allowed us to correlate these slopes with the corresponding relative gas-phase dissociation energies for binding of alkali ions to polyethers. The relative dissociation energies determined from the corresponding slopes were found to decrease in the order Na(+)  > K(+)  > Cs(+) for each polyether studied, and an order PPG ≈ PEG > PTHF can be established for each alkali metal ion.

Star-shaped micelles of polyisobutylene–polystyrene–polyisobutylene triblock copolymer in hexane solution

Abstract Polyisobutylene–polystyrene–polyisobutylene (PIB–PS–PIB) triblock copolymer was synthesized and studied in dilute hexane, toluene and tetrahydrofuran solution by the laser dynamic light scattering method. Star-shaped micelles were observed in hexane which is a good solvent for the PIB segments but a bad solvent for the PS segments. The diameters of the hard core and the micelle were estimated and the size and the size distribution of micelles were also determined by dynamic light scattering.

Direct analysis in real time mass spectrometry (DART-MS) of highly non-polar low molecular weight polyisobutylenes

Low molecular weight polyisobutylenes (PIB) with chlorine, olefin and succinic acid end-groups were studied using direct analysis in real time mass spectrometry (DART-MS). To facilitate the adduct ion formation under DART conditions, NH4 Cl as an auxiliary reagent was deposited onto the PIB surface. It was found that chlorinated adduct ions of olefin and chlorine telechelic PIBs, i.e. [M + Cl]- up to m/z 1100, and the deprotonated polyisobutylene succinic acid [MH]- were formed as observed in the negative ion mode. In the positive ion mode formation of [M + NH4 ]+ , adduct ions were detected. In the tandem mass (MS/MS) spectra of [M + Cl]- , product ions were absent, suggesting a simple dissociation of the precursor [M + Cl]- into a Cl- ion and a neutral M without fragmentation of the PIB backbones. However, structurally important product ions were produced from the corresponding [M + NH4 ]+ ions, allowing us to obtain valuable information on the arm-length distributions of the PIBs containing aromatic initiator moiety. In addition, a model was developed to interpret the oligomer distributions and the number average molecular weights observed in DART-MS for PIBs and other polymers of low molecular weight. Copyright