Noncovalent Interactions of Nucleic Acid Bases (Uracil, Thymine, and Adenine) with Alkali Metal Ions. Threshold Collision-Induced Dissociation and Theoretical Studies

The gas-phase interactions between lead(II) ions and 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil have been investigated by combining mass spectrometry and theoretical calculations. The most abundant complexes observed, namely [Pb(thiouracil) Ϫ H] ϩ , have been studied by MS/MS experiments. Cationization by the metal allows an unambiguous characterization of the sulfur position, several fragment ions being specific of each isomer. Moreover, compared with the uracil fragmentation, new fragmentation channels are observed: elimination of PbS or total reduction of the metal. Calculations performed on the different structures, including tautomers, show that sulfur is the preferred complexation site, suggesting the greater affinity of lead for sulfur. The most stable structures are always preferentially bidentate. Natural population analysis indicates a charge transfer from the base to the metal with a more pronounced covalent character for sulfur compared to oxygen. Energetic profiles associated with the main fragmentations have been described. (J Am Soc Mass Spectrom 2009, 20, 359 -369)

Section: Low-energy Cid Spectra Of [Pb(thiouracil)mentioning

confidence: 99%

Section: Structures and Relative Stabilities Of [Pb(thiouracil) ϫ H]mentioning

confidence: 99%

Gas-phase interactions between lead(II) ions and thiouracil nucleobases: A combined experimental and theoretical study

Salpin

Guillaumont

Tortajada

et al. 2009

“…In the former case, the mass spectra should ideally directly represent the solution phase chemistry. Gas-phase methods include cone voltage driven dissociation (called the "VC 50 " method) [12,13], collision-induced dissociation [14,15], guided ion beam tandem mass spectrometry [16,17], blackbody infrared radiative dissociation [18,19] and heated capillary dissocation [20,21].…”

mentioning

confidence: 99%

Mass spectrometric determination of association constants of adenylate kinase with two noncovalent inhibitors

Daniel

McCombie

Wendt

et al. 2003

Noncovalent complexes between chicken muscle adenylate kinase and two inhibitors, P 1 ,P 4 -di(adenosine-5')tetraphosphate (Ap4A) and P 1 ,P 5 -di(adenosine-5') pentaphosphate (Ap5A), were investigated with electrospray ionization mass spectrometry under non-denaturing conditions. The nonconvalent nature and the specificity of the complexes are demonstrated with a number of control experiments. Titration experiments allowed the association constants for inhibitor binding to be determined. Problems with concentration dependent ion yields are circumvented by a data evaluation method that is insensitive to the overall ionization efficiency. The K a values found were 9.0 ϫ 10 4 M Ϫ1 (Ap4A) and 4.0 ϫ S oft ionization mass spectrometry (MS), in particular matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), is well known for its ability to bring high molecular weight biomolecules into the gase phase and to even preserve noncovalent complexes [1][2][3][4][5][6][7][8][9][10]. Besides its established applications, a recurring question concerns the applicability of mass spectrometry to measuring noncovalent interaction strengths [11]. There are different approaches to measure the interaction strengths in the gas phase as well as in the liquid phase. In the former case, the mass spectra should ideally directly represent the solution phase chemistry. Gas-phase methods include cone voltage driven dissociation (called the "VC 50 " method) [12,13], collision-induced dissociation [14,15], guided ion beam tandem mass spectrometry [16,17], blackbody infrared radiative dissociation [18,19] and heated capillary dissocation [20,21].Some mass spectrometric studies have been reported in the literature for the determination of noncovalent interaction strengths. There are three basic methods to determine association constants that are reflective of those in solution: first, it is possible to record "melting curves" by raising the temperature of the analyte solution and to use MS to determine the percentage of intact complexes. Cheng et al. analyzed complementary DNA strands [22] and Fändrich et al. studied the chaperone GimC/prefolding homologue complex [13] with this method. Second, competition experiments can be used to evaluate the stability of noncovalent complexes. In Jørgensen's method [23,24], the relative intensities of the free host and the different complexes were used, whereas Kempen et al. employed the known concentration of a reference complex to determine the concentration of an unknown complex [25]. Third, a titration of a host with a guest (or vice versa) can be used. In this case, the mass spectrometric signals should accurately represent the concentrations of the species in solution. The titration method is documented in a number of publications, all of them convincingly showing the successful use of mass spectrometry for the quantitative determination of noncovalent binding constants of proteins and small molecules [26 -33]. This aspect was the main focus in most previous research; th...

