Theoretical Study of Metal Ion Binding in Modified and Natural Cytosine-Cytosine Base Pairs

Jakub Šebera^a,b, Kumiko Sugiyama^c, Akira Ono^c, Jos Mulder^d, C. Fonseca Guerra^d, F. Matthias Bickelhaupt^d, Yoshiyuki Tanaka^e, Vladimír Sychrovský^b

^a Institute of Physics, Academy of Sciences Czech Republic v.v.i, Na Slovance 2, CZ-182 21, Prague 8, Czech Republic

^bInstitute of Organic Chemistry and Biochemistry, Flemingovo nám. 2, 166 37 Prague, Czech Republic

^cDepartment of Material and Life Chemistry, Faculty of Engineering, Kanagawa University,3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama, Kanagawa 221-8686, Japan

^d Department of Theoretical Chemistry and Amsterdam Center for Multiscale ModelingVU University Amsterdam, De Boelelaan 10831081 HV Amsterdam, The Netherlands

^e Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aoba-ku, Sendai 980-8578, Japan

We present here the optimized geometries and stabilization energies of metal-mediated base pair C_A-M-C_A, where C_A is 4-N-carboxymethylcytosine and M is Ag⁺,Ni²⁺ and Cu²⁺. The second part of our work includes the optimized geometries, relative energies of individual isomers and conformers of metal-mediated base pair C-Ag⁺-C and the calculation of spin-spin coupling ¹J(N,Ag).

The calculations were performed using the DFT CAM-BLYP or B3LYP functional employing the continuum model of water solvent. The NMR spin-spin coupling constant ¹J(N,Ag) in C-Ag⁺-C base pair was calculated using the DFT-ZORA (Zero Order Regular Approximation) approach with the BLYP and B3LYP functionals.

We described several structurally possible metal binding modes of C_A-M-C_A base pairs. The C_A-Cu²⁺-C_A was found to be the most stable metal-mediated base pair as regards the calculated stabilization energy, which was in agreement with the melting temperature experiment for doping the DNA duplex 5‘-GTGACCAC_ATGCAGTG-3‘:CACTGGTC_AACGTCAC-5‘ with the three different metals. At the second part of our study, we found that the most stable isomer of C-Ag⁺-C base pair possessed the N3-Ag⁺-N3 linkage and the calculated ¹J(N,Ag) spin-spin coupling was in good agreement with experiment.

This work was supported by the Young Investigator’s Grant of the Human Frontier Science Program (HFSP), Grant Agency of the Czech Republic P205/10/0228, Technological Agency of the Czech Republic Grant no. TACR TA01011165, and by the Czech Science Foundation Grant No. P304/10/1951. The access to the MetaCentrum computing facilities is appreciated.