Vanadium Complexes Research Articles

Unravelling the potential of low-valent tunable vanadium complexes in the nitrogen reduction reaction (NRR).

Density functional theory calculations have been carried out to investigate the potential of several hitherto unknown low-valent tripodal vanadium complexes towards conversion of dinitrogen to ammonia as a function of different equatorial (PiPr2 and SiPr) and bridgehead groups (B, C and Si). All the newly proposed vanadium complexes were probed towards understanding their efficiency in some of the key steps involved in the dinitrogen fixation process. They were found to be successful in preventing the release of hydrazine during the nitrogen reduction reaction. We have performed a comprehensive mechanistic study by considering all the possible pathways (distal, alternate and hybrid) to understand the efficiency of some of the proposed catalysts towards the dinitrogen reduction process. The exergonic reaction free energies obtained for some of the key steps and the presence of thermally surmountable barrier heights involved in the catalytic cycle indicate that these complexes may be considered as suitable platforms for the functionalization of dinitrogen.

A Dinitrogen Divanadium Complex Supported by a Trisamidophosphine Ligand

Comprehensive SummaryThe reaction between tripodal trisamidophosphine ligand H3PN3Ar and V(Mes)3(THF) (Mes = mesityl) yields the vanadium(III) complex (PN3Ar)V (1) with an open site in the axial position, which could coordinate with THF, pyridine, and NH3 to form the corresponding adducts (2—4). The vanadium(III) center is redox‐active, as demonstrated by cyclic voltammetry methods and chemical oxidation or reduction. Notably, a novel dinitrogen divanadium complex with a bridging N2 ligand, {K(THF)}2{[PN3Ar]V}2(μ‐N2) (6), was synthesized via treatment of 1 with 1 equivalent of potassium naphthalenide in THF under a N2 atmosphere. The electronic structures and binding properties of 6 are evaluated and discussed based on its DFT calculations. Additionally, these vanadium complexes (1, 5, 6) can serve as catalysts for the conversion of N2 into N(SiMe3)3 in the presence of reductants and Me3SiCl.

In-Depth Mass Spectrometry Study of Vanadium(IV) Complexes with Model Peptides.

Investigating the speciation of vanadium complexes in the presence of potential biomolecular targets under physiological conditions remains challenging, and further experimental techniques are needed to better understand the mechanism of action of potential metallodrugs. The interaction of two model peptides (angiotensin I and angiotensin II) with three well-known oxidovanadium(IV) compounds with antidiabetic and/or anticancer activity, [VIVO(pic)2(H2O)], [VIVO(ma)2], and [VIVO(dhp)2] (where pic, ma, and dhp are picolinate, maltolate, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate anions, respectively), was investigated by ESI-MS/MS (electrospray ionization tandem mass spectrometry) and complemented by EPR (electron paramagnetic resonance) spectroscopy measurements and theoretical calculations at the DFT (density functional theory) level. The results demonstrated that vanadium-peptide bonds are preserved after HCD (higher energy collisional dissociation) fragmentation, allowing for the identification of binding sites through a detailed analysis of the fragmentation spectra. Angiotensin I (AT1) and angiotensin II (AT2) exhibited different coordination behaviors. AT1, with two His residues (His6, His9), prefers to form [AT1 + VOL] adducts with both histidine residues coordinated to the metal ion, while AT2, which has only His6, can bind the metal in a monodentate fashion, forming also [AT2 + VOL2] adducts. Insights from this study pave the way to ESI-MS/MS investigations of more complex systems, including target proteins and further development of vanadium-based drugs.

Periodic Trends and Fluxionality Effects on Transition Metal Catalyzed Sulfoxidation.

Despite the extended interest in d0 metal complexes as catalysts for peroxide activation and eventual oxygen transfer processes, there are still gaps in the understanding of how they proceed at the microscopic level. Herein, we have considered sulfide oxidation with cumyl hydroperoxide as a test system, performing the reaction with a series of eight different aminotriphenolate d0 metal complexes: Ti(IV), Zr(IV), Hf(IV), V(V), Nb(V), Ta(V), Mo(VI), and W(VI). The reactivity and selectivity of the catalytic systems, as well as the effect of a strong Lewis base (dimethylhexyl-N-oxide), have been determined experimentally, correlating kinetic values with Sanderson electronegativity values. Theoretical calculations of the catalytic cycles have been performed to have a clearer description of the role of the reactive peroxo species. Combining experimental results and DFT predictions, we propose suitable mechanisms for all eight metal aminotriphenolates, rationalizing the expected periodic trends, while also unveiling the unique reaction pathways available to highly flexible vanadium complexes.

