Gold(I) complexes such as auranofin have been used for decades to treat symptoms of rheumatoid arthritis and have also demonstrated a considerable potential as new anticancer drugs. The enzyme thioredoxin reductase (TrxR) is considered as the most relevant molecular target for these species. The here investigated gold(I) complexes with benzimidazole derived N-heterocyclic carbene (NHC) ligands represent a promising class of gold coordination compounds with a good stability against the thiol glutathione. TrxR was selectively inhibited by in comparison to the closely related enzyme glutathione reductase, and all complexes triggered significant antiproliferative effects in cultured tumor cells. More detailed studies on a selected complex revealed a distinct pharmacodynamic profile including the high increase of reactive oxygen species formation, apoptosis induction, strong effects on cellular metabolism (related to cell surface properties, respiration, and glycolysis), inhibition of mitochondrial respiration and activity against resistant cell lines.

Gold(I) complexes with a 1,3-diethylbenzimidazol-2-ylidene N-heterocyclic carbene (NHC) ligand of the type NHC-Au-L (L=-Cl, -NHC, or -PPh3) were comparatively evaluated as thioredoxin reductase (TrxR) inhibitors and antimitochondrial anticancer agents. Different effects were noted in various biochemical assays (e.g., inhibition of TrxR, cellular and mitochondrial uptake, or effects on mitochondrial membrane potential), and this was related to properties of the complexes such as bond dissociation energies and overall charge. Remarkable antiproliferative effects, a strong induction of apoptosis, and enhancement of reactive oxygen species (ROS) formation as well as other effects on tumor cell metabolism confirmed the promising potential of the complexes as novel anticancer chemotherapeutics.

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The DNA binding of polypyridyl (pp) (η 6 -hexamethylbenzene)ruthenium(II) complexes of the type [(η 6 -C 6 Me 6 )-RuCl(pp)](CF 3 SO 3 ) (pp = phen, tap, dpq, dppz, dppn) 1-5 and [(η 6 -C 6 Me 6 )Ru{(NH 2 ) 2 CS}(pp)](CF 3 SO 3 ) 2 (pp = dpq, dppz, dppn) 6-8 has been studied by UV/Vis spectroscopy, circular dichroism and viscosity measurements. Complexes 3-5, 7 and 8 are potent cytotoxic agents towards the human cancer cell lines MCF-7 and HT-29. Stable intercalative binding into CT DNA is indicated for the dpq and dppz complexes by large increases ∆T m of 12-25°C in the DNA thermal denaturation temperature for r = [complex]/[DNA] = 0.1. Large viscosity increases for DNA in the presence of 3 and 4 are also in accordance with this binding mode as are the pronounced hypochromic UV/Vis shifts for the π-π* transitions of the dppz ligands of 4 and 7 in the range 360-400 nm. A small ∆T m value of 2°C and effectively unchanged vis-

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