Structural and Energetic Effects of O2′-Ribose Methylation of Protonated Pyrimidine Nucleosides

  • C. C. He
  • L. A. Hamlow
  • Y. Zhu
  • Y.-w. Nei
  • L. Fan
  • C. P. McNary
  • P. Maître
  • V. Steinmetz
  • B. Schindler
  • I. Compagnon
  • P. B. Armentrout
  • M. T. RodgersEmail author
Research Article


The 2′-substituents distinguish DNA from RNA nucleosides. 2′-O-methylation occurs naturally in RNA and plays important roles in biological processes. Such 2′-modifications may alter the hydrogen-bonding interactions of the nucleoside and thus may affect the conformations of the nucleoside in an RNA chain. Structures of the protonated 2′-O-methylated pyrimidine nucleosides were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy, assisted by electronic structure calculations. The glycosidic bond stabilities of the protonated 2′-O-methylated pyrimidine nucleosides, [Nuom+H]+, were also examined and compared to their DNA and RNA nucleoside analogues via energy-resolved collision-induced dissociation (ER-CID). The preferred sites of protonation of the 2′-O-methylated pyrimidine nucleosides parallel their canonical DNA and RNA nucleoside analogues, [dNuo+H]+ and [Nuo+H]+, yet their nucleobase orientation and sugar puckering differ. The glycosidic bond stabilities of the protonated pyrimidine nucleosides follow the order: [dNuo+H]+ < [Nuo+H]+ < [Nuom+H]+. The slightly altered structures help explain the stabilization induced by 2′-O-methylation of the pyrimidine nucleosides.


Cytidine (Cyd) Cytosine (Cyt) Density functional theory (DFT) Electronic structure calculations Electrospray ionization (ESI) Energy-resolved collision-induced dissociation (ER-CID) Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) Gas-phase conformation Glycosidic bond stability Hydrogen-bonding interactions Hydrogen-stretching region Infrared multiple photon dissociation (IRMPD) action spectroscopy IR fingerprint region IRMPD spectrum IR spectrum 5-Methyluridine Nucleobase Nucleobase orientation Nucleoside Nucleoside modification 2′-O-methylation 2′-O-methylcytidine (Cydm) 2′-O-methyl-5-methyluridine (Thdm) 2′-O-methyluridine (Urdm) Protonation Pyrimidine nucleosides Quadrupole ion trap mass spectrometer (QIT MS) Simulated annealing Sugar puckering Survival yield analysis Tandem mass spectrometry Thymidine (Thd) Thymine (Thy) Uracil (Ura) Uridine (Urd) 



This work is financially supported by the National Science Foundation, under Grants OISE-0730072 and OISE-1357787 (for international travel expenses), DBI-0922819 (for the Bruker amaZon ETD QITMS employed in this work), and CHE-1709789 and CHE-1664618 (for other research costs). C.C.H., L.A.H., Y.Z., and Y.-w.N. are supported by the Wayne State University Thomas C. Rumble Graduate Fellowships and Summer Dissertation Fellowships. We thank Wayne State University C&IT for excellent computational resources and support. The skillful assistance of the CLIO staff is gratefully acknowledged.

Supplementary material

13361_2019_2300_MOESM1_ESM.pdf (18.9 mb)
ESM 1 (PDF 19328 kb)


  1. 1.
    Helm, M., Motorin, Y.: Detecting RNA modifications in the epitranscriptome: Predict and validate. Nat. Rev. Genet. 18, 275–291 (2017)Google Scholar
  2. 2.
    Banoub, J.H., Limbach, P.A.: Mass spectrometry of nucleosides and nucleic acids. CRC Press, Boca Raton (2010)Google Scholar
  3. 3.
    Dudley, E., Bond, L.: Mass spectrometry analysis of nucleosides and nucleotides. Mass Spectrom. Rev. 33, 302–331 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Edmonds, C.G., Crain, P.F., Gupta, R., Hashizume, T., Hocart, C.H., Kowalak, J.A., Pomerantz, S.C., Stetter, K.O., McCloskey, J.A.: Posttranscriptional modification of transfer-RNA in thermophilic archaea (archaebacteria). J. Bacteriol. 173, 3138–3148 (1991)CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Noon, K.R., Bruenger, E., McCloskey, J.A.: Posttranscriptional modifications in 16S and 23S rRNAs of the archaeal hyperthermophile sulfolobus solfataricus. J. Bacteriol. 180, 2883–2888 (1998)PubMedPubMedCentralGoogle Scholar
  6. 6.
