Synthesis, catalytic activity, phosphatase inhibition activity, and X-ray structural characterization of vanadium scorpionate complexes, (Tpms)VCl2(DMF) and (Tpms)VOCl(DMF)

The complexes (Tpms)VCl₂(DMF) (1), and (Tpms)VOCl(DMF) (2), have been synthesized and characterized. Complex 2 has also been structurally characterized via X-ray diffractometry. The vanadium(IV) center possesses a square pyramidal/distorted octahedral geometry with a facially coordinating Tpms⁻ ligand in a κ³-N,N,O coordination mode. The complex is the first structurally characterized example of a vanadium(IV) complex with Tpms⁻. Complex 2 shows catalytic activity towards oxidation of 3,5-di-tert-butyl catechol and also exhibits phosphatase inhibition characteristics on alkaline phosphatase. Tpms⁻ = trispyrazolylmethanesulfonate; DMF = N,N-dimethylformamide.     

Mono and oligonuclear vanadium complexes as catalysts for alkane oxidation: synthesis, molecular structure, and catalytic potential

A series of mono- and oligonuclear vanadium(V) and vanadium(IV) complexes containing various chelating N,O-, N₃-, and O₂-ligands have been prepared. The biphasic reaction of an aqueous solution of ammonium vanadate and a dichloromethane solution of hexamethylphosphoramide (hmpa) and pyrazine-2-carboxylic acid (pcaH) or pyrazine-2,5-dicarboxylic acid (pdcaH₂) or pyridine-2,5-dicarboxylic acid (pycaH₂) yields yellow crystals of [VO₂(pca)(hmpa)] (1), [(VO₂)₂(pdca)(hmpa)₂] (2), and [VO₂(pycaH)(hmpa)] (3), respectively. The single-crystal X-ray structure analyses reveal 1 and 3 to be mononuclear vanadium(V) complexes, in which a VO₂ unit coordinates to one nitrogen and one oxygen atom of a pca or pycaH chelating ligand, and 2 to be a dinuclear vanadium(V) complex, in which two VO₂ units are coordinated through one nitrogen and one oxygen atom of a pdca bridging ligand; in the three complexes the vanadium atoms also coordinate to the oxygen atom of a hmpa ligand. The reaction of N,N,N^′,N^′-tetrakis(2-benzimidazolylmethyl)-2-hydroxo-1,3-diaminopropane (hptbH) and VOSO₄ in methanol gives the cationic complex [(VO)₄(hptb)₂(μ-O)]⁴⁺ (4), which can be crystallized as the perchlorate salt. In this tetranuclear complex, two dinuclear vanadium(IV) units are held together by a μ-oxo bridge. The known complex [VOCl₂(tmtacn)] (5) was synthesized from the reaction of 1,4,7-trimethyl-1,4,7-triazacyclononane (tmtacn) and VCl₃ in acetonitrile; the reaction of tetrabutylammonium vanadate with pyro-cathecol (catH₂) in acetonitrile gives the known anionic complex [V(cat)₃]⁻ (6), in which the vanadium(V) center is bonded to three cat chelating ligands through the oxygen atoms, obtained as the tetrabutylammonium salt. All compounds synthesized are highly efficient oxidation catalysts for the reaction of cyclohexane with air and hydrogen peroxide in the presence of four equivalents of pcaH per vanadium, although the catalytic activity of the complexes containing bulky chelating ligands 4 and 5 is somewhat lower in the initial period of the reaction. During this period the active species are formed from the complexes and final turnover numbers are high. The catecholate ligands of complex 6 may reduce from V(V) to V(IV) in the beginning of the process, thus providing very high initial oxidation rates.     

Chloro-substituted dipicolinate vanadium complexes: Synthesis, solution, solid-state, and insulin-enhancing properties

