Gas-Phase Ionization Methods

Gas-phase methods for generating ions for mass spectrometry are the oldest and most popular methods. They are applicable to compounds that have a minimum vapor pressure of ca. 1CT6 Torr at a temperature at which the compound is stable this criterion applies to a large number of nonionic organic molecules with MW 1000. 

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Increasing molecular mass eventually limits the effectiveness of gas-phase ionization methods. What is the practical upper limit (approximately 1000 Da). 

Mass Spectrometric Detection for SFC. The advantages of coupling a chromatographic technique with mass spectrometry are considerable, as evidenced by the major role of GC-MS in mixture analysis. However, in contrast to GC, where the effluent is compatible with classical gas phase ionization methods, the ideal approach to interfacing SFC or HFLC with mass spectrometry is not immediately obvious. 

When ions are formed by gas-phase methods, tailing of the mass-spectral peak is likely to be more symmetric. There is, however, a focal point, known as the space-focus plane, in the drift region at which faster ions formed toward the rear of the source catch up with slower ions formed near the front of the source. This point is independent of mass (although ions of different mass arrive there at different times) and is located at a distance 2s, where s is the full depth of the source region for desorption methods, or the distance from the extraction grid to the center of the ionization zone for gas-phase ionization methods. 

Prompt fragmentation is that which is indistinguishable in time and location from the ionization event. In desorption methods such fragmentation takes place on (or very near) the surface for gas-phase ionization methods it occurs within the ionization zone. As shown in Figure 2.9a, fragment ions that are formed promptly are accelerated to the same final kinetic energies as molecular ions, so that their flight times follow the same square-root law. 

The difference in stabilities of cation radicals located on G, GG, and GGG sequences was initially investigated by Sugiyama and Saito [14], who employed ab initio methods to calculate the gas phase ionization potentials of nucleobases stacked in B-DNA geometries. Their results indicated large differences in potential for holes on G vs GG (0.47 eV) and GGG (0.68 eV) sequences. A similar G vs GG difference was calculated by Prat et al. [62]. These values suggest that GG and GGG are, in fact, deep hole traps and they have been widely cited as evidence to that effect [54, 63]. 

Experimental and theoretical studies of the basicity and acidity of benzene-substituted indoles were performed169. In aqueous solution, the pK values are above —4 for the bases and above 15 for the acids. Gas-phase ionization enthalpies have been calculated using the AMI semiempirical method. 

Atmospheric pressure chemical ionization (APCI) is a gas phase ionization process based on ion-molecule reactions between a neutral molecule and reactant ions [31]. The method is very similar to chemical ionization with the difference that ionization occurs at atmospheric pressure. APCI requires that the liquid sample is completely evaporated (Fig. 1.12). Typical flow rates are in the range 200-1000 xL min , but low flow APCI has also been described. First, an aerosol is formed with the help of a pneumatic nebulizer using nitrogen. The aerosol is directly formed in a heated quartz or ceramic tube (typical temperatures 200-500 °C) where the mobile phase and the analytes are evaporated. The temperature of the nebulized mobile phase itself remains in the range 120-150 °C due to evapo-... 

The choice of the ionization method depends on both the nature of the sample and the type of information required from the analysis (Table 23.2). A great variety of ionization methods exists that can be classified into six major categories gas-phase ionization, field desorption and ionization, particle bombardment, atmospheric pressure ionization, and the laser desorption. 

Ionization methods such as electron impact, chemical ionization, desorption chemical ionization, and negative-ion chemical ionization are all based on ionization of gas-phase samples and, thus, fall within the first category of gas-phase ionization. 

In atmospheric pressure chemical ionization (APCI) a similar interface to that used for ESI is used. A corona discharge is used to ionize the analyte in the atmospheric pressure region. The gas-phase ionization in APCI is more effective than ESI for analyzing less polar species. Both ESI and APCI are complementary methods that are well-suited for LC/MS techniques. 

Field ionization (FI) is a method that uses very strong electric fields to produce ions from gas-phase molecules. Its use as a soft ionization method in organic mass spectrometry is principally due to Beckey [8], Like El or Cl, FI is only suitable for gas-phase ionization. Therefore, the sample is introduced into the FI source by the same techniques that are commonly used in El and Cl sources, for example using a direct probe that can be heated or the eluent from a gas chromatograph. 

Table 20-1. Gas phase Ionization potential (eV) of DNA bases calculated using different theoretical methods... 

