"Head-to-head" double-hamburger-like structure of di-ruthenated d(GpG) adducts of mono-functional Ru-arene anticancer complexes.
Guanine bases in DNA are targets for some Ru-arene anticancer complexes. We have investigated the structure of the novel di-ruthenated d(GpG) adduct Ru2-GpG (where Ru = {(η6-biphenyl)-Ru(en)}2+(1')) in aqueous solution. 2D NMR results indicate that there are two conformers, supported by modeling studies. The major conformer I is a novel double-hamburger-like structure with a "head-to-head" (HH) base arrangement involving hydrophobic interactions between neighboring arene rings, the first example of a HH d(GpG) adduct constructed by weak interactions. Hence there are significant differences compared to Pt-d(GpG) adducts formed by cisplatin. There is no obviously rigid bending for the major conformer I. The minor conformer II of Ru2-GpG has a back-to-back structure, with two ruthenated guanine bases flipped away from each other. 19-23 base-pair oligodeoxyribonucleotides containing central TGGT sequences di-ruthenated by 1 show no directional bending, only slightly distorted di-ruthenated duplexes, consistent with the NMR data for conformer I. The structural differences and similarities of d(GpG) residues which are di-ruthenated or cross-linked by platination are discussed in the context of the biological activity of these metal complexes.
Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210046, China. liuhongke@njnu.edu.cn.
Hong-Ke
HK
Liu
Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 61265 Brno, Czech Republic. brabec@ibp.cz.
Hana
H
Kostrhunova
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. P.J.Sadler@warwick.ac.uk.
Abraha
A
Habtemariam
Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210046, China. liuhongke@njnu.edu.cn.
Yaqiong
Y
Kong
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. P.J.Sadler@warwick.ac.uk.
Robert J
RJ
Deeth
Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 61265 Brno, Czech Republic. brabec@ibp.cz.
Viktor
V
Brabec
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. P.J.Sadler@warwick.ac.uk.
Peter J
http://orcid.org/0000-0001-9160-1941
PJ
Sadler
D000970:Antineoplastic Agents / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D012428:Ruthenium / Q000737:chemistry*
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D056831:Coordination Complexes; D004247:DNA; D018736:DNA Adducts; D015226:Dinucleoside Phosphates; D012428:Ruthenium; C010574:biphenyl; C018309:guanylyl-(3'-5')-guanosine