Collisionally-Induced Dissociation of Substituted Pyrimidine Antiviral Agents: Mechanisms of Ion Formation Using Gas Phase Hydrogen/Deuterium Exchange and Electrospray Ionization Tandem Mass Spectrometry

Abstract

ESI and CID mass spectra were obtained for four pyrimidine nucleoside antiviral agents and the corresponding compounds in which the labile hydrogens were replaced by deuterium using gas-phase exchange. The number of labile hydrogens, x, was determined from a comparison of ESI spectra obtained with N(2) and with ND(3) as the nebulizer gas. CID mass spectra were obtained for [M + H](+) and [M - H](-) ions and the exchanged analogs, [M(D(x)) + D](+) and [M(D(x)) - D](-), produced by ESI using a SCIEX API-III(plus) mass spectrometer. Protonated pyrimidine antiviral agents dissociate through rearrangement decompositions of base-protonated [M + H](+) ions by cleavage of the glycosidic bonds to give the protonated bases with a sugar moiety as the neutral fragment. Cleavage of the glycosidic bonds with charge retention on the sugar moiety eliminates the base moiety as a neutral molecule and produces characteristic sugar ions. CID of protonated pyrimidine bases, [B + H](+), occurs through three major pathways: (1) elimination of NH(3) (ND(3)), (2) loss of H(2)O (D(2)O), and (3) elimination of HNCO (DNCO). Protonated trifluoromethyl uracil, however, dissociates primarily through elimination of HF followed by the loss of HNCO. CID mass spectra of [M - H](-) ions of all four antiviral agents show NCO(-) as the principal decomposition product. A small amount of deprotonated base is also observed, but no sugar ions. Elimination of HNCO, HN(3), HF, CO, and formation of iodide ion are minor dissociation pathways from [M - H](-) ions.