Ruthenation of duplex and single-stranded d(CGGCCG) by organometallic anticancer complexes.
We have studied the interaction of the organometallic anticancer ruthenium(II) complexes [(eta(6)-p-cymene)Ru(en)Cl][PF(6)] (1) and [(eta(6)-biphenyl)Ru(en)Cl][PF(6)] (2) (en=ethylenediamine) with the single-stranded (ss) DNA hexamer d(CGGCCG) (I) and the duplex d(CGGCCG)(2) (II) by HPLC, ESI-MS, and one- and two-dimensional (1)H and (15)N NMR spectroscopy. For ss-DNA, all three G's are readily ruthenated with [(eta(6)-arene)Ru(en)](2+), but for duplex DNA there is preferential ruthenation of G3 and G6, and no binding to G2 was detected. For monoruthenated duplexes, N7 ruthenation of G is accompanied by strong hydrogen bonding between G-O6 and en-NH for the p-cymene adducts. Intercalation of the non-coordinated phenyl ring between G3 and C4 or G6 and C5 was detected in the biphenyl adducts of mono- and diruthenated duplexes, together with weakening of the G-O6NH-en hydrogen bonding. The arene ligand plays a major role in distorting the duplex either through steric interactions (p-cymene) or through intercalation (biphenyl).
Liu
Hong-Ke
HK
School of Chemistry, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3 JJ, UK.
Wang
Fuyi
F
Parkinson
John A
JA
Bella
Juraj
J
Sadler
Peter J
PJ
D000970:Antineoplastic Agents / Q000737:chemistry*; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D011089:Polydeoxyribonucleotides / Q000737:chemistry*; D012015:Reference Standards; D012428:Ruthenium / Q000737:chemistry*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D011089:Polydeoxyribonucleotides; C019530:poly(dC-dG); D012428:Ruthenium; D004247:DNA