Fourier Transform-Ion Cyclotron Resonance FT-ICR

FT-ICR, first developed more than a decade ago (Comisarow and Marshall, 1974a,b), has become very popular in recent years for both analytical and ion/molecule reaction studies. In the literature this method is also frequently termed Fourier transform mass spectrometry (FTMS). The term FT-ICR, however, indicates the physical principles of the method more precisely and is less confusing the mathematical operation of Fourier transformation can also be applied to some other forms of mass spectrometry such as time-of-flight mass spectrometry as has been demonstrated recently (Knorr et al., 1986). 

The many applications of FT-ICR, showing its versatility, have been reviewed recently in a number of publications (Laude et al., 1986 Russell, 1986 Baykut and Eyler, 1986 Marshall, 1985 Nibbering, 1984, 1985a,b Gross and Rempel, 1984 Wanczek, 1984 Johlman et al., 1983). The basic principles of FT ICR can best be outlined on the basis of Fig. 1. This 

The angular or cyclotron frequency ooc of the ions, which have low, nearly thermal translational energies and random phases in their so-called cyclotron motion, is given to a first approximation by eqn (1), where q is the charge, v the velocity, m the mass of the ion and r the radius of its circular path 

For example, at a magnetic field strength of 1.2 T, the mass range m/z 10 to m/z 1000 corresponds to a frequency band from about 1.8 MHz (m/z 10) to 18 kHz (m/z 1000) and the radius of a circular path of an Ar ion with thermal velocity is 0.01-0.02 cm. After a certain trapping time of the ions, 

During the trapping time as defined in Fig. 2, ion/molecule reactions can take place where the ions have nearly thermal velocities and the molecules thermal velocities. Unwanted ions can be removed from the cell during this time by application to the transmitter plates of the cell of a series of ion-ejection pulses (see Fig. 2), which are appropriate to increase the radii of the ion orbits so much that the ions strike the walls of the cell, are discharged and pumped away. Other methods of removing unwanted ions from the cell 

If the thumb, first, and second fingers of the left hand are held at right angles to each other, the thumb shows the direction of curvature of a positive ion in a magnetic field. 

FT-ICRMS is often the best (sometimes only) solution for certain studies. Examples include top-down proteomics where intact, undigested proteins are analyzed (Section 3.5.1.3) and the analysis of highly complex mixtmes of small molecules, such as crude oil, where chromatography is of no value because of the presence of too many related components with similar retention times (Section 4.6). 

A difficulty with both the orbitrap and ICRMS is that their ability to provide very high resolution depends on keeping the ions in the analyzer for considerable periods of time, and this may not be compatible with the chromatographic timescale. For instance, when analyzing an ion of miz 800 with a 9.8 Tesla magnet, a 5 s transient is required to attain a resolution of -500,000, while a 0.5 s transient provides a 

The ICR cell is located within a superconducting magnet with the magnetic field perpendicular to the cell. 

Ions are injected into the cell at one end and are trapped by plates (grids) at both ends. 

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Comisarow M B and Marshall A G 1996 Early development of Fourier transform ion cyclotron resonance (FT-ICR) spectroscopy J. Mass Spectrom. 31 581-5... 

Instruments are available that can perform MS/MS type experiments using a single analyzer. These instruments trap and manipulate ions in a trapping cell, which also serves as the mass analyzer. The ion trap and fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers are examples. 

The kinetics study [38] utilized a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer to measure the pathway branching ratios. The ability to eject selected masses and the extremely high mass resolution of this technique ensured that the observed CD3CH2 was in fact a primary product of the reaction. Temporal profiles from this reaction are shown in Fig. 1. Noticeably absent from the mass spectrum are the cations C2D2H3 and... 

Various analyzers have been used to analyze phenolic compounds. The choice of the MS analyzer is influenced by the main objective of the study. The triple quadrupole (QqQ) has been used to quantify, applying multiple reaction monitoring experiments, whereas the ion trap has been used for both identification and structure elucidation of phenolic compounds. Moreover, time-of-flight (TOF) and Fourier-transform ion cyclotron resonance (FT-ICR) are mainly recommended for studies focused on obtaining accurate mass measurements with errors below 5 ppm and sub-ppm errors, respectively (Werner and others 2008). Nowadays, hybrid equipment also exists, including different ionization sources with different analyzers, for instance electrospray or atmospheric pressure chemical ionization with triple quadrupole and time-of-flight (Waridel and others 2001). 

Capillary electrophoresis (CE) either coupled to MS or to laser-induced fluorescence (LIF) is less often used in metabolomics approaches. This method is faster than the others and needs a smaller sample size, thereby making it especially interesting for single cell analysis [215] The most sensitive mass spectrometers are the Orbitrap and Fourier transform ion cyclotron resonance (FT-ICR) MS [213]. These machines determine the mass-to-charge ratio of a metabolite so accurate that its empirical formula can be predicted, making them the techniques of choice for the identification of unknown peaks. 

The proton affinities of 1,2- and 1,3-butadiene and of 2-butyne have been determined by Lias and Ausloos79 using equilibrium measurements in an Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Surprisingly, they were found to be almost identical. The bimolecular reactivity of the C4FL+ cations formed from the three isomers was also reported. 

