Two novel [2+2] metallo-assemblies based on a guanosine-substituted terpyridine ligand (1) coordinated to palladium(II) (2 a) and platinum(II) (2 b) are reported. These supramolecular assemblies have been fully characterized by NMR spectroscopy, ESI mass spectrometry and elemental analyses. The palladium(II) complex (2 a) has also been characterized by single crystal X-ray diffraction studies confirming that the system is a [2+2] metallo-rectangle in the solid state. The stabilities of these [2+2] assemblies in solution have been confirmed by DOSY studies as well as by variable temperature ¹H NMR spectroscopy. The ability of these dinuclear complexes to interact with quadruplex and duplex DNA was investigated by fluorescent intercalator displacement (FID) assays, fluorescence resonance energy transfer (FRET) melting studies, and electrospray mass spectrometry (ESI-MS). These studies have shown that both these assemblies interact selectively with quadruplex DNA (human telomeric DNA and the G-rich promoter region of c-myc oncogene) over duplex DNA, and are able to induce dimerization of parallel G-quadruplex structures.

A series of copper(II), nickel(II) and zinc(II) dimetallic complexes were prepared and their affinities towards arsenate investigated. Indicator displacement assays (IDAs) were carried out to establish the complexes with best affinities towards arsenate. A di-zinc complex (3) was selected and its arsenate-binding abilities investigated by isothermal titration calorimetry (ITC). The X-ray crystal structure of this metallo-receptor bound to arsenate is also reported, which allowed us to establish the binding mode between 3 and this oxyanion. Immobilising 3 onto HypoGel resin yielded a novel adsorbent (Zn–HypoGel) with high affinity for arsenate. Adsorption of arsenate from competitive solutions and natural groundwater was greater than that of the commercially used iron oxide Bayoxide E33. Zn–HypoGel could be efficiently and simply regenerated by washing with sodium acetate solution.

The reaction of tetrakis(pyridine-2-yl)pyrazine (tppz) with 2 equiv of (2,2′-bpy)Pt^II in water yields two isomeric dinuclear cations, [{Pt(2,2′-bpy)}₂(tppz)]⁴⁺, in which Pt coordination exclusively takes place through the two pairs of pyridine-2-yl nitrogen atoms. The two conformational isomers differ in their overall shape, with the formation of “Z” and “U” shapes, which are formed at 40 °C (Z isomer, 1) and under reflux conditions (U isomer, 2), respectively. X-ray crystal-structure analyses of the Z isomer, [{Pt(2,2′-bpy)}₂(tppz)](PF₆)₄⋅3 CHCl₃⋅4 H₂O (1 a), and of the U isomer, [{Pt(2,2′-bpy)}₂](PF₆)₄⋅2 CH₃CN⋅1.5 H₂O (2 a), were carried out. Co-crystallization of compound 2 with PtCl₂(2,2′-bpy) yielded [{Pt(2,2′-bpy)}₂(tppz)](BF₄)₄⋅[PtCl₂(2,2′-bpy)]⋅4.5 H₂O (3), in which the PtCl₂(2,2′-bpy) entity was sandwiched between the two 2,2′-bpy faces of the U-shaped cation (2). Quantum chemical calculations revealed that the U isomer was more stable than the Z isomer, both in the gas phase and in an aqueous environment. These two isomers display different affinities toward duplex DNA and human telomeric quadruplex DNA (Htelo), as concluded from CD spectroscopy and FID assays. Thus, the U isomer binds significantly more strongly to quadruplex DNA (DC₅₀=0.38 μM) than the Z isomer (DC₅₀=8.50 μM).