    Guymon, R., Pomerantz, S.C., Crain, P.F., McCloskey, J.A.: Influence of phylogeny on posttranscriptional modification of rRNA in thermophilic prokaryotes: The complete modification map of 16S rRNA of thermus thermophilus. Biochemistry-US. 45, 4888–4899 (2006)Google Scholar
  7. 7.
    Su, D., Chan, C.T.Y., Gu, C., Lim, K.S., Chionh, Y.H., McBee, M.E., Russell, B.S., Babu, I.R., Begley, T.J., Dedon, P.C.: Quantitative analysis of ribonucleoside modifications in tRNA by HPLC-coupled mass spectrometry. Nat. Protoc. 9, 828–841 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bjork, G.R., Ericson, J.U., Gustafsson, C.E.D., Hagervall, T.G., Jonsson, Y.H., Wikstrom, P.M.: Transfer-RNA modification. Annu. Rev. Biochem. 56, 263–287 (1987)CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Nelson, D.L., Cox, M.M.: Lehninger principles of biochemistry, 7th edn. W. H. Freeman and Company, New York (2017)Google Scholar
  10. 10.
    Wu, R.R., Yang, B., Berden, G., Oomens, J., Rodgers, M.T.: Gas-phase conformations and energetics of protonated 2′-deoxyguanosine and guanosine: IRMPD action spectroscopy and theoretical studies. J. Phys. Chem. B. 118, 14774–14784 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wu, R.R., Yang, B., Berden, G., Oomens, J., Rodgers, M.T.: Gas-phase conformations and energetics of protonated 2′-deoxyadenosine and adenosine: IRMPD action spectroscopy and theoretical studies. J. Phys. Chem. B. 119, 2795–2805 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wu, R.R., Yang, B., Frieler, C.E., Berden, G., Oomens, J., Rodgers, M.T.: N3 and O2 protonated tautomeric conformations of 2′-deoxycytidine and cytidine coexist in the gas phase. J. Phys. Chem. B. 119, 5773–5784 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wu, R.R., Yang, B., Frieler, C.E., Berden, G., Oomens, J., Rodgers, M.T.: Diverse mixtures of 2,4-dihydroxy tautomers and O4 protonated conformers of uridine and 2′-deoxyuridine coexist in the gas phase. Phys. Chem. Chem. Phys. 17, 25978–25988 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wu, R.R., Yang, B., Frieler, C.E., Berden, G., Oomens, J., Rodgers, M.T.: 2,4-dihydroxy and O2 protonated tautomers of dThd and Thd coexist in the gas phase: Methylation alters protonation preferences versus dUrd and Urd. J. Am. Soc. Mass Spectrom. 27, 410–421 (2016)Google Scholar
  15. 15.
    Zhu, Y., Hamlow, L.A., He, C.C., Strobehn, S.F., Lee, J.K., Gao, J., Berden, G., Oomens, J., Rodgers, M.T.: Influence of sodium cationization versus protonation on the gas-phase conformations and glycosidic bond stabilities of 2′-deoxyadenosine and adenosine. J. Phys. Chem. B. 120, 8892–8904 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Zhu, Y., Hamlow, L.A., He, C.C., Lee, J.K., Gao, J., Berden, G., Oomens, J., Rodgers, M.T.: Gas-phase conformations and N-glycosidic bond stabilities of sodium cationized 2′-deoxyguanosine and guanosine: Sodium cations preferentially bind to the guanine residue. J. Phys. Chem. B. 121, 4048–4060 (2017)Google Scholar
  17. 17.
    Zhu, Y., Roy, H.A., Cunningham, N.A., Strobehn, S.F., Gao, J., Munshi, M.U., Berden, G., Oomens, J., Rodgers, M.T.: Effects of sodium cationization versus protonation on the conformations and N-glycosidic bond stabilities of sodium cationized Urd and dUrd: solution conformation of [Urd+Na]+ is preserved upon ESI. Phys. Chem. Chem. Phys. 19, 17637–17652 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zhu, Y., Roy, H.A., Cunningham, N.A., Strobehn, S.F., Gao, J., Munshi, M.U., Berden, G., Oomens, J., Rodgers, M.T.: IRMPD action spectroscopy, ER-CID experiments, and theoretical studies of sodium cationized thymidine and 5-methyluridine: Kinetic trapping during the ESI desolvation process preserves the solution structure of [Thd+Na]+. J. Am. Soc. Mass Spectrom. 28, 2423–2437 (2017)Google Scholar
  19. 19.
