Mass spectrometry of nucleic acid constituents. Electron ionization spectra of selectively labeled adenines

Sethi, K Satinder; Gupta, S.P.; JENKINS, E. E.; Whitehead, Calvert W.; Townsend, Leroy B.; McCloskey, James A.

doi:10.1021/ja00376a017

Cited by 52 publications

(83 citation statements)

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“…Figure 3 shows the appearance energies and higher onsets determined in the present work. This includes the first and Scheme I in Sethi et al [15]). This is contrary to the appearance energies obtained by Dawley et al [17], which exclude a near-threshold formation of 43 u by HCN loss from 70 u, and a near-threshold formation of 27 u by HCN loss from 54 u.…”

Section: Total Ionization Cross Section and Normalization Of The Datamentioning

confidence: 99%

“…Studies with isotope labeled adenines [13][14][15] show that most of the fragmentation pathways exhibit largely random isotopic retention patterns, indicating the presence of multiple fragmentation pathways. Based on this we attribute the rapid rise of these ion yields, with powers p 2, to several onsets very close to each other due to the presence of parallel fragmentation pathways with similar appearance energies.…”

Section: Appearance Energiesmentioning

confidence: 99%

“…Rice and Dudek [12] have measured a mass spectrum of adenine for 70 eV electron impact and have identified three of the main sequential fragmentation pathways. Occolowitz [13], Barrio et al [14] and Sethi et al [15] have measured mass spectra with isotope labeled adenines, showing that most Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey Solov'yov, Nigel Mason, Gustavo García, Eugene Surdutovich. a e-mail: peter.vanderburgt@nuim.ie of the fragmentation pathways exhibit largely random isotopic retention patterns, and that multiple pathways of successive fragmentations occur in parallel. Minaev et al [16] have measured the absolute total ionization cross sections of adenine for electron energies up to 200 eV as well as partial cross sections for the production of 24 fragment ions at 95 eV.…”

Section: Introductionmentioning

confidence: 99%

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Electron impact fragmentation of adenine: partial ionization cross sections for positive fragments

2015

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Abstract. Using computer-controlled data acquisition we have measured mass spectra of positive ions for electron impact on adenine, with electron energies up to 100 eV. Ion yield curves for 50 ions have been obtained and normalized by comparing their sum to the average of calculated total ionization cross sections. Appearance energies have been determined for 37 ions; for 20 ions for the first time. All appearance energies are consistent with the fragmentation pathways identified in the literature. Second onset energies have been determined for 12 fragment ions (for 11 ions for the first time), indicating the occurrence of more than one fragmentation process e.g. for 39 u (C2HN + ) and 70 u (C2H4N + 3 ). Matching ion yield shapes (118-120 u, 107-108 u, 91-92 u, and 54-56 u) provide new evidence supporting closely related fragmentation pathways and are attributed to hydrogen rearrangement immediately preceding the fragmentation. We present the first measurement of the ion yield curve of the doubly charged parent ion (67.5 u), with an appearance energy of 23.5 ± 1.0 eV.

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Section: Total Ionization Cross Section and Normalization Of The Datamentioning

confidence: 99%

Section: Appearance Energiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electron impact fragmentation of adenine: partial ionization cross sections for positive fragments

2015

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“…The EI study of adenine showed that the major fragmentation path involves successive loss of HCN molecules. Studies of labeled adenines [29,30] demonstrated that the initially eliminated HCN contains the N1 atom and the loss of the NH 2 group was not observed. For guanine, the initial expulsion of neutral cyanamide (H 2 NCN) is the dominant fragmentation (from the pyrimidine's N1-C2-NH 2 moiety), and some NH 2 group elimination was observed as well.…”