Three vanadium complexes of chlorodipicolinic acid (4-chloro-2,6-dipicolinic acid) in oxidation states III, IV, and V were prepared and their properties characterized across the oxidation states. In addition, the series of hydroxylamido, methylhydroxylamido, dimethylhydroxylamido, and diethylhydroxylamido complexes were prepared from the chlorodipicolinato dioxovanadium(V) complex. The vanadium(V) compounds were characterized in solution by ⁵¹V and ¹H NMR and in the solid-state by X-ray diffraction and ⁵¹V NMR. Density Functional Theory (DFT) calculations were performed to evaluate the experimental parameters and further describes the electronic structure of the complex. The small structural changes that do occur in bond lengths and angles and partial charges on different atoms are minor compared to the charge features that are responsible for the majority of the electric field gradient tensor. The EPR parameters of the vanadium(IV) complex were characterized and compared to the corresponding dipicolinate complex. The chemical properties of the chlorodipicolinate compounds are discussed and correlated with their insulin-enhancing activity in streptozoticin (STZ) induced diabetic Wistar rats. The effect of the chloro-substitution on lowering diabetic hyperglycemia was evaluated and differences were found depending on the compounds oxidation state similar as was observed for the vanadium III, IV and V dipicolinate complexes (P. Buglyo, D.C. Crans, E.M. Nagy, R.L. Lindo, L. Yang, J.J. Smee, W. Jin, L.-H. Chi, M.E. Godzala III, G.R. Willsky, Inorg. Chem. 44 (2005) 5416-5427). However, a linear correlation of oxidation states with efficacy was not observed, which suggests that the differences in mode of action are not simply an issue of redox equivalents. Importantly, our results contrast the previous observation with the vanadium-picolinate complexes, where the halogen substituents increased the insulin-enhancing properties of the complex (T. Takino, H. Yasui, A. Yoshitake, Y. Hamajima, R. Matsushita, J. Takada, H. Sakurai, J. Biol. Inorg. Chem. 6 (2001) 133-142).     

Multinuclear nuclear magnetic resonance and density functional theoretical studies on the structure of bisperoxovanadium complexes with bidentate donors

Solid state and solution ⁵¹V and ¹³C NMR studies on four fundamental bisperoxovanadium complexes containing bidendate donor ligands were reported, together with DFT calculations of structural and NMR parameters. The ⁵¹V solid-state NMR characterization of the four complexes with [VO(O₂)₂L]ⁿ⁻ anion {abbr. bpVL, where L = oxalic acid dianion (ox), pyridine-2-carboxylic acid (pic), bipyridine (bipy), and 1,10-phenanthroline (phen)} show that the ligands have a significant effect on the electric-field gradient tensor, with the quadrupolar coupling constant ranging from 4.0 to 5.8 MHz. The experimental and theoretical results suggest that the vanadium center of bpVpic, bpVphen and bpVbipy in solid state and aqueous solution are all seven-coordinated except that bpVox is six-coordinated in aqueous solution. The steric space hindrance of the organic ligands and the bonding between vanadium with the coordination influences the activity of bpVL complexes.     

Synthesis and X-ray structural characterization of tris(l-glycinato)vanadium(III) and trans-tetraquadichlorovanadium(III) chloride

Despite the importance of V^III in biology, only three V^III complexes of naturally occurring amino acids have been structurally characterized. We report the structure of the first vanadium complex incorporating a glycine ligand, [V(Gly)₃] · 2DMSO, which crystallizes in a monoclinic system with space group Cc, a = 8.9186(5) Å, b = 21.5347(9) Å, c = 9.9064(5) Å and β = 110.536(3)°. The X-ray structural data show the central V^III metal octahedrally coordinated by three bidentate glycinato ligands arranged a mer configuration, with both Δ and Λ enantiomers present in the unit cell. The bulk sample was isolated as [V(Gly)₃] · DMSO · NaCl. Structural comparisons are made with the corresponding homoleptic glycinato complexes of Co^III, Cr^III and Ni^II. The structure of trans-[V(OH₂)₄Cl₂]Cl · 2H₂O has also been re-determined. This latter complex crystallizes in a monoclinic system in the P2(1)/c space group, a = 6.4381(9) Å, b = 6.3843(9) Å, c = 11.7980(17) Å and β = 98.057(2)°. The vanadium atom lies at a crystallographic inversion centre within the distorted octahedron formed by the four water and two chloride ligands.     

A dinuclear vanadium compound with 24-membered macrocycle generated via formation of S-C bonds

A dinuclear vanadium 24-membered macrocycle with double-ring, [V₂O₂L₂(μ-CH₃COO)]⁻ (H₂L = 3,3′-(1,3,4-thiadiazole-2,5-diyl)bis(sulfane-diyl) bis(4-hydroxypent-3-en-2-one)), was prepared in high yield from the reaction of VO₂(acac) with 2,5-dimercapto-1,3,4-thiadiazole dipotassium salt (K₂SSS) and acetylacetone (Hacac) at room temperature. Its closure of 24-membered macrocycle has resulted from the formation of U-shape units via S-C bonding between original SSS²⁻ and acac⁻ ligands, while the bridging CH₃COO⁻ has created from an unexpected decomposition of Hacac. The obtained two products were characterized by single crystal X-ray diffraction, XRD, ESR, TGA and magnetism analyses. A possible mechanism for formation of the bimetal 24-membered macrocycle has been discussed.     

