Jin-Gang Liu

Shape- and enantioselective interaction of Ru(II)/Co(III) polypyridyl complexes with DNA

Abstract This paper presents recent progress in our laboratory on the interaction of Ru(II)/Co(III) polypyridine complexes with DNA. The first part describes the effect on DNA binding of modulating the intercalative ligand and the size of the ancillary ligand of the complex. DNA binding modes and binding affinity can be modulated by ligand design. The second part focuses on the enantioselective DNA binding behavior of the Ru(II) complexes using absorption spectra, emission spectra, viscosity measurements, equilibrium dialysis and CD titrations. The enantiomers of the various Ru(II) complexes show diverse enantioselectivity on binding to DNA. Different equilibrium rates were observed for the enantiomers of the complex in a time-dependent dialysis experiment. The interesting effect of the “molecular switch” for DNA was observed for several Ru(II) complexes. Their DNA binding properties, together with the possible mechanism involved in the effect, are discussed in the last part.

DNA-binding and photocleavage studies of cobalt(III) polypyridyl complexes: [Co(phen)2IP]3+ and [Co(phen)2PIP]3+

Two complexes of [Co(phen)2IP]3+ (IP=imidazo[4,5-f][1,10]phenanthroline) and [Co(phen)2PIP]3+ (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline) have been synthesized and characterized by UV/VIS, IR, EA and mass spectra. The binding of the two complexes with calf thymus DNA has been investigated by absorption spectroscopy, cyclic voltammetry, viscosity measurements and DNA cleavage assay. The spectroscopic studies together with cyclic voltammetry and viscosity experiments support that both of the complexes bind to CT DNA by intercalation via IP or PIP into the base pairs of DNA. [Co(phen)2PIP]3+ binds more avidly to CT DNA than [Co(phen)2IP]3+, which is consistent with the extended planar and π system of PIP. Noticeably, the two complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.

POLYPYRIDYL RUTHENIUM(II) COMPLEXES CONTAINING INTRAMOLECULAR HYDROGEN-BOND LIGAND : SYNTHESES, CHARACTERIZATION, AND DNA-BINDING PROPERTIES

Two new ligands containing an intramolecular hydrogen bond, 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline (HPIP) and 2-(2-hydroxy-1-naphthyl)imidazo[4,5-f][1,10]phenanthroline (HNAIP), and their complexes [Ru(bpy)2(HPIP)](PF6)2·H2O (1) and [Ru(bpy)2(HNAIP)](PF6)2·2H2O (2) (bpy=2,2′-bipyridine) have been synthesized and characterized by UV–Vis, IR, 1H NMR, and mass spectra. The electrochemical behaviors of the two complexes were studied by cyclic voltammetry. The binding of the two complexes with calf thymus DNA has been investigated by absorption, luminescence titrations, steady-state emission quenching, and viscosity measurements. The results suggest that complex 1 intercalates into DNA base pairs via the ligand HPIP, while complex 2 binds with DNA by partially intercalating the ligand HNAIP. Complex 1 shows higher affinity to DNA than complex 2. The intrinsic binding constants K for complexes 1 (6.5±0.3×105 M−1) and 2 (8.3±0.4×104 M−1) together with [Ru(bpy)2PIP]2+ (4.7±0.2×105 M−1, PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline) were determined by absorption titration.

Synthesis, characterization and the effect of ligand planarity of [Ru(bpy)2L]2+ on DNA binding affinity.

Two structurally related ligands (L) 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene (taptp) and 2,3-diphenyl-1,4,8,9-tetraazatriphenylene (dptatp), and their related complexes of [Ru(bpy)2L]2+ have been synthesized and characterized by elemental analyses, 1H NMR and mass spectra. Their electrochemical properties were also examined. Both complexes emit intense luminescence in organic solvent but are quenched in water to different extents. The interactions of the complexes with calf thymus DNA have been investigated by viscosity, absorption, emission and circular dichroism spectra. The intrinsic binding constants of [Ru(bpy)2(taptp)]2+ and [Ru(bpy)2(dptatp)]2+ are 1.7 x 10(5) and 3.8 x 10(4) M-1, respectively. All data indicate that both complexes bind enantioselectively to double-stranded calf thymus DNA via the intercalative mode, with stronger affinity for the fully planar ligand complex of [Ru(bpy)2(taptp)]2+.

Synthesis, characterization and DNA-binding properties of novel dipyridophenazine complex of ruthenium (II) : [Ru(IP)2(DPPZ)]2+

Abstract A novel ruthenium(II) complex of dipyridophenazine (DPPZ) with the ancillary ligand imidazole[4,5- f ] [1,10]phenanthroline (IP), [Ru(IP) 2 (DPPZ)] (PF 6 ) 2 , has been synthesized and characterized by elemental analysis, 1D and 2D 1 H NMR, fast-atom bombardment mass spectra (FABMS), electronic spectroscopy and cyclic voltammetry. The DNA-binding properties of the complex were studied by spectroscopic methods. The intrinsic binding constant, K =2.1 × 10 7 M −1 , of the complex to calf thymus DNA has been determined by absorption titration in 5 mmol dm −3 Tris-HCl, 50 mmol dm −3 NaCl buffer (pH 7.0). The excited state lifetimes and luminescence quenching with [Fe(CN) 6 ] 4− as the quencher in the presence of DNA were also tested and mono-exponentiality was observed for the emission decay curves. Viscosity measurements together with the optical titrations unambiguously proved that the complex bound with DNA intercalatively and that the binding affinity to DNA was several times larger than that of the parent complex [Ru(bpy) 2 (DPPZ)] 2+ .

