Evidence for ion-ion interactions between peptides and anions (HSO₄⁻ or ClO₄⁻) derived from high-acidity acids.

The existence of gas-phase electrostatic ion-ion interactions between protonated sites on peptides ([Glu] Fibrinopeptide B, Angiotensin I and [Asn(1), Val(5)]-Angiotensin II) and attaching anions (ClO4(-) and HSO4(-)) derived from strong inorganic acids has been confirmed by CID MS/MS. Evidence for ion-ion interactions comes especially from the product ions formed during the first dissociation step, where, in addition to the expected loss of the anion or neutral acid, other product ions are also observed that require covalent bond cleavage (i.e. H2O loss when several carboxylate groups are present, or NH3 loss when only one carboxylate group is present). For [Glu] Fibrinopeptide B + HSO4, under CID, H2O water loss was found to require less energy than H2SO4 departure. This indicates that the interaction between HSO4(-) and the peptide is stronger than the covalent bond holding the hydroxyl group, and must be an ion-ion interaction. The strength and stability of this type of ion-pairing interaction are highly dependent on the accessibility of additional mobile charges to the site. Positive mobile charges such as protons from the peptide can be transferred to the attaching anion to possibly form a neutral that may depart from the complex. Alternatively, an ion-ion interaction can be disrupted by a competing proximal additional negatively charged site of the peptide that can potentially form a salt bridge with the positively charged site and thereby facilitate the attaching anion's departure.