DNA Binding of Some Chiral Metallointercalators Derived From9,10‐Phenanthrenediamine

Abstract

A study of the interaction with calf thymus DNA is described of a novel set of chiral ternary complex cations of general form [Ru(N4-tet)(phdi)]2+ (where N4 -tet is the chiral linear tetradentate R*R*-picchxn or R*-picchxnMe2). Individual equilibrium binding constants (KB) have been determined from spectroscopic titrations employing the hypochromism induced in the visible absorbance of the cations on interaction with the nucleic acid. These demonstrate both stereo- and enantioselectivity in the binding interactions. These KB data, together with induced circular dichroism and DNA thermal denaturation results, are all indicative of selective intercalation of the bidentate components of the cations into the nucleobase stack of the duplex. Supportive evidence for a secondary binding mode for the picchxn complexes is provided by the different mutagenicity profiles obtained for related cations.

Probing Site Specificity of DNA Binding Metallointercalators by NMR Spectroscopy and Molecular Modeling

“…Furthermore, β-phi also binds to [d(CGCGATCGCG)] 2 , showing changes in the 1D NMR spectra nearly identical to the R-phi-[d(CGC-GATCGCG)] 2 adduct. These results are consistent with previous work on these Ru complexes with calf thymus DNA (25). This loss of discrimination between Rand β-isomers could be occurring for two reasons.…”

“…The affinity measured for α-phi was higher than that for α-phen and α-dpq with the same oligonucleotide sequence but was still low for an intercalator where values of 10 5 −10 10 M -1 may be expected ( , ). The values are, however, qualitatively similar to those measured for these complexes using photometric hypochromism ( , ). Similar complexes (Ru and Rh complexes containing the phi ligand) have been reported with binding constants of 10 4 −10 6 M -1 ( , ), while anthraquinone intercalators have been reported with binding constants of 10 4 −10 5 M -1 ().…”

“…A number of other NOEs corroborate the conclusion that binding occurs at both of these central sites, albeit not simultaneously. Multiple binding modes have been noted previously with octahedral Ru complexes studied by 1 H NMR spectroscopy (6,14,15,25). It is notable that no major groove protons display NOEs to the Ru complex, despite displaying numerous intramolecular NOEs.…”

“…The lack of general consensus in octahedral metal complex−DNA binding studies reflects both the application of indirect techniques that may be interpreted in various ways and the variable role played by ancillary ligands in groove recognition and selectivity. In an effort to establish predictability for those factors that govern groove and sequence selectivity, we have undertaken a study of a series of complexes based on the Δ-[Ru(picchxnMe 2 )(bidentate)] 2+ template ( , ) [ picchxnMe 2 is N , N‘ -dimethyl- N , N‘ -di(2-picolyl)-1,2-diaminocyclohexane (); Figure ]. In this study, the stereochemistry of the Ru-picchxnMe 2 moiety and the nature of the bidentate ligand ( phen , dpq , phi ) have been varied.…”

A spectroscopic investigation of the self-association and DNA binding properties of a series of ternary ruthenium(II) complexes

“…In these complexes, the tetradentate is chosen to have characteristics that allow it to govern its DNA binding via helical DNA groove interactions, thereby providing a molecular recognition function. The metal ion provides a substitutionally inert octahedral geometry and the bidentate serves as the intercalating chromophore [27]. We have shown using 1 H NMR spectroscopy that some complexes of the general form [Ru(N 4 -tetradentate)(N 2 -bidentate)] 2+ self-associate in aqueous solution in a manner consistent with the intermolecular p-stacking of the bidentate ligands [10,24,28].…”