    Zhu, Y., Hamlow, L.A., He, C.C., Lee, J.K., Gao, J., Berden, G., Oomens, J., Rodgers, M.T.: Conformations and N-glycosidic bond stabilities of sodium cationized 2′-deoxycytidine and cytidine: Solution conformation of [Cyd+Na]+ is preserved upon ESI. Int. J. Mass Spectrom. 429, 18–27 (2018)Google Scholar
  20. 20.
    Salpin, J.Y., Scuderi, D.: Structure of protonated thymidine characterized by infrared multiple photon dissociation and quantum calculations. Rapid Commun. Mass Spectrom. 29, 1898–1904 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Filippi, A., Fraschetti, C., Rondino, F., Piccirillo, S., Steinmetz, V., Guidoni, L., Speranza, M.: Protonated pyrimidine nucleosides probed by IRMPD spectroscopy. Int. J. Mass Spectrom. 354, 54–61 (2013)CrossRefGoogle Scholar
  22. 22.
    Ung, H.U., Huynh, K.T., Poutsma, J.C., Oomens, J., Berden, G., Morton, T.H.: Investigation of proton affinities and gas phase vibrational spectra of protonated nucleosides, deoxynucleosides, and their analogs. Int. J. Mass Spectrom. 378, 294–302 (2015)CrossRefGoogle Scholar
  23. 23.
    Abo-Riziq, A., Crews, B.O., Compagnon, I., Oomens, J., Meijer, G., von Helden, G., Kabelac, M., Hobza, P., de Vries, M.S.: The mid-IR spectra of 9-ethyl guanine, guanosine, and 2′-deoxyguanosine. J. Phys. Chem. A. 111, 7529–7536 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    He, C.C., Hamlow, L.A., Devereaux, Z.J., Zhu, Y., Nei, Y.-w., Fan, L., McNary, C.P., Maitre, P., Steinmetz, V., Schindler, B., Compagnon, I., Armentrout, P.B., Rodgers, M.T.: Structural and energetic effects of O2′-ribose methylation of protonated purine nucleosides. J. Phys. Chem. B. 122, 9147–9160 (2018)CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Hamlow, L.A., Devereaux, Z.J., Roy, H.A., Cunningham, N.A., Berden, G., Oomens, J., Rodgers, M.T.: Impact of the 2'- and 3′-sugar hydroxyl moieties on gas-phase nucleoside structure. J. Am. Soc. Mass Spectrom. 30, 832–845 (2019)CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Hamlow, L.A., He, C.C., Devereaux, Z.J., Roy, H.A., Cunningham, N.A., Soley, E.O., Berden, G., Oomens, J., Rodgers, M.T.: Gas-phase structures of protonated arabino nucleosides. Int. J. Mass Spectrom. 438, 124–134 (2019)CrossRefGoogle Scholar
  27. 27.
    Hamlow, L.A., Zhu, Y., Devereaux, Z.J., Cunningham, N.A., Berden, G., Oomens, J., Rodgers, M.T.: Modified quadrupole ion trap mass spectrometer for infrared ion spectroscopy: Application to protonated thiated uridines. J. Am. Soc. Mass Spectrom. 29, 2125–2137 (2018)Google Scholar
  28. 28.
    Devereaux, Z.J., Roy, H.A., He, C.C., Zhu, Y., Cunningham, N.A., Hamlow, L.A., Berden, G., Oomens, J., Rodgers, M.T.: Influence of 2′-fluoro modification on glycosidic bond stabilities and gas-phase ion structures of protonated pyrimidine nucleosides. J. Fluor. Chem. 219, 10–22 (2019)CrossRefGoogle Scholar
  29. 29.
    Devereaux, Z.J., Zhu, Y., Rodgers, M.T.: Relative glycosidic bond stabilities of naturally occurring methylguanosines: 7-methylation is intrinsically activating. Eur. J. Mass Spectrom. (Chichester). 25, 16–29 (2019)CrossRefGoogle Scholar
  30. 30.
    Nei, Y.-w., Crampton, K.T., Berden, G., Oomens, J., Rodgers, M.T.: Infrared multiple photon dissociation action spectroscopy of deprotonated RNA mononucleotides: Gas-Phase conformations and energetics. J. Phys. Chem. A. 117, 10634–10649 (2013)Google Scholar
  31. 31.
