Vanadium Complexes Research Articles

Vanadium complexes: potential candidates for therapeutic applications

Vanadium complexes: potential candidates for therapeutic applications

Synthesis, Characterization, and Single-Crystal X-ray Structures of Refractory Metal Compounds as Precursors for the Single-Source Chemical Vapor Deposition of Metal Nitrides.

The chemical vapor deposition of refractory metal nitrides requires volatile precursors and has previously been achieved by using metal complexes containing a variety of imide ligands. Recently, the 1,4-di-tert-butyl-1,3-diazabutadiene (DAD) adduct of bis(tert-butylimide)dichloridemolybdenum(VI) was shown to be an excellent precursor for the single-source CVD of Mo2N thin films. Leveraging the success of this work, we prepared chromium and tungsten compounds with the same framework. Additionally, the framework has been modified slightly to allow the isolation of mono(tert-butylimide)trichloride complexes of vanadium, niobium, tantalum, and molybdenum(V) to extend the search for new vapor-phase precursors. These compounds were all fully characterized using the standard methods of multinuclear magnetic resonance spectroscopy, combustion analysis, and single-crystal X-ray diffraction. Their thermal properties were determined by using thermogravimetric analysis and differential scanning colorimetry to assess their utility as vapor-phase precursors. Finally, preliminary deposition studies were carried out to investigate their potential as single-source CVD precursors.

Synthesis, characterization and ethylene (Co)polymerization of binuclear Vanadium(IV) catalysts based on xanthene-bridged bis-salicylaldiminato ligands

Bimetallic complexes have attracted much attention due to their excellent catalytic performances in many fields. Herein six xanthene-bridged bis-salicylaldiminato [ON] bidentate binuclear vanadium(IV) complexes V2L1-V2L6 were synthesized and characterized by MALDI-TOF-MS, FTIR spectroscopy and elemental analysis, and the crystal structures of V2L1 and V2L2 were further characterized by XRD, in which each vanadium atom was found coordinated with three O, one Cl and one N atoms to form a twisted trigonal bipyramidal configuration. Under Et2AlCl and ethyl trichloroacetate (ETA) activation, all the binuclear vanadium(IV) complexes exhibited high activity over 106 g/mol(V)·h·atm towards ethylene polymerization and copolymerization with 1-hexene. The activity of binuclear V2L4 for ethylene polymerization was much higher than that of its mononuclear counterpart VL, indicating that strong bimetallic synergetic effect existed in these binuclear vanadium complexes. The substituents on the ligands have a great influence on the catalytic performances of the vanadium complexes. The introduction of bulky isopropyl group into the ligand had little effect on the activity, but the introduction of electron-withdrawing fluorine atoms could significantly increase the activity, suggesting that the electronic, rather than the steric factors had a greater impact. As the amount of fluorine substituent on the iminophenyl moiety of the complex increased, the catalytic activity increased appreciably. With five fluorine atoms on the benzene ring of the imine moiety, the complex V2L6 showed the highest activity of 1.10 × 107 g/mol(V)·h·atm for ethylene polymerization to produce the highest molecular weight of polyethylene. Furthermore, the introduction of fluorine atoms into ligands could also increase the catalytic activity of vanadium complexes, comonomer incorporation and molecular weight of obtained copolymer towards ethylene/1-hexene copolymerization. The highest copolymerization activity of V2L6 was 4.13 × 106 g/molV·h·atm, which was more than three time that of the fluorine-free complex V2L1. The insertion rate of 1-hexene for the fluorine-containing complex V2L3-V2L6 was also higher than that for V2L1.

MD Simulations to Calculate NMR Relaxation Parameters of Vanadium(IV) Complexes: A Promising Diagnostic Tool for Cancer and Alzheimer's Disease.