Recently, a number of efforts have sought to use new theoretical methods, particularly density functional theory (DFT), to predict redox potentials in solution. While considerable progress has been made toward predicting gas-phase ionization potentials, the role of solvation and coupled chemical reactions are of high importance to solution chemists. Baik and Friesner have recently discussed the ability of new methods for incorporating solvation effects into DFT calculations. Using these solvation methods, DFT calculations can be used to determine solution redox potentials to within 150mV.i ... 

A wide variety of desorption ionization methods is available [7] desorption chemical ionization (DCI), secondary-ion mass spectrometry (SIMS), fast-atom bombardment (FAB), liquid-SIMS, plasma desorption (PD), matrix-assisted laser desorption ionization (MALDI), and field desorption (FD). Two processes are important in the ionization mechanism, i.e., the formation of ions in the sample matrix prior to desorption, and rapid evaporation prior to ionization, which can be affected by very rapid heating or by sputtering by high-energy photons or particles. In addition, it is assumed that the energy deposited on the sample surface can cause (gas-phase) ionization reactions to occur near the interface of the solid or liquid and the vacuum (the so-called selvedge) or provide preformed ions in the condensed phase with sufficient kinetic energy to leave their environment. 

Atmospheric pressure chemical ionization, like electrospray ionization, is a mass spectrometer ionization source in which ionization occurs not in a vacuum but at atmospheric pressure. In contrast to electrospray ionization, in which the ionization process occurs in solution phase, atmospheric pressure chemical ionization is a gas-phase ionization process whereby gas-phase molecules are isolated from the carrier solvent before ionization [6]. Because the ionization mechanisms of APCI and electrospray are fundamentally different (gas-phase and liquid-phase ionization, respectively) the two methods have the potential to provide complimentary analyte characterization. To generalize, electrospray ionization is more... 

Mass spectrometry has been an established analytical technique in organic chemistry for many years. Until recently, however, the very low volatility of proteins made mass spectrometry useless for the investigation of these molecules. This difficulty has been circumvented by the introduction of techniques for effectively dispersing proteins and other macromolecules into the gas phase. These methods are called matrix-assisted laser desorption-ionization (MALDI) and electrospray spectrometry. We will focus on... 

The next gas-phase ionization technique for LC-MS is APPI. It is a relatively new method, and its strengths and weaknesses will become clear as the number of applications grows over time. Thus far APPI appears to work best at flow rates of 100-200 pi min At higher flow rates ionization efficiency is reduced. To increase sensitivity a dopant such as acetone, toluene, or anisole is introduced into the ionization region. First, the dopant is ionized by photons and next the dopant ions undergo ion-molecule reactions with ultimate ionization of the sample. Solvent components can have a major influence on the cascade of ion-molecule reactions, and should be selected with care. 

Because of the advances in the gas-phase ionization of biomacromolecules, such as electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), mass spectrometry (MS) has become a powerful tool for detection, identification, and structural analysis of proteins, peptides, and polynucleotides. The molecules ionized in a gas phase by these methods are subsequently analyzed by sector, quadrupole, ion-trap, or time-of-flight mass spectrometers. In particular, the MS systems consisting of ESI and triple-stage quadrupole (ESI/TSQ) or ion-trap (IT) mass spectrometry and MALDI time-of-flight (MALDl/TOF) mass spectrometry have been most widely applied to the field of protein chemistry for the accurate determination of molecular mass of proteins and peptides, determination of amino acid sequence, identification of proteins by peptide mass databases, and analysis of posttranslational modifications such as phosphorylation and glycosylation. In general, current techniques allow detenni-... 

The ionization potential and electron affinity of a molecule in solution are measured by the corresponding oxidation and reduction potentials (see Section 4.4). It has been shown that the oxidation potentials of even AHs run parallel to their gas-phase ionization potentials and the same seems to be true of the reduction potentials and electron affinities. The PMO method can therefore be used to estimate the relative reduction potentials of hydrocarbons in solution and hence the ease with which they react with alkali metals. One can also observe reversible electron transfer reactions between hydrocarbons and radical anions, e.g.,... 

The third critical point is the choice of the appropriate electronic structure method to treat the species in gas phase. The change of electronic configuration from the oxidized to the reduced species implies that electronic correlation effects are different and that spin-orbit coupling is likely to contribute differently for the two species. Most studies rely on DFT using either the PBE functional, a hybrid functional, or more recently a meta-functional of the Minnesota M06 family. Changing the functional can yield changes of the gas-phase ionization potential up to an eV. Unfortunately, we cannot compare these DFT values to the most reliable... 

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