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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.

Polyoxometalates (POMs) have become very significant in biomedical research for their structural diversity which renders them highly active against bacterial, viral and cancer diseases. In this study three different POMs were synthesized and nanoassemblies were made with chitosan (CTS), a natural biodegradable polymer with excellent drug carrier properties. The compounds were tested on two isoenzymes of alkaline phosphatases including tissue specific calf intestine alkaline phosphatase (CIAP) and tissue non-specific alkaline phosphatase (TNAP). Compound [TeW6O24]6− (TeW6) showed the highest activity (45.4 ± 11.3 nM) among tested compounds against TNAP. Similarly, chitosan-[TeW6O24]6− (CTS-TeW6) was proved to be a potent inhibitor of CIAP with Ki value of 22 ± 7 nM. A comparative study was made to evaluate their cytotoxic potential against HeLa cells. Among all tested compounds, Chitosan-[NaP5W30O110]14− (CTS-P5W30) has showed higher percent cytotoxicity (88 ± 10%) at 10 μM when compared with the standard anticancer drug vincristine (72 ± 7%). The study revealed that selected POMs proved excellent anticancer potential and were equally effective against alkaline phosphatase enzyme, an increased level of which may indicate cancer metastasis.

DOI: 10.1002/anie.201608122 URL: http://onlinelibrary.wiley.com/doi/10.1002/anie.201608122/abstract;jsessionid=EA15762917F9EFDF0130D79440646A99.f04t02 Filiació URV: SI Inclòs a la memòria: SI We introduce the class of discrete silver(I)-palladium(II)-oxo nanoclusters with the preparation of {Ag4Pd13} and {Ag5Pd15}. Both polyanions represent the first examples of noble metal-capped polyoxo-noble-metalates in a fully inorganic assembly, featuring an unprecedented host¿guest mode containing hetero- and homometallic Ag¿Pd and Ag¿Ag bonding interactions. Comprehensive theoretical calculations suggest that the Ag¿Pd metallic bonds originate partially from surface confinement of AgI guest ions onto the anionic polyoxopalladate host that is induced by strong electrostatic forces. This work opens the field of fully inorganic silver-palladium-oxo nanoclusters, which can be considered as discrete mixed noble metal precursors for the formation of monodisperse core¿shell nanoparticles, with high relevance for catalysis.

The development of rational synthetic procedures with desired nuclearity and high selectivity is a critical issue in inorganic chemistry. Here we demonstrate a comprehensive understanding of the template effect induced by metal cations in the formation mechanism of the class of polyoxopalladates ({MPd12L8} nanocube and {MPd15L10} nanostar) by combining computational and experimental techniques. The capture of a Mn+ guest ion by a peripheral palladium(II)-oxo shell leads to a competition between the parent Pd2+ addenda ion and the respective guest metal ion. The present study reveals that (i) the selection of the incorporated guest ion has a thermodynamic control, (ii) the main factors governing the formation of a particular polyanion are the charge and size of the guest cation, (iii) the electrostatic interaction between the cation and the surrounding oxo ligands and (iv) the dehydration ability of the cation. As expected from the number of observed {Mn+Pd12L8} species, trivalent cations M3+ were found to be good templates resulting in several examples of {M3+Pd12L8}, whereas monovalent cations M+ are much less prone to form {M+Pd12L8}. For tetravalent cations the dehydration energies are very large, however, the formation of {M4+Pd12L8} nanocubes is found to be still energetic favourable. Fully consistent with computational predictions, four novel polyoxo-12-palladates were synthesized: the La3+-centered nanocube [LaPd12O8(PhAsO3)8]5− (LaPd12-closed), the La3+-centered “open” nanocube [LaPd12O6(OH)3(PhAsO3)6(OAc)3]3− (LaPd12-open), the Ga3+-centered [GaPd12O8(PhAsO3)8]5− (GaPd12), and the In3+-analogue [InPd12O8(PhAsO3)8]5− (InPd12). All four compounds were fully characterized in the solid state and in solution by a multitude of physicochemical techniques, including 71