    Nei, Y.-w., Hallowita, N., Steill, J.D., Oomens, J., Rodgers, M.T.: Infrared multiple photon dissociation action spectroscopy of deprotonated DNA mononucleotides: Gas-Phase conformations and energetics. J. Phys. Chem. A. 117, 1319–1335 (2013)Google Scholar
  32. 32.
    Wu, R.R., He, C.C., Hamlow, L.A., Nei, Y.-w., Berden, G., Oomens, J., Rodgers, M.T.: Protonation induces base rotation of purine nucleotides pdGuo and pGuo. Phys. Chem. Chem. Phys. 18, 15081–15090 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Wu, R.R., He, C.C., Hamlow, L.A., Nei, Y.-w., Berden, G., Oomens, J., Rodgers, M.T.: N3 protonation induces base rotation of 2′-deoxyadenosine-5′-monophosphate and adenosine-5′-monophosphate. J. Phys. Chem. B. 120, 4616–4624 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Wu, R.R., Hamlow, L.A., He, C.C., Nei, Y.-w., Berden, G., Oomens, J., Rodgers, M.T.: The intrinsic basicity of the phosphate backbone exceeds that of uracil and thymine residues: Protonation of the phosphate moiety is preferred over the nucleobase for pdThd and pUrd. Phys. Chem. Chem. Phys. 19, 30351–30361 (2017)Google Scholar
  35. 35.
    Wu, R.R., Hamlow, L.A., He, C.C., Nei, Y.-w., Berden, G., Oomens, J., Rodgers, M.T.: N3 and O2 protonated conformers of the cytosine mononucleotides coexist in the gas phase. J. Am. Soc. Mass Spectrom. 28, 1638–1646 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Pedersen, S.O., Stochkel, K., Byskov, C.S., Baggesen, L.M., Nielsen, S.B.: Gas-phase spectroscopy of protonated adenine, adenosine 5′-monophosphate and monohydrated ions. Phys. Chem. Chem. Phys. 15, 19748–19752 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Chiavarino, B., Crestoni, M.E., Fornarini, S., Lanucara, F., Lemaire, J., Maitre, P., Scuderi, D.: Infrared spectroscopy of isolated nucleotides 1. The cyclic 3′,5′-adenosine monophosphate anion. Int. J. Mass Spectrom. 270, 111–117 (2008)CrossRefGoogle Scholar
  38. 38.
    Lanucara, F., Crestoni, M.E., Chiavarino, B., Fornarini, S., Hernandez, O., Scuderi, D., Maitre, P.: Infrared spectroscopy of nucleotides in the gas phase 2. The protonated cyclic 3′,5′-adenosine monophosphate. RSC Adv. 3, 12711–12720 (2013)CrossRefGoogle Scholar
  39. 39.
    Ligare, M.R., Rijs, A.M., Berden, G., Kabelac, M., Nachtigallova, D., Oomens, J., de Vries, M.S.: Resonant infrared multiple photon dissociation spectroscopy of anionic nucleotide monophosphate clusters. J. Phys. Chem. B. 119, 7894–7901 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Salpin, J.Y., MacAleese, L., Chirot, F., Dugourd, P.: Structure of the Pb2+-deprotonated dGMP complex in the gas phase: A combined MS-MS/IRMPD spectroscopy/ion mobility study. Phys. Chem. Chem. Phys. 16, 14127–14138 (2014)Google Scholar
  41. 41.
    Gidden, J., Bowers, M.T.: Gas-phase conformations of deprotonated and protonated mononucleotides determined by ion mobility and theoretical modeling. J. Phys. Chem. B. 107, 12829–12837 (2003)CrossRefGoogle Scholar
  42. 42.
    Dunin-Horkawicz, S., Czerwoniec, A., Gajda, M.J., Feder, M., Grosjean, H., Bujnicki, J.M.: Modomics: A database of RNA modification pathways. Nucleic Acids Res. 34, D145–D149 (2006)Google Scholar
  43. 43.
    Czerwoniec, A., Dunin-Horkawicz, S., Purta, E., Kaminska, K.H., Kasprzak, J.M., Bujnicki, J.M., Grosjean, H., Rother, K.: Modomics: A database of RNA modification pathways. 2008 update. Nucleic Acids Res. 37, D118–D121 (2009)Google Scholar
  44. 44.