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

Δ- and Λ-[Ru(bpy)2(HPIP)](PF6)2 (Δ-1 and Λ-1; bpy =2,2′-bipyridine, HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenan-throline), Δ- and Λ-[Ru(bpy)2(HNAIP)](PF6)2 (Δ-2 and Λ-2; HNAIP=2-(2-hydroxy-1-naphthyl)imidazo[4,5-f][1,10]phenanthroline), Δ- and Λ-[Ru(bpy)2 (HNOIP)](PF6)2 (Δ-3 and Λ-3; HNOIP=2-(2-hydroxy-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline), and Δ- and Λ-[Ru(bpy)2(DPPZ)](PF6)2 (Δ-4 and Λ-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 Λ enantiomer bound more rapidly than the Δ enantiomer and their different intercalative binding geometries were suggested to be responsible. (3) Both Δ-2 and Λ-2 bound weakly to CT-DNA; Δ-2 may bind through a partial intercalation mode, whereas Λ-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 Δ-3 and Λ-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, characterization and interaction of mixed polypyridyl ruthenium(II) complexes with calf thymus DNA

New mixed polypyridyl {HPIP = 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline, phen = 1,10-phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline, dmb = 4,4′-dimethyl-2,2′-bipyridine} ruthenium(II) complexes [Ru(phen)2(HPIP)]2+, [Ru(dmp)2(HPIP)]2+ and [Ru(dmb)2(HPIP)]2+ were synthesized and characterized by elemental analyses 1H-n.m.r., u.v.–vis. spectroscopy and cyclic voltammetry. Their DNA-binding properties were demonstrated by absorption, luminescence titrations, steady-state emission quenching and viscosity measurements. The results suggested that all the examined complexes bind with CT-DNA intercalatively. Methyl groups substituted at the 4,4′-positions of bpy has no obvious effect on its DNA binding, whereas substituents at the 2- and 9-positions of phen have an impressive effect on its DNA-binding, as revealed by the decreased binding affinity.

Synthesis, characterization and DNA-binding properties of [Ru(phen)2taptp]2+ and [Ru(phen)2dptatp]2+

Abstract Two structurally related complexes [Ru(phen)2taptp]2+ (1) and [Ru(phen)2dptatp]2+ (2), where taptp is 4,5,9,18-tetraazaphenanthreno[9,10-b]triphenylene and dptatp is 2,3-diphenyl-1,4,8,9-tetraazatriphenylene, were synthesized and characterized by elemental analyses and 1H NMR. The spectroscopic and electrochemical properties of complexes 1 and 2 were also examined. Both complexes can luminesce in organic solvent but are quenched in water to different extents. The interaction of the complexes with calf thymus DNA was studied by absorption and emission spectra, as well as viscosity and lifetime measurements. All the data indicate that both complexes bind with double-stranded calf thymus DNA via intercalative mode. Unlike its analog [Ru(bpy)2taptp]2+, [Ru(phen)2taptp]2+ shows negligible luminescence in water buffer but bright luminescence on binding to DNA, enabling it to be a sensitive probe for DNA conformation.

Enantioselective binding of Λ- and Δ-[Ru(bpy)2(HPIP)]Cl2 (HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline) to the hexanucleotide [d(5′-GTCGAC-3′)2]

Abstract Multidimensional NMR techniques (1D 1 HNMR, 2D DQF 1 H 1 H COSY and 2D 1 H 1 H NOESY), electrospray ionization mass spectrometry (ESI-MS) and electronic spectroscopy, were performed to study the interactions of the enantiomers Λ- and Δ-[Ru(bpy) 2 (HPIP)]Cl 2 , (HPIP=2-(2-hydroxyphenyl)imidazo[4,5- f ][1,10]phenanthro-line) with the self complementary hexanucleotide duplex d(5′-GTCGAC-3′) 2 . The results show that the Δ-[Ru(bpy) 2 (HPIP)]Cl 2 binds tightly to the oligonucleotide, by intercalation of the ligand HPIP, between the A5 and C6 base sequence of the same strand, probably through the minor groove. Λ-enantiomer binds weakly, suggesting groove interactions with the hexanucleotide duplex. ESI-MS spectrometry and UV-vis spectroscopy also confirmed these observations.

Studies of molecular recognition mechanism in supramolecular system of ruthenium(II) polypyridyl complexes and DNA

The recent studies on supramolecular system assembled by Ru(II) polypyridyl complexes and B-form double-stranded DNA is reviewed. These complexes have been studied as DNA spectroscopic tags and structural probes. The studies focus on the recognition parameters of these complexes binding to DNA, including the influence of the shape and size of intercalative ligand, the ancillary ligands and the effects of hydrogen bonding. Enantioselectivities of these complexes binding to DNA are also briefly discussed.