Exploring the Biological Effects of Anti-Diabetic Vanadium Compounds in the Liver, Heart and Brain.

The prevalence of diabetes mellitus and diabetes-related complications is rapidly increasing worldwide, placing a substantial financial burden on healthcare systems. Approximately 537 million adults are currently diagnosed with type 1 or type 2 diabetes globally. However, interestingly, the increasing morbidity rate is primarily influenced by the effects of long-term hyperglycemia on vital organs such as the brain, the liver and the heart rather than the ability of the body to use glucose effectively. This can be attributed to the summation of the detrimental effects of excessive glucose on major vascular systems and the harmful side effects attributed to the current treatment associated with managing the disease. These drugs have been implicated in the onset and progression of cardiovascular disease, hepatocyte injury and cognitive dysfunction, thereby warranting extensive research into alternative treatment strategies. Literature has shown significant progress in utilizing metal-based compounds, specifically those containing transition metals such as zinc, magnesium and vanadium, in managing hyperglycaemia. Amongst these metals, research carried out on vanadium reflected the most promising anti-diabetic efficacy in cell culture and animal studies. This was attributed to the ability to improve glucose management in the bloodstream by enhancing its uptake and metabolism in the kidney, brain, skeletal muscle, heart and liver. Despite this, organic vanadium was considered toxic due to its accumulative characteristics. To alleviate vanadium's toxic nature while subsequently manipulating its therapeutic properties, vanadium complexes were synthesized using either vanadate or vanadyl as a base compound. This review attempts to evaluate organic vanadium salts' therapeutic and toxic effects, highlight vanadium complexes' research and provide insight into the novel dioxidovanadium complex synthesized in our laboratory to alleviate hyperglycaemia-associated macrovascular complications in the brain, heart and liver.

Impact of Surface Modification on the Oxidation of Linear Aliphatic Alcohols by Vanadium Complexes Supported on Merrifield Resin with Mixed Functionality Ligands

AbstractTwo oxidovanadium(IV) complexes [VO(xbp‐sc)] (1) and [VO(xbp‐tc)] (2) were prepared using hydrazine‐ether mixed functionality ligands Hxbp‐sc (I) and Hxbp‐tc (II), respectively. Complexes 1 and 2 were carefully grafted separately into imidazole‐modified chloromethylated polystyrene (Ps−Im) and unmodified chloromethylated polystyrene (PS−Cl) beads. Successfully anchored vanadium complexes Ps−Im‐[VO(xbp‐sc)] (3), Ps−Im‐[VO(xbp‐tc)] (4), Ps‐[VO(xbp‐sc)] (5), and Ps‐[VO(xbp‐tc)] (6) were tested for their catalytic potential towards the oxidation of aliphatic alcohols in the presence of hydrogen peroxide. Polymer‐grafted catalysts display excellent substrate conversion compared to most recent reports and good recyclability up to three cycles without losing much reactivity. High TOF values in the range of 183–591 h−1 are observed for the supported catalysts 3–6. The highest substrate conversion is observed for ethanol (63–97 %) under the optimized reaction conditions. Mainly, better substrate conversion is obtained with imidazole‐modified polymer beads grafted catalysts 3 and 4 than those grafted on unmodified polymer beads (5 and 6). Moreover, catalysts with the semicarbazide group in their ligand framework (3 and 5) show better reactivity towards alcohol with fewer carbon atoms. On the contrary, alcohols with longer carbon chains oxidize more easily in the presence of the catalyst with thiosemicarbazide frameworks (4 and 6).

Nicotinohydrazide derived hydrazone ligated vanadium(V) complex: Supramolecular assembly and quantification of intermolecular interactions

In this study, the synthesis and characterization of nicotinohydrazide derived hydrazone ligated vanadium(V) complex together with the corresponding computational analyses was reported. The complex was synthesized by reaction of vanadium pentoxide with (E)-N'-((2-hydroxynaphthalen-1-yl)methylene)nicotinohydrazide in ethanol solution under reflux condition at 70 °C. The studied crystal was obtained via evaporation of the solvent at room temperature and structural features were determined using single-crystal XRD. The results confirmed the prevalent role of strong hydrogen bonds of the N–H···O, N–H···N and C–H···O type. These hydrogen bonding interactions play a very important role in stabilization of the complex. Furthermore, the hydrogen bonding and other weak interaction and other contacts play a significant role in the crystal packing.