    Machnicka, M.A., Milanowska, K., Oglou, O.O., Purta, E., Kurkowska, M., Olchowik, A., Januszewski, W., Kalinowski, S., Dunin-Horkawicz, S., Rother, K.M., Helm, M., Bujnicki, J.M., Grosjean, H.: Modomics: A database of RNA modification pathways-2013 update. Nucleic Acids Res. 41, D262–D267 (2013)Google Scholar
  45. 45.
    Limbach, P.A., Crain, P.F., McCloskey, J.A.: Summary: The modified nucleosides of RNA. Nucleic Acids Res. 22, 2183–2196 (1994)Google Scholar
  46. 46.
    Cantara, W.A., Crain, P.F., Rozenski, J., McCloskey, J.A., Harris, K.A., Zhang, X.N., Vendeix, F.A.P., Fabris, D., Agris, P.F.: The RNA modification database, RNAMDB: 2011 update. Nucleic Acids Res. 39, D195–D201 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Bjork, G.R., Durand, J.M.B., Hagervall, T.G., Leipuviene, R., Lundgren, H.K., Nilsson, K., Chen, P., Qian, Q., Urbonavicius, J.: Transfer RNA modification: Influence on translational frameshifting and metabolism. FEBS Lett. 452, 47–51 (1999)Google Scholar
  48. 48.
    Urbonavicius, J., Qian, O., Durand, J.M.B., Hagervall, T.G., Bjork, G.R.: Improvement of reading frame maintenance is a common function for several tRNA modifications. EMBO J. 20, 4863–4873 (2001)CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Yarian, C., Townsend, H., Czestkowski, W., Sochacka, E., Malkiewicz, A.J., Guenther, R., Miskiewicz, A., Agris, P.F.: Accurate translation of the genetic code depends on tRNA modified nucleosides. J. Biol. Chem. 277, 16391–16395 (2002)CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Agris, P.F., Vendeix, F.A.P., Graham, W.D.: tRNA's wobble decoding of the genome: 40 years of modification. J. Mol. Biol. 366, 1–13 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Kawai, G., Yamamoto, Y., Kamimura, T., Masegi, T., Sekine, M., Hata, T., Iimori, T., Watanabe, T., Miyazawa, T., Yokoyama, S.: Conformational rigidity of specific pyrimidine residues in transfer-RNA arises from posttranscriptional modifications that enhance steric interaction between the base and the 2′-hydroxyl group. Biochemistry-US. 31, 1040–1046 (1992)Google Scholar
  52. 52.
    Yokoyama, S., Watanabe, T., Murao, K., Ishikura, H., Yamaizumi, Z., Nishimura, S., Miyazawa, T.: Molecular mechanism of codon recognition by transfer-RNA species with modified uridine in the 1st position of the anticodon. Proc. Natl. Acad. Sci. USA. 82, 4905–4909 (1985)Google Scholar
  53. 53.
    Sprinzl, M., Hartmann, T., Weber, J., Blank, J., Zeidler, R.: Compilation of transfer-RNA sequences and sequences of transfer genes. Nucleic Acids Res. 17, R1–R172 (1989)CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Ladner, J.E., Jack, A., Robertus, J.D., Brown, R.S., Rhodes, D., Clark, B.F.C., Klug, A.: Structure of yeast phenylalanine transfer-RNA at 2.5 Å resolution. Proc. Natl. Acad. Sci. USA. 72, 4414–4418 (1975)Google Scholar
  55. 55.
    Gross, H.J., Simsek, M., Raba, M., Limburg, K., Heckman, J., Rajbhandary, U.L.: 2'-O-methyl ribothymidine: A component of rabbit liver lysine transfer-RNA. Nucleic Acids Res. 1, 35–43 (1974)Google Scholar
  56. 56.
    Lubini, P., Zurcher, W., Egli, M.: Stabilizing effects of the RNA 2′-substituent: Crystal structure of an oligodeoxynucleotide duplex containing 2'-O-methylated adenosines. Chem. Biol. 1, 39–45 (1994)Google Scholar
  57. 57.
    Prusiner, P., Sundaralingam, M.: Molecular and crystal structure of the modified nucleoside 2'-O-methyladenosine. A novel 2′-exo-3′-endo 2T3 sugar pucker. Acta Crystallogr. B. 32, 161–169 (1976)CrossRefGoogle Scholar
  58. 58.
