From Intercalation to Groove Binding: Switching the DNA‐Binding Mode of Isostructural Transition‐Metal Complexes

Abstract

The interaction with duplex DNA of a small library of structurally related complexes that all contain a d6-metal ion coordinated to either the 2,2′:4,4′′:4′,4′′′-quaterpyridyl ligand or its methylated derivative are reported. This library is made up of a mixture of newly synthesised and previously reported systems. Despite their structural similarities the complexes display an almost 20-fold variation in binding affinities. Although effects due to the overall charge of the complexes are apparent, the differences in binding characteristics are deeper than this; indeed, in a number of cases, changes in overall charge have little effect on binding affinity. Intriguingly, despite interacting with DNA through unfused ring systems, although two of the complexes studied are groove binders, the majority are non-classical intercalators. A rationale for these effects has been obtained through a combination of experimental and computational studies.

DNA Oxidation Photoinduced by Norharmane Rhenium(I) Polypyridyl Complexes: Effect of the Bidentate N,N′‐Ligands on the Damage Profile

“…It is well known that some positively charged metal complexes with bidentate planar ligands, such as phen or dppz, can interact with double‐stranded DNA through intercalation and/or groove‐binding, among others . However, chemical structure of the bidentate ligands as well as electronic charge distribution on the complex can modulate the mode and extent of this interaction . To further evaluate the contribution of intercalation of the three Re I ‐complexes investigated herein to the overall interaction with ctDNA, ethidium bromide (EtBr) fluorescence displacement experiments were employed.…”

“…[6b, 8b] However,c hemical structure of the bidentate ligands as well as electronic charge distribution on the complex can modulate the mode and extento ft his interaction. [30] To further evaluate the contribution of intercalationo ft he three Re Icomplexesi nvestigatedh erein to the overall interaction with ctDNA, ethidium bromide (EtBr) fluorescence displacement experiments were employed. Resultsw ith the free ligand nHo were included for comparison.…”

Tuning the Cellular Uptake Properties of Luminescent Heterobimetallic Iridium(III)–Ruthenium(II) DNA Imaging Probes

“…A poor aptitude for nuclear uptake is most likely due to the poor aqueous solubility of many cyclometalated systems, which is often the limiting factor in the wider use of such systems as probes in biologically relevant conditions. [18] Considering the vital biological significance of DNA and the prominent role of the nucleus within cell biology, this is a clear deficiency within this area of research. The few Ir III -based nuclear imaging agents reported include Ir III (DMSO) 2 systems that emit after reacting with histidine-containing nuclear proteins, [19,20] a conjugate based on a Ir III centre tethered to a cell-penetrating peptide [21] and an Ir III dipyridoquinoxaline complex that demonstrates evidence of nuclear staining alongside other intracellular targets.…”

A Family of Potent Ru(II) Photosensitizers with Enhanced DNA Intercalation: Bimodal Photokillers

“…This is attributed to the fact that CC1–CC3 are by far more water‐soluble than the ones carrying hexafluorophosphates as counterions ( CF1–CF3 ), and, therefore, are characterized by increased mobility in PBS solutions allowing them to intercalate stronger to CT‐DNA. Compared to other ruthenium polypyridyl based complexes, evaluated in a similar manner , our compounds present K app values of one order of magnitude higher.…”

“…The K b values obtained by these absorption titration experiments are slightly lower compared to the K app values obtained by the EtBr displacement studies, but, nevertheless, of the same order of magnitude. Such deviations are often met in the literature . The phenomena of hypo‐ or hyperchromism are suggested to arise through an intercalatative mode of binding, which, in our case, most probably involves strong π – π stacking interactions between the long planar aromatic moieties of the LP1 ligand of complexes CF1–CF3 and CC1–CC3 and the base pairs of CT‐DNA.…”