N⁷, O⁶bridging 9-ethylguanine (9-EtGH) groups in dinuclear metal–metal bonded complexes with bond orders of one, two or four

Abstract

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

Chlorido-, aqua-, 9-ethylguanine- and 9-ethyladenine-adducts of cytotoxic ruthenium arene complexes containing O,O-chelating ligands

“…The X-ray crystal structure of [(g 6 -p-cym)Ru(Ph 2 acac)9EtG-N7]CF 3 SO 3 AE 2tol (5 AE 2tol) shows binding of ruthenium to N7 of 9EtG in accordance with the solution studies. The Ru-N7 distances of 2.126(3) Å and 2.140(3) Å for both molecules in the asymmetric unit in the structure of 5 AE 2tol are at the higher end of the range for known Ru II complexes containing bound guanine derivatives [35][36][37], including Ru II arene complexes [7,11,14,38,39]. Thus the comparatively weaker interaction observed in solution appears to be reflected in the solid state structure.…”

Mass spectrometric study of dirhenium biscarboxylate:purine dinucleotide complexes

“…A color change from blue to green occurred within 3 days. The N7/X6 (X = O in G, X = N in A) nucleobase bridging modes of the A‐ or G‐bound products shown in Scheme were based on X‐ray single crystal and NMR structure determinations of dinuclear metal complexes coordinated to model purine bases 14. The purine binding modes of complexes 2 and 3 have not been unambiguously determined in this present study.…”

Interactions of Metal—Metal‐Bonded Antitumor Active Complexes with DNA Fragments and DNA

“…Findings in our laboratories have shown that adenine and guanine bases bind to the dirhodium core in an alternative manner that involves displacement of eq bridging groups. The crystal structure Figure 8) 42 revealed the presence of unprecedented bridging guanine groups spanning the dirhodium unit via N7/O6 in a cis disposition and H-H or head-to-tail (H-T) 43 orientations. These X-ray studies provided the first hard evidence for guanine O6 participation in binding to dimetal units.…”