The recognition by Rosenberg et al. in 1969 that cis-(NH3)2-PtC12 (cisplatin) is an antitumor agent1 and its eventual approval as a chemotherapeutic drug triggered an enormous response in the chemical and medical research communities.'" During the last two decades, inorganic chemists have sought to gain insight into the mechanism whereby Pt(I1) and Pt(1V) complexes inhibit DNA replication by designing and structurally characterizing key model compound^.^.^ In recent years, increasing emphasis has been placed on the screening and tailoring of non-platinum complexes in the hope of discovering drugs that are effective against cancers other than those treated by ~isplatin.~ Among the inorganic compounds that have been documented to exhibit substantial carcinostatic activity are dinuclear complexes of Re,lO Ru,11 and Rh;9J2-18 a common feature of these is the presence of at least two bridging carboxylate ligands as depicted in the molecular drawings in Scheme 1. A goal of our research in this area is to develop the substitution chemistry of these and other biologically active dinuclear compounds with purine bases and their corresponding nucleosides and nucleotides. At theoutset of our investigation, we were aware of reports that the antitumor agent dirhodium tetraacetate reacts with adenine but not guanine bases. The latter conclusion was based partly on the observation that, upon addition of guanine and guanosine, the blue-green color of the tetraacetate complex persists. This is in contrast to the corresponding reactions of Rh2(02CCH3)4 with adenine bases, which undergo a dramatic color change from blue-green to pink.lkl* We have recently discovered, however, that Rhz(02-CCH3)4(MeOH)2 does in fact react with guanine bases in H2O or MeOH to yield substitution products that contain two purine f Michigan State University. K.R.D. is a Camille and Henry Dreyfus Teacher-Scholar, 1991-1995, and Fellow of the Alfred P. Sloan Foundation,

Dinuclear metal carboxylates of Mo, Ru and Rh with 2 equiv. of 9-ethylguanine (9-EtGH) give complexes containing [M~(O~CR)~(~-E~GH)~(SO~V)~]~+ cations; structural characterization shows these to contain unusual N7,06-bridging 9-EtGH groups in 'head-to-tail' (HT) or 'head-to-head' (HH) orientations, and establishes this bridging mode for metal-metal bond orders of 1-4.The antitumour activity of cisplatinl has prompted extensive investigation into its mechanism of action and into the development of other metal-based chemotherapeutic agents.2 Considerable insight into the mechanism has been achieved, with modelling studies establishing that the metal is able to bind to two adjacent guanine bases within a DNA ~trand,3,~ including one that is part of a double helix.4 Our interest has centred on dinuclear carboxylates of Rh,5 Re6 and Ru7 that exhibit low levels of carcinostatic activity. We wondered how two linked metal centres could affect their binding modes to DNA, suspecting significant differences with mononuclear centres. Thus, we have investigated the binding of guanine and adenine derivatives to dinuclear complexes, and have reported that reactions of [Rh2(02CR)4L2] (R = Me, L = MeOH; R = CF3, L = Me2CO) with 9-ethylguanine (9-EtGH) yield products that contain two guanine ligands in unprecedented N7,06 bridging modes across the Rh-Rh single bond.8 We have now discovered that 9-EtGH can similarly bridge complexes with increased M-M bond orders up to four, suggesting that this unusual binding mode may be a general structural motif in dimetal-guanine chemistry, with obvious implications for binding of all dinuclear metal complexes to DNA.Treatment of a pink solution of [ M O ~( O ~C M ~) ~-(MeCN)6](BF4)29 with 2 equiv. of 9-EtGH in MeCN gave a slow colour change to orange. Single crystals of

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