The biological applications of metals and metal complexes

Over the course of biological evolution, approximately 25 to 30 elements have been recognized as essential for the proper functioning of biological systems since the emergence of life [...]LA/P/0101/2020info:eu-repo/semantics/publishedVersio

Polyoxidovanadates' interactions with proteins: an overview

Polyoxidovanadates (POVs, previously named polyoxovanadates) are a subgroup of polyoxidometalates (POMs, previously named polyoxometalates) with interesting pharmacological actions that have been tested as potential antidiabetic, antibacterial, antiprotozoal, antiviral, and anticancer drugs. They contain mainly vanadium and are able to interact with proteins, affecting various biological processes. The most studied POV is the isopolyoxidovanadate decavanadate (V-10), which interacts with proteins and/or enzymes such as tyrosine protein phosphatases, P-type ATPases, RNA triphosphatases, myosin and actin. However, in many POVs-protein systems, the binding sites and/or the residues involved in the interaction are not identified. In the present review, the interactions of POVs, as well as linear trivanadate (V-3), both linear and cyclic tetravanadate (V-4) and two proposed heptavanadate (V-7; which are better described by V-10 molecules), with proteins are described through X-ray crystallographic studies. Interactions with POVs through theoretical and spectroscopic studies of proteins related to muscle contraction, serum, oxidative stress, and diabetes were also discussed. In sum, herein, we describe POVs' interactions with various proteins including acid phosphatase A, receptor tyrosine kinase, ectonucleoside triphosphate diphosphohydrolase (NTPDases), transient receptor potential cation channel (TRPM4), phosphoglucomutases, P-type ATPases, myosin, actin, transferrin, albumin, and glucosidases, among others. The putative POVs' effects on proteins are impacted by the POV' stability and speciation. The modes of POVs' interactions include H-bond, electrostatic, H-bond + electrostatic, van der Waals, and covalent binding. The spectroscopic, X-ray and computational results, the sites and modes of binding are described in detail. (C) 2021 The Authors. Published by Elsevier B.Vinfo:eu-repo/semantics/publishedVersio

The preyssler-type polyoxotungstate exhibits anti-quorum sensing, antibiofilm, and antiviral activities

The increase in bacterial resistance to antibiotics has led researchers to find new compounds or find combinations between different compounds with potential antibacterial action and with the ability to prevent the development of antibiotic resistance. Polyoxotungstates (POTs) are inorganic clusters that may fulfill that need, either individually or in combination with antibiotics. Herein, we report the ability of the polyoxotungstates (POTs) with Wells-Dawson P2W18, P2W17, P2W15, and Preyssler P5W30 type structures to differently affect Gram-negative and Gram-positive microorganisms, either susceptible or resistant to antibiotics. The compound P5W30 showed the highest activity against the majority of the tested bacterial strains in comparison with the other tested POTs (P2W15, P2W17 and P2W18) that did not show inhibition zones for the Gram-negative bacteria, A. baumanii I73775, E. coli DSM 1077, E. coli I73194, K. pneumoniae I7092374, and P. aeruginosa C46281). Generally, the results evidenced that Gram-positive bacteria are more susceptible to the POTs tested. The compound P5W30 was the one most active against S. aureus ATCC 6538 and MRSA16, reaching <0.83 mg·mL−1 (100 µM) and 4.96 mg·mL−1 (600 µM), respectively. Moreover, it was verified by NMR spectroscopy that the most promising POT, P5W30, remains intact under all the experimental conditions, after 24 h at 37 ◦C. This prompted us to further evaluate the anti-quorum sensing activity of P5W30 using the biosensor Chromobacterium violaceum CV026, as well as its antibiofilm activity both individually and in combination with the antibiotic cefoxitin against the methicillin-resistant Staphylococcus aureus 16 (MRSA16). P5W30 showed a synergistic antibacterial effect with the antibiotic cefoxitin and chloramphenicol against MRSA16. Moreover, the antibiofilm activity of P5W30 was more pronounced when used individually, in comparison with the combination with the antibioticcefoxitin. Finally, the antiviral activity of P5W30 was tested using the coliphage Qβ, showing a dosedependent response. The maximum inactivation was observed at 750 µM (6.23 mg·mL−1 ). In sum, P5W30 shows anti-quorum sensing and antibiofilm activities besides being a potent antibacterial agent against S. aureus and to exhibit antiviral activities against enteric viruses.info:eu-repo/semantics/publishedVersio

Antibacterial Activity of Polyoxometalates Against Moraxella catarrhalis

The antibacterial activity of 29 different polyoxometalates (POMs) against Moraxella catarrhalis was investigated by determination of the minimum inhibitory concentration (MIC). The Preyssler type polyoxotungstate (POT) [NaP5W30O110]14− demonstrates the highest activity against M. catarrhalis (MIC = 1 μg/ml) among all tested POMs. Moreover, we show that the Dawson type based anions, [P2W18O62]6−, [(P2O7)Mo18O54]4−, [As2Mo18O62]6−, [H3P2W15V3O62]6−, and [AsW18O60]7− are selective on M. catarrhalis (MIC range of 2-8 μg/ml). Among the six tested Keggin type based POTs ([PW12O40]3−, [H2PCoW11O40]5−, [H2CoTiW11O40]6−, [SiW10O36]8−, [SbW9O33]9−, [AsW9O33]9−), only the mono-substituted [H2CoTiW11O40]6− showed MIC value comparable to those of the Dawson type group. Polyoxovanadates (POVs) and Anderson type POMs were inactive against M. catarrhalis within the tested concentration range (1-256 μg/ml). Four Dawson type POMs [P2W18O62]6−, [(P2O7)Mo18O54]4−, [As2Mo18O62]6−, [H3P2W15V3O62]6− and the Preyssler POT [NaP5W30O110]14− showed promising antibacterial activity against M. catarrhalis (MICs &lt; 8 μg/ml) and were therefore tested against three additional bacteria, namely S. aureus, E. faecalis, and E. coli. The most potent antibacterial agent was [NaP5W30O110]14−, exhibiting the lowest MIC values of 16 μg/ml against S. aureus and 8 μg/ml against E. faecalis. The three most active compounds ([NaP5W30O110]14−, [P2W18O62]6−, and [H3P2W15V3O62]6−) show bacteriostatic effects in killing kinetics study against M. catarrhalis. We demonstrate, that POM activity is mainly depending on composition, shape, and size, but in the case of medium-size POTs (charge is more than −12 and number of addenda atoms is not being higher than 22) its activity correlates with the total net charge

