Charged residue model

There are alternative explanations for the actual mechanism by which these ions are produced, e.g. the ion-evaporation [11] and charge-residue models [12], and these have been debated for some time. 

According to the ion-evaporation model, the droplets become smaller until a point is reached at which the surface charge is sufficiently high for direct ion evaporation into the gas phase to occur. In the case of the charge-residue model, repeated Coulombic explosions take place until droplets are formed that contain a single ion. Evaporation of the solvent continues until an ion is formed in the vapour phase. 

The elder model of ion formation, the charged-residue model (CRM), assumes the complete desolvation of ions by successive loss of all solvent molecules from droplets that are sufficiently small to contain just one analyte molecule in the end of a cascade of Coulomb fissions. [9,42,84] The charges (protons) of this ultimate droplet are then transferred onto the molecule. This would allow that even large protein molecules can form singly charged ions, and indeed, CRM is supported by this fact. [23]... 

The mechanisms for the formation of gas phase ions from droplets are not fully understood and two therories have been proposed the ion evaporation model (lEV) and the charge residue model (CR) [28]. The lEV model proposes that the ions are directly emitted into the gas phase when, after evaporation and... 

Two mechanisms have been proposed to account for the formation of gas-phase ions from very small and highly charged droplets. The first mechanism, proposed by Dole et al. [10,11], depends on the formation of extremely small droplets which should contain only one ion. Solvent evaporation from such a droplet will lead to a gas-phase ion. Mass spectrometric determinations by Dole and co-workers were by and large unsuccessful, but the charge residue model (CRM) proposed by them survived. A more detailed consideration of, and support for, the mechanism was later provided by Rollgen et al. [25,26]. 

The first applications of ESI in MS date from 1968. Dole et al. [5-6] investigated the possibility to transfer macromolecules from the liquid phase to the gas phase by electrospraying dilute solutions in a nitrogen bath gas. The hypothesis of Dole and cowoikers was that macro-ions can be produced by desolvating the charged droplets produced in electrospray. This ionization mechanism is called the charge residue model. 

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 ... 

The first theory is the charged residue model (CRM) first proposed by Dole [31], who was one of the first people to study the gas phase ion production in an electrospray. In Dole s model, the droplets undergo jet fission until very small droplets, on the order of a few nanometers, are created that contain only single ions. Continuing solvent evaporation from these drops yields a single gas phase ion. 

Fig. 32.19 The charged residue model (CRM) and ion evaporation model (lEM) of gas phase ion generation from charged electrospray droplets...

Figure 2.21. Desorption of ions from charged droplets into the gas phase (a) charge-residue model (b) ion-desorption model (From ref. 81.)...

In the mid-1960s. Dole and co-workers were the first to combine electrospray nebulization with MS. Their hypothesis was that the nebulization of a dilute protein solution would lead to gas-phase protein ions as a result of continued solvent evaporation and Coulomb explosion. This would in the end lead to a very small droplet containing only one charged protein molecule. This small droplet can be considered as a solvated protein ion. Desolvation of this ion by solvent evaporation results in a gas-phase protein ion. This model is nowadays called the charge-residue model. 

When, 15 years later, the Nobel-prize laureate Fenn and his co-workers continued the work of Dole with other analytes than proteins, they found results not in agreement with the charge-residue model. Therefore, they adopted another model, described in the mid-1970s by two Canadian scientists Iribarne and Thomson. In this so-called ion-evaporation model, it has been thermodynamically demonstrated that ions may escape from a sufficiently small droplet with a sufficient number of charges. This model also requires the analyte to be present as a preformed ion in solution. 

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... 

Unfortunately, this picture got corrupted when data were shown of good ESI performance for organic bases in positive-ion mode from basic solutions. This so-called wrong-way-around electrospray indicates that yet another mechanism will be operative. Nebulization of analyte solutions was initially adopted in LC-MS to achieve a gentle transfer of neutral molecules from the liquid phase to the gas phase by soft desolvation, which is a process similar to the processes described by the charge-residue model, but now for neutral species. Gas-phase ion-molecule reactions between these neutral analyte molecules and ion-evaporated buffer ions, for instance, NH/, will also lead to protonated molecules. It appears that this gas-phase chemical ionization rather than the liquid-phase process is just another process involved in ESI. A summary of the ionization processes is given in Figure 2. 

Although Fenn initially emphasized the importance of ion evaporation in ion formation by electrospray ionization, extensive research has demonstrated that, depending on the analyte and the experimental conditions, the charge-residue model and the ion-evaporation model are both important. In addition, especially in the analysis of small molecules, gas-phase ion-molecule reactions appear to play an important role in ion formation by electrospray ionization. 

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