Aqueous acid-base chemistry involving dioxovanadium(V) complexes of 2,6-pyridinedimethanol, and the X-ray structures of Na[VO2{2,6-(OCH2)2NC5H3}] · 4H2O and [1-H-2,6-(HOCH2)2NC5H3]Cl

Reaction of NH₄VO₃ with 2,6-pyridinedimethanol in water at 85 °C followed by the room temperature addition of HCl (aq) yields [HVO₂(pydim)]_x (pydim = 2,6-pyridinedimethanolato dianion), as a sparingly soluble off-white solid. This acid may be deprotonated by titration with NaOH (aq), yielding Na[VO₂(pydim)] · 4H₂O, which has been structurally characterized by single-crystal X-ray diffraction. Treating Na[VO₂(pydim)] · 4H₂O with HCl (aq) regenerates [HVO₂(pydim)]_x, but reaction with additional NaOH (aq) displaces the pyridinedimethanolato ligand from the vanadium center. Similarly, treating [HVO₂(pydim)]_x with excess HCl (aq) strips the pyridinedimethanolato ligand from the vanadium center and yields the adduct [H₃(pydim)]⁺Cl⁻ as one component in a mixture of products. This adduct has been structurally characterized by single-crystal X-ray diffraction. The optimum pH range for stable dioxovanadium(V) complexes stabilized by the 2,6-pyridinedimethanolato ligand is at least 1.5-9.4.     

Glutathione transferases with vanadium-binding activity isolated from the vanadium-rich ascidian Ascidia sydneiensis samea

Some ascidians accumulate vanadium in vanadocytes, which are vanadium-containing blood cells, at high levels and with high selectivity. However, the mechanism and physiological significance of vanadium accumulation remain unknown. In this study, we isolated novel proteins with a striking homology to glutathione transferases (GSTs), designated AsGST-I and AsGST-II, from the digestive system of the vanadium-accumulating ascidian Ascidia sydneiensis samea, in which the digestive system is thought to be involved in vanadium uptake. Analysis of recombinant AsGST-I confirmed that AsGST-I has GST activity and forms a dimer, as do other GSTs. In addition, AsGST-I was revealed to have vanadium-binding activity, which has never been reported for GSTs isolated from other organisms. AsGST-I bound about 16 vanadium atoms as either V(IV) or V(V) per dimer, and the apparent dissociation constants for V(IV) and V(V) were 1.8 × 10⁻⁴ M and 1.2 × 10⁻⁴ M, respectively. Western blot analysis revealed that AsGSTs were expressed in the digestive system at exceptionally high levels, although they were localized in almost all organs and tissues examined. Considering these results, we postulate that AsGSTs play important roles in vanadium accumulation in the ascidian digestive system.     

Oxidation of thiocyanate by iron(V) in alkaline medium

The oxidation of thiocyanate by iron(V) (Fe(V)) was studied as a function of pH in alkaline solutions by a premix pulse radiolysis technique. The rates decrease with an increase in pH. The rate law for the oxidation of SCN⁻ by Fe(V) was obtained as −d[Fe(V)]/dt = k₁₀{[H⁺]²/([H⁺]² + K₂[H⁺] + K₂K₃)}[Fe(V)][SCN⁻], where k₁₀ = 5.72 ± 0.19 × 10⁶ M⁻¹ s⁻¹, pK₂ = 7.2, and pK₃ = 10.1. The reaction precedes via a two-electron oxidation, which converts Fe(V) to Fe(III). Thiocyanate reacts approximately 10³× faster with iron(V) than does with iron(VI).     