Early phase diagnosis of human diseases has still been a challenge in the medicinal field, and one of the efficient non-invasive techniques that is vastly used for this purpose is magnetic resonance imaging (MRI). MRI is able to detect a wide range of diseases and conditions, including nervous system disorders and cancer, and uses the principles of NMR relaxation to generate detailed internal images of the body. For such investigation, different metal complexes have been studied as potential MRI contrast agents. With this in mind, this work aims to investigate two systems containing the vanadium complexes [VO(metf)2]·H2O (VC1) and [VO(bpy)2Cl]+ (VC2), being metformin and bipyridine ligands of the respective complexes, with the biological targets AMPK and ULK1. These biomolecules are involved in the progression of Alzheimer's disease and triple-negative breast cancer, respectively, and may act as promising spectroscopic probes for detection of these diseases. To initially evaluate the behavior of the studied ligands within the aforementioned protein active sites and aqueous environment, four classical molecular dynamics (MD) simulations including VC1 + H2O (1), VC2 + H2O (2), VC1 + AMPK + H2O (3), and VC2 + ULK1 + H2O (4) were performed. From this, it was obtained that for both systems containing VCs and water only, the theoretical calculations implied a higher efficiency when compared with DOTAREM, a famous commercially available contrast agent for MRI. This result is maintained when evaluating the system containing VC1 + AMPK + H2O. Nevertheless, for the system VC2 + ULK1 + H2O, there was observed a decrease in the vanadium complex efficiency due to the presence of a relevant steric hindrance. Despite that, due to the nature of the interaction between VC2 and ULK1, and the nature of its ligands, the study gives an insight that some modifications on VC2 structure might improve its efficiency as an MRI probe.

Stability constants of vanadium(III) complexes with 1,10-phenanthroline and the amino acids phenylalanine, methionine, serine and threonine

In this work we report a study of ternary complexes of V(III) with 1,10-phenanthroline (Phen) and the amino acids phenylalanine (Phe, HL), methionine (Met, HL), serine (Ser, HL) and threonine (Thr, HL) in aqueous solution with an ionic medium of 3.0 mol/L KCl at 25 °C. The systems were studied by electromotive force (emf(H)) measurements. Analysis of the potentiometric data with the least-squares program LETAGROP indicates formation of complexes of the type VHL, V(Phen)(L)(OH)2, [V2O(Phen)(L)]3+ and [V2O(Phen)2(L)2]2+ in all the systems studied. The species distribution diagrams are briefly discussed. Also, the dimer [V2O(Phen)(L)]3+ was characterized by UV-Vis spectroscopy.

Vanadium (IV) Complex Synthesized Using Natural Product Lawsone as Efficient Catalyst for Oxidation of Activated sp3 C−H Bond

AbstractThe vanadium (IV) complex has been synthesized from naturally occurring lawsone and characterized by FT‐IR, UV‐Visible, ESI‐MS, powder XRD, and EPR spectroscopy. DFT calculation was performed for the optimization of complex geometry. The selective oxidation of diphenylmethane to benzophenone with tert‐butylhydrogenperoxide (TBHP) as an oxidant, was evaluated using the vanadium (IV) complex. The effect of several reaction parameters, such as temperature, catalyst quantity, and solvent type, was investigated. Under the optimal reaction conditions, diphenylmethane was transformed to benzophenone with a 96 % conversion with complete selectivity confirmed by GC‐MS. Further, the scope of the catalyst could be extended for the oxidation of other substrate having benzylic sp3 C−H bond.

Synthesis, Spectroscopic Characterization, Catalytic and Biological Activity of Oxidovanadium(V) Complexes with Chiral Tetradentate Schiff Bases

New oxidovanadium(V) complexes, VOL1–VOL10, with chiral tetradentate Schiff bases obtained by monocondensation reaction of salicylaldehyde derivatives with 1S,2S-(+)-2-amino-1-(4-nitrophenyl)-1,3-propanediol. All complexes have been characterized using different spectroscopic methods, viz. IR, UV-Vis, circular dichroism, one- (1H, 51V) and two-dimensional (COSY, NOESY) NMR spectroscopy, and elemental analysis. Furthermore, the catalytic ability of all compounds in the epoxidation of styrene, cyclohexene, and its naturally occurring monoterpene derivatives, i.e., S(−)-limonene and (−)-α-pinene has also been studied, using two different oxidants, i.e., aqueous 30% H2O2 or tert-butyl hydroperoxide (TBHP). In addition, the biological properties of these chiral oxidovanadium(V) compounds, but also cis-dioxidomolybdenum(VI) complexes with the same chiral Schiff bases, were studied. Their cytotoxic and cytoprotective activity studies with the HT-22 hippocampal neuronal cells revealed a concentration-dependent effect in the range of 10–100 μM. Moreover, vanadium(V) complexes, in contrast to cis-dioxidomolybdenum(VI) compounds, demonstrated higher cytotoxicity and lack of cytoprotective ability against H2O2-induced cytotoxicity.

