Positive-Negative Ion-Pairing Reactions Involving Impurities such as Na

1 Positive-Negative Ion-Pairing Reactions Involving Impurities such as Na+ 

Sodium ions are a common impurity in solvents used for ESI. Analyte samples (especially proteins) are often contaminated by sodium ions in the production process, while sample solution storage in glass vessels also contributes to the sodium contamination. The extensive evaporation of solvent in the ESI process promotes solution ion-pairing reactions. When the analyte is a protein, ion-pairing reactions will involve Na and the ionized acid residues of the protein, see Eq. (1.16a). Similarly, impurity anions such as Cl will ion pair with ionized basic residues of the protein (see Eq. (1.16b)). 

The occurrence of these ion pairing reactions was demonstrated by Verkerk and Kebarle [53]. In the collisional activation stage of the ESI-MS dissociation occurs following Eq. (1.17)  

Thus the Na adduct remains while the Cl pulls off a proton from the basic residue of the protein. In general there are at least several acidic residues at the surface of proteins and the addition of sodium to most of these leads to mass spectra that are difficult to interpret. The authors [53] also demonstrated that one can prevent the undesirable sodium addition by adding a millimolar concentration of ammonium acetate to the solution. Because the concentration of ammonium acetate is mucdi higher than that of the impurity ions, ion pairing of NH with the acidic residue CH3CH2CO2 and ion pairing of CH3CO2 with the basic residue occur as shown below  

This result may seem an undesirable change. However in the dean up stages of the ESI-MS these ion pairs are unstable intramolecular proton transfer occurs followed by dissociation resulting in the products (Eq. (1.19))  

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