A new disubstituted terpyridine ligand and the corresponding tri-copper(II) complex have been prepared and characterised. The binding affinity and binding mode of this tri-copper complex (as well as the previously reported mono- and di-copper analogues) towards duplex DNA were determined by using UV/Vis spectroscopic titrations and fluorescent indicator displacement (FID) assays. These studies showed the three complexes to bind moderately (in the order of 10⁴ M⁻¹) to duplex DNA (ct-DNA and a 26-mer sequence). Furthermore, the number of copper centres and the nature of the substituents were found to play a significant role in defining the binding mode (intercalative or groove binding). The nuclease potential of the three complexes was investigated by using circular plasmid DNA as a substrate and analysing the products by agarose-gel electrophoresis. The cleaving activity was found to be dependent on the number of copper centres present (cleaving potency was in the order: tri-copper>di-copper>mono-copper). Interestingly, the tri-copper complex was able to cleave DNA without the need of external co-reductants. As this complex displayed the most promising nuclease properties, cell-based studies were carried out to establish if there was a direct link between DNA cleavage and cellular toxicity. The tri-copper complex displayed high cytotoxicity against four cancer cell lines. Of particular interest was that it displayed high cytotoxicity against the cisplatin-resistant MOLT-4 leukaemia cell line. Cellular uptake studies showed that the tri-copper complex was able to enter the cell and more importantly localise in the nucleus. Immunoblotting analysis (used to monitor changes in protein levels related to the DNA damage response pathway) and DNA-flow cytometric studies suggested that this tri-copper(II) complex is able to induce cellular DNA damage.

This study shows that the relaxivity and optical properties of functionalised lanthanide-DTPA-bis-amide complexes (lanthanide=Gd³⁺ and Eu³⁺, DTPA=diethylene triamine pentaacetic acid) can be successfully modulated by addition of specific anions, without direct Ln³⁺/anion coordination. Zinc(II)-dipicolylamine moieties, which are known to bind strongly to phosphates, were introduced in the amide “arms” of these ligands, and the interaction of the resulting Gd–Zn₂ complexes with a range of anions was screened by using indicator displacement assays (IDAs). Considerable selectivity for polyphosphorylated species (such as pyrophosphate and adenosine-5′-triphosphate (ATP)) over a range of other anions (including monophosphorylated anions) was apparent. In addition, we show that pyrophosphate modulates the relaxivity of the gadolinium(III) complex, this modulation being sufficiently large to be observed in imaging experiments. To establish the binding mode of the pyrophosphate and gain insight into the origin of the relaxometric modulation, a series of studies including UV/Vis and emission spectroscopy, luminescence lifetime measurements in H₂O and D₂O, ¹⁷O and ³¹P NMR spectroscopy and nuclear magnetic resonance dispersion (NMRD) studies were carried out.

A series of bis(dicyclohexylphosphino)methane (dcpm)-containing gold(I) thiolate complexes with urea receptors, 1–3, has been successfully designed and synthesized, and their photophysical and anion-binding properties have been studied. The linker between the thiolate and the urea group, and the electronic environment of the urea moiety, have been found to exert a great influence on the photophysical and anion-binding properties of the complexes. Complex 3 displays an intense long-lived orange-red luminescence at around 620 nm in the solid state and in the glass state at 77 K, which is considerably red shifted from the band seen in a solution of dichloromethane at room temperature, suggesting the presence of Au⋅⋅⋅Au interactions. Upon introducing an electron-withdrawing NO₂ group, complex 1 was found to show high selectivity and sensitivity for F⁻ through a drastic color change from yellow to red. The anion-binding constants of the complexes have been determined from electronic absorption and ¹H NMR spectroscopy titration studies and the data were found to fit well to a 1:1 binding model for the interactions between the complexes and the anions. Complexes 1 and 2 show the same anion selectivity trend of F⁻>AcO⁻>H₂PO₄⁻>Cl⁻≈Br⁻≈I⁻, which is consistent with the trend in anion basicity. In addition, complex 1 has been shown to exhibit higher binding affinity for anions compared with those of complexes 2 and 3, probably due to the higher acidity of the urea moiety as a result of the introduction of the NO₂ group.