“…The affinities of alkali-metal ions with nucleobases have been investigated by both the kinetic method and threshold collision-induced dissociation mass spectrometry [2,3]. On the basis of the research work on the formation of gas-phase ion-molecule complexes, Fujii [4] concluded that the alkali-metal ion affinity generally followed the order of Li ϩ Ͼ Na ϩ Ͼ K ϩ .Various mass spectrometric methods have been used to characterize metal ion biomolecular interaction at the molecular level, to determine the site of metal ion attachment to the biomolecular and its effect on altering the properties and reactivities of the biomolecule [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. ESI-MS was shown to be an excellent means for characterizing of oligonucleotides [18,19], and provide unambiguous identification of singly and multiplycharged ions of deprotonated, protonated, and metalated oligonucleotides.…”

mentioning

confidence: 99%

“…Alkali-metal ion affinities are a good basis for analysis and modeling of such interactions in complex systems. The affinities of alkali-metal ions with nucleobases have been investigated by both the kinetic method and threshold collision-induced dissociation mass spectrometry [2,3]. On the basis of the research work on the formation of gas-phase ion-molecule complexes, Fujii [4] concluded that the alkali-metal ion affinity generally followed the order of Li ϩ Ͼ Na ϩ Ͼ K ϩ .…”

mentioning

confidence: 99%

Cleavage reactions of the complex ions derived from self-complementary deoxydinucleotides and alkali-metal ions using positive ion electrospray ionization with tandem mass spectrometry

Xiang

Abliz

Takayama

2004

The dissociation reactions of the adduct ions derived from the four self-complementary deoxydinucleotides, d(ApT), d(TpA), d(CpG), d(GpC), and alkali-metal ions were studied in detail by positive ion electrospray ionization multiple-stage mass spectrometry (ESI-MS n ). For the [M ϩ H] ϩ ions of the four deoxydinucleotides, elimination of 5Ј-terminus base or loss of both of 5Ј-terminus base and a deoxyribose were the major dissociation pathway. The ESI-MS n spectra showed that Li ϩ , Na ϩ , and Cs ϩ bind to deoxydinucleotides mainly by substituting the H ϩ of phosphate group, and these alkali-metal ions preferred to bind to pyrimidine bases rather than purine bases. For a given deoxydinucleotide, the dissociation pathway of T he interaction between organic compounds or biologically active molecules and alkali-metal cations in the gas phase has attracted much attention. Such interactions may relate to chemical and biological processes occurring in solution; for example, ion salvation, catalysis, transport through membranes, affinity of active compounds toward receptors, and antibiotic activity [1]. The alkali metal ions, especially Na ϩ and K ϩ , are of particular importance in the mechanism of action of some biomolecules. Alkali-metal ion affinities are a good basis for analysis and modeling of such interactions in complex systems. The affinities of alkali-metal ions with nucleobases have been investigated by both the kinetic method and threshold collision-induced dissociation mass spectrometry [2,3]. On the basis of the research work on the formation of gas-phase ion-molecule complexes, Fujii [4] concluded that the alkali-metal ion affinity generally followed the order of Li ϩ Ͼ Na ϩ Ͼ K ϩ .Various mass spectrometric methods have been used to characterize metal ion biomolecular interaction at the molecular level, to determine the site of metal ion attachment to the biomolecular and its effect on altering the properties and reactivities of the biomolecule [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. ESI-MS was shown to be an excellent means for characterizing of oligonucleotides [18,19], and provide unambiguous identification of singly and multiplycharged ions of deprotonated, protonated, and metalated oligonucleotides.Knowledge of the fundamental modes of metal ion binding to simple DNA and RNA compounds will greatly improve our understanding of how metal ions interact with nucleic acids of more complexity. Deoxydinucleotides are the smallest subunits in nucleic acids bearing sequence information of DNA.The dissociation reactions of protonated molecular ions from 12 possible hetero-deoxyribonucleotides were previously studied using fast atom bombardment with tandem mass spectrometry [5,6]. It was proposed