Metal ion induced pairing of cytosine bases formation of i-motif structures identified by ion spectroscopy Anouk Rijs Juehan Gao, Giel Berden, Jos Oomens FELIX Laboratory Radboud University, Nijmegen, The Netherlands © M. Molle

Cytosine: one of the four nucleobases in DNA 4 5 3 6 2 1 cytosine

Non-Watson-Crick base pairing: mismatch pairing i-motif Cytosine pairing with cytosine, sharing one proton: Hemi-protonated cytosine dimer

Spectroscopic evidence for the gaseous i-motif (1-MeCy-d2)2 D+ wavenumber (cm-1) Oomens, Moehlig, Morton, JPCL 2010, 1, 2891

IR ion spectroscopy – experimental

FELIX - Free Electron Laser International user facility 2 calls for proposals per year Range of ancillary equipment www.ru.nl/felix Contact Britta Redlich! undulator magnets IR-beam Wavelength tunable 3 – 150 mm Pulse energy <100 mJ per 5 ms pulse FWHM bandwidth >0.4% of l International user facility gun e-beam accelerator mirror

Silver(I)-induced pairing of Cytosine

Spectroscopic evidence for an i-motif structure in C-Ag+-C kJ/mol Berdakin, Steinmetz, Maitre, Pino, JPCA 2014, 118, 3804

Low-energy tautomers of neutral cytosine 5-methylcytosine keto/amine enol/amine enol/amine Lowest at MP2 C1 C2 C3 Alkali metal ion binding stabilizes C1 Yang, Wu, Polfer, Berden, Oomens, Rodgers, JASMS 2013, 24, 1523 C6 C4 C5 keto/imine keto/imine keto/amine Yang, Wu, Berden, Oomens, Rodgers, JPCB 2013, 117, 14191

IR spectra of monomeric Cu+-C complexes C1N3O 0 kJ/mol C1O +4.0 kJ/mol +9.4 mixture of 2 structures C1N3O not previously identified covalent interaction B3LYP/6-311G(2df,2p) – MP2/6-311G(2df,2p)

IR spectra of MeCN-Cu+-C complexes C1O 0 kJ/mol +2.4 C1N3 +6.0 kJ/mol mixture of 2 structures Cu(I) binds to O or N3 covalent interactions

IR spectra of C-Cu+-C complexes C1N3C1N3 0 kJ/mol i-motif structure Single structure Cu(I) binds to N3 add’l stabilization by H-bonds covalent interactions

Cu+ and Ag+ induce the i-motif structure How about alkali metal ions?

IR spectrum of C-Na+-C complex Na+ binds to N3 and O No add’l H-bonds electrostatic interactions No i-motif structure! C1N3OC1N3O

IR spectra of C-M+-C complexes Li+ All alkali metal ions bind to N3 and O Parallel displaced structure No i-motif structure! Na+ K+

Molecular orbitals C-Na+-C C-Cu+-C HOMO HOMO - 4 HOMO HOMO - 45

Computed parameters C – M+ - C complexes Ionic radius M+ partial charge D(N…O) Dissociation energy Li+ 0.90 +0.731 0.002 141 Na+ 1.16 +0.839 0.003 117 K+ 1.52 +0.885 1.86 104 Cu+ 0.91 +0.609 1.19 260 Ag+ 1.29 - 2.0 195 H+ +0.462 0.04   NPA

Monomeric Cu+-C complexes: two structures co-exist Conclusions Monomeric Cu+-C complexes: two structures co-exist Copper and silver complexes have i-motif structure  H-bonding preferred over Cu+-O bonding Alkali metal ions induce parallel displaced structure  M+-O bonding preferred over H-bonding

Acknowledgements Juehan Gao Giel Berden Britta Redlich Lex v.d. Meer & FELIX staff Dutch Astrochemistry Network VICI Access to SARA Supercomputer

Low-energy tautomers of protonated cytosine O-protonated is lowest in energy keto/amine enol/amine enol/amine keto/imine keto/imine keto/amine Yang, Wu, Berden, Oomens, Rodgers, JPCB 2013, 117, 14191

Cytosine: one of the four nucleobases in DNA 4 5 3 6 2 1