Computational study of the interaction of DNA bases with vanadium(IV) and (V) complexes derived from the anticancer VCp2Cl2

We present a computational study on derivatives of the anticancer VCp2Cl2 and their interaction with bases of DNA. The derivatives were obtained by substituting the cyclopentadiene of VCp2Cl2 by ligands H2O, NH3, C2O42−, OH−, Cl− and O2−. Oxidation states IV and V of vanadium were considered, a total of 20 complexes are included. This study addresses the role of ligands in the interaction of vanadium complexes with nucleophilic sites of guanine, adenine, cytosine and thymine. The methodology M06-2X/cc-pVTZ was employed, and the effects of the solvent were considered. Results suggest that there is a high affinity for guanine and cytosine, particularly when H2O and NH3 ligands are considered. These findings are confirmed by the bond lengths, bond orders and charge analysis. Our results provide a clue about the ligands that favor the interaction of vanadium with DNA bases and may help the future design of vanadium-based anticancer drugs.

Substitution Kinetics, Albumin and Transferrin Affinities, and Hypoxia All Affect the Biological Activities of Anticancer Vanadium(V) Complexes.

Limited stability of most transition-metal complexes in biological media has hampered their medicinal applications but also created a potential for novel cancer treatments, such as intratumoral injections of cytotoxic but short-lived anticancer drugs. Two related V(V) complexes, [VO(Hshed)(dtb)] (1) and [VO(Hshed)(cat)] (2), where H2shed = N-(salicylideneaminato)-N'-(2-hydroxyethyl)-1,2-ethanediamine, H2dtb = 3,5-di-tert-butylcatechol, and H2cat = 1,2-catechol, decomposed within minutes in cell culture medium at 310 K (t1/2 = 43 and 9 s for 1 and 2, respectively). Despite this, both complexes showed high antiproliferative activities in triple-negative human breast cancer (MDA-MB-231) cells, but the mechanisms of their activities were radically different. Complex 1 formed noncovalent adducts with human serum albumin, rapidly entered cells via passive diffusion, and was nearly as active in a short-term treatment (IC50 = 1.9 ± 0.2 μM at 30 min) compared with a long-term treatment (IC50 = 1.3 ± 0.2 μM at 72 h). The activity of 1 decreased about 20-fold after its decomposition in cell culture medium for 30 min at 310 K. Complex 2 showed similar activities (IC50 ≈ 12 μM at 72 h) in both fresh and decomposed solutions and was inactive in a short-term treatment. The activity of 2 was mainly due to the reactions among V(V) decomposition products, free catechol, and O2 in cell culture medium. As a result, the activity of 1 was less sensitive than that of 2 to the effects of hypoxic conditions that are characteristic of solid tumors and to the presence of apo-transferrin that acts as a scavenger of V(V/IV) decomposition products in blood serum. In summary, complex 1, but not 2, is a suitable candidate for further development as an anticancer drug delivered via intratumoral injections. These results demonstrate the importance of fine-tuning the ligand properties for the optimization of biological activities of metal complexes.

A comprehensive review of anti-diabetic activity of vanadium-based complexes via PTP-1B inhibition mechanism

Inorganic salts of the vanadium have been found to mimic insulin in treating diabetic mellitus. In comparison to inorganic vanadium salts, complexes of vanadium with appropriate organic ligands can improve tissue absorption, efficacy, and reduce toxicity of the metal. An organic vanadyl derivative [bis(ethylmaltolato)oxovanadium(IV)] has been reported as a potential diabetes medication and is currently undergoing phase II clinical trials. The mechanism suggests that vanadium complexes inhibit the enzyme protein tyrosine phosphatase-1B(PTP-1B). Pharmacological, Biochemical and genetic evidences strongly suggest that inhibiting the PTP-1B enzyme could treat both diabetes and obesity, making PTP-1B an interesting target for drug development. Studies have also showed that the over expression of PTP-1B is involved in diabetic and obese patients and its inhibition may be an effective strategy in their treatment. Despite the fact that many natural PTP-1B inhibitors demonstrated promising clinical potential, there is no clinically used PTP-1B inhibitor, most likely due to low activity or a lack of selectivity. Search for more potent and selective PTP-1B inhibitors is still going on. As a result, inhibiting protein tyrosine 1B could be a new therapeutic option for patients at risk of type II diabetes mellitus and obesity. Many vanadium compounds are available as of now, as experimental probes for examining the mechanism of altered insulin action. However more studies are needed to establish its clinical use. Hence it has been proposed to prepare and characterize novel vanadium metal complexes with different coordination environments around vanadyl ion and check their anti diabetes activity.

