Enantiomeric ruthenium(II) complexes binding to DNA: binding modes and enantioselectivity

Abstract

A series of enantiomerically pure polypyridyl ruthenium(II) complexes, delta- and lambda-[Ru(bpy)2 (HPIP)](PF6)2 (delta-1 and lambda-1; bpy=2,2'-bipyridine, HPIP = 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline), delta and lambda-[Ru(bpy)2(HNAIP)](PF6)2 (delta-2 and lambda-2; HNAIP = 2-(2-hydroxy-1-naphthyl)imidazo[4,5-f][1,10]phenanthroline), delta- and lambda-[Ru(bpy)2 (HNOIP)](PF6)2 (delta-3 and lambda-3; HNOIP = 2-(2-hydroxy-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline), and delta- and lambda-[Ru(bpy)2(DPPZ)](PF6)2 (delta-4 and lambda-4; DPPZ= dipyridophenazine), have been synthesized. Binding behavior of these chiral complexes to calf thymus DNA (CT-DNA) has been investigated by electronic absorption, steady-state emission, and circular dichroism spectroscopies, as well as by viscosity measurements and equilibrium dialysis binding studies. Several points came from the results. (1) The DNA-binding properties were distinctly different for the [Ru(bpy)2L]2+ (L=HPIP, HNAIP, HNOIP) series of ruthenium(II) complexes, which indicates that the photophysical behavior of the complexes on binding to DNA can be modulated through ligand design. (2) Different binding rates of individual enantiomers of complexes 1 and 4 to DNA were observed through dialysis experiments. The lambda enantiomer bound more rapidly than the lambda enantiomer and their different intercalative binding geometries were suggested to be responsible. (3) Both delta-2 and lambda-2 bound weakly to CT-DNA; delta-2 may bind through a partial intercalation mode, whereas lambda-2 may bind in the DNA groove. (4) There was no noticeable enantioselectivity for complexes 1, 3, and 4 on binding to CT-DNA. Both of their enantiomers can intercalate into DNA base pairs. It is noted that delta-3 and lambda-3 exhibited almost identical spectral changes on addition of CT-DNA, and a similar binding manner of the isomers to the double helix was proposed.

Synthesis and Characterization of the Diastereomers Λ‐ and Δ‐[Ru(bpy)2(m‐bpy‐Gly‐L‐His‐L‐Lys)]Cl2−1H NMR Studies on Their Interactions with the Deoxynucleotide Duplex d[(5′‐CGCGAATTCGCG‐3′)2]

“…This work together with photo cleavage experiments of the oligonucleotides by such complexes is in progress. [19,20] and the ligand 4Ј-methyl-2,2Ј-bipyridine-4-carboxylic acid (m-bpy-COOH) were synthesized according to literature. ) and m-bpy-COOH (0.105 g) were suspended in 70% ethanol in water (10 mL) and the mixture was heated to reflux overnight.…”

“…Assignments were made by comparison with similar complexes of known configuration. [20,28] the spectra of both isomers only one set of proton signals for the two bpy ligands were observed. The influence of the third non-symmetric ligand m-bpy-GHK on the bpy proton signals is insignificant and the differences in their magnetic environments are non-detectable.…”

“…These complexes were used as precursors for the synthesis of the tris(chelates) Λ-and ∆-[Ru(bpy) 2 (m-bpy-COOH)] 2ϩ . [20,21] Both pyridine molecules in the complex cis-[Ru(bpy) 2 (py) 2 ] 2ϩ were substituted by the chelate ligand m-bpy-COOH (m-bpy-COOH ϭ 4Ј-methyl-2,2Ј-bipyridine-4-carboxylic acid), the optical purity being retained in the resultant compounds. The carboxyl group of the ligand (mbpy-COOH) remained free due to the higher propensity of the phenanthroline nitrogen donor atoms over the oxygen atoms for coordination to the Ru II ion [24] assisted by the formation of a very stable five-membered chelate ring.…”

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

“…For example, ruthenium metallo-intercalators containing bipy as an ancillary ligand have been shown to bind to DNA and it was possible to fine tune both DNA binding properties and enantioselectivity by changing the characteristics of the intercalating ligand. 65,66 The presence of a metal center in close proximity to DNA allows also to perform chemical reactions leading to DNA modification and cleavage. 54,67,68 Photochemical oxidation has been obtained using a Rhodium(III) complex containing the Phi ligand (which is a major groove metallo-intercalator), 69 thus allowing direct hydrogen abstraction from the major groove to be observed.…”

DNA Binding, Photocleavage, and Topoisomerase Inhibition of Functionalized Ruthenium(II)‐Polypyridine Complexes

“…Varying the number of intercalative ligands can create some interesting differences in the space configuration and the electron-density distribution of Ru II -polypyridine complexes [31 -33] [36 -44]. In fact, the left-handed L-enantiomer of the octahedral complex has also been reported to show preference upon binding to right-handed DNA under some conditions [25] [45] [46]. Therefore, the factors governing the enantioselectivity on the DNA binding for Ru II -polypyridine complexes should be further elucidated with more detailed studies.…”