Gas-phase ion/ion reactions of transition metal complex cations with multiply charged oligodeoxynucleotide anions

Abstract

Multiply deprotonated hexadeoxyadenylate anions, (A 6 ϪnH) nϪ , where n ϭ 3-5, have been subjected to reaction with a range of divalent transition-metal complex cations in the gas phase. The cations studied included the bis-and tris-1,10-phenanthroline complexes of Cu II , Fe II , and Co II , as well as the tris-1,10-phenanthroline complex of Ru II . In addition, the hexadeoxyadenylate anions were subjected to reaction with the singly charged Fe III and Co III N,N=-ethylenebis(salicylideneiminato) complexes. The major competing reaction channels are electron-transfer from the oligodeoxynucleotide anion to the cation, the formation of a complex between the anion and cation, and the incorporation of the transition-metal into the oligodeoxynucleotide. The latter process proceeds via the anion/cation complex and involves displacement of the ligand(s) in the transition-metal complex by the oligodeoxynucleotide. Competition between the various reaction channels is governed by the identity of the transition-metal cation, the coordination environment of the metal complex, and the oligodeoxynucleotide charge state. In the case of the divalent metal phenanthroline complexes, competition between electron-transfer and metal ion incorporation is particularly sensitive to the coordination number of the reagent metal complexes. Both electron-transfer and metal ion incorporation occur to significant extents with the bis-phenanthroline ions, whereas the trisphenanthroline ions react predominantly by metal ion incorporation. To our knowledge this work reports the first observations of the gas-phase incorporation of multivalent transition-metal cations into oligodeoxynucleotide anions and represents a means for the selective incorporation of transition-metal counter-ions into gaseous oligodeoxynucleotides. [6 -8] have allowed the formation of gas-phase ions of biopolymers, including oligodeoxynucleotides (ODNs), making these ions amenable to study by mass spectrometry. Like peptides and proteins, ODNs are amphoteric, [9] allowing formation of either positively or negatively charged ions. Formation of negatively charged oligonucleotides is quite facile using ESI and, as a result, negatively charged ODN ions have been the most widely studied [9]. Oligodeoxynucleotide ions with bound metals formed by MALDI or ESI, especially those containing transition metals, have shown fragmentation behavior, which is distinct and complementary to that of ions devoid of metals [6 -8].The study of the interaction of transition metals with DNA is of critical importance, given the variety of roles such interactions fulfill. Transition-metal complexes display nuclease activity and consequently complexes such as (methidium-propyl-EDTA)iron(II) have been utilized as footprinting agents [10]. Ruthenium(II) complexes have been extensively examined as spectroscopic probes of local DNA structure [11,12]. The mechanism of action of the chemotherapeutic agent cisplatin involves binding to DNA to prevent replication [13][14][15]. Mass spectrometry has been u...

Transition metal complex cations as reagents for gas-phase transformation of multiply deprotonated polypeptides

“…The summary of the percentages of observed products from each pathway is shown in Table 1. The same tendencies were also noted for oligonucleotide anions [16]. For a given anion, the higher tendency for NETD with Cu(phen) 2 2ϩ• can be attributed to its higher recombination energy as discussed elsewhere [16].…”

“…The fragmentation behavior of peptide anions that also contain one or more metal counter-ions is little explored, however. Recently, we described the use of transition-metal complex cations for gas-phase insertion of a transition-metal into oligonucleotide anions and for extracting an electron from oligonucleotide anions [16]. Both types of reactions result in the transformation of multiply deprotonated oligonucleotides into another ion type (i.e., an oligonucleotide anion with a transition-metal counter-ion and a distonic radical anion, respectively).…”

Ion/Ion Reactions: New Chemistry for Analytical MS

“…This method provides a higher degree of control in forming metal cationized species than the conventional approach of dissolving a salt of the metal of interest in the analyte solution prior to electrospray. Whereas the insertion of metal ions into polypeptide cations is emphasized here, the insertion of metal cations into multiply-deprotonated oligonucleotides (40) and peptides (41) by ion/ion reactions has also been demonstrated.…”

“…The net result is the transformation of (M+H) + to (M+2H) 2+ . Overall efficiencies [i.e., the percentage of the initial (M+H) + ion population converted to (M+2H) 2+ ] of a few tens of percent have been measured (40). An analogous set of reactions has been shown to be effective for transforming (M−H) − to (M−2H) 2− ions (43).…”

Gas-Phase Chemistry of Multiply Charged Bioions in Analytical Mass Spectrometry

“…Also, whereas lipid ions are usually singly protonated, metallation has also been applied to increase the charge states of glycerophosphocholine lipids in order to conduct ETD experiments (78). Although most metallation procedures are carried out by adding metal salts to the solution prior to electrospray, an alternative method involves reacting the ESI-generated multiply charged ions with various metal-containing ion complexes of the opposite polarity in the gas phase (79–85). An example is the transfer of Au(I) to a disulfide-linked peptide via ion/ion reaction with AuCl 2 − (84).…”