Role of organic solvent and influence of oxidant in the oxidation of linalool catalyzed by molybdenum and vanadium complexes

The coordination complexes [MoO2(SAP)]2 [Mo] and [VO(SAP)]2O [V] (SAP = salicylideneamino-phenolato) were tested as pre-catalysts for oxidation of a biomass-issued substrate, linalool (L). The reaction was studied using different oxidants, TBHP (in water or in decane) or H2O2 (in water with/without acetonitrile). Efficient linalool (L) conversions were obtained with selectivity towards two selected products, 2-(5-methyl-5- vinyltetrahydro-furan-2-yl propan-2-ol) (1) and 2,2,6- trimethyl-6-vinyltetrahydro-2H-pyran-3-ol (2) depending on pre-catalysts and oxidant. Green metrics have been calculated and showed the role of organic solvent for the process.

Extractive Spectrophotometric Determination and Theoretical Investigations of Two New Vanadium(V) Complexes.

Two new vanadium (V) complexes involving 6-hexyl-4-(2-thiazolylazo)resorcinol (HTAR) and tetrazolium cation were studied. The following commercially available tetrazolium salts were used as the cation source: tetrazolium red (2,3,5-triphenyltetrazol-2-ium;chloride, TTC) and neotetrazolium chloride (2-[4-[4-(3,5-diphenyltetrazol-2-ium-2-yl)phenyl]phenyl]-3,5-diphenyltetrazol-2-ium;dichloride, NTC). The cations (abbreviated as TT+ and NTC+) impart high hydrophobicity to the ternary complexes, allowing vanadium to be easily extracted and preconcentrated in one step. The complexes have different stoichiometry. The V(V)-HTAR-TTC complex dimerizes in the organic phase (chloroform) and can be represented by the formula [(TT+)[VO2(HTAR)]]2. The other complex is monomeric (NTC+)[VO2(HTAR)]. The cation has a +1 charge because one of the two chloride ions remains undissociated: NTC+ = (NT2+Cl-)+. The ground-state equilibrium geometries of the constituent cations and final complexes were optimized at the B3LYP and HF levels of theory. The dimer [(TT+)[VO2(HTAR)]]2 is more suitable for practical applications due to its better extraction characteristics and wider pH interval of formation and extraction. It was used for cheap and reliable extraction-spectrophotometric determination of V(V) traces in real samples. The absorption maximum, molar absorptivity coefficient, limit of detection, and linear working range were 549 nm, 5.2 × 104 L mol-1 cm-1, 4.6 ng mL-1, and 0.015-2.0 μg mL-1, respectively.

Interaction of Vanadium Complexes with Proteins: Revisiting the Reported Structures in the Protein Data Bank (PDB) since 2015.

The structural determination and characterization of molecules, namely proteins and enzymes, is crucial to gaining a better understanding of their role in different chemical and biological processes. The continuous technical developments in the experimental and computational resources of X-ray diffraction (XRD) and, more recently, cryogenic Electron Microscopy (cryo-EM) led to an enormous growth in the number of structures deposited in the Protein Data Bank (PDB). Bioinorganic chemistry arose as a relevant discipline in biology and therapeutics, with a massive number of studies reporting the effects of metal complexes on biological systems, with vanadium complexes being one of the relevant systems addressed. In this review, we focus on the interactions of vanadium compounds (VCs) with proteins. Several types of binding are established between VCs and proteins/enzymes. Considering that the V-species that bind may differ from those initially added, the mentioned structural techniques are pivotal to clarifying the nature and variety of interactions of VCs with proteins and to proposing the mechanisms involved either in enzymatic inhibition or catalysis. As such, we provide an account of the available structural information of VCs bound to proteins obtained by both XRD and/or cryo-EM, mainly exploring the more recent structures, particularly those containing organic-based vanadium complexes.