A refreshing approach to understanding the action on DNA of vanadium (IV) and (V) complexes derived from the anticancer VCp2Cl2

A computational study based on derivatives of the anticancer VCp2Cl2 compound and their interaction with representative models of deoxyribonucleic acid (DNA) is presented. The derivatives were obtained by substituting the cyclopentadienes of VCp2Cl2 with H2O, NH3, OH−, Cl−, O2− and C2O42− ligands. The oxidation states IV and V of vanadium were considered, so a total of 20 derivative complexes are included. The complexes interactions with DNA were studied using two different models, the first model considers the interactions of the complexes with the pair Guanine-Cytosine (G-C) and the second involves the interaction of the complexes with adjacent pairs, that is, d(GG). This study compares methodologies based on density functional theory with coupled cluster like calculations (DLPNO-CCSD(T)), the gold standard of electronic structure methods. Furthermore, the change in the electron density of the hydrogen bonds that keep bonded the G-C pair and d(GG) pairs, due to the presence of vanadium (IV) and (V) complexes is rationalize. To this aim, quantities obtained from the topology of the electron densities are inspected, particularly the value of the electron density at the hydrogen bond critical points. The approach allowed to identify vanadium complexes that lead to significant changes in the hydrogen bonds indicated above, a key aspect in the understanding, development, and proposal of mechanisms of action between metal complexes and DNA.

Integrated quantum chemical calculations, predictive toxicity assessment, absorption, distribution, metabolism, excretion and toxicity profiling and molecular docking analysis to unveil the therapeutic potential of non‐oxovanadium(IV) and organotin(IV) complexes targeting breast cancer cells

AbstractIn this work, theoretical calculations of o‐phenylphenol‐based non‐oxovanadium(IV) and organotin(IV) complexes, previously prepared and reported by our group, have been carried out by density functional theory (DFT). Density functional theory quantum chemical computations were used to explore the structural and spectroscopic characteristics of the complexes in this study. The inhibitory nature of complexes were revealed via molecular docking research, which were performed against selected breast cancer cell proteins, 5NWH and 3HB5. The optimization and stability of complexes 1–6, were conducted using optimized DFT/B3LYP/6–311++G (d, p) level. Simulated computations of the molecular electrostatic potential surface were also performed to analyze the reactive behavior of the non‐oxovanadium(IV) and organotin(IV) complexes. The stability and molecular reactivity of the molecules were computed using the HOMO‐LUMO energies, energy gap, chemical potential (μ), electronegativity (χ), hardness (η), and softness (S) values. In silico analysis through molecular docking, ADMET properties and toxicity evaluation was used to assess its anticancer activity, drug‐likeness property and toxicity. The binding constant value, evaluated from molecular docking, was found to be very promising, −10.1 kcal mol−1 observed for vanadium complex 5 and the complexes were found to exhibit inhibition constant as low as 0.0378 μMol. Root‐mean‐square deviation (RMSD) has been carried out to validate molecular docking studies, which have been found to be below 2.0 Å for the complexes, indicating successful docking of the ligand‐protein complex by the program. The complexes, evaluated for their toxicity behavior in terms of Lethal Dose, based on Globally Harmonized System (GHS), have been found to be chemical safe falling under the category III and V and hence can find use as future metallo‐based drugs.

Hydrazone-flavonol based oxidovanadium(V) complexes: Synthesis, characterization and antihyperglycemic activity of chloro derivative in vivo

Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium(V) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L-ONO)]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D 1H and proton-decoupled 13C(1H) NMR spectroscopy, alongside extensive 2D 1H1H COSY, 1H13C HMQC, and 1H13C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6–31++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature-dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex 2, featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity in vivo. The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium(V) hydrazone complexes as antidiabetic and insulin-mimetic agents.