    Chow, S., Wen, K., Sanghvi, Y.S., Theodorakis, E.A.: Novel synthesis of 2'-O-methylguanosine. Bioorg. Med. Chem. Lett. 13, 1631–1634 (2003)CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Lee, C.H., Tinoco, I., Jr.: Studies of the conformation of modified dinucleoside phosphates containing 1,N6-ethenoadenosine and 2'-O-methylcytidine by 360-MHz 1H nuclear magnetic resonance spectroscopy. Investigation of the solution conformations of dinucleoside phosphates. Biochemistry-US. 16, 5403–5414 (1977)Google Scholar
  60. 60.
    Barbe, S., Le Bret, M.: Effect of a water molecule on the sugar puckering of uridine, 2′-deoxyuridine, and 2'-O-methyl uridine inserted in duplexes. J. Phys. Chem. A. 112, 989–999 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Yathindra, N., Sundaralingam, M.: Effect of O(2′)-methylation on the stability of polynucleotide helices. Biopolymers. 18, 2721–2731 (1979)CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Hingerty, B., Bond, P.J., Langridge, R., Rottman, F.: Conformation of 2'-O-methyl cytidine, a modified furanose component of ribonucleic acids. Biochem. Biophys. Res. Commun. 61, 875–881 (1974)CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Cheng, D.M., Sarma, R.H.: Nuclear magnetic resonance study of the impact of ribose 2'-O-methylation on the aqueous solution conformation of cytidylyl-(3′->5′)-cytidine. Biopolymers. 16, 1687–1711 (1977)CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Kawai, G., Ue, H., Yasuda, M., Sakamoto, K., Hashizume, T., McCloskey, J. A., Miyazawa, T., Yokoyama, S.: Relation between functions and conformational characteristics of modified nucleosides found in tRNAs. Nucleic Acids Symp. Ser. 49–50 (1991).Google Scholar
  65. 65.
    Masaki, Y., Miyasaka, R., Ohkubo, A., Seio, K., Sekine, M.: Linear relationship between deformability and thermal stability of 2'-O-modified RNA hetero duplexes. J. Phys. Chem. B. 114, 2517–2524 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Majlessi, M., Nelson, N.C., Becker, M.M.: Advantages of 2'-O-methyl oligoribonucleotide probes for detecting RNA targets. Nucleic Acids Res. 26, 2224–2229 (1998)CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Lesnik, E.A., Guinosso, C.J., Kawasaki, A.M., Sasmor, H., Zounes, M., Cummins, L.L., Ecker, D.J., Cook, P.D., Freier, S.M.: Oligodeoxynucleotides containing 2'-O-modified adenosine - synthesis and effects on stability of DNA-RNA duplexes. Biochemistry-US. 32, 7832–7838 (1993)Google Scholar
  68. 68.
    Egli, M.: Structural aspects of nucleic acid analogs and antisense oligonucleotides. Angew. Chem. Int. Ed. 35, 1895–1910 (1996)CrossRefGoogle Scholar
  69. 69.
    Lesnik, E.A., Freier, S.M.: What affects the effect of 2′-alkoxy modifications? 1. Stabilization effect of 2′-methoxy substitutions in uniformly modified DNA oligonucleotides. Biochemistry-US. 37, 6991–6997 (1998)Google Scholar
  70. 70.
    Davis, D. R.: Biophysical and conformational properties of modified nucleosides in RNA (nuclear magnetic resonance studies). In: Grosjean, H., Benne, R. (eds.) Modification and editing of RNA, chap. 5, pp. 85–102. ASM Press, Washington, DC (1998)Google Scholar
  71. 71.
    Valle, J.J., Eyler, J.R., Oomens, J., Moore, D.T., van der Meer, A.F.G., von Helden, G., Meijer, G., Hendrickson, C.L., Marshall, A.G., Blakney, G.T.: Free electron laser-Fourier transform ion cyclotron resonance mass spectrometry facility for obtaining infrared multiphoton dissociation spectra of gaseous ions. Rev. Sci. Instrum. 76, 23103 (2005)CrossRefGoogle Scholar
  72. 72.
