Collision-activated dissociation (CAD) has been employed to assess the gas-phase fragmentation behavior of a series of 1:1 oligodeoxynucleotide (ODN):metal complexes over a range of charge states, using several ten-residue ODNs and a wide array of alkali, alkaline earth, and transition metals. For parent species in low to intermediate charge states, complexation with Ca ϩ2 , Sr ϩ2 , or Ba ϩ2 altered the relative intensity of M-B species, promoting loss of cytosine over loss of guanine. The relative intensities of sequence ions were largely unaffected. This behavior was most prevalent for isomeric sequences with complementary residues at the 5=-and 3=-termini, suggesting that metal complexation may change the gas-phase conformation and/or conformational dynamics for some sequences. In higher charge states, some ODN/ Ba ϩ2 complexes produced abundant fragment ions corresponding to metallated a n Ϫm species, which are not commonly observed in CAD mass spectra for deprotonated ODNs. The formation of these ions was most favored for complexes between Ba ϩ2 and ODN sequences with a thymine residue at Position 6. Literature precedent exists for the formation of a n Ϫm ions from sequences in which covalent modification generates one or more neutral sites along the phosphate backbone. ODN/metal adducts in high charge states possess only a few acidic protons, and the juxtaposition of these neutral phosphate groups near thymine residues and the bound Ba ϩ2 ion may direct formation of the metallated a n Ϫm species. and function of DNA and RNA. Mono-and divalent cations are thought to induce bending in DNA duplexes [1,2], and are also known to stabilize triplex [3,4], and quadruplex [5,6] structures. Metal cations are also required for the proper folding and function of many forms of RNA, including most ribozymes [7,8]. The interactions of DNA with several natural products [9] and synthetic drugs and drug candidates [10,11] are known to be metal-mediated.Mass spectrometry (MS) is well-established as a useful tool for the structural characterization and sequencing of nucleic acids [12][13][14], and has also been employed to characterize a number of nucleic acid/metal ion interactions [15]. Several previous studies have focused on the interactions of the anticancer therapeutic cisplatin or its derivatives with DNA [16 -22]. Relatively few studies have addressed binary interactions of nucleic acids and metal cations [23][24][25][26][27]. Most of these studies have focused primarily on complexes with the smaller alkali and alkaline earth metals (e.g., Na ϩ , Mg ϩ2 ), although a few complexes with transition metals [25,26] or f-block elements [23,25] have also been investigated. The fragmentation behavior of these complexes has been characterized using parent species in relatively low charge states (often Ϫ2), but intermediate and high charge state precursors have not been studied. A more complete characterization of the entire charge state envelope produced by electrospray ionization would not only enhance our theoretical underst...