Electrospray ionization charge-residue model

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. 

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. 

ESI was first proposed by Malcolm Dole in 1968 who noticed that the Coulombic fission cascade would eventually lead to sufficiently small drops which contained a single solute molecule that retained some of the drop charge such that a fully desolvated gas phase ion would ultimately be left once all the solvent evaporates, this mechanism being known as the charge residue model (CRM). These efforts were, however, largely unsuccessful practically due to the use of an ion-drift spectrometer to which the electrospray was interfaced. It was John Fenn, then at Yale University, who later developed a practical method for electrospray ionization mass spectrometry (ESI-MS) that allowed the identification and structure analysis of biomacromolecules of virtually unlimited molecular weights to an accuracy of 0.01% by averaging... 

Hogan CJ Jr, Carroll JA, Rohrs HW, Biswas R Gross ML. Combined charged residue-field emission model of macromolecular electrospray ionization. Anal Chem. 2009 81 369 77. 

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