Vanadium(IV)‐oxo Corrole Catalyzed Selective Oxidative Cleavage of Alkenes to Aldehydes

AbstractA practical and efficient protocol for oxidative cleavage of olefinic bonds especially in arylated olefins has been demonstrated. Herein, an oxo[5,10,15‐tris(4‐nitrophenyl)corrolato]vanadium (IV) complex (cat.), has been successfully synthesized and the existence of two tautomeric forms of this complex in solution has been established. Oxo[5,10,15‐tris(4‐nitrophenyl)corrolato]vanadium (IV) (cat.) in the presence of H2O2 cleaves olefinic bonds to yield the corresponding aldehyde compounds. In general, a high valent, oxo‐(porphyrinoid)‐metal complex catalyzes the epoxide formation reactions, however, in the present case, we have observed the exclusive formation of aldehydes. The reaction offered aryl aldehydes with good yields and excellent selectivity. A mechanism was also proposed for these catalysis reactions.

Moderate DNA and high SARS-CoV-2 spike protein affinity of oxidovanadium(IV) complexes of 2-furoic acid hydrazones: In silico and in vitro approach

The interaction of five neutral heteroleptic octahedral paramagnetic mononuclear oxidovanadium(IV) complexes of general composition [VIVO(bpy)L], where L is a dianionic tridentate ONO-donor hydrazone ligand derived from 2-furoic acid hydrazide and salicylaldehyde and its 5-substituted derivatives with spike protein SARS-CoV-2 was investigated in silico and in vitro. Molecular docking indicates that the complexes have high affinity for SARS-CoV-2 spike protein binding, and that the complex with a nitro substituent on the salicylaldehyde component of the hydrazone ligand has the highest binding potential. The interaction of this complex was examined by spectrofluorimetry utilizing spectrofluorimetric titration, thermodynamic measurements and FRET analysis. The results suggest van der Walls forces and hydrogen bonding as the dominant modes of interaction of the complex with the SARS-CoV-2 spike protein, which is in agreement with theoretical predictions. Molecular docking was further employed to investigate the interaction of vanadium complexes with SARS-CoV-2 omicron variant (BA.1) RBD with human ACE2 protein. The interaction of the complex with CT DNA was investigated using electron spectroscopy and thermodynamic considerations. The complexes showed a moderate affinity for DNA as groove binders. The groove binding was confirmed by molecular docking with B-DNA. Also, druglikness properties of complexes were assessed by SwissADME. The strong antioxidant activity of the complexes, comparable to ascorbic acid, was evaluated by the DPPH method. This is the first experimental research that supports the thesis of molecular docking that vanadium compounds could be druggable against SARS-CoV-2 virus proteins.

Vanadium complex as a potential modulator of the autophagic mechanism through proteins PI3K and ULK1: development, validation and biological implications of a specific force field for [VO(bpy)2Cl]

The modulation of autophagy has been presented as a very useful strategy in anticancer treatments. In this sense, the vanadium complex (VC) bis(2,2'-bipyridine)chlorooxovanadium(IV), [VO(bpy)2Cl], is known for its ability to induce autophagy in triple-negative breast cancer cells (TNBC). An excellent resource to investigate the role of VC in the induction of autophagy is to make use of Molecular Dynamics (MD) simulations. However, until now, the scarcity of force field parameters for the VC prevented a reliable analysis. The autophagy signaling pathway starts with the PI3K protein and ends with ULK1. Therefore, in the first stage of this work, we developed a new AMBER force field for the VC (VCFF) from a quantum structure, obtained by DFT calculations. In the second stage, the VCFF was validated through structural analyses. From this, it was possible to investigate, through docking and MD (200 ns), the performance of the PI3K-VC and ULK1-VC systems (third stage). The analyses of this last stage involved RMSD, hydrogen bonds, RMSF and two pathways for the modulation of autophagy. In general, this work fills in the absence of force field parameters (FF) for VC by proposing an efficient and new FF, in addition to investigating, at the molecular level, how VC is able to induce autophagy in TNBC cells. This study encourages new parameterizations of metallic complexes and contributes to the understanding of the duality of autophagic processes. Communicated by Ramaswamy H. Sarma

Antioxidant Activity and Protective Effects of an Oxovanadium (IV) Complex on Heart and Aorta Injury of STZ-Diabetic Rats.

