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

Abstract

Both cis- and trans-RuCl2(DMSO)4 (cis-Ru and trans-Ru) react with ApG, GpA, d(ApG) and d(GpA) to yield products with bifunctional metal coordination of the bases. For each dinucleotide one major product and several minor species are formed. This is in contrast to previous results on analogous reactions between trans-Ru and d(GpG) where a substantial amount of an intermediate species was found. The rates of reaction between dinucleotides and cis-Ru are approximately 20-fold slower than for trans-Ru. The compounds formed 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 conformation with the glycosidic angles being in the anti range. Coupling constants indicate 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 contrast to the different mode of interaction suggested earlier for cis- and trans-Ru complexes with DNA. trans-Ru interacts with the deoxyoctanucleotide d(CCTGGTCC), giving two main products during the first 2 h of incubation time. Four H8 guanine resonances are shifted downfield, characteristic of N7 metal coordination. The products are not analyzed in detail, but it is suggested that the structures may be described as two chiral G(N7/N7) chelates.

Mechanistic information on the reaction of cis- and trans-[RuCl2(DMSO)4] with d(T2GGT2) derived from MALDI-TOF and HPLC studies☆

“…This suggestion contrasts with previously proposed monodentate binding of the cis analogue to DNA [11]. In addition, the possibility of bidentate adduct-formation involving adenine and guanine bases as target nucleotides has been suggested [10].…”

“…However, the detailed mechanism of interactions of cis and trans isomers of the Ru(II) complex with DNA has not been clarified. Recently, a bidentate coordination mode has been proposed for both isomers in their interactions with DNA [10]. This suggestion contrasts with previously proposed monodentate binding of the cis analogue to DNA [11].…”

“…The d(T 2 GGT 2 ) oligonucleotide used in our studies provides a well-defined binding site for the ruthenium centre (i.e., the -GG-pair) [10], while the adjacent thymine bases mimic the polyelectrolyte nature of DNA [22]. Thus, the use of d(T 2 GGT 2 ) simplifies the reaction system in comparison to DNA, but at the same time preserves to some extent its electrostatic properties which often play an important role during interactions with charged metal complexes.…”

Metal‐Ion‐Coordinating Properties of the Dinucleotide 2′‐Deoxyguanylyl(5′→3′)‐2′‐deoxy‐5′‐guanylate (d(pGpG)3−): Isomeric Equilibria Including Macrochelated Complexes Relevant for Nucleic Acids

“…It is important to note in this context that d(pG) and pG derivatives behave identically toward metal ions as far as binding to the phosphate group or the nucleobase moiety is concerned. [20][21][22] This means that the 2'-hydroxy group has no direct effect on the metal-ion-coordinating properties in the physiological pH range as the 2'-OH/3'-OH unit of the ribose residue has a pK a of about 12.5. [23] A very small indirect effect due to the slightly altered acidbase properties between oxy and deoxy derivatives [17,22] is possible, but this is strictly a relative one and is cancelled out if the small pK a differences are taken into account.…”

A computational study on DNA bases interactions with dinuclear tetraacetato-diaqua-dirhodium(II,II) complex

“…Also, the activity of Ru(III) complexes has been thoroughly studied [8][9][10][11]. The first phase of clinical trials has been recently passed by transCl 4 (Me 2 SO)(Im)Ru(III) (Im = imidazole) (cf.…”