Activation of Molecular Oxygen by a Cobalt(II) Tetra-NHC Complex*.

The first dicobalt(III) µ2 -peroxo N-heterocyclic carbene (NHC) complex is reported. It can be quantitatively generated from a cobalt(II) compound bearing a 16-membered macrocyclic tetra-NHC ligand via facile activation of dioxygen from air at ambient conditions. The reaction proceeds via an end-on superoxo intermediate as demonstrated by EPR studies and DFT. The peroxo moiety can be cleaved upon addition of acetic acid, yielding the corresponding CoIII acetate complex going along with H2 O2 formation. In contrast, both CoII and CoIII complexes are also studied as catalysts to utilize air for olefin and alkane oxidation reactions; however, not resulting in product formation. The observations are rationalized by DFT-calculations, suggesting a nucleophilic nature of the dicobalt(III) µ2 -peroxo complex. All isolated compounds are characterized by NMR, ESI-MS, elemental analysis, EPR and SC-XRD.

Fluorescent palladium(II) and platinum(II) NHC/1,2,3-triazole complexes: antiproliferative activity and selectivity against cancer cells.

Fluorescent Pd(ii) and Pt(ii) complexes bearing 4-methylene-7-methoxycoumarin (MMC) and 2,6-diispropylphenyl (Dipp) substituted NHC/1,2,3-triazole hybrid ligands are described. Depending on the reaction conditions two different ligand coordination modes are observed, i.e., bidentate solely coordinating via NHCs or tetradentate coordinating via NHCs and 1,2,3-triazoles. All Dipp substituted complexes show antiproliferative activity against cervix (HeLa) and breast (MCF-7) human carcinoma cells. The activity significantly depends on the coordination mode, with the tetradentate motif being notably more effective (HeLa: IC50 = 3.9 µM to 4.7 µM; MCF-7: IC50 = 2.07 µM to 2.35 µM). Amongst the MMC series, only the Pd(ii) complex featuring the bidentate coordination mode is active against HeLa (IC50 = 6.1 µM). In contrast to its structurally related Dipp derivative (SI = 0.6), it shows a high selectivity for HeLa (SI > 16) compared to healthy skin cells (HaCaT). According to fluorescence microscopy, this compound is presumably located in late endosomes or lysosomes.

Mimicking reactive high-valent diiron-µ2-oxo intermediates of nonheme enzymes by an iron tetracarbene complex.

The first diiron(iii,iv)-µ2-oxo tetracarbene complex is isolated and characterized by SC-XRD, UV/Vis, EPR, Evans' NMR and elemental analysis. CV indicates the presence of a transient high-valent diiron(iv)-µ2-oxo species. Its formation and decay is investigated via UV/Vis kinetics and NMR.

Gold(I) Bis(1,2,3-triazol-5-ylidene) Complexes as Promising Selective Anticancer Compounds.

The synthesis and antiproliferative activity of Mes- and iPr-substituted gold(I) bis(1,2,3-triazol-5-ylidene) complexes in various cancer cell lines are reported, showing nanomolar IC50 values of 50 nM (lymphoma cells) and 500 nM (leukemia cells), respectively (Mes < iPr). The compounds exclusively induce apoptosis (50 nM to 5 µM) instead of necrosis in common malignant blood cells (leukemia cells) and do not affect non-malignant leucocytes. Remarkably, the complexes not only overcome resistances against the well-established cytostatic etoposide, cytarabine, daunorubicin, and cisplatin but also promote a synergistic effect of up to 182% when used with daunorubicin. The present results demonstrate that gold(I) bis(1,2,3-triazol-5-ylidene) complexes are highly promising and easily modifiable anticancer metallodrugs.

Electronic Finetuning of a Bio-inspired Iron(II) tetra-NHC Complex by trans Axial Isocyanide Substitution.