    Polfer, N.C., Oomens, J., Moore, D.T., von Helden, G., Meijer, G., Dunbar, R.C.: Infrared spectroscopy of phenylalanine Ag(I) and Zn (II) complexes in the gas phase. J. Am. Chem. Soc. 128, 517–525 (2006)CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Polfer, N.C., Oomens, J.: Reaction products in mass spectrometry elucidated with infrared spectroscopy. Phys. Chem. Chem. Phys. 9, 3804–3817 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Maitre, P., Le Caer, S., Simon, A., Jones, W., Lemaire, J., Mestdagh, H.N., Heninger, M., Mauclaire, G., Boissel, P., Prazeres, R., Glotin, F., Ortega, J.M.: Ultrasensitive spectroscopy of ionic reactive intermediates in the gas phase performed with the first coupling of an IR FEL with an FTICR-MS. Nucl. Instrum. Methods Phys. Res. A. 507, 541–546 (2003)Google Scholar
  75. 75.
    Stuart, B.H.: Infrared spectroscopy: Fundamentals and applications. In: Ando, D.J. (ed.) Analytical techniques in the sciences. John Wiley & Sons, Ltd, Chichester (2004)Google Scholar
  76. 76.
    Rijs, A., Oomens, J.: Gas-phase IR spectroscopy and structure of biological molecules. Top. Curr. Chem. (2015).Google Scholar
  77. 77.
    MacAleese, L., Maitre, P.: Infrared spectroscopy of organometallic ions in the gas phase: from model to real world complexes. Mass Spectrom. Rev. 26, 583–605 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Lemaire, J., Boissel, P., Heninger, M., Mauclaire, G., Bellec, G., Mestdagh, H., Simon, A., Le Caer, S., Ortega, J.M., Glotin, F., Maitre, P.: Gas phase infrared spectroscopy of selectively prepared ions. Phys. Rev. Lett. 89, 273002-3 (2002)Google Scholar
  79. 79.
    Bakker, J.M., Besson, T., Lemaire, J., Scuderi, D., Maitre, P.: Gas-phase structure of a π-allyl-palladium complex: efficient infrared spectroscopy in a 7 T Fourier transform mass spectrometer. J. Phys. Chem. A. 111, 13415–13424 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Prazeres, R., Glotin, F., Insa, C., Jaroszynski, D.A., Ortega, J.M.: Two-colour operation of a free-electron laser and applications in the mid-infrared. Eur. Phys. J. D. 3, 87–93 (1998)CrossRefGoogle Scholar
  81. 81.
    Bakker, J.M., Sinha, R.K., Besson, T., Brugnara, M., Tosi, P., Salpin, J.Y., Maitre, P.: Tautomerism of uracil probed via infrared spectroscopy of singly hydrated protonated uracil. J. Phys. Chem. A. 112, 12393–12400 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Schindler, B., Joshi, J., Allouche, A.R., Simon, D., Chambert, S., Brites, V., Gaigeot, M.P., Compagnon, I.: Distinguishing isobaric phosphated and sulfated carbohydrates by coupling of mass spectrometry with gas phase vibrational spectroscopy. Phys. Chem. Chem. Phys. 16, 22131–22138 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Schindler, B., Renois-Predelus, G., Bagdadi, N., Melizi, S., Barnes, L., Chambert, S., Allouche, A.R., Compagnon, I.: MS/IR, a new MS-based hyphenated method for analysis of hexuronic acid epimers in glycosaminoglycans. Glycoconj. J. 34, 421–425 (2017)Google Scholar
  84. 84.
    Schindler, B., Barnes, L., Gray, C.J., Chambert, S., Flitsch, S.L., Oomens, J., Daniel, R., Allouche, A.R., Compagnon, I.: IRMPD spectroscopy sheds new (infrared) light on the sulfate pattern of carbohydrates. J. Phys. Chem. A. 121, 2114–2120 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Bertsimas, D., Tsitsiklis, J.: Simulated annealing. Stat. Sci. 8, 10–15 (1993)CrossRefGoogle Scholar
  86. 86.
    Wolinski, K., Hinton, J. F., Wishart, D. S., Sykes, B. D., Richards, F. M., Pastone, A., Saudek, V., Ellis, P. D., Maciel, G. E., McIver, J. W., Jr, Blizzard, A. C., Santry, D. P., Pople, J. A., Ostlund, N. S., Ducasse, L., Hoarau, J., Pesquer, M., Kondo, M., Ando, I., Chujo, R., Nishioka, A., Vauthier, E. C., Odiot, S., Tonnard, F., Baker, J. D., Zerner, M. C., Beveridge, D. V., Anderson, W. P., Cundari, T. R., Bingham, R. C., Dewar, M. J. S., Lo, D. H., Li, J., Mello, P. C., Jug, K., Thiel, W., Zoebisch, E. G., Healy, E. F., Stewart, J. J. P., Fraser, M., Hayes, D. M.: HyperChem(TM) Professional 8.0, Hypercube, Inc., Gainesville, FL (2004)Google Scholar
  87. 87.
    Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, J.A., Jr., Peralta, J. E., Ogliaro, F., Bearpark, M. J., Heyd, J., Brothers, E. N., Kudin, K. N., Staroverov, V. N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A. P., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, N. J., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, Ö., Foresman, J. B., Ortiz, J. V., Cioslowski, J., Fox, D. J.: Gaussian 09, Revision A.02, Gaussian, Inc., Wallingford, CT, USA (2016).Google Scholar
  88. 88.
    Hunter, E.P., Lias, S.G.: Proton affinity evaluation. In: Linstrom, P.J., Mallard, W.G. (eds.) NIST chemistry webbook, NIST standard reference database number 69. National Institute of Standards and Technology, Gaithersburg (2018)Google Scholar
  89. 89.
    Wu, R.R., Rodgers, M.T.: Tautomerization lowers the activation barriers for N-glycosidic bond cleavage of protonated uridine and 2′-deoxyuridine. Phys. Chem. Chem. Phys. 18, 24451–24459 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Wu, R.R.: Studies Toward A Detailed Understanding Of The Intrinsic Properties Of Nucleic Acid Constituents: Gas-Phase Conformations, Energetics, and Glycosidic Bond Stability (2016). Wayne State University Dissertations. 1496.Google Scholar
  91. 91.
    Wu, R.R., Rodgers, M.T.: O2 protonation controls threshold behavior for N-glycosidic bond cleavage of protonated cytosine nucleosides. J. Phys. Chem. B. 120, 4803–4811 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Altona, C., Sundaralingam, M.: Conformational-analysis of sugar ring in nucleosides and nucleotides - New description using concept of pseudorotation. J. Am. Chem. Soc. 94, 8205–8212 (1972)Google Scholar
  93. 93.
    Saenger, W. Principles of Nucleic Acid Structure, Springer-Verlag, New York pp. 51–104 (1984).Google Scholar
  94. 94.
    Moore, D.T., Oomens, J., van der Meer, L., von Helden, G., Meijer, G., Valle, J., Marshall, A.G., Eyler, J.R.: Probing the vibrations of shared, OH+O-bound protons in the gas phase. ChemPhysChem. 5, 740–743 (2004)Google Scholar
  95. 95.
    Heine, N., Fagiani, M.R., Rossi, M., Wende, T., Berden, G., Blum, V., Asmis, K.R.: Isomer-selective detection of hydrogen-bond vibrations in the protonated water hexamer. J. Am. Chem. Soc. 135, 8266–8273 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Cooper, T.E., O'Brien, J.T., Williams, E.R., Armentrout, P.B.: Zn2+ has a primary hydration sphere of five: IR action spectroscopy and theoretical studies of hydrated Zn2+ complexes in the gas phase. J. Phys. Chem. A. 114, 12646–12655 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Contreras, C.S., Polfer, N.C., Oomens, J., Steill, J.D., Bendiak, B., Eyler, J.R.: On the path to glycan conformer identification: Gas-phase study of the anomers of methyl glycosides of N-acetyl-D-glucosamine and N-acetyl-D-galactosamine. Int. J. Mass Spectrom. 330, 285–294 (2012)Google Scholar
  98. 98.
    Santini, G.P.H., Pakleza, C., Auffinger, P., Moriou, C., Favre, A., Clivio, P., Cognet, J.A.H.: Dinucleotide tpt and its 2'-O-Me analogue possess different backbone conformations and flexibilities but similar stacked geometries. J. Phys. Chem. B. 111, 9400–9409 (2007)CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.Department of ChemistryWayne State UniversityDetroitUSA
  2. 2.Department of ChemistryUniversity of UtahSalt Lake CityUSA
  3. 3.Laboratoire de Chimie Physique (UMR8000), Université Paris-Sud, CNRSUniversité Paris SaclayOrsayFrance
  4. 4.Univ Lyon, Université Claude Bernard Lyon 1, CNRSInstitut Lumière MatièreVilleurbanneFrance

Personalised recommendations