With few exceptions, magnetic sector instruments are comparatively large devices capable of high resolution and accurate mass determination, and suited for a wide variety of ionization methods. Double-focusing sector instruments are the choice of MS laboratories with a large chemical diversity of samples. In recent years, there is a tendency to substitute these machines by TOE or by Fourier transform ion cyclotron resonance (FT-ICR) instruments. 

Comisarow, M.B. Marshall, A.G. The Early Development of Fourier Transform Ion Cyclotron Resonance (FT-ICR) Spectroscopy. J. Mass Spectrom. 1996, 37,581-585. 

Magnetic sector instruments (Chap. 4.3) were used first to demonstrate the beneficial effects of resolution on ESI spectra of biomolecules. [96,103,104] Fourier transform ion cyclotron resonance (FT-ICR, Chap. 4.6) instruments followed. [105-107] The more recently developed orthogonal acceleration of time-of-flight (oaTOF, Chap. 4.2 and 4.7) analyzers also present an effective means to resolve all or at least most peaks. [108-110]... 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

It has been predicted that both cations are unstable toward a facile isomerization to a more stable complex HE /CgHg, 38. For the silyl species this was confirmed by fourier transform ion cyclotron resonance (FT-ICR) experiments, which demonstrated that indeed HSi" /C6H6 is formed and not the isomeric trivalent 7-si-lanorbornadienylium. Similarly, it was shown by our group that the 2,3-benzo-annelated 7-silanorbornadienylium 39 undergoes, at ambient temperature in nonpolar solvents, a fast isomerization to the complex PhSi /tetraphenylnaphthalene (TPN), 40, which decomposes yielding TPN as the only detectable product. ... 

The gas-phase ionization of 2,4,6-tribromobenzene in the presence of m-fluoropyridine afforded the A -aryI -m-fluoropyridinc adduct from which the biradical cation was generated by loss of two bromine radicals.232 This biradical species was isolated and characterized using Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry and its chemical properties are discussed. FT-ICR was also used to isolate and characterize the products of electron ionization of fluorinated acetyl compounds, which included a biradical anion.233... 

Fornarini, Matire, and co-workers110 have recently used Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry assaying the multiphoton dissociation behavior (IR-MPD) of the C3H7+ ion. This study has confirmed the conclusions of the computational results discussed above. The IR spectra recorded in solution and in a solid matrix display close resemblance to the spectral characteristics found by the IR-MPD study. Theoretical studies also indicated that the virtually free methyl rotation allows the interconversion of the two enantiomers of the isopropyl cation. 

In recent years the application of electrospray ionization (ESI) mass spectrometry, quadrupole time-of-flight (QqTOF) mass spectrometry, and Fourier transform ion cyclotron resonance (FT-ICR) are used for further structural characterization of DOM (Kujawinski et al., 2002 Kim et al., 2003 Stenson et al., 2003 Koch et al., 2005 Tremblay et al., 2007 Reemtsma et al., 2008). MS/MS capabilities provide the screening for selected ions, and FT-ICR allows exact molecular formula determination for selected peaks. In addition, SEC can be coupled to ESI and FTICR-MS to study different DOM fractions. Homologous series of structures can be revealed, and many pairs of peaks differ by the exact masses of -H2, -O, or -CH2. Several thousand molecular formulas in the mass range of up to more than 600 Da can be identified and reproduced in element ratio plots (O/C versus H/C plots). Limitations of ESI used by SEC-MS are shown by These and Reemtsma (2003). 

The analytically important features of Fourier transform ion cyclotron resonance (FT/ICR) mass spectrometry (1) have recently been reviewed (2-9) ultrahigh mass resolution (>1,000,000 at m/z. < 200) with accurate mass measurement even 1n gas chromatography/mass spectrometry experiments sensitive detection of low-volatility samples due to 1,000-fold lower source pressure than in other mass spectrometers versatile Ion sources (electron impact (El), self-chemical ionization (self-Cl), laser desorption (LD), secondary ionization (e.g., Cs+-bombardment), fast atom bombardment (FAB), and plasma desorption (e.g., 252cf fission) trapped-ion capability for study of ion-molecule reaction connectivities, kinetics, equilibria, and energetics and mass spectrometry/mass spectrometry (MS/MS) with a single mass analyzer and dual collision chamber. 

In this section the use of commercially available devices based on Penning traps, namely, Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers, is presented. Since its introduction in 1974 [60], the FT-ICR technique has been applied to a plethora of problems in organic, inorganic, and physical chemistry and... 

To benefit general readers, the discussion has been limited to methodologies that are accessible to nonspecialists and that can be carried out on commercially available spectrometers without special modifications. The chapter illustrates the principles of mass spectrometry by demonstrating how various techniques [MALDI, ESI, Fourier transform ion cyclotron resonance (FT-ICR), ion traps, and tandem mass spectrometry (MS-MS)] work. It also provides examples of utilizing mass spectrometry to solve biological and biochemical problems in the field of protein analysis, protein folding, and noncovalent interactions of protein-DNA complexes. 

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