STUDYING THE COMPLEXATION OF V(V) WITH 3-[2-HYDROXY-3- SULFO-5-NITROPHENYLAZO]-PENTADIONE-2,4 IN THE PRESENCE OF A THIRD COMPONENT

In the present study, we investigated the formation of the complex vanadium c 3-[2-hydroxy-3- sulfo-5-nitrophenylazo]-pentadione-2,4 (R) in the presence of cationic surfactants (CPAS) including cetylpyridinium chloride (CPCl), cetylpyridinium bromide (CPBr), and cetyltrimethylammonium bromide (CTMABr). The study on the pH dependence of complexation revealed that the release of the VR complex occurred at pH=4 with a maximum absorption at λ=425 nm, while the reagent exhibited a maximum absorption at 383 nm. In the presence of the third component, three-component compounds VR-СPBr, VR-CPBr, and VR-CTMABr were formed. The absorption maxima of the mixed-ligand complexes V(V) were bathochromic relative to the absorption maxima of the binary complex, with λmax values of 437 nm, 449 nm, and 454 nm, respectively. The optimal pH for complexation was found to be in the acidic region at pH 4.0, 3.0, and 3.0, respectively. The impact of the third component and reagent concentrations on complex formation was also investigated, with the maximum yield of VR complex was achieved at a concentration of 8·10-5 M R, VR-CPCl at 8·10-5 M R and 8•10-4 M CPCl, VR-CPBr at 8•10-5 M R and 8•10-4 M CPBr, and VR-CTMABr at 8•10-5 M R and 8•10-4 M CTMABr. The optimal ratio of reacting components was determined to be 1:2 and 1:2:2, respectively. The compliance with Beer's law was confirmed, and molar absorption coefficients were calculated from saturation curves. The developed method was applied to the determination of vanadium (V) in the waters of the Akstafa rivers in the Kazakh region of the Azerbaijan Republic. Keywords: complexation of vanadium(V), cationic surfactants, cetylpyridinium chloride, cetylpyridinium bromide, cetyltrimethylammonium bromide.

Polymeric carriers of vanadyl ions based on copolymers of N-vinylpyrrolidone with vinylimines

In this study, a series of new chelating copolymers containing 20% azomethine groups, poly(N-vinylpyrrolidone-co-vinylsalicylideneimine) (poly[VP-co-VSalI]), poly(N-vinylpyrrolidone-co-vinylpicolinideneimine) (poly[VP-co-VPicI]), poly(N-vinylpyrrolidone-co-vinylpyridoxylideneimine) (poly[VP-co-VPyrI]) with M = 63000 Da and their vanadium(IV) complexes – poly(VP-co-VSalI)-VO, poly(VP-co-VPicI)-VO, poly(VP-co-VPyrI)-VO, were designed and synthesized. These are intended for the delivery and pH-dependent release of vanadium species in the intestine environment. The chelating polymers were obtained from poly(N-vinylpyrrolidone-co-N-vinylamine) (poly[VP-VAm]) by polymer-analogous transformations with the corresponding aldehydes. The vanadium content, determined by ICP-AES and spectrophotometric methods, was 5.36%, 4.99%, and 9.1% of the dry mass for poly(VP-co-VSalI)-VO, poly(VP-co-VPyrI)-VO, and poly(VP-co-VPicI)-VO, respectively. XPS data confirmed that only vanadium(IV) is presented in the complexes. All complexes demonstrated a pH-dependent release of low molecular weight vanadium species, making them promising candidates for the development of vanadium-containing systems for oral administration. These systems protect the main vanadium content in the stomach but can release biologically active ions in the intestine.

New Schiff bases and their vanadium complexes: Synthesis, characterization, and biological assessment for antibacterial and antiviral action

From the perspective of possible antiviral and antibacterial activity of vanadium‐based complexes, we report the synthesis of new Schiff base ligand (L4) and a new Schiff‐base‐vanadium complex (C2). Both the ligand and the complex were characterized by Fourier transform infrared spectroscopy and Nuclear magnetic resonance techniques. Single‐crystal X‐ray Diffraction analysis has been used to confirm the structure of ligand L4 and complex C2. In addition, L1–4 and C1–3 were tested for their antibacterial effects against Escherichia coli and Staphylococcus aureus. Among the compounds, L2 demonstrated the most potent inhibition of both bacteria, exhibiting the lowest values for minimum inhibitory concentration (CMI) and minimum bactericidal concentration (CMB) (CMI = 0.16, CMB = 0.31 against E. coli, and CMI = CMB = 0.16 against S. aureus). Additionally, L2 produced the largest inhibition zones with diameters of 15.5 ± 0.15 against E. coli and 14.5 ± 0.04 against S. aureus. Furthermore, the antiviral efficacy of L1, L2, L4, C1, C2, and C3 against RNA viruses was assessed. C2 and C3 exhibited the most potent antiviral activity among the tested compounds.

