Gas-phase conformations of deprotonated trinucleotides (dGTT−, dTGT−, and dTTG−): the question of zwitterion formation

Gidden, Jennifer; Bowers, Michael T.

doi:10.1016/s1044-0305(02)00866-8

Cited by 48 publications

(56 citation statements)

References 55 publications

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“…The gasphase conformations of a series of free mononucleotide, dinucleotide, and trinucleotide ions were investigated by using matrix-assisted laser desorption ionization and ion-mobility experiment by Bowers and coworkers (27)(28)(29)(30). Our group has developed an experimental technique that couples an electrospray ionization source with a magnetic-bottle photoelectron spectrometer (31) to investigate multiply charged anions and solution species in the gas phase (32,33).…”

Section: Dna Oxidation ͉ Nucleotidementioning

confidence: 99%

Direct experimental observation of the low ionization potentials of guanine in free oligonucleotides by using photoelectron spectroscopy

Yang

Wang

Vorpagel

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

143

208

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Photodetachment photoelectron spectroscopy is used to probe the electronic structure of mono-, di-, and trinucleotide anions in the gas phase. A weak and well defined threshold band was observed in the photoelectron spectrum of 2 -deoxyguanosine 5 -monophosphate at a much lower ionization energy than the other three mononucleotides. Density function theory calculations revealed that this unique spectral feature is caused by electron-detachment from a orbital of the guanine base on 2 -deoxyguanosine 5 -monophosphate, whereas the lowest ionization channel for the other three mononucleotides takes place from the phosphate group. This low-energy feature was shown to be a ''fingerprint'' in all the spectra of dinucleotides and trinucleotides that contain the guanine base. The current experiment provides direct spectroscopic evidence that the guanine base is the site with the lowest ionization potential in oligonucleotides and DNA and is consistent with the fact that guanine is most susceptible to oxidation to give the guanine cation in DNA damage. DNA oxidation ͉ nucleotideT he ionization of nucleotide plays very important roles in the chemistry and biology of DNA. Induced by electrophiles or ionizing radiation, the electron-deficient site (hole) on the nucleotide and its migration may lead directly to DNA damage (1-6). In most cases, guanine is the initial oxidation site, or the electron-loss center ultimately moves through the DNA stack to end up at a guanine base (7). This observation is attributed to the low ionization potential (IP) of guanine relative to the other DNA bases (8-10). Thus, the electronic structure of nucleotides and their ionization properties are essential for understanding the mechanism of DNA damage. Extensive experimental and theoretical studies have focused on these topics (11)(12)(13)(14)(15)(16)(17)(18)(19). In particular, LeBreton and coworkers (9,[20][21][22][23][24] have investigated the ionization of nucleic acid bases, sugar residue, and the phosphate in the gas phase by using UV photoelectron spectroscopy (PES) and then combining these studies and molecular orbital calculations to address the electronic structure of the nucleotides. Gas-phase studies probe the intrinsic electronic properties of the nucleotides and provide important experimental data to compare with and verify theoretical results and methods.Matrix-assisted laser desorption ionization (25) and electrospray ionization (26) techniques provide powerful tools for characterizing biological molecules in the gas phase. The gasphase conformations of a series of free mononucleotide, dinucleotide, and trinucleotide ions were investigated by using matrix-assisted laser desorption ionization and ion-mobility experiment by Bowers and coworkers (27-30). Our group has developed an experimental technique that couples an electrospray ionization source with a magnetic-bottle photoelectron spectrometer (31) to investigate multiply charged anions and solution species in the gas phase (32, 33). Here, we report a PES study on a series of s...

