👤 Peter A. Lay

Rhenium(I) tricarbonyl complexes are widely studied for their cell imaging properties and anti-cancer and anti-microbial activities, but the complexes with S-donor ligands remain relatively unexplored. A series of six fac-[Re(NN)(CO)3(SR)] complexes, where (NN) is 2,2′-bipyridyl (bipy) or 1,10-phenanthroline (phen), and RSH is a series of thiocarboxylic acid methyl esters, have been synthesized and characterized. Cellular uptake and anti-proliferative activities of these complexes in human breast cancer cell lines (MDA-MB-231 and MCF-7) were generally lower than those of the previously described fac-[Re(NN)(CO)3(OH2)]+ complexes; however, one of the complexes, fac-[Re(CO)3(phen)(SC(Ph)CH2C(O)OMe)] (3b), was active (IC50 ∼ 10 μM at 72 h treatment) in thiol-depleted MDA-MB-231 cells. Moreover, unlike fac-[Re(CO)3(phen)(OH2)]+, this complex did not lose activity in the presence of extracellular glutathione. Taken together these properties show promise for further development of 3b and its analogues as potential anti-cancer drugs for co-treatment with thiol-depleting agents. Conversely, the stable and non-toxic complex, fac-[Re(bipy)(CO)3(SC(Me)C(O)OMe)] (1a), predominantly localized in the lysosomes of MDA-MB-231 cells, as shown by live cell confocal microscopy (λex = 405 nm, λem = 470–570 nm). It is strongly localized in a subset of lysosomes (25 μM Re, 4 h treatment), as shown by co-localization with a Lysotracker dye. Longer treatment times with 1a (25 μM Re for 48 h) resulted in partial migration of the probe into the mitochondria, as shown by co-localization with a Mitotracker dye. These properties make complex 1a an attractive target for further development as an organelle probe for multimodal imaging, including phosphorescence, carbonyl tag for vibrational spectroscopy, and Re tag for X-ray fluorescence microscopy. Show less

Twelve Re(I) tricarbonyl diimine (2,2′-bipyridine and 1,10-phenanthroline) complexes with thiotetrazolato ligands have been synthesised and fully characterised. Structural characterisation revealed the capacity of the tetrazolato ligand to bind to the Re(I) centre through either the S atom or the N atom with crystallography revealing most complexes being bound to the N atom. However, an example where the Re(I) centre is linked via the S atom has been identified. In solution, the complexes exist as an equilibrating mixture of linkage isomers, as suggested by comparison of their NMR spectra at room temperature and 373 K, as well as 2D exchange spectroscopy. The complexes are photoluminescent in fluid solution at room temperature, with emission either at 625 or 640 nm from the metal-to-ligand charge transfer excited states of triplet multiplicity, which seems to be exclusively dependent on the nature of the diimine ligand. The oxygen-sensitive excited state lifetime decay ranges between 12.5 and 27.5 ns for the complexes bound to 2,2′-bipyrdine, or between 130.6 and 155.2 ns for those bound to 1.10-phenanthroline. Quantum yields were measured within 0.4 and 1.5%. The complexes were incubated with human lung (A549), brain (T98g), and breast (MDA-MB-231) cancer cells, as well as with normal human skin fibroblasts (HFF-1), revealing low to moderate cytotoxicity, which for some compounds exceeded that of a standard anti-cancer drug, cisplatin. Low cytotoxicity combined with significant cellular uptake and photoluminescence properties provides potential for their use as cellular imaging agents. Furthermore, the complexes were assessed in disc diffusion and broth microdilution assays against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa) bacterial strains, which revealed negligible antibacterial activity in the dark or after irradiation. Show less