On the driving forces behind the change of reduction potentials and the prediction of redox properties through analysis of EPR hyperfine couplings in VO(acac)2pyr and VO(acac)2 imidazole complexes. A DFT study

The use of vanadium complexes for potential applications in medicine largely depends on the structural properties of the complex itself, as well as on the electronic configuration of the metal and its oxidation state. When the vanadium complex binds to biomolecules or by binding solvent molecules to the complex, there is a change in the structure but also a change in the redox properties of the complex. Using theoretical methods, especially Density Functional theory (DFT), it is possible to determine which factors influence changes in the redox properties of the complex. Furthermore, by calculating the Electron Paramagnetic Resonance (EPR) constants of hyperfine coupling, it is possible to obtain not only data on the electronic configuration, but also to predict changes in redox properties upon changes in the structure of the complex. DFT results show that the binding of pyridine or imidazole to the VO(acac)2 complex leads to a lowering of the redox potential. The largest changes in the redox potential were observed in the case when the incoming ligand binds in a cis position relative to the VO bond.

New Nanosized V(III), Fe(III), and Ni(II) Complexes Comprising Schiff Base and 2-Amino-4-Methyl Pyrimidine: Synthesis, Properties, and Biological Activity.

A new synthesis of mixed ligand complexes vanadium(III), iron(III), and nickel(II), [M : L1 : L2], where L1 = Schiff base 2-((E)-((4-(((E)-benzylidene)amino)phenyl)imino)methyl)-naphthalene-1-ol (C24H18N2O) as for L2 = AMPY 2-amino-4-methyl pyrimidine (C5H7N3) were prepared in powder and investigated. Element analysis, molar conductivity, FT-IR, UV-vis, and magnetic susceptibility values have been acquired to describe the generated complexes. The values of vanadium(III), iron(III), and nickel(II) compounds are, respectively, 2.88 BM, 5.96 BM, and 2.92 BM, demonstrating that all compounds conform to the recommended octahedral geometry. Thermal gravimetric analysis (TGA) is used to further assess the complexes and establish the temperature stability and degradation of the metal complexes. The calculations abstracted from XRD patterns propose nanosized complexes (average size 29-50 nm). The microstructures of the samples have also been investigated by scanning electron microscopy (SEM). The disc diffusion method was used to assess and analyze the inhibition of the growth of compounds against harmful bacterial and fungal strains. The prepared complexes were tested against three strains of bacteria, one gram-positive strain (Bacillus subtilis), two gram-negative strains (Escherichia coli and Pseudomonas aeruginosa), and one fungus (Aspergillus fumigatus). The complexes inferred antimicrobial activity against the studied organisms. Specifically, vanadium(III) and nickel(II) are more effective than iron(III), making them promising drugs.

Approaches to selective and potent inhibition of glioblastoma by vanadyl complexes: Inducing mitotic catastrophe and methuosis

Drug resistance has been a major problem for cancer chemotherapy, especially for glioblastoma multiforme that is aggressive, heterogeneous and recurrent with <3% of a five-year survival and limited methods of clinical treatment. To overcome the problem, great efforts have recently been put in searching for agents inducing death of tumor cells via various non-apoptotic pathways. In the present work, we report for the first time that vanadyl complexes, i.e. bis(acetylacetonato)oxidovanadium (IV) (VO(acac)2), can cause mitotic catastrophe and methuotic death featured by catastrophic macropinocytic vacuole accumulation particularly in glioblastoma cells (GCs). Hence, VO(acac)2 strongly suppressed growth of GCs with both in vitro (IC50 = 4–6 μM) and in vivo models, and is much more potent than the current standard-of-care drug Temozolomide. The selective index is as high as ∼10 or more on GCs over normal neural cells. Importantly, GCs respond well to vanadium treatment regardless whether they are carrying IDH1 wild type gene that causes drug resistance. VO(acac)2 may induce methuosis via the Rac-Mitogen-activated protein kinase kinase 4 (MKK4)-c-Jun N-terminal kinase (JNK) signaling pathway. Furthermore, VO(acac)2-induced methuosis is not through a immunogenicity mechanism, making vanadyl complexes safe for interventional therapy. Overall, our results may encourage development of novel vanadium complexes promising for treatment of neural malignant tumor cells.

Elucidation of Design Criteria for V-based Redox Mediators: Structure-Function Relationships that Dictate Rates of Heterogeneous Electron Transfer.

