Method ionization

Ionization Method Ionization Agent Strengths Limitations 

El Electrons ( 70eV) Extensive fragmentation, reproducible spectra, searchable large reference compound El libraries Limited to volatile/ nonpolar molecules 

Cl Gaseous ions Abundant molecular ions with controllable fragmentation Limited to nonpolar and moderately polar molecules, limited fragmentation 

An inherent limitation for El and Cl methods is the requirement that the sample analyzed must be volatile. Both methods do not produce MS data for 

The latest addition to DI methods is DESI [10]. It directs an aqueous spray from an electrospray apparatus onto the sample on a surface. In the process, the fast nebulizing gas jet transports the charged droplets and impacts the 

Electron ionization (El) is surely the ionization method most widely employed (Mark and Dunn, 1985). This method was proposed and used from the early days of mass spectrometry (MS) applications in the chemical world and is still of wide interest. This interest is due to the presence of libraries of El mass spectra, which allows easy identification of unknown previously studied analytes. The El method suffers from two limitations It is based on the gas-phase interactions between the neutral molecules of the analyte and an electron beam of mean energy 70 eV. This interaction leads to the deposition of internal energy in the molecules of the analyte, which is reflected in the production of odd-electron molecular ([M]+ ) and fragment ions. These ions are highly diagnostic from a structural point of view. 

the first limitation of El is related to sample vaporization, usually obtained by heating the sample under vacuum conditions (10 5-10 6Torr) present in the ion source. Unfortunately, for many classes of compounds the intermolecular bonds (usually through hydrogen bridges) are stronger than the intramolecular ones and the result of heating is the pyrolysis of the analyte. The El spectrum so obtained is not that of analyte, but that of its pyrolysis products. As examples of 

Mass Spectrometry in Grape and Wine Chemistry, by Riccardo Flamini and Pietro Traldi 

The second limitation of El is related to internal energy deposition. For many classes of compounds it is too high, leading to extensive fragmentation of the molecule and to the absence of a molecular ion, generally considered the most important information received from a mass spectrometric measurement. 

However, El can be, and is, successfully employed in the analysis of volatile compounds and is mainly employed linked to gas chromatographic methods (GC/MS). This approach has been extensively used in the field of grape and wine chemistry, allowing to obtain valid results on low molecular weight, low-medium polarity compounds, as described in Part II. 

The large number of ionization methods, some of which are highly specialized, precludes complete coverage. The most common ones in the three general areas of gas-phase, desorption, and evaporative ionization are described below. 

These methods usually require chemical derivatization to produce volatile species with sufficient vapour pressure to form a gas in the MS sample compartment. The sample may be introduced either by itself, for electron impact (El) methods, or mixed with a large excess of another gas for chemical ionization (Cl). The volatile sample mixture is bombarded with a beam of electrons with energies (typically up to 100 eV) which may be captured to produce negatively charged species (M ), or where electron impact is sufficient to displace electrons and produce positive ions (M ). This may also result in fragmentation of the unstable radicals produced from the sample molecules, and the characteristic fragmentation patterns are frequently useful in structural identification. 

Both these ionization methods are best suited to relatively small molecules, and have been used extensively for analysis of simple per-methylated carbohydrates. They cannot usually be applied to much less volatile species such as peptides, proteins or other macromolecules. 

In fast atom bombardment (FAB), the sample is introduced as a viscous liquid - often dissolved in a solvent such as glycerol (propane-1,2,3-triol) -which is then bombarded with a stream of energetic atoms or ions (typically argon or xenon at energies up to 30 keV) rather than electrons. This results in sputtering of molecules from the sample, and a proportion of them are also ionized. Fragmentation may also occur during collision and ionization. This cloud of ions is then directed into the mass spectrometer for analysis. This method is typically useful for peptides or small proteins of RMM up to about 10,0(X). 

Variants of this method can be used to sample directly the eluant from chromatographic separations. 

Nowadays, the more sophisticated MS instruments combine a range of ionization and analysis methods. 

---

A connnon feature of all mass spectrometers is the need to generate ions. Over the years a variety of ion sources have been developed. The physical chemistry and chemical physics communities have generally worked on gaseous and/or relatively volatile samples and thus have relied extensively on the two traditional ionization methods, electron ionization (El) and photoionization (PI). Other ionization sources, developed principally for analytical work, have recently started to be used in physical chemistry research. These include fast-atom bombardment (FAB), matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ES). 

FigureBl.7.2. Schematic representations of alternative ionization methods to El and PI (a) fast-atom bombardment in which a beam of keV atoms desorbs solute from a matrix (b) matrix-assisted laser desorption ionization and (c) electrospray ionization.

The ion current resulting from collection of the mass-separated ions provides a measure of the numbers of ions at each m/z value (the ion abundances). Note that for this ionization method, all ions have only a single positive charge, z = 1, so that m/z = m, which means that masses are obtained directly from the measured m/z values. Thus, after the thermal ionization process, m/z values and abundances of ions are measured. The accurate measurement of relative ion abundances provides highly accurate isotope ratios. This aspect is developed more fully below. 

A major advantage of the TOF mass spectrometer is its fast response time and its applicability to ionization methods that produce ions in pulses. As discussed earlier, because all ions follow the same path, all ions need to leave the ion source at the same time if there is to be no overlap between m/z values at the detector. In turn, if ions are produced continuously as in a typical electron ionization source, then samples of these ions must be utihzed in pulses by switching the ion extraction field on and off very quickly (Figure 26.4). 

