Structural investigation into the threading intercalation of a chiral dinuclear ruthenium(II) polypyridyl complex through a B-DNA oligonucleotide

Herein we report the separation of the three stereoisomers of the DNA light-switch compound [{Ru(bpy)2}2(tpphz)]4+ (tpphz = tetrapyrido[3,2-a:2',3'-c:3″,2″-h:2‴,3‴-j]phenazine) by column chromatography and the characterization of each stereoisomer by X-ray crystallography. The interaction of these compounds with a DNA octanucleotide d(GCATATCG).d(CGATATGC) has been studied using NMR techniques. Selective deuteration of the bipyridyl rings was needed to provide sufficient spectral resolution to characterize structures. NMR-derived structures for these complexes show a threading intercalation binding mode with slow and chirality-dependent rates. This represents the first solution structure of an intercalated bis-ruthenium ligand. Intriguingly, we find that the binding site selectivity is dependent on the nature of the stereoisomer employed, with Λ RuII centers showing a better intercalation fit

In situ synchrotron x-ray study of ultrasound cavitation and its effect on solidification microstructures

Considerable progress has been made in studying the mechanism and effectiveness of using ultrasound waves to manipulate the solidification microstructures of metallic alloys. However, uncertainties remain in both the underlying physics of how microstructures evolve under ultrasonic waves, and the best technological approach to control the final microstructures and properties. We used the ultrafast synchrotron X-ray phase contrast imaging facility housed at the Advanced Photon Source, Argonne National Laboratory, US to study in situ the highly transient and dynamic interactions between the liquid metal and ultrasonic waves/bubbles. The dynamics of ultrasonic bubbles in liquid metal and their interactions with the solidifying phases in a transparent alloy were captured in situ. The experiments were complemented by the simulations of the acoustic pressure field, the pulsing of the bubbles, and the associated forces acting onto the solidifying dendrites. The study provides more quantitative understanding on how ultrasonic waves/bubbles influence the growth of dendritic grains and promote the grain multiplication effect for grain refinement

The circular dichroism and the chirality of the unsymmetric-cis- and the trans-(+)D-bis(diethylenetriamine)cobalt(III) ion

The circular dichroism of the systems u-cis-(+)D-[Co(dien)2]3+ and trans-(+)D-[Co(dien)2]3+ indicates the stereochemical configuration of the former, and indicates in the latter a new type of chirality which has hitherto not been realized, but which will be present in metal–polyamine complexes.F. R. Keene, G. H. Searle and S. F. Maso

Noncovalent DNA binding of metal complexes

Over the last 30 years there has been increasing interest in utilizing kinetically inert transition-metal complexes as noncovalent DNA- and RNA-binding agents. Metal complexes can interact with nucleic acids through a variety of different modes, with the particular mode of binding being predictably governed by the metal complex structure. Furthermore, there are an increasing number of studies highlighting the biological applications of a broad range of nucleic acid-binding metal complexes. The aim of this chapter is to provide an up-to-date and comprehensive discussion of the interactions of metal complexes with nucleic acids, with the major emphasis on work published over the last 20 years. So that this chapter can be more readily placed into context, a relatively detailed description of the structure of DNA and RNA is also presented

Binding of a flexibly-linked dinuclear ruthenium(II) complex to adenine-bulged DNA duplexes

Using 1H NMR spectroscopy and molecular modelling, the DNA binding of a chiral dinuclear ruthenium(ii) complex {Δ,Δ-[{Ru(phen)2}2(μ-bb7)]4+; phen = 1,10-phenanthroline, bb7 = 1,7-bis[4(4′-methyl-2,2′-bipyridyl)]-heptane} involving a bridging ligand containing a flexible aliphatic chain has been studied. The binding of the ruthenium(ii) complex was examined with the non-self-complementary duplexes d(CCGAGAATCGGCC):d(GGCCGATTCCGG) (containing a single adenine bulge: designated SB) and d(CCGAGCCGTGCC):d(GGCACGAGCCGG) (containing two adenine bulge sites separated by two base-pairs: designated DB). The NMR data indicated that the ruthenium(ii) complex bound at the bulge site of SB, with one ruthenium centre located at the bulge site with the second metal centre binding with lower affinity and selectivity in the duplex region adjacent to the bulge site. Less specific binding is inferred from chemical shift changes of nucleotide protons two to five base pairs from the single adenine bulge. The ruthenium(ii) complex selectively bound the DB duplex with one metal centre located at each bulge site. The NMR results also suggested that the metal complex binding induced greater changes to the structure of the SB duplex, compared with the DB duplex. Modelling indicates the bridging ligand allowed each ruthenium(ii) metal centre to bind one adenine bulge of the doubly-bulged duplex without disrupting the DNA structure, using the additional torsional flexibility conferred by the aliphatic bridging ligand. However, the second ruthenium(ii) metal centre is not able to bind in the minor groove of the singly-bulged duplex without disrupting the structure, as the metal centre is too bulky. The results of this study suggest dinuclear ruthenium(ii) complexes have considerable potential as probes for DNA and RNA sequences that contain two bulge sites separated by a small number of base-pairs.Damian P. Buck, Jacob A. Paul, Michelle J. Pisani, J. Grant Collins and F. Richard Keen

A tetranuclear polypyridylruthenium(II) complex as a selective stain for extracellular vesicle penetration through brain microvascular endothelium

A new photoluminescent polypyridylruthenium(II) stain for extracellular vesicles (EVs) released from lipopolysaccharide-stimulated THP-1 monocytes enabled important new insights into how the bacteria-induced immune system affects the blood-brain barrier (BBB). These included previously unknown aspects of EV interactions with BBB microvascular endothelial cells and the extracellular matrix relevant to human brain diseases.Kartika Wardhani, Aviva Levina, Biyun Sun, Georges E. R. Grau, F. Richard Keene, J. Grant Collins and Peter A. La

The dichotomy in the DNA-binding behaviour of ruthenium(II) complexes bearing benzoxazole and benzothiazole groups

The substituted tris(bipyridine)ruthenium(II) complexes {[Ru(bpy)2(4,4′-bbob)]2+ and [Ru(bpy)2(5,5′-bbob)]2+ [where bpy = 2,2′-bipyridine and bbob = bis(benzoxazol-2-yl)-2,2′-bipyridine] have been prepared and compared to the previously studied complex [Ru(bpy)2(4,4′-bbtb)]2+ [where bbtb = bis(benzothiazol-2-yl)-2,2′-bipyridine]. From the UV/VIS titration studies, Δ-[Ru(bpy)2(4,4′-bbob)]2+ displays a stronger association than the Λ-isomer with calf-thymus DNA (ct-DNA). For [Ru(bpy)2(5,5′-bbob)]2+, there appears to be minimal interaction with ct-DNA. The results of fluorescence titration studies suggest that [Ru(bpy)2(4,4′-bbob)]2+ gives an increase in emission intensity with increasing ct-DNA concentrations, with an enantiopreference for the Δ isomer, confirmed by membrane dialysis studies. The fluorescent intercalation displacement studies revealed that [Ru(bpy)2(4,4′-bbob)]2+ and [Ru(bpy)2(5,5′-bbob)]2+ display a preference for more open DNA structures such as bulge and hairpin sequences. While Λ-[Ru(bpy)2(4,4′-bbtb)]2+ has shown the most significant affinity for all the oligonucleotides sequences screened in previous studies, it is the Δ isomer of the comparable benzoxazole ruthenium(II) complex (Δ-[Ru(bpy)2(4,4′-bbob)]2+) that preferentially binds to DNA