Redox mediators are attractive solutions for addressing the stringent kinetic stipulations required for efficient energy conversion processes. In this work, we compare the electrochemical properties of four vanadium complexes, namely [V(acac)3], [V6O7(OMe)12], [nBu4N]3[V6O13(TRISNO2)2], and [nBu4N]5[V18O46(NO3)] in non-aqueous solutions on glassy carbon electrodes. The goal of this study is to investigate the electron transfer kinetics and diffusivity of these compounds under identical experimental conditions to develop an understanding of structure-function relationships that dictate the physicochemical properties of vanadium oxide assemblies. Complex selection was dictated by two criteria - (1) nuclearity of the transition metal complexes (2) distribution of electron density in the native electronic configuration. Our analyses establish that electronic communication between metal centers significantly impacts charge transfer kinetics of these vanadium-based compounds.

In-vitro and in-silico analysis and antitumor studies of novel Cu(II) and V(V) complexes of N-p-Tolylbenzohydroxamic acid

Copper(L2Cu) and vanadium(L2VOCl) complexes of N-p-tolylbenzohydroxamic acid (LH) ligand have been investigated for DNA binding efficacy by multiple analytical, spectral, and computational techniques. The results revealed that complexes as groove binders as evidenced by UV absorption. Fluorescence studies including displacement assay using classical intercalator ethidium bromide as fluorescent probe also confirmed as groove binders. The viscometric analysis too supports the inferences as strong groove binders for both the complexes. Molecular docking too exposed DNA as a target to the complexes which precisely binds L2Cu, in the minor groove region while L2VOCl in major groove region. Molecular dynamic simulation performed on L2Cu complex revealing the interaction of complex with DNA within 20 ns time. The complex stacked into the nitrogen bases of oligonucleotides and the bonding features were intrinsically preserved for longer simulation times. In-vitro cytotoxicity study was undertaken employing MTT assay against the breast cancer cell line (MCF-7). Potential cytotoxic activities were observed for L2Cu and L2VOCl complexes with IC50 values of showing 71 % and 74 % of inhibition respectively.

A Non-Toxic Binuclear Vanadium(IV) Complex as Insulin Adjuvant Improves the Glycemic Control in Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) complications are a burden to health care systems due to the associated consequences of poor glycemic control and the side effects of insulin therapy. Recently. adjuvant therapies, such as vanadium compounds, have gained attention due to their potential to improve glucose homeostasis in patients with diabetes. In order to determine the anti-diabetic and antioxidant effects of the oxidovanadium(IV) complex (Et3NH)2[{VO(OH}2)(ox)2(µ-ox)] or Vox2), rats with streptozotocin (STZ)-induced diabetes were treated with 30 and 100 mg/kg of Vox2, orally administered for 12 days. Vox2 at 100 mg/kg in association with insulin caused a 3.4 times decrease in blood glucose in STZ rats (424 mg/dL), reaching concentrations similar to those in the normoglycemic animals (126 mg/dL). Compared to insulin alone, the association with Vox2 caused an additional decrease in blood glucose of 39% and 65% at 30 and 100 mg/kg, respectively, and an increased pancreatic GSH levels 2.5 times. Vox2 alone did not cause gastrointestinal discomfort, diarrhea, and hepatic or renal toxicity and was not associated with changes in blood glucose level, lipid profile, or kidney or liver function. Our results highlight the potential of Vox2 in association with insulin in treating diabetes.

Theoretical Insights into Different Complexation Modes of Dioxovanadium(V) Compounds with Pyridoxal Semicarbazone/Thiosemicarbazone/S-Methyl-iso-thiosemicarbazone Ligands.

Vanadium complexes have gained considerable attention as biologically active compounds. In this contribution, three previously reported dioxovanadium(V) complexes with pyridoxal semicarbazone, thiosemicarbazone, and S-methyl-iso-thiosemicarbazone ligands are theoretically examined. The intermolecular stabilization interactions within crystallographic structures were investigated by Hirshfeld surface analysis. These experimental structures were optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,N,O,S)/def2-TZVP(V) level of theory, and crystallographic and optimized bond lengths and angles were compared. High correlation coefficients and low mean absolute errors between these two data sets proved that the selected level of theory was appropriate for the description of the system. The changes in structures and stability were examined by adding explicit solvent molecules. The Quantum Theory of Atoms in Molecules (QTAIM) was employed to analyze the intramolecular interactions with special emphasis on the effect of substituents. A good correlation between electron density/Laplacian and interatomic distance was found. Through molecular docking simulations towards Bovine Serum Albumin (BSA), the binding affinity of complexes was further investigated. The spontaneity of binding in the active position of BSA was shown. Further experimental studies on this class of compounds are advised.