Inhibition of SERCA and PMCA Ca2+-ATPase activities by polyoxotungstates

Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phospho-tungstate anions [P2W18O62]6-(intact, {P2W18}), [P2W17O61]10-(monolacunary, {P2W17}), [P2W15O56]12-(trilacunary, {P2W15}), [H2P2W12O48]12-(hexalacunary, {P2W12}), [H3P2W15V3O62]6- (trivanadium-substituted, {P2W15V3}) and by Preyssler-type anion [NaP5W30O110]14-({P5W30}). The speciation in the solu-tions of tested POTs was investigated by 31P and 51V NMR spectroscopy. The tested POTs inhibited SERCA Ca2+- ATPase activity, whereby the Preyssler POT showed the strongest effect, with an IC50 value of 0.37 mu M. For {P2W17} and {P2W15V3} higher IC50 values were determined: 0.72 and 0.95 mu M, respectively. The studied POTs showed to be more potent inhibitors of PMCA Ca2+-ATPase activity, with lower IC50 values for {P2W17}, {P5W30} and {P2W15V3}.info:eu-repo/semantics/publishedVersio

The aquaporin-3-inhibiting potential of polyoxotungstates

Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells-Dawson P2W18, P2W12, and P2W15, and Preyssler P5W30 structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P2W18, P2W12, and P5W30 being the most potent (50% inhibitory concentration (IC50) = 0.8, 2.8, and 3.2 µM), and P2W15 being the weakest (IC50 > 100 µM). The selectivity of P2W18 toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P2W12 and P2W18 on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P2W18 strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.Fundação para a Ciência e a Tecnologia (FCT) (PTDC/BTM-SAL/28977/2017, PTDC/MED-QUI/31721/2017, UID/DTP/04138/2019, UIDB/04326/2020, SFRH/BD/117586/2016. Austrian Science Fund (FWF) P27534, M2203info:eu-repo/semantics/publishedVersio

Oxo-Replaced Polyoxometalates: There Is More than Oxygen

The presence of oxo-ligands is one of the main required characteristics for polyoxometalates (POMs), although some oxygen ions in a metallic environment can be replaced by other nonmetals, while maintaining the POM structure. The replacement of oxo-ligands offers a valuable approach to tune the charge distribution and connected properties like reducibility and hydrolytic stability of POMs for the development of tailored compounds. By assessing the reported catalytic and biological applications and connecting them to POM structures, the present review provides a guideline for synthetic approaches and aims to stimulate further applications where the oxo-replaced compounds are superior to their oxo-analogues. Oxo-replacement in POMs deserves more attention as a valuable tool to form chemically activated precursors for the synthesis of novel structures or to upgrade established structures with extraordinary properties for challenging applications

The Smallest Polyoxotungstate Retained by TRIS-Stabilization

A polycondensation reaction of the orthotungstate anion WO42–, buffered at pH 7.5 in a TRIS-HCl (0.15 M) solution, results in the first example of a discrete polyoxotungstate anion, with just two W ions stabilized with TRIS ligands. It was isolated and characterized as Na2[WVI2O6(C4O3NH10)2]·6H2O by single-crystal and powder X-ray diffraction, FT-IR spectroscopy, thermogravimetrical analysis (TGA), and elemental analysis in solid state and by electro-spray ionization mass spectrometry (ESI-MS), 13C, and 183W NMR, as well as Raman spectroscopy in solution. This synthesis demonstrates the crucial and new role of the added tris-alkoxy ligand in the development of a new hybrid TRIS-isopolytungstate with the lowest known nuclearity (so far) and the terminal oxygens substituted with two nitrogen atoms arising from amines of the TRIS ligands

Polioxovanadates com atividades biomédicas emergentes

Polyoxovanadates (POVs) are a subclass of a larger family of polyanionic group V and VI metal-oxo clus ters that are known as polyoxometalates (POMs). POMs have been found to have antidiabetic, antibacte rial, antiprotozoal, antiviral and anticancer activities, which have sparked interest in their use as bioinorganic drugs. Among POVs, decavanadate ([V10O28] 6 ; V10) is an isopolyoxovanadate recently described to have several medicinal applications. In the present review, recent insights into POVs with emergent anticancer, antimicrobial and antiviral applications are described. Additionally, POVs’ stability and speciation under experimental biological conditions as well as POVs (in particular, V10) in vivo and ex vivo effects are highlighted. Finally, we report the most important 21st century studies of POVs’ effects and/or targets against cancer, bacteria and viruses including: apoptosis, cell cycle arrest, interference with ions transport system, inhibition of mRNA synthesis, cell morphology changes, changes in metabolic pathways, phosphorylase enzyme inhibition and cell signaling, formation of reactive oxygen species, lipid peroxidation, inhibition of viral mRNA polymerase, inhibition of virus binding to the host cell, penetra tion and interaction with virus protein cages.RASSR79857, FJC2019-039135-I, P33927, P33089info:eu-repo/semantics/publishedVersio