Synthesis of vanadium(IV,V) hydroxamic acid complexes and in vivo assessment of their insulin-like activity

We synthesized vanadyl (oxidation state +IV) and vanadate (oxidation state +V) complexes with the same hydroxamic acid derivative ligand, and assessed their glucose-lowering activities in relation to the vanadium biodistribution behavior in streptozotocin-induced diabetic mice. When the mice received an intraperitoneal injection of the complexes, the vanadate complex more effectively lowered the elevated glucose levels compared with the vanadyl one. The glucose-lowering effect of the vanadate complex was linearly related to its dose within the range from 2.5 to 7.5 mg V/kg. In addition, pretreatment of the vanadate complex induced a larger insulin-enhancing effect than the vanadyl complex. Both complexes were more effective than the corresponding inorganic vanadium compounds. The vanadyl and vanadate complexes, but not the inorganic vanadium compounds, resulted in almost the same organ vanadium distribution. Consequently, the observed differences in the insulin-like activity between the complexes would reflect the potency of the two compounds in the +IV and +V oxidation states in the subcellular region.     

Reactivity studies of a pseudo three-coordinate vanadium(II) complex: Synthesis of terminal oxo and sulfido complexes of vanadium(IV) and S-S and Se-Se reductive bond cleavage reactions

Terminal oxo and sulfido complexes in the form of (nacnac)VE(Ntol₂) (nacnac = [ArNC(CH₃)]₂CH⁻, Ar = 2,6-(CHMe₂)₂C₆H₃, Ntol₂ = ⁻N(C₆H₄-4-Me), E = O (1), S (2)) were isolated from treatment of the masked three-coordinate vanadium(II) complex, (nacnac)V(Ntol₂), with C₅H₅NO and S₈, respectively. Both vanadium(IV) species, 1 and 2, have been characterized by room temperature X-band EPR spectroscopic studies, and in the case of complex 1, a single crystal molecular structure confirmed the presence of a terminal oxo moiety. Moreover, reaction of (nacnac)V(Ntol₂) with diphenyl-disulfide and diphenyl-diselenide results in the reductive cleavage of these compounds to produce the vanadium(III) complexes (nacnac)V(XPh)(Ntol₂) (X = S, (3), Se (4)). A molecular structure of the phenylsulfide complex, 3, confirmed formation of the d² complex resulting from reductive cleavage of the S-S bond.     

Vanadium compounds induced mitochondria permeability transition pore (PTP) opening related to oxidative stress

Vanadium compounds have been regarded as promising in therapeutic treatment of diabetes and in cancer prevention. In the present work, we studied the effects of vanadium compounds on mitochondria to investigate the mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with a variety of vanadium compounds, i.e. VOSO₄, NaVO₃, and vanadyl complexes with organic ligands. Our studies indicated that VO²⁺, , VO(acac)₂ and VOcit (1-100 μM) could induce mitochondrial swelling in a concentration dependent manner and disrupt mitochondrial membrane potential (Δψ_m) in a time dependent manner, which is quite different from the rapid Δψ_m collapse caused by Ca²⁺ or CCCP (carbonyl cyanide m-chlorophenylhydrazone, a mitochondrial uncoupling reagent). Release of cytochrome c (Cyt c) was observed and could be inhibited by cyclosporin A (CsA), an inhibitor of the mitochondrial permeability transition pore (PTP). Interestingly, VOdipic caused release of Cyt c without mitochondrial swelling and Δψ_m disruption, an action previously only observed on the Bax protein, suggesting a potentially role of VOdipic in regulating PTP opening. In addition, all the vanadium compounds tested stimulated mitochondrial production of reactive oxygen species (ROS). Antioxidants, i.e. vitamin C and E, significantly delayed the Δψ_m disruption. Overall, our experimental evidence indicated vanadium compounds exhibited multiple actions on mitochondria. Vanadium compounds did induce oxidative stress on mitochondrial and thus caused PTP opening, which led to collapse of Δψ_m and Cyt c release as the initiation of cell apoptosis.     

Anti-diabetic effects of sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate in streptozotocin-induced diabetic rats

The evaluation of the anti-diabetic effects of an organic vanadium(V) complex in streptozotocin (STZ)-induced diabetic rats was investigated. The STZ-induced diabetic rats were orally administrated with sodium 4-amino-2,6-dipicolinatodioxovanadium(V) dihydrate (V5dipic-NH₂), a vanadium(V) coordination compound. The compound was administered through drinking water at a concentration of 0.1 mg/mL for 20 days, and then the concentration was increased to 0.3 mg/mL for the following 20 days. At the end of the experiment, V5dipic-NH₂ statistically significantly reduced the levels of blood glucose (P < 0.01), serum total cholesterol (P < 0.01), triglycerides (P < 0.01) and the activities of serum aspartate amino transferase (P < 0.05) and alkaline phosphatase (P < 0.01) compared to untreated diabetic animals. After treatment with 0.3 mg/mL V5dipic-NH₂, the oral glucose tolerance was improved in diabetic animals (P < 0.01). In addition, the daily intake of elemental vanadium was markedly decreased in V5dipic-NH₂-treated diabetic rats compared to vanadyl sulfate (VOSO₄)-treated diabetic rats, which suggested that the anti-diabetic activity of the element vanadium was elevated after being modified with an organic ligand. These results suggested that V5dipic-NH₂, as an organic vanadium compound, is more effective than inorganic vanadium salt at alleviating the symptoms of diabetes.     