Diabetic people have a much higher rate of cardiovascular disease than healthy people. Therefore, heart and aortic tissues are target tissues in diabetic research. In recent years, the synthesis of new vanadium complexes and investigation of their antidiabetic/lowering effect on the blood glucose levels and antioxidant properties are increasing day by day. Our study aimed to examine the effects of synthesized oxovanadium (IV) complex of 2-[(2,4-dihydroxybenzylidene]hydrazine-1-[(N-(2-hydroxybenzylidene)](S-methyl)carbothioamide [VOL] on diabetic heart and aortic tissues, as well as in vitro lactate dehydrogenase (LDH) and myeloperoxidase (MPO) inhibition, antioxidant properties, and reducing power. Electrochemical characterization of the VOL was carried out by using Cyclic Voltammetry (CV) and Linear Sweep Voltammetry (LSV) methods. In addition, in silico drug-likeness and ADME prediction were also investigated. For in vivo study, male Swiss albino rats were randomly selected and separated into four groups which are control, control + VOL, diabetic and diabetic + VOL. After the experimental procedure, biochemical parameters were investigated in homogenates of heart and aorta tissues. The results showed that VOL has a protective effect on heart and aortic tissue against oxidative stress. According to electrochemical experiments, one reversible oxidative couple and one irreversible reductive response were observed for the complex. In addition, in vitro LDH and MPO inhibition of VOL was examined. It was found that VOL had a protective effect on heart and aortic tissues of diabetic rats, and caused the inhibition of LDH and MPO in in vitro studies. On the other hand, evaluating the synthesized VOL according to in silico drug-likeness and absorption, distribution, metabolism, and excretion (ADME) prediction, it was found that VOL has drug-like properties and exhibited high gastrointestinal absorption. The VOL had a therapeutic impact on the heart and aortic tissues of diabetic rats, according to the findings.

Vanadium(V) Complexes Containing Unsymmetrical N-Heterocyclic Carbene Ligands: Highly Efficient Synthesis and Catalytic Behavior towards Ethylene/Propylene Copolymerization

Vanadium(V) Complexes Containing Unsymmetrical N-Heterocyclic Carbene Ligands: Highly Efficient Synthesis and Catalytic Behavior towards Ethylene/Propylene Copolymerization

New Vanadium Complexes with Natural Ligands and Potent Antimicrobial Activity

New Vanadium Complexes with Natural Ligands and Potent Antimicrobial Activity

One Pot Synthesis of Oximes from Carbonyl Compounds Catalysed by Vanadium( V) Complex

Background: An eco-friendly catalyst was synthesized in good yield and characterized by various physicochemical techniques. The catalytic performance of the environmentally benign complex was investigated via slurry synthesis of oximes. The catalytic studies were successfully carried out using a simple protocol. The fascinating advantage of this protocol is cost effectiveness, simple work up, good yield, short reactions time, and milder reaction conditions. Methods: The complex was prepared by reaction of vanadium pentoxide with hydrazone ligand in 1:1 molar ratios, and to this reaction mixture, potassium carbonate (0.14 g, 1 mmol) was added and ground till fine yellow colour powder appeared. Oximations were carried out by reacting the substrates, 15 % H2O2, ammonia and vanadium(V) complex. The reaction was taken in a mortar and ground till a fine powder appeared. After completion of the reaction, the crude product was extracted using dichloromethane/water in 1:2, v/v, evaporated and dried under vacuum. Results: We synthesized different varieties of oximes using our newly synthesized complex as a catalyst. The products were characterized by 1H NMR and 13C NMR spectroscopy. The completion of the reaction was monitored by checking the complete disappearance of the aldehyde proton and the appearance of oxime protons. We also grew some single crystals of the products to provide further supporting evidences about the formation of products. Conclusion: Oximation of various carbonyl compounds was prepared quantitatively under the slurry condition, using {[K(H¬2O)3][V(O)2L]}2 as a catalyst. The catalytic reactions can be carried out under mild conditions, with ease of scalability, and straightforward work-up procedure, which makes the present protocols greener and better alternative methods for the synthesis of oximes.