Collisionally-induced dissociation of purine antiviral agents: mechanisms of ion formation using gas phase hydrogen/deuterium exchange and electrospray ionization tandem mass spectrometry.
ESI and CID mass spectra were obtained for two purine nucleoside antiviral agents (acycloguanosine and vidarabine) and one purine nucleotide (vidarabine monophosphate) and the corresponding compounds in which the labile hydrogens were replaced by deuterium 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(Dx)+D](+) and [M(Dx)-D](-), produced by ESI using a Sciex API-IIIplus mass spectrometer. Compositions of product ions and mechanisms of decomposition were determined by comparison of the CID mass spectra of the undeuterated and deuterated species. Protonated purine 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 same bonds with charge retention on the sugar moiety gives low abundance ions, due to the low proton affinity of the sugar moiety compared to that of purine base. CID of protonated purine bases [B+H](+) occurs through two major pathways: (1) elimination of NH(3) (ND(3)) and (2) loss of NH(2)CN (ND(2)CN). Minor pathways include elimination of HNCO (DNCO), loss of CO, and loss of HCN (DCN). Deprotonated acycloguanosine and vidarabine exhibit the deprotonated base [B-H](-) as a major fragment from glycosidic bond cleavage and charge delocalization on the base. Deprotonated vidarabine monophosphate, however, shows predominantly phosphate related product ions. CID of deprotonated guanine shows two principal pathways: (1) elimination of NH(3) (ND(3)) and (2) loss of NH(2)CN (ND(2)CN). Minor pathways include elimination of HNCO (DNCO), loss of CO, and loss of HCN (DCN). The dissociation reactions of deprotonated adenine, however, proceed by elimination of HCN and (2) elimination of NCHNH (NCHND). The mass spectra of the antiviral agents studied in this paper may be useful in predicting reaction pathways in other heteroaromatic ring decompositions of nucleosides and nucleotides.
Kamel
Amin M
AM
Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton Laboratories, Groton, CT 06340, USA. amin_m_kamel@groton.pfizer.com
Munson
Burnaby
B
D000212:Acyclovir / Q000737:chemistry; D000225:Adenine / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry*; D041961:Deuterium Exchange Measurement; D005740:Gases / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D007477:Ions; D015394:Molecular Structure; D011522:Protons; D011687:Purines / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D014740:Vidarabine / Q000737:chemistry; D001084:Vidarabine Phosphate / Q000737:chemistry
D000998:Antiviral Agents; D005740:Gases; D007477:Ions; D011522:Protons; D011687:Purines; D001084:Vidarabine Phosphate; D006147:Guanine; D006859:Hydrogen; D014740:Vidarabine; D000225:Adenine; C030985:purine; D000212:Acyclovir