Yanlong Zhu1, Lucas Hamlow1, Chenchen He1, Xun Bao1, Juehan Gao2, Jos Oomens2, M. T. Rodgers1*
1Department of Chemistry, Wayne State University, Detroit, MI, 482022Radboud University Nijmegen, Institute for Molecules and Materials, FELIX Facility, Toernooiveld 7,
6525ED Nijmegen, The Netherlands
Gas-Phase Conformations and Energetics of Sodium Cationized 2’-Deoxyguanosine and Guanosine:
IRMPD Action Spectroscopy and Theoretical Studies
Introduction The local structures of DNA and
RNA are influenced by protonation, deprotonation and noncovalent binding interactions with metal cations.
Effects of the conformations of DNA and RNA nucleic acidsNeutralize the overall negative
charge along deprotonated phosphate backbone
Conformations of phosphate moieties
Nucleobase flippingSugar puckering H-bonding or π-stacking
interactionsStabilize quadruplex structures
W. Saenger, Principles of Nucleic Acid Structure, Springer, New York, 1988.Lippert, B. Coordin Chem Rev 2000, 200, 487.
N
NN
N
NH2
O
XO
HHHH
PO
O
ONH
N
N
O
NH2N
O
X
HHHH
O
PO
O
O
N
NH2
ONO
XO
HHHH
PO
O
O
NH
O
ONO
XO
HHHH
PO
O
ONH
O
ON
O
XO
HHHH
PO
O
O
O
dAdo or Ado
dGuo or Guo
dCyd or Cyd
dThd or Thd
dUrd or Urd
X = H or OH
Na+
Polfer, N. C.; Oomens, J.; Suhai, S.; Paizs, B. J Am Chem Soc 2007, 129, 5887.
Free Electron Laser (FEL)
Infrared Multiple Photon Dissociation(IRMPD) Action Spectroscopy
IRMPD Spectroscopy Setup
IRMPD yield = (∑If)/(Ip + ∑If) 1mM dGuo or Guo, NaCl
MeOH:H2O=90%:10%
IRMPD Mechanism• Absorption of
photons by a resonant vibrational mode
• Intramolecular Vibrational Redistribution (IVR)
• Ei ≥ D0 unimolecular dissociation
Polfer, N. C.; Oomens, J. Mass Spectrom Rev 2009, 28, 468.
Simulated Annealing (Hyperchem, Amber force field)Calculate candidate structures for higher level
optimization Quantum Chemical Calculations (Gaussian)
Optimization and vibrational frequency analyses: B3LYP/6-31G* Single point energy calculations B3LYP/6-311+G(2d,2p)
Frequencies were scaled by a factor of 0.9646. Calculated vibrational frequencies were broadened
using a 20 cm-1 fwhm Gaussian line shape
Theoretical Calculations
endo-configurationC2’ or C3’ atom
on the same side ofthe ring as C5’ atom
Conformation of Sodium Cationized Nucleoside
anti-orientationFacilitates
Watson-CrickBase pairing
syn-orientation
DisruptsWatson-CrickBase pairing
1. Sodium Cation Binding Position
2. Nucleobase Orientation
3. Sugar Configration
exo-configurationC2’ or C3’ atom
on the opposite side of
the ring as C5’ atom
C2’-endo C3’-endo
C2’-exo C3’-exo
C2’C3’
C5’C2’
C3’C5’
C2’C3’
C5’
C2’C3’
C5’
IRMP
D Yi
eld
0.0
0.5