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Section: Dna Oxidation ͉ Nucleotidementioning

confidence: 99%

Direct experimental observation of the low ionization potentials of guanine in free oligonucleotides by using photoelectron spectroscopy

Yang

Wang

Vorpagel

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

143

208

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“…Measuring the drift time directly linked to the mobility of an ion yields information about its structure because compact ions, which have necessarily relatively small collision cross sections, move faster than extended ones, which have large collision cross sections. The gas-phase conformations of many oligonucleotides have been investigated by ion mobility: deprotonated mononucleotides [19,20], dinucleotides [21], trinucleotides [22], deprotonated oligothymidines [23], DNA complexes [24], G-quadruplex [25,26], etc.…”

mentioning

confidence: 99%

Detection of oligonucleotide gas-phase conformers: H/D exchange and ion mobility as complementary techniques

Balbeur

Widart

Leyh

et al. 2008

J. Am. Soc. Mass Spectrom.

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Gas-phase hydrogen/deuterium exchange of small oligonucleotides (dTG, dC 6 and C 6 ) with CD 3 0D was performed in the second hexapole of a Fourier transform ion-cyclotron resonance (FTICR) mass spectrometer. Ion activation experiments were conducted by accelerating the ions at the entrance of the H/D exchange cell under conditions promoting exclusively collisional isomerization. These experiments allowed us to assess the presence of several conformers, and to probe the height of the isomerization barrier separating these conformers. Hydrogen/deuterium (H/D) exchange combined with mass spectrometry has become an efficient tool for obtaining conformational information about isolated biomolecules in the gas phase [1-18J. The rate of gasphase H/D exchange has been shown to be a function of the reagent used for exchange (nature and concentration), the charge state of the biomolecule, the gasphase basicity/acidity of exchangeable sites, and the internal structure of the biomolecular ions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Probing the number of exchanged hydrogens and the H/D exchange kinetics makes it possible to distinguish ion populations and to elucidate their structural and thermochemical features. Gas-phase H/D exchange has been applied extensively for structural studies of proteins and peptides [1-6J and is now also most commonly used for structural characterizations of oligonucleotides [7][8][9][10][11][12][13][14][15][16][17][18]. Mononucleotides studies have shown Address reprint requests to Miss Dorothee Balbeur, Laboratory of Mass Spectrometry, University of Liege, 3 Allee de la Chimie Bat. B6c, B-4000 Liege, Belgium. E-mail: dbalbeur@ulg.ac.be that the extent and rate of exchange depend on the nucleobase (nature, space orientation, and gas-phase acidity of the exchangeable hydrogen), and on the position (3' or 5') and flexibility of the terminal phosphate group [7-11J. Moreover, these studies have been in favor of the relay mechanism [7][8][9][10][11]. The latter was shown not to be relevant for dinucleotides [14J. Furthermore, gas-phase H/D exchange of dinucleotides has been shown to be controlled by hydrogen accessibility rather than by the chemical nature of the heteroatom bearing the exchangeable hydrogen. Studies of larger oligonucleotides have also been published. Gas-phase H/D exchange reactions were performed on DNA duplexes and on the corresponding single strands. They showed that H/D exchange was slower for the duplex than for the single strands [15, 16J. In a previous study, a quadruplex was shown to undergo very fast H/D exchange compared with its constituent monomer, an unexpected situation for such a compact and rigid structure [17J. Gas-phase H/D exchange of 5-mer phosphorothioate oligonucleotides was also examined; bimodal exchange profiles were observed, suggesting that each ion could adopt more than one gas-phase conformation [18J.The present work focuses on the bimodal H/D exchange of oligonucleotides. A simple interpretation of such a behavior is that one ...

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“…The significance of this result is discussed subsequently. Previous studies have shown that ion cross sections for a particular type of structure do depend on energy, but these effects are typically observed over a much wider energy range (i.e., 20-60 kcal/mol) than the very small 3-kcal/mol range investigated here [37,38,45,47]. The range of the cross sections in those studies over a small (e.g., 3 kcal/mol) range obscures any weak trend with energy as is the case in this study.…”

Section: Calculated Cross Sectionsmentioning

confidence: 57%

“…Both AMBER* [28,37,38,45,48,49] and CHARMm [33,35,52] have been extensively used to obtain low-energy structures for comparison with ion mobility data. Structures calculated by using MMFF were also included in this study because evaluations of different force fields by others suggest that this force field can provide accurate results when compared with experimental data [70] or higher levels of theory [71].…”

