| Abstract
| - Nitrogen-tethered half-sandwich RuII arene complexes can form bifunctional GG adducts, as illustrated by the X-ray structure of a bis-9-ethylguanine complex. However, the second G is only weakly bound, mainly monofunctional adducts are formed on DNA, and the complexes exhibit low cytotoxicity toward ovarian cancer cells.
- The tethered RuII half-sandwich complexes [η6:η1-C6H5(CH2)nNH2)RuCl2] 1 (n = 3) and 2 (n = 2) have beensynthesized as potential bifunctional anticancer complexes, and their X-ray crystal structures have been determined.They hydrolyze rapidly in aqueous solution to give predominantly mono-aqua mono-chlorido species. Mono-9EtGadducts, where 9EtG = 9-ethylguanine, form rapidly, but the second 9EtG binds more slowly and more weakly.In the X-ray crystal structure of the di-9EtG adduct [(η6:η1-C6H5(CH2)3NH2)Ru(9EtG)2](CF3SO3)2·H2O (8·H2O), oneof the Ru−N7 bonds is significantly longer than the other (2.1588(18) vs 2.101(2) Å). The bound guanine basesadopt a head-to-head configuration, stabilized by tether NH2 hydrogen bonding to C6O of 9EtG. The X-ray crystalstructure of the dinitrato complex [(η6:η1-C6H5(CH2)3NH2)Ru(NO3)2] (3) showed both nitrates to be bound to ruthenium.This complex readily rutheniated calf thymus DNA but failed to produce stop sites on pSP73KB plasmid DNAduring DNA transcription by an RNA polymerase. This suggested that only monofunctional DNA adducts formed,as did interstrand cross-linking assays. Also, the unwinding angle induced in negatively supercoiled DNA (9 ± 1°)was less than that induced by cisplatin (13°). These findings may explain why complexes such as 1 and 2 exhibitedlow cytotoxicities (IC50 values >100 μM) toward A2780 human ovarian cancer cells.
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