Therapeutic Properties of Vanadium Complexes

Vanadium is a hard, silver-grey transition metal found in at least 60 minerals and fossil fuel deposits. Its oxide and other vanadium salts are toxic to humans, but the toxic effects depend on the vanadium form, dose, exposure duration, and route of intoxication. Vanadium is used by some life forms as an active center in enzymes, such as the vanadium bromoperoxidase of ocean algae and nitrogenases of bacteria. The structure and biochemistry of vanadate resemble those of phosphate, hence vanadate can be regarded as a phosphate competitor in a variety of biochemical enzymes such as kinases and phosphatases. In this review, we describe the biochemical pathways regulated by vanadium compounds and their potential therapeutic benefits for a range of disorders including type 2 diabetes, cancer, cardiovascular disease, and microbial pathology.

Bio-monitoring of atmospheric heavy metal pollution of major emergency events using moss bags:a case study in Xichang

In order to trace and monitor the atmospheric heavy metal pollution in Xichang City, an investigation activity was carried out with a sort of moss (Taxiphyllum taxirameum) (packed in moss bags) as a biological indicator for monitoring heavy metal pollution. The investigation was conducted from the period from April 2019 to April 2020, during which two grave emergency events occurred during spring monitoring period from January 15 to April 15, 2020, i.e., COVID-19 and "3.30"severe forest fire in Xichang, which inevitably affected the atmospheric quality. Based on the concentration analysis of 12 kinds of heavy metal, including Al, Cr, Fe, Cu, Ni, Pb, Mn, Hg, Zn, V, As and Ba contained in the moss and the local meteorological data, comparing those informative data before and after the time when the emergency events toke place, the paper made an analysis on the impacts of two enormous emergency events on the air pollution of heavy metal in Xichang. The results showed that total amount of enrichment of above-mentioned 12 heavy metals in spring (January 15 to April 15, 2020) is (12.85 +or- 1.57) mg/g, which was significantly higher than in the other three seasons (p < 0.01), but no significant discrepancies about the total enrichment amount in the other three seasons (p > 0.05). Primarily because of COVID-19 pandemic, the level of motor vehicles emissions cut down, and the decrease of the tourism in the related areas perhaps causing the decline of pollution of Pb. In addition, the decrease of unbalanced emission of pollutants led to a noted increase of atmospheric oxidation in urban area, thus boosting the formation of secondary particulate matter, and the particulate matter from surrounding industrial sources was transported into the urban area;as a result, remarkable increases of Hg concentration of moss within the moss bags were detected downwind the industrial area located in the urban fringe. Consequently, the investigation showed that the moss-bag method is an effective biological tool for monitoring air heavy metal pollution, which could reflect the impacts of major pollution events on air quality.

Controlling effect of TiO2 carrier on formed vanadium species for effective catalytic oxidization of chlorobenzene

Catalytic oxidization of the dioxins is critical to the atmosphere since medical-waste incineration is globally increased due to COVID-19. Vanadium supported TiO2 is the most-widely investigated catalyst. However, previous reports usually investigated V-Ti relationships after vanadate was loaded on TiO2 and an activation was completed. In comparison, this work emphasizes on the influence of TiO2 surface chemistries on properties of formed vanadium species during a thermal activation. The vanadate loaded TiO2 are detailedly analyzed by both experimental characterizations and theoretical calculations. As a result, TiO2 with more Ti4+ is inclined to be reductive, and promotes the formation of more low-valence vanadium and surface vacancies. On the contrary, TiO2 with more Ti3+ is inclined to be oxidative, and promotes the formation of more lattice oxygens and high-valence vanadium. When they were compared in catalytic oxidization of chlorobenzene, the Ti4+-induced catalyst attains a conversion of 98.0 % at 250 °C, far bigger than that (11.3 %) of the Ti3+-induced catalyst. The main result of this work helps readers to understand the process of the catalyst preparation, which is in favor of producing a more effective catalyst by regulating the catalyst carrier.

The dual therapeutic effect of metformin nuclei-based drugs modified with one of Tulbaghia violacea extract compounds

Novel Schiff base was synthesized from the condensation reaction of metformin with [4-(Diethylamino) benzaldehyde (NBM). Different metal complexes were prepared using Pd (II), Pt (II), Cu (II), and V (IV) metal ions. All complexes showed the nonelectrolytic behavior. So, the expected molecular formulas for complexes were [Pd (NBM)Cl2], [Pt (NBM)Cl2], [Cu (NBM)2Cl2] and [VO (NBM)2]. The cytotoxicity of (NBM) Schiff base and its metal complexes on human cancer cell line, MCF-7, was investigated. V (IV) and Cu (II) complexes showed potential blood glucose lowering effect higher than the commercial metformin drug. VO (II) complex has superior antioxidant activity more than the other synthesized compounds and the standard ascorbic acid. Molecular docking investigation proved the presence of interesting interactions between all synthesized compounds with the active site amino acids of EGFR tyrosine kinase (anticancer activity). The molecular docking of metal complexes has observed effective inhibition for the specific mTOR protein that is expected to aid the growth of the COVID-19 virus. © 2022 John Wiley & Sons, Ltd.

Decavanadate interactions with the elements of the SARS-CoV-2 spike protein highlight the potential role of electrostatics in disrupting the infectivity cycle.