Guanine-rich sequences of DNA can assemble into tetrastranded structures known as G-quadruplexes. It has been suggested that these secondary DNA structures could be involved in the regulation of several key biological processes. In the human genome, guanine-rich sequences with the potential to form G-quadruplexes exist in the telomere as well as in promoter regions of certain oncogenes. The identification of these sequences as novel targets for the development of anticancer drugs has sparked great interest in the design of molecules that can interact with quadruplex DNA. While most reported quadruplex DNA binders are based on purely organic templates, numerous metal complexes have more recently been shown to interact effectively with this DNA secondary structure. This Review provides an overview of the important roles that metal complexes can play as quadruplex DNA binding molecules, highlighting the unique properties metals can confer to these molecules.

Guaninreiche DNA-Sequenzen können sich zu viersträngigen Aggregaten anordnen, die als G-Quadruplexe bezeichnet werden. Man nimmt an, dass diese DNA-Sekundärstrukturen an der Regulation verschiedener biologischer Schlüsselprozesse beteiligt sind. Im menschlichen Genom kommen guaninreiche Sequenzen mit dem Potenzial zur Bildung von G-Quadruplexen beispielsweise im Telomer sowie in den Promoterregionen bestimmter Onkogene vor. Die Identifizierung dieser Sequenzen als neue Zielstrukturen für Tumortherapeutika hat großes Interesse an der Entwicklung von Verbindungen ausgelöst, die mit Quadruplex-DNA wechselwirken können. Die meisten bekannten Quadruplex-DNA-Bindungssubstanzen beruhen zwar auf rein organischen Templaten, später wurde aber nachgewiesen, dass auch viele Metallkomplexe mit dieser DNA-Sekundärstruktur effiziente Wechselwirkungen eingehen. Dieser Aufsatz gibt einen Überblick über die wichtigen Funktionen, die Metallkomplexe als Quadruplex-DNA-Bindungssubstanzen haben können, und diskutiert die besonderen Eigenschaften von Metallzentren auf diese Verbindungen.

The selective recognition of anionic species by molecular receptors is an area of increasing interest due to the important roles played by anions in biological systems and the environment. An attractive approach for the recognition of anions is to use metal-based receptors, which provides some important advantages over purely organic hosts. Metallo-hosts can combine the structural and functional properties of metal centres with the recognition capabilities of organic ligands to selectively bind anionic guests. In our group we have developed different approaches for the synthesis of this type of metallo-receptors. One of these approaches is based on the use of the anion of interest as a templating agent to link together different organic and metal-containing building blocks into assemblies that have high selectivity for the templating anion. This microreview aims to give an overview of the research carried out in the author's group in this area over the past few years. Relevant examples from other groups are discussed and, where appropriate, compared to the work carried out in our group.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Cover Picture: Metalloreceptors for the molecular recognition of anions or anion templates for the synthesis of metalloreceptors? Both! This figure shows the crystal structures of two metallohosts with the corresponding anionic guest “trapped” within the hydrogen-bonding clefts. In one case (structure shown at the top), the complex was prepared without the need for an anion template. Once formed, this dipalladium complex with urea-containing ligands binds a range of different anions in competing solvents. The structure shown at the bottom of the figure is that of a tetrametallohost, which only forms in the presence of the appropriate anionic template. This microreview on p. 357 ff aims to give an overview of the research carried out in the author's group in the area of anion recognition and templation in coordination chemistry.

The synthesis of two new azo phenyl thiourea compounds and their optical response to different anions is reported herein. Solution studies in methanol indicate that cyanide induces a colour change in these dyes (whereas no changes are observed in the presence of other anions, such as F⁻, Cl⁻, Br⁻, CH₃COO⁻, H₂PO₄⁻, HSO₄⁻). Interestingly, in DMSO these dyes are responsive not only to cyanide, but also to fluoride, acetate and dihydrogen phosphate. Each of these anions induces a different colour change. In the second part of the paper, we report the attachment of one of these dyes onto nanostructured TiO₂ and Al₂O₃ films. The stability of these sensitised films to pH was studied and we concluded that the sensitised Al₂O₃ films are more robust, and hence, better than the TiO₂ for anion sensing. The dye-sensitised Al₂O₃ films were immersed in solutions of different anions and their response studied. The films can detect cyanide down to 3 ppm in aqueous solution with relatively good selectivity over other anions.