The synthesis of trans axially substituted mono- (1 a) and bis(tert-butylisocyanide) (1 b) derivatives of the highly active homogeneous bio-inspired iron(II) olefin epoxidation (pre-)catalyst 1 bearing an equatorial macrocyclic tetra N-heterocyclic carbene and two trans axial labile acetonitrile ligands is reported. NMR spectroscopy and SC-XRD indicate a considerable π-backdonation from the iron(II) centres to the isocyanide ligand(s). The impact of isocyanide substitution on the electronic features of the complexes is studied by cyclic voltammetry revealing a significant increase in half-cell potential assignable to the reversible Fe(II)/Fe(III) redox couple with an increasing number of isocyanides as a result of their π-accepting properties: E1/2 =0.15 V (1), E1/2 =0.35 V (1 a), E1/2 =0.44 V (1 b).

Improved Antiproliferative Activity and Fluorescence of a Dinuclear Gold(I) Bisimidazolylidene Complex via Anthracene-Modification.

A straightforward modification route to obtain mono- and di-substituted anthroyl ester bridge functionalized dinuclear Au(I) bis-N-heterocyclic carbene complexes is presented. The functionalization can be achieved starting from a hydroxyl-functionalized ligand precursor followed by transmetallation of the corresponding Ag complex or via esterification of the hydroxyl-functionalized gold complex. The compounds are characterized by NMR-spectroscopy, ESI-MS, elemental analysis and SC-XRD. The mono-ester Au complex shows quantum yields around 18%. In contrast, the corresponding syn-di-ester Au complex, exhibits significantly lower quantum yields of around 8%. Due to insufficient water solubility of the di-ester, only the mono-ester complex has been tested regarding its antiproliferative activity against HeLa- (cervix) and MCF-7- (breast) cancer cell lines and a healthy fibroblast cell line (V79). IC50 values of 7.26 µM in the HeLa cell line and 7.92 µM in the MCF-7 cell line along with selectivity indices of 8.8 (HeLa) and 8.0 (MCF-7) are obtained. These selectivity indices are significantly higher than those obtained for the reference drugs cisplatin or auranofin.

Exploring different coordination modes of the first tetradentate NHC/1,2,3-triazole hybrid ligand for group 10 complexes.

Synthesis and characterisation of the first tetradentate N-heterocyclic carbene (NHC)/1,2,3-triazole hybrid ligand obtained by means of copper(i) catalyzed "click" chemistry and its application for the synthesis of group 10 complexes is reported. For palladium(ii), two complexes with different ligand coordination modes were obtained. One compound depicts a NCCN coordination sphere with all 1,2,3-triazole and NHC moieties coordinating to the metal, whereas the other one depicts a CCCC coordination sphere resulting from NHC coordination of two ligands. The non-coordinating 1,2,3-triazoles form strong intramolecular hydrogen bonds as proven by SC-XRD. The resulting rigid conformation is retained in solution even at 70 °C as demonstrated by variable temperature NMR spectroscopy. In contrast to palladium(ii), both nickel(ii) and platinum(ii) exclusively form complexes with a CCCC coordination sphere regardless of reaction conditions. Both compounds share characteristics with their palladium(ii) counterpart, including strong intramolecular hydrogen bonds.

A bench stable formal Cu(iii) N-heterocyclic carbene accessible from simple copper(ii) acetate.

For years, Cu(iii)NHCs have been proposed as active intermediates in Cu(i)NHC catalyzed reactions, yielding the desired products by reductive elimination, but until today, no one has ever reported the characterisation of such a compound. When working on the synthesis of biomimetic transition metal (NHC) complexes and their application in homogeneous catalysis, we recently found a highly unusual reactivity for Cu(ii) acetate in the presence of a particular cyclic tetra(NHC) ligand. Therein, the formation of the first stable CuNHC compound, displaying Cu in the formal oxidation state +III, by simple disproportionation of Cu(ii) acetate in dimethyl sulfoxide (DMSO) was observed. At elevated temperatures selective mono-oxidation of the NHC ligand occurs, even under anaerobic conditions. Acetate was identified as the origin of the oxygen atom by 18O-labelling experiments. The remarkably high stability of the title compound was furthermore proven electrochemically by cyclic voltammetry. An in-depth investigation of its reactivity revealed the involvement of four additional compounds. Three of them could be isolated and characterised by 1H/13C-NMR, single crystal XRD, mass spectrometry and elemental analysis. The fourth, a Cu(i)NHC intermediate, formed by formal reductive elimination from the Cu(NHC)3+ compound, was characterised in situ by 1H/13C-NMR and computational methods.