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nH-Perfluoroalkyl carboxylic acids (nH-PFCAs) are emerging pollutants. Their identification by ion mobility is frustrated by the nH-PFCAs having unexpectedly small collision cross sections (CCS). Theory and experiment agree that this is because nH-PFCA ions undergo internal hydrogen bridging, and this insight will help guide the creation of more accurate methods for pollutant identification. [ABSTRACT FROM AUTHOR]

The recent accurate and precise determination of the electron affinity (EA) of the astatine atom At0 warrants a re‐investigation of the estimated thermodynamic properties of At0 and astatine containing molecules as this EA was found to be much lower (by 0.4 eV) than previous estimated values. In this contribution we estimate, from available data sources, the following thermodynamic and physicochemical properties of the alkali astatides (MAt, M = Li, Na, K, Rb, Cs): their solid and gaseous heats of formation, lattice and gas‐phase binding enthalpies, sublimation energies and melting temperatures. Gas‐phase charge‐transfer dissociation energies for the alkali astatides (the energy requirement for M+At− ➔ M0 + At0) have been obtained and are compared with those for the other alkali halides. Use of Born‐Haber cycles together with the new AE (At0) value allows the re‐evaluation of ΔHf (At0)g (=56 ± 5 kJ/mol); it is concluded that (At2)g is a weakly bonded species (bond strength <50 kJ/mol), significantly weaker bonded than previously estimated (116 kJ/mol) and much weaker bonded than I2 (148 kJ/mol), but in agreement with the finding from theory that spin‐orbit coupling considerably reduces the bond strength in At2. The hydration enthalpy (ΔHaq) of At− is estimated to be −230 ± 2 kJ/mol (using ΔHaq[H+] = −1150.1 kJ/mol), in good agreement with molecular dynamics calculations. Arguments are presented that the largest alkali halide, CsAt, like the smallest, LiF, will be only sparingly soluble in water, following the generalization from hard/soft acid/base principles that "small likes small" and "large likes large." [ABSTRACT FROM AUTHOR]

The recent accurate and precise determination of the electron affinity (EA) of the astatine atom At0 warrants a re‐investigation of the estimated thermodynamic properties of At0 and astatine containing molecules as this EA was found to be much lower (by 0.4 eV) than previous estimated values. In this contribution we estimate, from available data sources, the following thermodynamic and physicochemical properties of the alkali astatides (MAt, M = Li, Na, K, Rb, Cs): their solid and gaseous heats of formation, lattice and gas‐phase binding enthalpies, sublimation energies and melting temperatures. Gas‐phase charge‐transfer dissociation energies for the alkali astatides (the energy requirement for M+At− ➔ M0 + At0) have been obtained and are compared with those for the other alkali halides. Use of Born‐Haber cycles together with the new AE (At0) value allows the re‐evaluation of ΔHf (At0)g (=56 ± 5 kJ/mol); it is concluded that (At2)g is a weakly bonded species (bond strength <50 kJ/mol), significantly weaker bonded than previously estimated (116 kJ/mol) and much weaker bonded than I2 (148 kJ/mol), but in agreement with the finding from theory that spin‐orbit coupling considerably reduces the bond strength in At2. The hydration enthalpy (ΔHaq) of At− is estimated to be −230 ± 2 kJ/mol (using ΔHaq[H+] = −1150.1 kJ/mol), in good agreement with molecular dynamics calculations. Arguments are presented that the largest alkali halide, CsAt, like the smallest, LiF, will be only sparingly soluble in water, following the generalization from hard/soft acid/base principles that "small likes small" and "large likes large." [ABSTRACT FROM AUTHOR]

We report here on the use of a prototype matrix-assisted laser desorption/ionization (MALDI)-triple quadrupole mass spectrometer for quantitative analysis of six antiretroviral drugs in lysates of peripheral blood mononuclear cells (PBMC). Of the five investigated MALDI matrixes, 2,5-dihydroxybenzoic acid (DHB) and the novel 7-hydroxy-4-(trifluoromethyl)coumarin (HFMC) showed the broadest application ranges for the antiretroviral drugs. For DHB, the mean relative errors ranged from 8.3 (ritonavir) to 4.3% (saquinavir). The mean precisions (CV) ranged from 17.3 (nevirapine) to 10.8% (saquinavir). The obtained lower limits of quantitation (LLOQ) readily allow clinical applications using just I million PBMC from HIV-infected patients under therapy. The new matrix HFMC was used for quantitative analysis of the HW protease inhibitor indinavir using a stainless steel target plate as well as a target plate with a novel, strongly hydrophobic fluoropolymer coating. Using the coated target plate, the mean relative error improved from 10.1 to 4.6%, the mean precision from 33.9 to 9.9% CV, and the LLOQ from 16 to 1 fmol. In addition, the measurement time for one spot went down from 6 to only 2.5 s.

