Liu Hong-Ke, Wang Fuyi, Parkinson John A, Bella Juraj, Sadler Peter J
School of Chemistry, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3 JJ, UK.
Chemistry. 2006 Aug 7;12(23):6151-65. doi: 10.1002/chem.200600110.
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), 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).
我们通过高效液相色谱（HPLC）、电喷雾电离质谱（ESI-MS）以及一维和二维氢核磁共振（¹H NMR）与氮核磁共振（¹⁵N NMR）光谱，研究了有机金属抗癌钌（II）配合物[（η⁶-对异丙基苯）钌（乙二胺）氯][六氟磷酸根]（1）和[（η⁶-联苯）钌（乙二胺）氯][六氟磷酸根]（2）（乙二胺=乙二胺）与单链（ss）DNA六聚体d（CGGCCG）（I）和双链d（CGGCCG）₂（II）的相互作用。对于单链DNA，所有三个鸟嘌呤（G）都很容易被[（η⁶-芳烃）钌（乙二胺）]²⁺钌化，但对于双链DNA，G3和G6优先被钌化，未检测到与G2的结合。对于单钌化双链体，G的N7钌化伴随着对异丙基苯加合物中G-O6与乙二胺-NH之间的强氢键作用。在单钌化和双钌化双链体的联苯加合物中，检测到未配位的苯环插入G3与C4或G6与C5之间，同时G-O6NH-乙二胺氢键减弱。芳烃配体通过空间相互作用（对异丙基苯）或插入作用（联苯）在扭曲双链体方面起主要作用。
