Ion Formation in ESI

Until now, our discussion of electrospray was rather technical with an emphasis on interface design and occasional reference to applications. Next we shall consider the physicochemical aspects of the ESI process. This section presents answers to basic questions such as to why an electrospray does occur at all, how isolated gas phase ions are formed from droplets, and what rules are governing the charge state (distribution) of those incipient gas phase ions [88-90]. Ion formation in ESI can be considered to be composed of three steps i) creation of an electrically charged spray, ii) dramatic reduction of the droplets size, and finally iii) liberation of fully desolvated ions. 

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Note There is a continuing debate about ion formation in ESI. [79,87,95] In summary, it may be assumed that CRM holds valid for large molecules [9] while the formation of smaller ions is better described by lEM. [79,95]... 

The discussion of ion formation in ESI has revealed that the appearance of an ESI spectrum can largely be influenced by the actual experimental conditions as defined by the pH of the sprayed solution, the flow of nebulizing or drying gas, and the temperature of these or of a desolvation capillary. In particular, the degree of... 

Fig. 10.2 Principle of ionisation source and at atmospheric pressure. The charged aerosol is mechanism of gaseous ion formation in ESI- evaporated due to Coulomb explosions to MS. The sample solution is admitted through a smaller droplets which finally result in desol-small capillary from which the spray is formed vated macro-ions.

Models have been developed on ion formation in ESI, but there is still no consensus on the mechanism by which sample ions are obtained for mass spectrometric analysis. These models rely on the existence of preformed ions in solution i.e., the ions observed in the mass spectra were presumed to be present originally as ionized molecules in solution. According to the charged residue model of Dole et al., the evaporation of solvent from a charged droplet increases the surface field xmfil the Raleigh limit is reached ... 

Significant research has been done to prove the correctness of either of these models and/or to falsify one of them. From these studies, it appears that both models contribute to ion formation in ESI. The importance of either effect depends on the analyte. Therefore, ESI is best considered as a mixed-mode ionization. Some effects are more readily explained from the charge-residue model, some other from the ion-evaporation model. An important prerequisite for both models is that analytes should be present as preformed ions in solution. This indicates an analytical strategy to enhance the analyte ionization... 

The whole process of ion formation in ESI can be subdivided into three sections ... 

It soon became evident that due to the principle of ion formation in ESI, multiply charged ions are predominantly formed. Multicharging can result in very complex mass spectra, especially when different charge states of a polymer series overlap each other. On the other hand, due to the detection of m/z values, very large masses can be easily determined in this way. This can be used to overcome the limited m/z range of mass analyzers (typically m/z 4000-16000). 

The formation of RDX cluster ions in LC/MS and the origin of the clustering agents have been studied in order to determine whether the clustering anions originate from self-decomposition of RDX in the source or from impurities in the mobile phase [19], IsotopicaUy labeled RDX ( C3-RDX and Ng-RDX) were used in order to estabhsh the composition and formation route of RDX adduct ions produced in ESI and APCI sources. Results showed that in ESI, RDX clusters with formate, acetate, hydroxyacetate and chloride anions, present in the mobile phase as impurities at ppm levels. In APCI, part of the RDX molecules decompose, yielding NO2 species, which in turn cluster with a second RDX molecule, producing abundant [M- -N02] cluster ions. 

This ionization method is soft in that it does not cause the analyte molecule to fragment into multiple ions as older ionization methods often do. The use of the unfragmented, or molecular ion, greatly simplifies the resulting mass spectra, which greatly facilitates interpretation of the data. As ESI depends on preformed ions being solution, ion adducts are seen in the case of positive ion formation. In most cases these are proton (H" ") adducts, but sodium (Na" ") and potassium (K ") are seen also. This form of ionization works with protic and polar analytes that readily form protonated species such as primary amines. 

A problem with electrospray ionisation is its low tolerance for impurities or additives. Buffer and salt concentrations of more than 0.1 mM can prevent sufficient ion formation in the electrospray process, as can certain detergents at concentrations of more than 10 p.M. Buffers commonly used in bioanalysis contain 100 mM phosphate and 150mM NaCl and are thus unsuitable for ESI-MS. 

The formation of solvent—analyte noncovalently bound complexes (e.g., [M -F H + ACN], [M -F H -F MeOH]", etc.) complicates molecular ion determination in ESI—APCI MS (Table 10.1). The relative abundances of these solvent cluster ions depend on the components in the solution phase, ionization mode, spray voltage, capillary temperature, sheath gas pressure, as well as auxiliary gas flow. Zhao et al. (2004) recently reported that acetonitrile could be reduced to ethyl amine under ESI conditions (Scheme 1). They demonstrated that the M -F 46 ion in the mass spectrum represented the ethyl amine adduction ([M -F H -F CH3CH2NH2] ) when the ESI—MS was performed by infusion of the compound in acetonitrile and water (1% HCOOH -F 1% NH4OH) (1 1 V v). Moreover, they showed the same analyte produced a moderate [M + H + CD3CH2NH2] (M -F 49) signal when acetonitrile-ds was used as the organic solvent (Scheme 1). 

Later, it was discovered that a short tapered capillary ( 1 cm), placed in proximity ( 1 mm) to the MS inlet, could also support electrospray - even in the absence of a power supply, electrical grounding, or ultrasound [109]. Since there was no direct electric contact at the sample capillary, this method was named contactless atmospheric pressure ionization (C-API) [109] or contactless ESI [110]. Figure 2.15 shows the putative mechanism of the ion formation in C-API. Rearrangement of electric charges at the end of the tapered capillary is induced by the electric field present near the MS inlet. 

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