Interaction of cis- and trans-RuCl2(DMSO)(4) with the nucleotides GpA, d(GpA), ApG, d(ApG) and d(CCTGGTCC): high-field NMR characterization of the reaction products

Both cis- and trans-RuCl2(DMSO)(4) (cis-Ru and trans-Ru) react with ApG, Gp A, d(ApG) and d(GpA) to yield products with bifunctional metal coordination of the bases. For each dinucleotide one major product and several minor sp ecies are formed. This is in contrast to previous results on analogous reac tions between trams-Ru and d(GpG) where a substantial amount of an intermed iate species was found. The rates of reaction between dinucleotides and cis -Ru are approximately 20-fold slower than for trans-Ru. The compounds forme d with the two isomers exhibit identical proton NMR spectra, suggesting the same coordination mode for ruthenium in the final product. The two purine bases are coordinated to ruthenium through N7 in a head-to-head conformatio n with the glycosidic angles being in the anti range. Coupling constants in dicate a relatively pure 3'-endo conformation for the 5'-sugar and mainly 2 '-endo for the 3'-sugar. The similar bifunctional binding mode of cis- and trans-Ru(II) with dinucleotides as evident from the NMR spectra are in cont rast to the different mode of interaction suggested earlier for cis- and tr ans-Ru complexes with DNA. trans-Ru interacts with the deoxyoctanucleotide d(CCTGGTCC), giving two main products during the first 2 h of incubation ti me. Four H8 guanine resonances are shifted downfield, characteristic of N7 metal coordination. The products are not analyzed in detail, but it is sugg ested that the structures may be described as two chiral G(N7/N7) chelates.