The study of metastable ions concerns substances that have been ionized by electrons and have undergone fragmentation. The stable molecular ions that are formed by soft ionization methods (chemical ionization. Cl field ionization, FI) need a boost of extra energy to make them fragment, but in such cases other methods of investigation than linked scanning are generally used. 

For solids, there is now a very wide range of inlet and ionization opportunities, so most types of solids can be examined, either neat or in solution. However, the inlet/ionization methods are often not simply interchangeable, even if they use the same mass analyzer. Thus a direct-insertion probe will normally be used with El or Cl (and desorption chemical ionization, DCl) methods of ionization. An LC is used with ES or APCI for solutions, and nebulizers can be used with plasma torches for other solutions. MALDI or laser ablation are used for direct analysis of solids. 

When mass spectrometry was first used as a routine analytical tool, El was the only commercial ion source. As needs have increased, more ionization methods have appeared. Many different types of ionization source have been described, and several of these have been produced commercially. The present situation is such that there is now only a limited range of ion sources. For vacuum ion sources, El is still widely used, frequently in conjunction with Cl. For atmospheric pressure ion sources, the most frequently used are ES, APCI, MALDI (lasers), and plasma torches. 

There are methods for vaporizing solids of low volatility by placing them on a thin wire, which is then raised to a high temperature within a fraction of a second (direct chemical ionization, DCI). This rapid heating allows some vaporization without decomposition, but with the development of later ionization methods, it is now rarely used. 

Ionization Method Type of Molecular Ion Formed Good Molecular Mass Information Abundant Fragment Ions MS/MS Needed for Structural Information Accurate Values for Isotope Ratios... 

The above direct process does not produce a high yield of ions, but it does form many molecules in the vapor phase. The yield of ions can be greatly increased by applying a second ionization method (e.g., electarn ionization) to the vaporized molecules. Therefore, laser desorption is often used in conjunction with a second ionization step, such as electron ionization, chemical ionization, or even a second laser ionization pulse. 

Usually, FAB yields molecular or quasi-molecular ions, which have little excess of internal energy and therefore do not fragment. This ionization method is mild and good for obtaining molecular mass (molecular weight) information. 

TOF mass spectrometry is ideally suited to those ionization methods that inherently produce ions in pulses, as with pulsed laser desorption or Cf-radionuclide ionization. 

In its simplest form, a mass spectrometer is an instmment that measures the mass-to-charge ratios ml of ions formed when a sample is ionized by one of a number of different ionization methods (1). If some of the sample molecules are singly ionized and reach the ion detector without fragmenting, then the ml ratio of these ions gives a direct measurement of the molecular weight. The first instmment for positive ray analysis was built by Thompson (2) in 1913 to show the existence of isotopic forms of the stable elements. Later, mass spectrometers were used for precision measurements of ionic mass and abundances (3,4). 

Low ionizing potentials or soft ionization methods are necessary to observe the parent ions in the mass spectra of many S-N compounds because of their facile thermal decomposition. Mass spectrometry has been used to investigate the thermal breakdown of S4N4 in connection with the formation of the polymer (SN). On the basis of the appearance potentials of various S Ny fragments, two important steps were identified ... 

Unfortunately, not every compound shows a molecular ion in its mass spectrum. Although M+ is usually easy to identify if it s abundant, some compounds, such as 2,2-dimelhylpropane, fragment so easily that no molecular ion is observed (Figure 12.3). In such cases, alternative "soft" ionization methods that do not use electron bombardment can prevent or minimize fragmentation. 

Most biochemical analyses by MS use either electrospray ionization (ESI) or matrix-assisted laser desorption ionization (MALD1), typically linked to a time-of-flight (TOF) mass analyzer. Both ESI and MALDl are "soft" ionization methods that produce charged molecules with little fragmentation, even with biological samples of very high molecular weight. 

Chapter 12, Structure Determination Mass Spectrometiy and Infrared Spectroscopy—A new Section 12.4 discusses mass spectrometry of biological molecules, focusing on time-of-flight instruments and soft ionization methods such as MAI.DI. 

Electron Impact Ionization Electron impact ionization (ei) is by far the most commonly used ionization method. The effluent from the GC enters... 

Verification of the molecular weight of thiirene dioxides by mass spectrometry, employing the conventional electron-impact (El) ionization method, has been unsuccessful due to the absence or insignificant intensity of molecular ion peaks in their mass spectra. The base peak is rather characteristic, however, and corresponds to the formation of the disubstituted acetylene ion by loss of sulfur dioxide91 (equation 3). 

Various ionization methods were used to bombard phenol-formaldehyde oligomers in mass spectroscopic analysis. The molecular weights of resole resins were calculated using field desorption mass spectroscopy of acetyl-derivatized samples.74 Phenol acetylation was used to enable quantitative characterization of all molecular fractions by increasing the molecular weights in increments of 42. 

Ionic internal emulsifiers, 237-238 Ionization methods, 408-409 IPDI, 219... 

It is particularly difficult to study charge transfer reactions by the usual internal ionization method since the secondary ions produced will always coincide with ions produced in primary ionization processes. Indeed these primary ions frequently constitute the major fraction of the total ion current, and the small intensity changes originating from charge transfer reactions are difficult to detect. For example, Field and Franklin (5) were unable to detect any charge transfer between Xe + and CH4 by the internal ionization method although such reactions have been observed using other techniques (3, 9,22). 

---