Recent Developments in the Interactions of Classic Intercalated Ruthenium Compounds: [Ru(bpy)₂dppz]2+ and [Ru(phen)₂dppz]2+ with a DNA Molecule

Abstract

[Ru(bpy)₂dppz]²⁺ and [Ru(phen)₂dppz]²⁺ as the light switches of the deoxyribose nucleic acid (DNA) molecule have attracted much attention and have become a powerful tool for exploring the structure of the DNA helix. Their interactions have been intensively studied because of the excellent photophysical and photochemical properties of ruthenium compounds. In this perspective, this review describes the recent developments in the interactions of these two classic intercalated compounds with a DNA helix. The mechanism of the molecular light switch effect and the selectivity of these two compounds to different forms of a DNA helix has been discussed. In addition, the specific binding modes between them have been discussed in detail, for a better understanding the mechanism of the light switch and the luminescence difference. Finally, recent studies of single molecule force spectroscopy have also been included so as to precisely interpret the kinetics, equilibrium constants, and the energy landscape during the process of the dynamic assembly of ligands into a single DNA helix.

Keywords: binding mode; intercalated ruthenium compounds; molecular light switch; sensitive luminescent reporter; single molecule force spectroscopy.

Figure 1

Different DNA forms. Reproduced with permission from the authors of [3,5]. Copyright © 2001, Royal Society of Chemistry. Copyright © 2014, Science China Press. B-DNA—DNA double helix. A-DNA—It is a right-handed double helix fairly similar to the more common B-DNA form, but with a shorter, more compact helical structure. Z-DNA—It is a left-handed double helical structure in which the helix winds to the left in a zigzag pattern.

Figure 2

Chemical structures of intercalated ruthenium compounds. Reproduced with permission from the authors of [15]. Copyright © 1992, American Chemical Society.

Figure 3

Mechanism of the molecular light switch proposed by Olson et al. Reproduced with permission from the authors of [14]. Copyright © 1997, American Chemical Society.

Figure 4

The structure of Δ-[Ru(bpy)₂dppz]²⁺ bound to the oligonucleotide. (a,b) front view (a) and view rotated 90° around the helix axis (b). Three DNA-binding modes were observed, as follows: (1) metallo-insertion, whereby the ruthenium complex (red) inserts the dppz ligand into the DNA duplex (grey) at the mismatched sites through the minor groove, extruding the mispaired adenosines (blue); (2) metallo-intercalation, whereby the complex (green) binds between two well-matched base pairs; (3) end-capping, whereby the complex (yellow) stacked with the terminal Watson-Crick pair of the duplex. Reprinted with permission from the authors of [26]. Copyright © 2012, Springer Nature.

Figure 5

(a) Crystal structure of Δ-[Ru(phen)₂dppz]²⁺ with oligonucleotide d(CCGGTACCGG)₂. (b) Crystal structure of Λ-[Ru(phen)₂dppz]²⁺ with oligonucleotide d(CCGGATCCGG)₂. The C1C2/G9G10 intercalated Ru complex is in dark blue, and the C1C2/G9G10 semi-intercalated Ru complex is in light blue. The central AT/TA intercalated Ru complex (purple) in (a) is treated as a whole complex of 0.5 occupancy per oligonucleotide strand. Reprinted with permission from the authors of [27]. Copyright © 2012, Springer Nature. (c) Crystal structure of rac-[Ru(phen)₂dppz]²⁺ with oligonucleotide d(ATGCAT)₂. The Δ-[Ru(phen)₂dppz]²⁺ is in purple, and the Λ-[Ru(phen)₂dppz]²⁺ is in pink. Reprinted with permission from the authors of [52]. Copyright © 2013, American Chemical Society.

Figure 6

Five possible binding modes for Δ-[Ru(phen)₂(dppz)]²⁺ to DNA. (A) The complex binds at, or adjacent to, a mismatch site. (B) Insertion into well-matched sites with less than three H-bonds between the bases. (C) Canted intercalation into a well-matched base pair leaves one dppz nitrogen atom entirely exposed to solvent. (D) Model for intercalation by a Δ enantiomer at a 5′-AT/AT-3′ step. (E) Semi-intercalation by an ancillary ligand into the DNA duplex, exposing both of the phenazine nitrogen atoms to the solvent. Reprinted with permission from the authors of [54]. Copyright © 2016, Oxford University Press.

Figure 7

Dependence of [Ru(phen)₂dppz]²⁺ binding on force. (a) Titration curve fits using the McGhee–von Hippel model. (b) Binding constant dependence on force. (c) Binding site size dependence on force. Reprinted with permission from the authors of [29]. Copyright © 2009, Springer Nature.