In this work different substituted N-aryl and aroylamides were attached to the free N-atom of 1-methylimidazole, bridged by an ethylene chain. Then these new imidazolium salts were reacted with Au(I)Cl, Ru(II)p-cymene, Rh(I)-COD and Rh(III)-Cp*-precursors to give the respective carbene complexes. The coordination of the ligands to gold was performed by a direct synthesis from the imidazolium salt, whereas the coordination to Ru(II), Rh(I) and Rh(III) were performed by using the silver carbene as transmetallation agent.
Furthermore aroyl-imidazolium salts were transformed with platinum dichloride in DMSO to platinum carbene complexes with an new coordination motif of the carbene. In these coordinated the platinum(II)atom is complexed in square planar geometry by the imidazolyliden acting as a tridendate, dianionic C,N,C ligand. A DMSO molecule is also bound to the metal centre. This can be exchanged by another aroyl imidazolyliden ligand to give homo- and heteroleptic bis(carbene) complexes, in which they act as a neutral, monodentate ligands.
All synthesized ligands and carbene complexes were fully characterized by ¹H- and 13C-NMR spectroscopy, mass spectrometry and in some cases by X-ray crystallography and elemental analysis.
The N-aryl gold(I) carbene complexes were evaluated in biological studies. Theses studies showed that all tested complexes have an inhibitory effect towards the PARP-1 enyzme. It is found in cellnucleus and activated by damage of DNA. Repair mechanisms are activated by bonding of the enzyme to DNA. Significant damage leads to an overactivation of PARP-1 and the cell induces apoptosis. This fact is very interesting for development of cytostatic agents in cancer therapy. The dichloro derivate shows the best effect with an IC50 value of 40 nM followed by the phenyl derivate with an IC50 value of 50 nM. Less effective is the trifluoromethyl derivate with an IC50 value of 68 nM. With an IC50 value of 100 nM the nitro derivate has the lowest activity.