Polyoxidometalates (POMs) exhibit a range of biological properties that can be exploited for a variety of therapeutic applications. However, their potential utility as antivirals has been largely overlooked in the ongoing efforts to identify safe, effective and robust therapeutic agents to combat COVID-19. We focus on decavanadate (V10), a paradigmatic member of the POM family, to highlight the utility of electrostatic forces as a means of disrupting molecular processes underlying the SARS-CoV-2 entry into the host cell. While the departure from the traditional lock-and-key approach to the rational drug design relies on less-specific and longer-range interactions, it may enhance the robustness of therapeutic agents by making them less sensitive to the viral mutations. Native mass spectrometry (MS) not only demonstrates the ability of V10 to associate with the receptor-binding domain of the SARS-CoV-2 spike protein, but also provides evidence that this association disrupts the protein binding to its host cell-surface receptor. Furthermore, V10 is also shown to be capable of binding to the polybasic furin cleavage site within the spike protein, which is likely to decrease the effectiveness of the proteolytic processing of the latter (a pre-requisite for the viral fusion with the host cell membrane). Although in vitro studies carried out with SARS-CoV-2 infected cells identify V10 cytotoxicity as a major factor limiting its utility as an antiviral agent, the collected data provide a compelling stimulus for continuing the search for effective, robust and safe therapeutics targeting the novel coronavirus among members of the POM family.

Tris(2-Pyridylmethylamine)V(O)2 Complexes as Counter Ions of Diprotonated Decavanadate Anion: Potential Antineoplastic Activity.

The synthesis and theoretical-experimental characterization of a novel diprotanated decavanadate is presented here due to our search for novel anticancer metallodrugs. Tris(2-pyridylmethyl)amine (TPMA), which is also known to have anticancer activity in osteosarcoma cell lines, was introduced as a possible cationic species that could act as a counterpart for the decavanadate anion. However, the isolated compound contains the previously reported vanadium (V) dioxido-tpma moieties, and the decavanadate anion appears to be diprotonated. The structural characterization of the compound was performed by infrared spectroscopy and single-crystal X-ray diffraction. In addition, DFT calculations were used to analyze the reactive sites involved in the donor-acceptor interactions from the molecular electrostatic potential maps. The level of theory mPW1PW91/6-31G(d)-LANL2DZ and ECP = LANL2DZ for the V atom was used. These insights about the compounds' main interactions were supported by analyzing the noncovalent interactions utilizing the AIM and Hirshfeld surfaces approach. Molecular docking studies with small RNA fragments were used to assess the hypothesis that decavanadate's anticancer activity could be attributed to its interaction with lncRNA molecules. Thus, a combination of three potentially beneficial components could be evaluated in various cancer cell lines.

Vanadium as potential therapeutic agent for COVID-19: A focus on its antiviral, antiinflamatory, and antihyperglycemic effects.

An increasing evidence suggests that vanadium compounds are novel potential drugs in the treatment of diabetes, atherosclerosis, and cancer. Vanadium has also demonstrated activities against RNA viruses and is a promising candidate for treating acute respiratory diseases. The antidiabetic, antihypertensive, lipid-lowering, cardioprotective, antineoplastic, antiviral, and other potential effects of vanadium are summarized here. Given the beneficial antihyperglycemic and antiinflammatory effects as well as the potential mechanistic link between the COVID-19 and diabetes, vanadium compounds could be considered as a complement to the prescribed treatment of COVID-19. Thus, further clinical trials are warranted to confirm these favorable effects of vanadium treatment in COVID-19 patients, which appear not to be studied yet.

Are vanadium complexes druggable against the main protease Mpro of SARS-CoV-2? - A computational approach.

In silico techniques helped explore the binding capacities of the SARS-CoV-2 main protease (Mpro) for a series of metalloorganic compounds. Along with small size vanadium complexes a vanadium-containing derivative of the peptide-like inhibitor N3 (N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-N1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl] methyl }but-2-enyl)-l-leucinamide) was designed from the crystal structure with PDB entry code 6LU7. On theoretical grounds our consensus docking studies evaluated the binding affinities at the hitherto known binding site of Chymotrypsin-like protease (3CLpro) of SARS-CoV-2 for existing and designed vanadium complexes. This main virus protease (Mpro) has a Cys-His dyad at the catalytic site that is characteristic of metal-dependent or metal-inhibited hydrolases. Mpro was compared to the human protein-tyrosine phosphatase 1B (hPTP1B) with a comparable catalytic dyad. HPTP1B is a key regulator at an early stage in the signalling cascade of the insulin hormone for glucose uptake into cells. The vanadium-ligand binding site of hPTP1B is located in a larger groove on the surface of Mpro. Vanadium constitutes a well-known phosphate analogue. Hence, its study offers possibilities to design promising vanadium-containing binders to SARS-CoV-2. Given the favourable physicochemical properties of vanadium nuclei, such organic vanadium complexes could become drugs not only for pharmacotherapy but also diagnostic tools for early infection detection in patients. This work presents the in silico design of a potential lead vanadium compound. It was tested along with 20 other vanadium-containing complexes from the literature in a virtual screening test by docking to inhibit Mpro of SARS-CoV-2.

Screening possible drug molecules for Covid-19. The example of vanadium (III/IV/V) complex molecules with computational chemistry and molecular docking.

We are still facing a Covid-19 pandemic these days and after the aggressively infection control measures taken by the governments in the whole world, there is a need of a rapid pharmaceutical solution in order to control this crisis. The computer aided chemistry and molecular docking is a rapid tool for drug screening and investigation. Moreover, more metal-based drugs are tested daily by research institutes for their antiviral activity. Here, we make use of theoretical studies on previously published biological active complex molecules of vanadium as an example of evaluating possible drug candidates before entering the laboratory. We used DFT calculation studies for structural elucidation and optimization of the molecules and molecular docking studies on several Covid-19 related proteins. Our findings suggest that drug discovery should always be computer -aided. Additionally, it is found that Vtocdea and VXn molecules are seem to be good candidates for further studies as antiviral agents.