In this report we explore the use of MALDI-FTICR mass spectrometry for the quantitative analysis of five HIV-1 protease inhibitors in cell lysates. 2,5-Dihydroxybenzoic acid (DHB) was used as the matrix. From a quantitative perspective, DHB is usually a poor matrix due to its poor shot-to-shot and poor spot-to-spot reproducibilities. We found that the quantitative precisions improved significantly when DMSO (dimethylsulfoxide) was added to the matrix solution. For lopinavir and ritonavir, currently the most frequently prescribed HIV-1 protease inhibitors, the signal-to-noise ratios improved significantly when potassium iodide was added to the matrix solution. The mean quantitative precisions, expressed as % relative standard deviation, were 6.4% for saquinavir, 7.3% for lopinavir, 8.5% for ritonavir, 11.1% for indinavir, and 7.2% for nelfinavir. The mean quantitative accuracies, expressed as % deviation, were 4.5% for saquinavir, 6.0% for lopinavir, 5.9% for ritonavir, 6.6% for indinavir, and 8.0% for nelfinavir. The concentrations measured for the individual quality control samples were all within 85-117% of the theoretical concentrations. The lower limits of quantification in cell lysates were 4 fmol/[micro]L for saquinavir, 16 fmol/[micro]L for lopinavir, 31 fmol/[micro]L for ritonavir, and 100 fmol/[micro]L for indinavir and nelfinavir. The mean mass accuracies for the protease inhibitors were [greater than or equal to] 40.28 ppm using external calibration. Our results show that MALDI-FTICR mass spectrometry can be successfully used for precise, accurate, and selective quantitative analyses of HW-1 protease inhibitors in cell lysates. In addition, the lower limits of quantification obtained allow clinical applications of the technique.

In this report, we discuss key issues for the successful application of MALDI-TOF mass spectrometry to quantify drugs. These include choice and preparation of matrix, nature of cationization agent, automation, and data analysis procedures. The high molecular weight matrix mesotetrakis(pentafluorophenyl)porphyrin eliminates chemical noise in the low-mass range, a 'brushing' spotting technique in combination with prestructured target plates enables fast preparation of homogeneous matrix crystals, and addition of [Li.sup.+] leads to intense cationized drug species. Complex biological samples were cleaned up using a 96-well solid-phase extraction plate, and the purified samples were automatically spotted by a pipetting robot. To obtain a suitable data analysis procedure for the quantitative analysis of drugs by MALDI-TOF mass spectrometry, various data processing parameters were evaluated on our two model drugs lopinavir and ritonavir. Finally, and most importantly, it is shown that the above-described procedure can be successfully applied to quantify clinically relevant concentrations of lopinavir, an HIV protease inhibitor, in extracts of small numbers of peripheral blood mononuclear cells (1 X [10.sup.6]).

Previous experimental studies of the water elimination from ionized ethyl acetate (EA-1) and its enol, C[H.sup.2]=C(OH)O[C.sub.2][H.sub.5.sup..+] (EA-2), provide no mechanistic proposals, but note that the reaction is complex because all hydrogen atoms and both oxygen atoms participate. Loss of [H.sub.2]O is the predominant process observed for the metastable ions, yielding ionized methyl vinyl ketone, C[H.sub.3]C(=O)CH=C[H.sub.2.sub.+] (MVK), as the product ion. Metastable keto-alcohol ions C[H.sub.3]C(=O)C[H.sub.2]C[H.sub.2]O[H.sup..+] (HB-1) also abundantly lose [H.sub.2]O, yielding MVK at the thermochemical threshold. Using the CBS-QB3 model chemistry and complementary RRKM calculations, we have examined plausible mechanisms for the water elimination from metastable ions EA-1/2 and HB-1. Our calculations support the proposal that (i) ions HB-1 dissociate into MVK at the thermochemical threshold via a 1,4-H shift and a consecutive [1,2]-hydroxycarbene shift, and (ii) ions EA-1/2 undergo a three-step isomerization reaction into HB-1, which serves as the precursor for the ensuing water elimination. It is further shown that synergy between theory and experiment leads to a complex, yet transparent, mechanistic picture of the isomerization and dissociation behaviour of ionized ethyl acetate, which accounts for the labelling results. Key words: tandem mass spectrometry, CBS-QB3 model chemistry, reaction mechanism, hydroxycarbene shift. Les etudes experimentales anterieures sur l'elimination d'eau a partir d'acetate d'ethyle ionise (EA-1) et de son enol, C[H.sub.2]=C(OH)O[C.sub.2][H.sub.5.sup..+] (EA-2) ne permettent pas de faire des propositions relatives au mecanisme, mais indiquent que la reaction est complexe parce que tousles atomes d'hydrogene ainsi que les deux atomes d'oxygene participent. La perte de [H.sub.2]O est le processus predominant qui est observe avec les ions metastables et elle conduit a la formation de methylvinylcetone ionisee, C[H.sub.3]C(=O)CH=C[H.sub.2.sup..+] (MVK), comme produit ionique. Au seuil thermodynamique, les ions du ceto-alcool metastable, C[H.sub.3]C(=O)C[H.sub.2]C[H.sub.2]O[H.sup..+] (HB-l) perdent aussi abondamment de l'eau pour conduire a la formation de MVK. Utilisant la modelisation chimique CBS-QB3 et des calculs RRKM complementaires, on a examine divers mecanismes plausibles pour l'elimination d'eau a partir des ions metastables EA-1/2 et HB-1. Les resultats de ces calculs confirment la proposition a l'effet que (i) au seuil thermodynamique, les ions HB-1 se dissocient en MVK par le biais d'un deplacement 1,4 d'hydrogene et un deplacement [1,2]-hydroxycarbene consecutif et (ii) les ions EA-1/2 subissent une reaction d'isomerisation en trois etapes qui conduit au HB-1 qui sert de precurseur pour l'elimination d'eau qui suit. On a aussi demontre qu'une synergie entre la theorie et les experiences conduisent une proposition de mecanisme, transparente malgre sa complexite, pour l'isomerisation de l'acetate d'ethyle ionise et le comportement de sa dissociation qui permet de tenir compte des resultats de marquage. Mots cles : spectroscopie de masse en tandem, modelisation chimique CBS-QB3, mecanisme reactionnel, deplacement d' hydroxycarbene. [Traduit par la Redaction], Introduction Since the inception of electron ionization (EI) mass spectrometry as a powerful method for the structure analysis of organic molecules in the mid 1950s, the gas-phase ion chemistry of [...]

