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Impact of Sodium Cationization on Gas-Phase Conformations of DNA and RNA Cytidine Mononucleotides

  • L. A. Hamlow
  • Y.-w. Nei
  • R. R. Wu
  • J. Gao
  • J. D. Steill
  • G. Berden
  • J. Oomens
  • M. T. RodgersEmail author
Research Article

Abstract

Gas-phase conformations of the sodium-cationized forms of the 2′-deoxycytidine and cytidine mononucleotides, [pdCyd+Na]+ and [pCyd+Na]+, are examined by infrared multiple photon dissociation action spectroscopy. Complimentary electronic structure calculations at the B3LYP/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) level of theory provide candidate conformations and their respective predicted IR spectra for comparison across the IR fingerprint and hydrogen-stretching regions. Comparisons of the predicted IR spectra and the measured infrared multiple photon dissociation action spectra provide insight into the impact of sodium cationization on intrinsic mononucleotide structure. Further, comparison of present results with those reported for the sodium-cationized cytidine nucleoside analogues elucidates the impact of the phosphate moiety on gas-phase structure. Across the neutral, protonated, and sodium-cationized cytidine mononucleotides, a preference for stabilization of the phosphate moiety and nucleobase orientation is observed, although the details of this stabilization differ with the state of cationization. Several low-energy conformations of [pdCyd+Na]+ and [pCyd+Na]+ involving several different orientations of the phosphate moiety and sugar puckering modes are observed experimentally.

Keywords

Cytidine (Cyd) Cytidine-5′-monophosphate (pCyd) Density functional theory (DFT) 2′-Deoxycytidine (dCyd)  2′-Deoxycytidine-5′-monophosphate (pdCyd) Electronic structure calculations Electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) Gas-phase conformation Hydrogen-bonding interactions Hydrogen-stretching region Infrared multiple photon dissociation (IRMPD) action spectroscopy IR fingerprint region IRMPD spectrum IR spectrum Mononucleotide Nucleobase Nucleobase orientation Nucleoside Phosphate moiety Protonation Quadrupole ion trap mass spectrometer (QIT MS) Simulated annealing Sodium cationization Sugar puckering Tandem mass spectrometry 

Notes

Acknowledgements

Financial support for this work was provided by the National Science Foundation, grant numbers OISE-0730072 (for the FEL IRMPD measurements and international travel), DBI-0922818 (for the Bruker amaZon ETD QITMS), and CHE-1709789 (other research costs). Financial support of the FELIX facility by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) is also gratefully acknowledged. Support from the Thomas C. Rumble Graduate Fellowship is acknowledged by Y.-w. Nei and L.A. Hamlow, with additional support from a Wilfried Heller Research Fellowship and Wayne State University Summer Dissertation Fellowship by Y.-w. Nei. Computational resources for this work were provided by Wayne State University C&IT. The skilled assistance of the FELIX staff is also greatly appreciated.

Supplementary material

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© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.Department of ChemistryWayne State UniversityDetroitUSA
  2. 2.Institute for Molecules and Materials, FELIX LaboratoryRadboud UniversityNijmegenNetherlands

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