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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 μ M. 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 μ m, was observed. [ABSTRACT FROM AUTHOR]

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.