Cytotoxic properties of rhenium(I) tricarbonyl complexes of N-heterocyclic carbene ligands.

A family of eight rhenium(I) tricarbonyl complexes bearing pyridyl-imidazolylidene or bis-imidazolylidene ligands in combination with a series of N-acetyl amino acids ligands (glycine, isoleucine, and proline) and an acetate have been synthesised and characterised. These complexes are of interest as potential anticancer agents, where the oxygen bound carboxylate ligand can exchange with water giving rise to cytotoxic cationic complexes. The pseudo-first-order aquation rate constants for the complexes were evaluated using 1H NMR time-course experiments and for the complexes of the bis-imidazolylidene ligand the average k1 value was 6.22 × 10-5 s-1 while for the pyridyl-imidazolylidene ligand the aquation rate was slower with the average k1 value being 3.00 × 10-5 s-1. Cytotoxicity studies in three cancer cell lines (MDA-MB-231, PC3 and HEPG2) showed that the Re(I) complexes of the bis-imidazolylidene ligand were significantly more toxic than those of the pyridyl-imidazolylidene ligand.

Charge neutral rhenium tricarbonyl complexes of tridentate N-heterocyclic carbene ligands that bind to amyloid plaques of Alzheimer's disease.

Two tridentate ligand systems bearing N-heterocyclic carbene (NHC), amine and carboxylate donor groups coupled to benzothiazole- or stilbene-based amyloid binding moieties were synthesised. Reaction of the imidazolium salt containing pro-ligands with Re(CO)5Cl yielded the corresponding rhenium metal complexes which were characterised by NMR, and X-ray crystallography. These ligands are of interest for the potential preparation of technetium-99m imaging agents for Alzheimer's disease and the capacity of these rhenium complexes bind to amyloid fibrils composed of amyloid-ß peptide and amyloid plaques in human frontal cortex brain tissue was evaluated using fluorescence microscopy. These studies show that the complexes bound efficiently to amyloid-ß fibrils and some evidence of binding to amyloid-ß plaques.

Synthesis, conformational analysis and antibacterial activity of Au(I)-Ag(I) and Au(I)-Hg(II) heterobimetallic N-heterocyclic carbene complexes.

A post-synthetic modification and metallation procedure has been used to prepare a family of heterobimetallic Au(i)-Ag(i) and Au(i)-Hg(ii) complexes featuring either symmetrical or asymmetrical bis-N-heterocyclic carbene ligands with methylene or ethylene linker groups. This synthetic approach is versatile and allows for the synthesis of heterobimetallic complexes bearing asymmetrical ligands that differ in the nature of the NHC wingtip substituents (dimethyl, diethyl or ethyl-methyl) and for the selective placement of the different metal ions. The synthesised complexes were characterised using 1H and 13C NMR spectroscopy and high resolution mass spectrometry (HR-MS) and in the case of complexes 4a, 5b and 8b by X-ray crystallography. The complexes of the methylene linked bridging ligands display conformational isomerism in solution and the conformations adopted by selected compounds were examined using variable temperature (VT) 1H NMR studies. The antibacterial properties of the heterobimetallic Au(i)-Ag(i) complexes in addition to the corresponding homobimetallic Ag(i)2, Au(i)2 complexes were evaluated against clinically relevant Gram-positive and Gram-negative bacterial strains. The homobimetallic Au(i)2 complex and precursor pro-ligand displayed no antibacterial activity up to 256 µg mL-1, whereas the homobimetallic Ag(i)2 was active against all Gram-positive and Gram-negative bacterial strains tested (MIC = 8-32 µg mL-1). Interestingly, both Au(i)-Ag(i) heterobimetallic complexes displayed similar broad-spectrum activity (MIC = 4-32 µg mL-1) to the Ag(i)2 homobimetallic complex.

Stepwise Synthesis of Tetra-imidazolium Macrocycles and Their N-Heterocyclic Carbene Metal Complexes.

A modular stepwise synthetic method has been developed for the preperation of tetra-imidazolium macrocycles. Initially a series of three bis(imidazolylmethyl)benzene precursors were alkylated with 1,2-dibromoethane to produce the corresponding bis-bromoethylimidazolium bromide salts. In the second step the bis-bromoethylimidazolium bromide salts were reacted with selected bis(imidazolylmethyl)benzene molecules to produce a series of two symmetrical and three asymmetrical tetra-imidazolium macrocycles. These tetra-imidazolium salts act receptors for anions and 1H-NMR titration studies were used to determine the association constants between two of the macrocycles and the halide anions chloride, bromide and iodide. The tetra-imidazolium salts are precursors for N-heterocyclic carbene (NHC) ligands and the corresponding silver(I), gold(I), and palladium(II) NHC complexes have been prepared. Varied structures were obtained, which depend on the chosen macrocyclic ligand and metal ion and in the case of the coinage metals Ag(I) and Au(I), mono, di, and hexanuclear complexes were formed.