Oxidation of DNA and RNA by Oxoruthenium(IV) Metallointercalators:  Visualizing the Recognition Properties of Dipyridophenazine by High-Resolution Electrophoresis

Abstract

The binding specificity for the intercalating Ru(tpy)(dppz)O2+ complex (tpy = 2,2‘,2‘‘-terpyridine; dppz = dipyridophenazine) was investigated for duplex DNA, HIV-1 TAR DNA and RNA, and tRNAPhe. Unlike other dppz compounds studied to date, this compound cleaves nucleic acids at short range, and the resulting cleavage pattern can therefore be directly related to the recognition properties of the dppz ligand. To assign the intercalative recognition sites, a comparison was first made between the cleavage patterns of Ru(tpy)(dppz)O2+ and Ru(tpy)(bpy)O2+ (bpy = 2,2‘-bipyridine), which differs from Ru(tpy)(dppz)O2+ only by the absence of the intercalative dppz functionality. Cleavage sites common to both complexes were assigned to binding properties other than intercalation, whereas any additional sites observed for Ru(tpy)(dppz)O2+ were strongly implicated as the sites of intercalative recognition. It was necessary, however, to distinguish between those sites which represent a strong binding affinity and those sites which were instead made more accessible to cleavage by binding of another equivalent of the intercalating complex at a remote site. We therefore investigated the cleavage pattern of Ru(tpy)(bpy)O2+ with and without the classical intercalator Pt(tpy)(HET)+ (HET = 2-hydroxyethanethiolate) to determine the effect of decoupling the intercalative recognition and oxidation chemistry. In this experiment, sites where cleavage inhibition was observed were indicative of intercalative recognition by the platinum complex, whereas sites where cleavage enhancement was observed strongly suggested that intercalative binding at a remote site had altered the structure of the nucleic acid. Comparison of the cleavage patterns of Ru(tpy)(bpy)O2+ and Ru(tpy)(dppz)O2+ for a duplex oligonucleotides, tRNA, and stem−loop structures suggests a recognition pattern for the dppz ligand very similar to that of classical intercalators.

Effect of hydrophobicity on intercalative binding of some surfactant copper(II) complexes with tRNA

“…In contrast to DNA, very small attention has been paid to the binding properties of RNA with transition metal complexes. Plenty of work pertaining to the RNA-binding properties [6][7][8], catalysts of RNA hydrolysis cleavage [9], shape-selective probes of RNA tertiary structure [10], agents of RNA oxidation cleavage [11], and approval of mismatches in RNA [12,13] has also been reported, but the RNA-binding properties of surfactant copper(II) complexes remain very fragmentary as compared to their DNA binding studies. To deeply understand the RNA-binding properties and concede important fundamental data for RNA-targeting drugs, much work is required.…”

Tuning the Thermotropic and Lyotropic Properties of Liquid‐Crystalline Terpyridine Ligands

“…In particular, terpy and its multiple derivatives have been used advantageously as building blocks for the engineering of novel supramolecular structures such as spiral lines, [26] dendrimers, [27] micelles, [28] polymers, [29,30] and liquid-crystalline soft materials. [31] Formation of ordered architectures on surfaces, [32][33][34] functional molecular devices, [35] and biochemical applications [36] are particularly challenging.…”

The up-regulation of ferritin expression using a small-molecule ligand to the native mRNA

“…We have focused on complexes based on Ru(tpy)(bpy)O 2ϩ (tpy, 2,2Ј,2Љ-terpyridine; bpy, 2,2Ј-bipyridine), which oxidizes guanines in RNA based on their solvent accessibility (35,36). Reaction of the ferritin IRE with Ru(tpy)(bpy)O 2ϩ produces cleavage at guanine with intensities that track the solvent accessibilities determined from NMR structures (16,37).…”