The enthalpy of formation of the methoxycarbonyl ion was investigated using ab initio molecular orbital calculations at the Gaussian-2 level of theory. Results suggested that the heat of formation of the methoxycarbonyl cation, CH3OC=O+ and some of its key isomers should be revised to CH3-O-C+=O. The revised enthalpy value was found to lead to a 13 kcal/mol stabilization due to the methyl substitution in H-O-C+=O.

The mechanics of dissociation of ionized 1,2-ethanediol and 1,2-propanediol was investigated using ab initio molecular orbital measurements. Results confirmed the hypothesis that the key processes in the rearrangement of HOCH2CH2OH(super *-) and HOCH2CH(CH3)OH(super *-) are sequential transfers of a proton and an electron occurring from one partner to other in ion-dipole compounds rather than prompt hydrogen atoms shifts occurring in distonic ions.

Fragmentation of methyl formate cation radical through the CH3OH...C=O.+ hydrogen-bridged complex was studied using mass spectrometric methods and ab initio moleclar orbital calculations. The radical's unimolecular dissociation was found to be similar with that of ionized methyl acetate. Moreover, the process resulted in the formation of either CH3OH.+ or CH2OH+ ions with varying charge and spin properties. The experimental data regarding the unimolecular rearrangement of the cation were consistent with theoretical calculations.

Abstract Background A Java™ application is presented, which compares large numbers (n > 100) of raw FTICR mass spectra from patients and controls. Two peptide profile matrices can be produced simultaneously, one with occurrences of peptide masses in samples and another with the intensity of common peak masses in all the measured samples, using the peak- and background intensities of the raw data. In latter way, more significantly differentially expressed peptides are found between groups than just using the presence or absence in samples of common peak masses. The software application is tested by searching angiogenesis related proteins in glioma by comparing laser capture micro dissected- and enzymatic by trypsin digested tissue sections. Results By hierarchical clustering of the presence-absence matrix, it appears that proteins, such as hemoglobin alpha and delta subunit, fibrinogen beta and gamma chain precursor, tubulin specific chaperone A, epidermal fatty acid binding protein, neutrophil gelatinase-associated lipocalin precursor, peptidyl tRNA hydrolase 2 mitochondrial precursor, placenta specific growth hormone, and zinc finger CCHC domain containing protein 13 are significantly different expressed in glioma vessels. The up-regulated proteins in the glioma vessels with respect to the normal vessels determined by the Wilcoxon-Mann-Whitney test on the intensity matrix are vimentin, glial fibrillary acidic protein, serum albumin precursor, annexin A5, alpha cardiac and beta actin, type I cytoskeletal 10 keratin, calcium binding protein p22, and desmin. Peptide masses of calcium binding protein p22, Cdc42 effector protein 3, fibronectin precursor, and myosin-9 are exclusively present in glioma vessels. Some peptide fragments of non-muscular myosin-9 at the C-terminus are strongly up-regulated in the glioma vessels with respect to the normal vessels. Conclusion The less rigorous than in general used commercial propriety software de-isotope algorithm results in more mono-isotopic peptide masses and consequently more proteins. Centroiding of peptide masses takes place by taking the average over more spectra in the profile matrix. Cytoskeleton proteins and proteins involved in the calcium signaling pathway seem to be most up-regulated in glioma vessels. The finding that peptides at the C-terminus of myosin-9 are up-regulated could be ascribed to splicing or fragmentation by proteases.