Mechanisms underlying the cytotoxic activity of syn/anti-isomers of dinuclear Au(I) NHC complexes.

The syn- and anti-isomers of dinuclear Au(I) complexes of the type Au2(RLOH)(PF6)2 (R = isopropyl or mesityl) bearing 2-hydroxyethane-1,1-diyl-bridged bisimidazolylidene ligands were separated by reversed phase high performance liquid chromatography (HPLC) and characterized by NMR spectroscopy, elemental analysis, ESI mass spectrometry as well as single crystal X-ray diffraction analysis. Evaluation of the antiproliferative activity of the isolated isomers has shown very small difference in their cytotoxic behavior in various cancer cell lines. Additional counter-anion exchange (hexafluorophosphate to chloride) allows to increase the water solubility of synAu2(MesLOH)(PF6)2 and leads to higher antiproliferative activity when compared to the hexafluorophosphate-complex. Both isomers were treated with l-cysteine as nucleophilic thiol source and only the anti-isomer shows dissociation of one bisimidazolylidene ligand after 24 h. In the case of the syn-isomer, density functional theory calculations indicate a lower reactivity due to the higher steric hindrance of the N-substituents and additional hydrogen bond interaction, which prevents a nucleophilic attack. When the N-substituent is replaced by the bulkier mesityl group, both conformations remain unreactive and result to be the most cytotoxic complexes in the above-mentioned cancer cell lines. Interestingly, synAu2(MesLOH)(PF6)2 exhibits a high selectivity in the MCF-7 cell line with a selectivity index (SI) of 19, which is superior to auranofin (SI < 1), making this compound an ideal candidate for further studies. Preliminary mechanistic studies reveal that the cytotoxic complexes possess mitochondrial-TrxR inhibition properties in the nanomolar range. Additionally, the cellular distribution studies by ICP-MS and nuclear microscopy have shown that the compound accumulates in the membranes. These results suggest that the mitochondrial membrane is the main target for this type of dinuclear complexes, causing oxidative stress by inhibiting mitochondrial thioredoxin reductase.

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.

Dinuclear zwitterionic silver(i) and gold(i) complexes bearing 2,2-acetate-bridged bisimidazolylidene ligands.

Four novel dinuclear Ag(i) and Au(i) NHC complexes bearing two 2,2-acetate-bridged bisimidazolylidene ligands (R = Me and iPr) of zwitterionic and metallacyclic forms are reported. The functionalized methylene bridge of the ligands leads to water soluble complexes, which have been characterized by NMR and IR spectroscopy, elemental analysis and single crystal X-ray diffraction in the case of La-H2-PF6, Ag2(La)2, Ag2(Lb)2 and Au2(La)2. Dimerization processes caused by hydrogen bonding or Ag(i)-carboxylate interactions in the solid state were observed for La-H2-PF6 and Ag2(La)2. DOSY NMR experiments confirmed that both bisimidazolium salts appear as dimers in aqueous solutions, in contrast to the corresponding monomeric Ag(i) and Au(i) complexes. Both gold(i) complexes form syn- and anti-isomers analogous to the reference coinage metal-based complexes. Protonation studies of the syn-isomer gold(i) complex Au2(La)2 were successful, whereas post-modification esterification or amidation reactions were not feasible. Additionally, decarboxylation reactions (thermally induced Krapcho- or oxidative Hunsdiecker-type) of the bisimidazolium salts were observed. Thus, the proximity of the carboxyl moiety to imidazolium/imidazolylidene rings seems to negatively affect stability and reactivity.

Effect of Conducting Salts in Ionic Liquid Electrolytes for Enhanced Cyclability of Sodium-Ion Batteries.

