Eleven tested anions were able to form adducts with neutral oligosaccharides at low cone voltage in negative ion mode electrospray mass spectrometry. Among them, fluoride and acetate have the abilities to significantly enhance the absolute abundance of [M-H]- for neutral oliogosaccharides. The chloride adduct has the best stability among all the adduct species investigated. For the above three anions, CID of adduct species may be used for structural determination of neutral oligosaccharides. In the presence of F- and Ac-, simultaneous detection of acidic oligosaccharides and neutral oligosaccharides was achieved. The ratio of Cl- : non-Cl-containing product ions obtained in CID spectra of chloride adducts of disaccharides was used to differentiate anomeric configurations of disaccharides. Density functional theory (DFT) was employed to evaluate the optimized structures of chloride adducts of disaccharides. The formation and decomposition of chloride adducts with oligosaccharides of different acidities were investigated in MALDI mass spectrometry.

A new “best match” match model has been developed to account for adduct formation on multiply charged peptides observed in negative ion electrospray mass spectrometry. To obtain a stable adduct, the model necessitates an approximate matching of apparent gas-phase basicity (GBapp) of a given proton bearing site on the peptide with the gas-phase basicity (GB) of the anion attaching at that site. Evidence supporting the model is derived from the fact that singly charged adducts were only observed for lower GB anions: HSO4-, I-, CF3COO-. Ions that have medium GBs (NO3-, Br-, H2PO4-) only form adducts having -2 charge states, whereas Cl- (higher GB) can form adducts having -3 charge states. Hydrogen bonds are the main interactions pertinent to the “Best Match” model, however, ion-ion interactions formed between peptides ([Glu]Fibrinopeptide B, Angiotensin I or [Asn1,Val5]-Angiotensin II) and low GB anions (ClO4- or HSO4-) have been established by CID-MS/MS. Evidence for ion-ion interactions comes especially from product ions formed during the first dissociation step, where, in addition to the expected loss of the anion or neutral acid, other product ions that require covalent bond cleavage (i.e., H2O or NH3 loss) are also observed. In this study, the “Best Match” model is further supported by the decomposition behavior of adducts formed when Na+/H+ exchange has occurred on peptides. Na+/H+ exchanges were found to occur preferentially at higher acidity sites. Without any Na+/H+ exchange, F- and CH3COO- can hardly form observable adducts with [Glu]Fibrinopeptide B. However, after multiple Na+/H+ exchanges, F- and CH3COO- do form stable adducts. This phenomenon can be rationalized by considering that Na+ cations serve to “block” the highly acidic sites, thereby forcing them to remain overall neutral. This leaves the less acidic protons available to match with higher GB anions. According to the "best match" model, high GB anions will match with high GBapp sites on the peptide, whereas low GB anions will match with low GBapp peptide sites. High charge states readily augment GBapp of the peptide (through-space effect). Na+/H+ exchanges substantially decrease GBapp by neutralizing charged sites, while slightly increasing intrinsic GBs by the inductive effect.