Mass spectrometry intermediate-pressure

TTigh pressure mass spectrometry has recently provided much detailed kinetic data (5, 12, 13, 14, 15, 17, 22, 24, 26, 29) concerning ionic reactions heretofore unobtainable by other means. This information has led to increased understanding of primary reaction processes and the fate of ionic intermediates formed in these processes but under conditions distinctly different from those which prevail in irradiated gases near room temperature and near atmospheric pressure. Conclusive identification and measurements of the rate constants of ionic reactions under the latter conditions remain as both significant and formidable problems. 

These data thus show that high-pressure mass spectrometry can, in addition to its many other impressive capabilities, be a powerful tool for the determination of lifetimes of transient intermediates on the 10 s timescale. 

At the higher pressures of other ion-molecule techniques, such as flowing afterglow or pulsed high-pressure mass spectrometry," both of which operate with a bath gas pressure of about 1 torr, collisions of such an excited intermediate with the bath gas occur on a nanosecond to microsecond time-scale, in competition with the unimolecular dissociation rate. For these techniques, ions that are the... 

The development of mass spectrometric ionization methods at atmospheric pressures (API), such as the atmospheric pressure chemical ionization (APCI)99 and the electrospray ionization mass spectrometry (ESI-MS)100 has made it possible to study liquid-phase solutions by mass spectrometry. Electrospray ionization mass spectrometry coupled to a micro-reactor was used to investigate radical cation chain reaction is solution101. The tris (p-bromophenyl)aminium hexachloro antimonate mediated [2 + 2] cycloaddition of trans-anethole to give l,2-bis(4-methoxyphenyl)-3,4-dimethylcyclobutane was investigated and the transient intermediates 9 + and 10 + were detected and characterized directly in the reacting solution. However, steady state conditions are necessary for the detection of reactive intermediates and therefore it is crucial that the reaction must not be complete at the moment of electrospray ionization to be able to detect the intermediates. 

Even a technique as complicated as direct liquid-introduction mass spectrometry has been coupled with reactor systems to provide real-time compositional analysis, as described in a series of articles by Dell Orco and colleagues.32-34 In their work, these authors used a dynamic dilution interface to provide samples in real time to un-modified commercial ionization sources (electrospray (ESI) and atmospheric pressure chemical ionization (APCI)). Complete speciation was demonstrated due to the unambiguous assignment of molecular weights to reactants, intermediates, and products. 

K. Giles, B.H. Bateman, Evaluation of a stacked-ring RF ion transmission device at intermediate pressures. Proceedings of the 49th ASMS Conference in Mass Spectrometry and Allied Topics, May 27-31,2001, Chicago, IL. 

Transient intermediates are most commonly observed by their absorption (transient absorption spectroscopy see ref. 185 for a compilation of absorption spectra of transient species). Various other methods for creating detectable amounts of reactive intermediates such as stopped flow, pulse radiolysis, temperature or pressure jump have been invented and novel, more informative, techniques for the detection and identification of reactive intermediates have been added, in particular EPR, IR and Raman spectroscopy (Section 3.8), mass spectrometry, electron microscopy and X-ray diffraction. The technique used for detection need not be fast, provided that the time of signal creation can be determined accurately (see Section 3.7.3). For example, the separation of ions in a mass spectrometer (time of flight) or electrons in an electron microscope may require microseconds or longer. Nevertheless, femtosecond time resolution has been achieved,186 187 because the ions or electrons are formed by a pulse of femtosecond duration (1 fs = 10 15 s). Several reports with recommended procedures for nanosecond flash photolysis,137,188-191 ultrafast electron diffraction and microscopy,192 crystallography193 and pump probe absorption spectroscopy194,195 are available and a general treatise on ultrafast intense laser chemistry is in preparation by IUPAC. 

Holcapek, M., Jandera, P., and Zderadicka, P., High performance liquid chromatography-mass spectrometric analysis of sulfonated dyes and intermediates, J. Chromatogr. A., 926,175-186, 2001 Reemtsma, T., The use of liquid chromatography-atmospheric pressure ionization-mass spectrometry in water analysis — 11 Obstacles, Trends Anal. Chem., 20, 533-542, 2001. 

Inutan, E.D. Wang, B. Trimpin, S., Commercial intermediate pressure MALDl ion mobiUty spectrometry mass spectrometer capable of producing highly charged laserspray ionization ions, AnoZ. Chem. 2011, 83, 678-684. 

Reich, R.F. CudzUo, K. Yost, R.A. Quantitative imaging of cocaine and its metabohtes in postmortem brain tissue by intermediate-pressure M ALDI/hnear in trap tandem mass spectrometry. Proc. 56 ASMS Conference on Mass Spectrometry arul Allied Topics, Denver, CO, June 1-5, 2008. 

Ion-Molecule Reactions In this approach, the structure of the target ion is determined by reacting it with a neutral molecule, and the products of the reaction are compared with those that result in a similar reaction with an ion of known structure. Reactions are conducted normally in the ion cyclotron resonance cell at a low pressure (ca. 10 torr) or in a quadrupole ion trap at a moderate pressure (ca. 10 torr). Sampled ions have a lifetime in the millisecond range and thus have survived fragmentation. Because those ion-molecule reactions that are detectable in mass spectrometry are usually exothermic, the intermediate adduct is rarely observed. Therefore, the structural features of the target ion or its adduct are derived from either the fragmentation pattern or from isotope-labeling experiments. 

Wang, C.-H., Huang, M.-W., Lee, C.-Y, Chei, H.-L., Huang, J.-P, Shiea, J. (1998) Detection of a Thermally Unstable Intermediate in the Wittig Reaction Using Low-temperature Liquid Secondary Ion and Atmospheric Pressure Ionization Mass Spectrometry. J. Am. Soc. Mass Spectrom. 9 1168-1174. 

Garrett, T.J., et al. (2006) Imaging of small molecules in tissue sections with a new intermediate-pressure MALDI linear ion trap mass spectrometer. International Journal of Mass Spectrometry,260,11. 

Applications of atmospheric pressure ionization mass spectrometry (API-MS) to the study of reaction intermediates and mechanisms are reviewed. API-MS, especially ESI-MS, has provided many opportunities to intercept and characterize the key intermediates from the reaction mixtures. Combined with tandem mass spectro-metric (MS/MS) methods, this technique has been extensively used for structural characterization of organic compounds and mechanism deduction of some organic reactions. Furthermore, API-MS affords a straightforward approach to trapping and identifying short-lived intermediates. 

In the last decade, mass spectrometry has developed at a tremendous rate. This expansion has been driven by the growing knowledge of ionization methods at atmospheric pressure (API), mainly electrospray ionization (ESI) [1], which makes the investigation of liquid solutions possible by mass spectrometry. ESI is used for ionic species in solution, and this ionization method opened up the access to the direct investigation of chemical reactions in solution via mass spectrometry. In principle, ESI make possible the detection and study not only of reaction substrates and products, but even short-lived reaction intermediates as they are present in solution, providing new insights into the mechanism of several studied reactions. 

Meurer, E.C., Rocha, L.L, Pilli, R.A., Eberlin, M.N., and Santos, L.S. (2006) Transient intermediates of the Tebbe reagent intercepted and characterized by atmospheric pressure chemical ionization mass spectrometry. Rapid Commun. Mass Spectrom., 20,2626-2629. 

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