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Mono substituted heteropolyoxidovanadates, when compared to effects of a corresponding isopolyoxidovanadate (POV), were found to be more effective initiators of signal transduction by a G protein-coupled receptor (GPCR), specifically the luteinizing hormone receptor (LHR). Here we report that LHRs signal productively when CHO cells expressing the receptor are treated with two heteropolyoxidovanadates PtIV in monoplatino(IV)nonavanadate(V) ([H2PtVIVV9O28]5-, V9Pt), and MoIV in monomolybdo(VI)nonavanadate(V) (Mo[VIVV9O28]5-, V9Mo). Both substituted decavanadate derivatives were more effective than decavanadate which is more charged, has greater stability and forms the [V10O28]6- anion (V10) in cell culture medium at pH 7.4. For viable CHO cells expressing 10 k or 32 k LHR/cell and treated with 11 μM V9Pt and 13 μM V9Mo, mono substituted heteropolyoxidovanadates significantly decreased the packing of plasma membrane lipids for about 1 h. This brief change in membrane structure was accompanied by increased aggregation of LHR and cell signaling as indicated by increased intracellular levels of cAMP. More pronounced changes in lipid packing and LHR signaling were associated with short acting heteropolyoxidovanadates than with the more stable V10. When LHR was overexpressed, V9Pt and V9Mo had little or no effect on membrane lipid packing or receptor aggregation and the LHR was constitutively activated as indicated by elevated intracellular cAMP levels. Speciation of V9Pt and V9Mo in H2O and cell medium was monitored using 51V NMR spectroscopy and confirmed that V9Pt and V9Mo had greater effects on CHO cells despite decomposing more rapidly in the cell growth medium. Thus, under conditions that promote CHO cell growth, V9Pt and V9Mo, despite their smaller molecular charge and their reduced stability, favor LHR signaling over that induced by V10. Importantly, under the same experimental conditions, CHO cells treated with V9Pt and V9Mo do not exhibit as strong toxic effects observed for cells treated with the longer lived V10. In summary, unlike the longer lived V10 which is more growth inhibitory to cells, monosubstituted heteropolyoxidovanadates are more effective in transiently initiating signaling by a G protein-coupled receptor but, because of rapid hydrolysis, inhibit cell growth less.

We have synthesized and structurally characterized the 4-palladium(II)-containing 30-tungsto-4-arsenate(V), [Pd4(As2W15O56)2]16- (1), which represents the first palladium(II)-containing tungstoarsenate(V). The title polyanion 1 was prepared by a simple one-pot procedure in aqueous medium and characterized by single-crystal X-ray diffraction (XRD), thermogravimetric analysis (TGA), cyclic voltammetry, elemental analysis, and 183W nuclear magnetic resonance (NMR), infrared (IR), and ultraviolet-visible (UV-vis) spectroscopies. Polyanion 1 consists of four Pd2+ ions that are coordinated in a square-planar geometry to two trilacunary [As2W15O56]12- Wells-Dawson fragments resulting in a sandwich-type assembly. Catalytic studies on 1 revealed that it is an efficient catalyst precursor for the Suzuki-Miyaura cross-coupling reactions of various aryl halides in aqueous and nonaqueous media.

The 36‐NiII‐containing 54‐tungsto‐6‐silicate, [Ni36(OH)18(H2O)36(SiW9O34)6]6− (Ni36 ) was synthesized by a simple one‐pot reaction of the Ni2‐pivalate complex [Ni2(μ‐OH2)(O2CCMe3)4(HO2CCMe3)4] with the trilacunary [SiW9O34]10− polyanion precursor in water and structurally characterized by a multitude of physicochemical techniques including single‐crystal XRD, FTIR, TGA, elemental analysis, magnetic and electrochemical studies. Polyanion Ni36 comprises six equivalent {NiII 6SiW9} units which are linked by Ni−O−W bridges forming a macrocyclic assembly. Magnetic studies demonstrate that the {Ni6} building blocks in Ni36 remain magnetically intact while forming a hexagonal ring with antiferromagnetic exchange interactions between adjacent {Ni6} units. Electrochemical studies indicate that the first reduction is reversible and associated with the WVI/V couple, whereas the second reduction is irreversible attributed to the NiII/0 couple., The 36‐NiII‐containing 54‐tungsto‐6‐silicate, [Ni36(OH)18(H2O)36(SiW9O34)6]6− (Ni36 ) was discovered and shown to contain more nickel centers than any other polyoxometalate (POMs) known to date. Polyanion Ni36 comprises six equivalent {NiII 6SiW9} units which are linked by Ni−O−W bridges forming a macrocyclic assembly. Magnetic studies indicate antiferromagnetic communication between the six {Ni6} subunits. Electrochemical studies indicate that the first reduction is reversible and associated to the WVI/V couple while the second reduction is irreversible and associated to the NiII/0 couple.

Inhibitory effects of two monosubstituted decavanadates by Pt

We have synthesized and structurally characterized the 4-palladium(II)-containing 30-tungsto-4-arsenate(V), [Pd

The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has called for an urgent need for dedicated antiviral therapeutics. Metal complexes are commonly underrepresented in compound libraries that are used for screening in drug discovery campaigns, however, there is growing evidence for their role in medicinal chemistry. Based on previous results, we have selected more than 100 structurally diverse metal complexes for profiling as inhibitors of two relevant SARS‐CoV‐2 replication mechanisms, namely the interaction of the spike (S) protein with the ACE2 receptor and the papain‐like protease PLpro. In addition to many well‐established types of mononuclear experimental metallodrugs, the pool of compounds tested was extended to approved metal‐based therapeutics such as silver sulfadiazine and thiomersal, as well as polyoxometalates (POMs). Among the mononuclear metal complexes, only a small number of active inhibitors of the S/ACE2 interaction was identified, with titanocene dichloride as the only strong inhibitor. However, among the gold and silver containing complexes many turned out to be very potent inhibitors of PLpro activity. Highly promising activity against both targets was noted for many POMs. Selected complexes were evaluated in antiviral SARS‐CoV‐2 assays confirming activity for gold complexes with N‐heterocyclic carbene (NHC) or dithiocarbamato ligands, a silver NHC complex, titanocene dichloride as well as a POM compound. These studies might provide starting points for the design of metal‐based SARS‐CoV‐2 antiviral agents., Despite their increasing relevance in medicinal chemistry, metal complexes are still underrepresented in compound screening libraries for drug discovery. In this work more than 100 metal complexes were evaluated as inhibitors of two targets in the SARS‐CoV‐2 life cycle, the interaction of the spike protein with the ACE2 receptor and the protease PLpro. The most active inhibitors were studied for antiviral effects in SARS‐CoV‐2 infected cells and led to the discovery of active compounds that will provide starting points for future drug design.