Section: Methodsmentioning

confidence: 99%

“…Higher level calculations are often done on low-energy structures identified at the mechanics level. Ion mobility has been used to characterize a wide range of ion structures including carbon clusters [25][26][27], amino acids [28,29], peptides [30][31][32][33][34][35][36][37], proteins [39][40][41][42][43], DNA [44][45][46][47], and synthetic polymers [48][49][50]. Bowers and coworkers showed that the cross sections of gas-phase valinomycin-alkali ion complexes are the same for lithiated and sodiated species, but steadily increase for potassiated, rubidiated, and cesiated complexes [51].…”

mentioning

confidence: 99%

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Evaluation of ion mobility spectroscopy for determining charge-solvated versus salt-bridge structures of protonated trimers

Wong

Williams

Counterman

et al. 2005

J. Am. Soc. Mass Spectrom.

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The cross sections of five different protonated trimers consisting of two base molecules and trifluoroacetic acid were measured by using ion mobility spectrometry. The gas-phase basicities of these five base molecules span an 8-kcal/mol range. These cross sections are compared with those determined from candidate low-energy salt-bridge and charge-solvated structures identified by using molecular mechanics calculations using three different force fields: AMBER*, MMFF, and CHARMm. With AMBER*, the charge-solvated structures are all globular and the salt-bridge structures are all linear, whereas with CHARMm, these two forms of the protonated trimers can adopt either shape. Globular structures have smaller cross sections than linear structures. Conclusions about the structure of these protonated trimers are highly dependent on the force field used to generate low-energy candidate structures. With AMBER*, all of the trimers are consistent with salt-bridge structures, whereas with MMFF the measured cross sections are more consistent with charge-solvated structures, although the assignments are ambiguous for two of the protonated trimers. Conclusions based on structures generated by using CHARMm suggest a change in structure from charge-solvated to salt-bridge structures with increasing gas-phase basicity of the constituent bases, a result that is most consistent with structural conclusions based on blackbody infrared radiative dissociation experiments for these protonated trimers and theoretical calculations on the uncharged base-acid pairs. T he structure of a molecule in solution depends both on intramolecular interactions and on intermolecular interactions between the molecule and solvent. Gas-phase studies can provide information about the intrinsic properties of a molecule. From such measurements, information about solvent effects can be inferred. A number of different methods can provide information about molecular structure in the gas phase, even complex systems, such as large synthetic or biological polymers. These methods include spectroscopy [1][2][3][4][5], hydrogen/deuterium exchange [6-12], dissociation [13][14][15][16][17][18], proton transfer reactivity [19][20][21][22], and ion mobility mass spectrometry . These methods have been used to obtain information about protein conformation and folding, DNA duplex structure, and in a wide variety of other interesting applications.Of these methods, ion mobility mass spectrometry, a method pioneered by Bowers and Jarrold for ion structure characterization, has several advantages, including rapid measurement time, minimal perturbation of ground state structure, exquisite temperature control, and the ability to investigate kinetics of structural change over a limited time. With ion mobility, ions are injected into a drift tube where they thermalize through collisions with an introduced background gas, typically helium. In the presence of an applied electric field, ions are made to drift through an elevated pressure region. Based on the drift time through this tube...

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Gas-phase conformations of deprotonated trinucleotides (dGTT⁻, dTGT⁻, and dTTG⁻): the question of zwitterion formation

Cited by 48 publications

References 55 publications

Direct experimental observation of the low ionization potentials of guanine in free oligonucleotides by using photoelectron spectroscopy

Direct experimental observation of the low ionization potentials of guanine in free oligonucleotides by using photoelectron spectroscopy

Detection of oligonucleotide gas-phase conformers: H/D exchange and ion mobility as complementary techniques

Evaluation of ion mobility spectroscopy for determining charge-solvated versus salt-bridge structures of protonated trimers

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