1.0
1.5
Frequency (cm-1)600 800 1000 1200 1400 1600 1800
0.0
0.2
0.4
IRMPD Spectra of Sodium Cationized dGuo and Guo
Fragmentation pathways of [dGuo+Na]+ and [Guo+Na]+:Major: [Nuo+Na]+ [Gua+Na]+ + SugarMinor: [Nuo+Na]+ Na+ + Nuo
[dGuo+Na]+
[Guo+Na]+
[dGuo+Na]+
[Guo+Na]+
Frequency (cm-1)600 800 1000 1200 1400 1600 1800Re
lativ
e Int
ensit
y
0
500
1000
Frequency (cm-1)600 800 1000 1200 1400 1600 1800Re
lativ
e Int
ensit
y
0
500
1000
Ground-State Structures of [dGuo+Na]+ and [Guo+Na]+
[dGuo+Na]+(O6,N7)ANa+--- O6,N7anti, C3’-endo0.0 kJ/mol
[Guo+Na]+(O6,N7)ANa+--- O6,N7anti, C2’-endo0.0 kJ/mol
[dGuo+Na]+(O6,N7)A
[Guo+Na]+(O6,N7)A
Sodium Cation Binding to dGuo at O6 and N7
0.0
0.5
1.0
Rela
tive I
nten
sity
0
500
1000
0
500
1000
Frequency (cm-1)600 800 1000 1200 1400 1600 1800
0
500
1000
[dGuo+Na]+
(O6,N7)Banti, C2’-endo5.7 kJ/mol
[dGuo+Na]+
(O6,N7)Canti, C2’-endo5.8 kJ/mol
[dGuo+Na]+
(O6,N7)Dsyn, C2’-endo14.2 kJ/mol
[dGuo+Na]+(O6,N7)B
[dGuo+Na]+(O6,N7)C
[dGuo+Na]+(O6,N7)D
[dGuo+Na]+ IRMPD Spctrum
Sodium Cation Binding to Guo at O6 and N7
0.0
0.3
0.6
Rela
tive I
nten
sity
0
500
1000
0
500
1000
Frequency (cm-1)600 800 1000 1200 1400 1600 1800
0
500
1000
[Guo+Na]+
(O6,N7)Bsyn, C2’-endo1.4 kJ/mol
[Guo+Na]+
(O6,N7)Canti, C3’-endo3.9 kJ/mol
[Guo+Na]+
(O6,N7)Danti, C2’-endo7.0 kJ/mol
[Guo+Na]+(O6,N7)B
[Guo+Na]+(O6,N7)C
[Guo+Na]+(O6,N7)D
[Guo+Na]+ IRMPD Spctrum
Sodium Cation Binding to dGuo and Guo at N3
0.0
0.5
1.0
Rela
tive I
nten
sity
0
500
1000
0.0
0.3
0.6
Frequency (cm-1)600 800 1000 1200 1400 1600 1800
0
500
1000
[dGuo+Na]+
(N3,O4′,O5′)Asyn, C2’-exo53.3 kJ/mol
[Guo+Na]+
(N3,O4’,O5’)Asyn, C2’,C3’-endo58.0 kJ/mol
[dGuo+Na]+(N3,O4′,O5′)A
[Guo+Na]+ IRMPD Spectrum
[Guo+Na]+(N3,O4’,O5’)A
[dGuo+Na]+ IRMPD Spectrum
Conclusions
Fragmentation pathways of [dGuo+Na]+ and [Guo+Na]+:Major: [Nuo+Na]+ [Gua+Na]+ + SugarMinor: [Nuo+Na]+ Na+ + Nuo
In both cases, preferential binding position of the sodium cation is O6 and N7 position on guanine.
Nucleobase remains in an anti-orientation.
Sugar puckering of [dGuo+Na]+: C3’-endoSugar puckering of [Guo+Na]+: C2’-endo
Conclusions
[dGuo+Na]+
Na+--- O6,N7anti, C3’-endo
VS. VS.[Guo+Na]+
Na+--- O6,N7anti, C2’-endo
[dGuo+H]+
H+--- N7anti, C3’-endo
[Guo+H]+
H+--- N7anti, C3’-endo
Wu, R. R.; Yang, B.; Berden, G.; Oomens, J.; Rodgers, M. T. J Phys Chem B 2014, 118, 14774.
Professor M. T. Rodgers
Rodgers Group Members:Harrison RoyRanran Wu
Chenchen HeLucas Hamlow
National Science Foundation
FELIX GroupDr. Cliff Frieler
Thomas Rumble Fellowship
Acknowledgements
FELIX Facility
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