The electrochemical performance of ionic liquid electrolytes containing different sodium salts dissolved in 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMPTFSI) evaluated in a half-cell configuration using spherical P2-Na0.6Co0.1Mn0.9O2+z (NCO) cathodes are reported. Among the various electrolytes investigated, sodium bis(fluorosulfonyl)imide (NaFSI) (0.5 M) in BMPTFSI shows the best electrochemical performance with a significant improvement in cycling stability (90% capacity retention after 500 cycles at 50 mA g-1 in a half cell versus Na metal anode) compared with conventional NaClO4 (1 M) in ethylene carbonate/propylene carbonate electrolytes (39% retention after 500 cycles). Cyclic voltammetry (CV) studies reveal that ionic liquid electrolytes are stable up to 4.8 V versus Na/Na+. When NaFSI and NaTFSI are used as conducting salts, X-ray photoelectron spectroscopy results prove that the cathode electrolyte interface (CEI) is composed of components resulting from the decomposition of the TFSI anion and the deposition of the BMP cation. On the other hand, the CEI layer of the electrode cycled in an electrolyte containing NaClO4 in BMPTFSI follows a different pathway of TFSI decomposition and consists mainly of sodium fluoride. Similarly, plating studies were used to understand the stability of different ionic liquids in contact with metallic sodium. It was found that the excellent capacity retention for the electrolyte consisting of NaFSI salt is related to the formation of a stable CEI and solid electrolyte interphase layers.

Ru(O2CCF3)2(PPh3)2 and ruthenium phosphine complexes bearing fluoroacetate ligands: synthesis, characterization and catalytic activity.

The dinuclear ruthenium(ii) phosphine complexes Ru2Cl(O2CCHxF3-x)3(PPh3)4(µ-H2O) (x = 0, 1, 2), containing fluoroacetate ligands, were prepared from RuCl2(PPh3)3 and NaO2CCHxF3-x in tBuOH. The X-ray characterization of these complexes reveals a bridging water molecule, stabilized by hydrogen bonds with the fluoroacetate ligands. The isolation of the complex Ru(O2CCF3)2(PPh3)2 is described, starting from RuCl2(PPh3)3 or Ru2Cl(O2CCF3)3(PPh3)4(µ-H2O) and TlO2CCF3, correcting the reported preparation in which Ru2Cl(O2CCF3)3(PPh3)4(µ-H2O) was obtained. Ru(O2CCF3)2(PPh3)2 easily reacts with CO, affording Ru(O2CCF3)2(CO)2(PPh3)2. The protonation of Ru(OAc)2(dppb) with trifluoroacetic acid in the presence of bidentate O and N donor ligands affords the complexes Ru(O2CCF3)2(dppb)(LL) (LL = ethyleneglycol, ethylenediamine), which are catalytically active in the transfer hydrogenation of ketones with 2-propanol. In the reduction of cyclohexanone, the glycol derivative displays a higher catalytic activity than the diamine complex, reaching a TOF of 22 000 h-1.

Synthesis and physicochemical characterization of room temperature ionic liquids and their application in sodium ion batteries.

Sodium ion batteries (SIBs) based on IL electrolytes have attracted great attention, particularly in large-scale energy storage systems for renewable energy due to the abundance of sodium and the excellent safety resulting from the use of non-flammable ionic liquid (IL) electrolytes. In this article, a series of 15 functionalized room temperature ionic liquids (RTILs) suitable as electrolytes is presented. Special emphasis was laid on the purity of the synthesized RTILs and a consistent and uniform characterization of their physicochemical properties. Evaluation of the viscosity, conductivity, and thermal and electrochemical stabilities resulted in clear structure-property relationships, rendering the ether functionalized RTILs most promising for application in SIBs. Electrochemical investigations of the ether functionalized IL electrolytes in SIB half cells (Na0.6Mn0.9Co0.1O2 as cathode material) proved their compatibility with a SIB system. Stable cycling performance was achieved with the piperidinium based RTIL IL 6 outperforming the organic electrolyte by far with a retention of 81% after 350 cycles. These results show the suitability of RTILs to enhance the performance of SIB systems and serve as a basis for the design of high performance IL electrolytes.