Section: Initial Expulsion Of Nitrile or Ammoniamentioning

confidence: 99%

Ammonia elimination from protonated nucleobases and related synthetic substrates

Qian

Yang

et al. 2007

J. Am. Soc. Mass Spectrom.

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The results are reported of mass-spectrometric studies of the nucleobases adenine 1h (1, R ϭ H), guanine 2h, and cytosine 3h. The protonated nucleobases are generated by electrospray ionization of adenosine 1r (1, R ϭ ribose), guanosine 2r, and deoxycytidine 3d (3, R ϭ deoxyribose) and their fragmentations were studied with tandem mass spectrometry. In contrast to previous EI-MS studies of the nucleobases, NH 3 elimination does present a major path for the fragmentations of the ions [1h ϩ H] ϩ , [2h ϩ H] ϩ , and [3h ϩ H] ϩ . The ion [2h ϩ H Ϫ NH 3 ] ϩ also was generated from the acyclic precursor 5-cyanoamino-4-oxomethylenedihydroimidazole 13h and from the thioether derivative 14h of 2h (NH 2 replaced by MeS). The analyses of the modes of initial fragmentation is supported by density functional theoretical studies. Conjugate acids 15-55 were studied to determine site preferences for the protonations of 1h, 2h, 3h, 13h, and 14h. The proton affinity of the amino group hardly ever is the substrate's best protonation site, and possible mechanisms for NH 3 elimination are discussed in which the amino group serves as the dissociative protonation site. The results provide semi-direct experimental evidence for the existence of the pyrimidine ring-opened cations that we had proposed on the basis of theoretical studies as intermediates in nitrosative nucleobase deamination. [1,2]. This chemistry has been studied extensively because of the dietary and environmental exposure of humans to these substances [3][4][5]. Toxicological studies of deamination became more significant when it was recognized that endogenous nitric oxide [6,7] causes nitrosation [8,9], and that this process is accelerated by chronic inflammatory diseases [10,11]. It has been known for a long time that deamination of adenine 1, guanine 2, and cytosine 3 (Scheme 1) results in the formation of hypoxanthine, xanthine, and uracil, respectively, and these products are thought to result from DNA base diazonium ions 4-6, respectively, by direct nucleophilic dediazoniation. The discovery of oxanine formation [12][13][14] in the nitrosative deamination of guanine challenged the generality and completeness of this mechanism. Theoretical studies revealed that unimolecular dediazoniation of guaninediazonium ion 5 is accompanied or immediately followed by pyrimidine ringopening [15,16] and that cytosine-catalysis promotes the process [17,18]. The resulting 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole is a highly reactive intermediate and undergoes acid-catalyzed 1,4-addition via cyano-N or imino-N protonated 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazoles, 9 and 10, respectively [19].Labeling studies support this reaction mechanism for oxanine formation [20]. Moreover, we synthesized 5-cyanoamino-4-imidazolecarboxamide and studied its cyclization chemistry [21] and its proficiency for cross-link formation [22]. The unimolecular dediazoniation of the diazonium ions of adenine and cytosine can proceed without ring-opening but the cations 7 and 11 formed in this...

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“…The set of KIEs for the three ADAs were determined under competitive conditions. The intrinsic [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] N], [6-13 C], and [6- 30 Adenylate kinase (AK), pyruvate kinase (PK), hexokinase, and bovine spleen adenosine deaminase (BtADA) were purchased from Sigma. Phospho-D-ribosyl-1-pyrophosphate (PRPP) synthase and adenine phosphoribosyltransferase (APRTase) were purified according to the methods reported previously.…”

Section: Introductionmentioning

confidence: 99%

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

2007

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Adenosine deaminases (ADAs) from human, bovine and Plasmodium falciparum sources were analyzed by kinetic isotope effects (KIEs) and shown to have distinct but related transition states. Human adenosine deaminase (HsADA) is present in most mammalian cells and is involved in Band T-cell development. The ADA from Plasmodium falciparum (PfADA) is essential in this purine auxotroph and its inhibition is expected to have therapeutic effects for malaria. Therefore ADA is of continuing interest for inhibitor design. where N1 protonation is partial and the bond order to the attacking hydroxyl nucleophile is nearly complete. The key structural variation among PfADA, HsADA and BtADA transition states lies in the degree of N1 protonation with the decreased bond lengths of 1.92 Å, 1.55 Å and 1.28 Å, respectively. Thus, PfADA has the earliest and BtADA has most developed transition state. This conclusion is consistent with the 20 to 36-fold increase of k cat in comparing PfADA with HsADA and BtADA.

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Mass spectrometry of nucleic acid constituents. Electron ionization spectra of selectively labeled adenines

Cited by 52 publications

References 0 publications

Electron impact fragmentation of adenine: partial ionization cross sections for positive fragments

Electron impact fragmentation of adenine: partial ionization cross sections for positive fragments

Ammonia elimination from protonated nucleobases and related synthetic substrates

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

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