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The left-handed Z-DNA has been identified as a gene regulating element. Therefore the generation of Z-DNA through metal complexes might be an innovative way for the regulation of gene expression. Use of the new dinuclear complex N,N,N',N'-tetrakis-[2-(3,5-dimethylpyrazol-1-yl)ethyl]-1,3-propylenediamine-bis(nickel(II) dinitrate) (2) reversibly induced Z-DNA formation. However, when a 1:1 ratio of metal/dinucleating ligand was used as a control, the midpoint of the B- to Z-DNA transition was at the same nickel concentration as in case of the dinuclear complex. The novel mononuclear analogue, N-methyl-N,N-bis-[2-(3,5-dimethylpyrazol-1-yl)ethyl]amine-nickel(II)-dinitrate (3) was inducing the Z-DNA at a similar ratio versus nucleotides as free nickel(II) itself. For the first time, proton and nickel binding constants for the bis-[2-(pyrazol-1-yl)ethyl]amine ligand system are reported and discussed. Both nickel complexes 2 and 3 were structurally characterized by single crystal analysis. Furthermore, the synthesis of the two new ligands, N,N,N',N'-tetrakis-[2-(3,5-dimethylpyrazol-1-yl)ethyl]-1,2-propylenediamine (4) and N-methyl-N,N-bis-[2-(3,5-dimethylpyrazol-1-yl)ethyl]amine (5) is described. The two major synthetic pathways leading to polypyrazoyl amines in general are critically discussed with respect to yield, reproducibility and handling of the intermediates.

Novel photoactive (metallo)porphyrins were synthesised and characterised. When irradiated with light at a wavelength greater than 600 nm, these porphyrins act as photosensitisers and show high cytotoxicity towards two different human cancer cell lines with IC50 values down to 0.4 μM. A paramagnetic copper(II) porphyrin is the first photosensitiser to display excellent phototoxicity, explained by the electron paramagnetic resonance (EPR) spin trapping of hydroxy radicals and experimentally confirmed by the discovery of elevated levels of reactive oxygen species (ROS) inside A2780 cells after irradiation with red light. This finding indicates that paramagnetic compounds should be considered for photodynamic therapy (PDT). Furthermore, an additive effect of cisplatin and a zinc porphyrin, both at subtherapeutic concentrations of 0.22 μm, was observed.

Metal ions bind to nucleic acids at various positions. This binding can be modulated by using metal complexes with appropriate ligands. Novel mono- and especially dinuclear metal complexes could be a powerful tool to detect rare, but still physiologically relevant, forms of DNA, e.g. the left-handed Z-DNA. In this review, our recent research activities in this area of bioinorganic chemistry are summarized. A special emphasis is laid on the synthetic challenges that arose upon the synthesis of the polyamine ligands. Further, some rather unusual approaches to elucidate the solution structure of copper bound to guanosine monophosphate with the help of pulsed EPR techniques like ENDOR and HYSCORE are described.

Pulse EPR spectroscopy is sued to investigate possible structural features of the copper(II) ion coordinated to poly(dG-dC) poly(dG-dC) in a frozen aqueous solution, and the structural change of the polynucleotide induced by the presence of the metal ion. Two different copper species were identified and their geometry explained by a molecular model. According to this model, one species is exclusively coordinated to a single guanine with the N7 nitrogen atom forming a coordinative bond with the copper. In the other species, a guanine and a cytosine form a ternary complex together with the copper ion. A copper crosslink between the N7 of guanine and N3 of cytosine is proposed as the most probable coordination site. Moreover, no evidence was found for an interaction of either copper species with a phosphate group or equatorial water molecules. In addition, circular dichroism (CD) spectroscopy showed that the DNA of the Cu-II-poly(dG-dC)center dot poly(dG-dC) adducts resembles the left-handed Z-form. These results suggest that metal-mediated Hoogsteen base pairing, as previously proposed for a right-handed DNA duplex, can also occur in a double-stranded left-handed DNA.

Metal ions bind to nucleic acids at various positions. This binding can be modulated by using metal complexes with appropriate ligands. Novel mono- and especially dinuclear metal complexes could be a powerful tool to detect rare, but still physiologically relevant, forms of DNA, e.g. the left-handed Z-DNA. In this review, our recent research activities in this area of bioinorganic chemistry are summarized. A special emphasis is laid on the synthetic challenges that arose upon the synthesis of the polyamine ligands. Further, some rather unusual approaches to elucidate the solution structure of copper bound to guanosine monophosphate with the help of pulsed EPR techniques like ENDOR and HYSCORE are described.

In this article we briefly describe our recent results concerning the interaction of mononuclear [M(CO)3]+ (M = Re, 99Tc and 99mTc) based complexes with guanine and plasmid DNA for chemo- and/or radiotherapeutic purposes. Furthermore, studies with mono- and dinuclear, coordinatively unsaturated Ni(II) and Cu(II) complexes inducing B- to Z-DNA transitions are outlined. The strong interaction of [M(CO)3]+ with one guanine allows the direct introduction of this core into oligodeoxynucleotides (ODN), without their previous derivatization, for further elucidation of their biological behavior. Vectors labeled in this way can later be used in radioimaging or -therapy studies. The [M(CO)3]+ core can also mediate the introduction of further biologically active or, for analytical purposes, fluorescent molecules. Alternatively, ODNs can be derivatized with amino acid based chelators such as histidine. We describe the induction of structural changes in plasmid DNA observed after reaction with the [M(CO)3]+ moiety. This indicates a cisplatin-like behavior useful for future chemotherapy. Finally, studies of the interaction of mono- and dinuclear complexes with ODN inducing B- to Z-DNA transitions are described and compared to the effect of common electrolytes alone. A clear correlation between salt type and salt concentration was found. These complexes have a strong potential to be used for analytical or biological purposes as well.