Enzyme inhibition,radical scavenging,and spectroscopic studies of vanadium(IV)–hydrazide complexes

Spectroscopic, enzyme-inhibition, and free-radical scavenging properties of a series of hydrazide ligands and their vanadium(IV) complexes have been investigated. Analytical and spectral data indicate the presence of a dimeric unit with two oxovanadium(IV) ions (VO²⁺) coordinated with two hydrazide ligands along with two water molecules. All complexes are stable in the solid state, but exhibit varying degrees of stability in solution. Binding of the coordinating solvent such as DMSO is indicated at the 6th position of vanadium in the dimeric unit followed by conversion to a monomeric intermediate species, [VOL(DMSO)3]1+ (L = hydrazide ligand). The free hydrazide ligands are inactive against snake venom phosphodiesterase I (SVPD), whereas oxovanadium(IV) complexes of these ligands show varying degrees of inhibition and are found to be non-competitive inhibitors. The superoxide and nitric oxide radical scavenging properties have been determined. Hydrazide ligands are inactive against these free radicals, whereas their V(IV) complexes show varying degrees of inhibition. Structure–activity relationship studies indicate that the electronic and/or steric factors that change the geometry of the complexes play an important role in their inhibitory potential against SVPD and free radicals.     

Ternary oxovanadium(IV) complexes with amino acid-Schiff base and polypyridyl derivatives: synthesis, characterization, and protein tyrosine phosphatase 1B inhibition

To investigate the structure-activity relationship of vanadium complexes in inhibiting protein tyrosine phosphatase1B (PTP1B), eight mixed-ligand oxovanadium(IV) complexes, [V^IVO(SalAla)(NN)] (H₂SalAla for salicylidene alanine, NN for N,N′-donor heterocyclic base, namely, 2,2′-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3), dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 4)), [V^IVO(SalLys)(dpq)] (5), [V^IVO(SalLys)(dppz)] (6), [V^IVO(SalAsp)(dppz)], (7) and [V^IVO(SalTrp)(dppz)] (8)), of which 3-8 are new, have been prepared and characterized by elemental analysis, infrared, UV-visible, electrospray ionization mass spectrometry and conductivity. The molar conductance data confirmed the non-electrolytic nature of the complexes in DMSO solution. The coordination in [V^IVO (SalAla)(phen)] (2) was confirmed by X-ray crystal structure analysis. The oxidation state of V(IV) with d¹ configuration in 2 was confirmed by EPR. The speciation of VO-SalAla-phen in aqueous solution was investigated by potentiometric pH titrations. The results indicate that the main species are two ternary complexes at the pH range 7.0-7.4. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of PTP1B with IC₅₀ values in the range of 62-597 nM, approximately 3-10 fold weaker in potency than those of similar mixed-ligand oxovanadium(IV) complexes of salicylidene anthranilic acid (SAA) derivative with polypyridyl ligands, except complex 8, which exhibits comparable or better inhibition activity than those of the mixed-ligand oxovanadium(IV) complexes of SAA derivative with polypyridyl ligands. The results demonstrate that the structures of vanadium complexes influence the PTP1B inhibition activity. Kinetics assays reveal that complex 2 inhibits PTP1B in a competitive manner.     

Reduction of vanadium(V) with ascorbic acid and isolation of the generated oxovanadium(IV) species

The interaction of sodium metavanadate and VOCl₃ with ascorbic acid, one of the possible natural reducing agents of vanadium(V) to oxovanadium(IV), has been investigated. Three new VO²⁺ complexes could be isolated as microcrystalline powders. One of them, of composition K_1.5Na_0.5[VO(HAsc)(OH)₃], contains ascorbic acid as a monodentate ligand. In the other two, K[VO(Diketo)(OH)]·H₂O and Na₃[VO(Diketo)₂(OH)], the enolized form of 2,3-diketogulonic acid (one of the oxidation products of ascorbic acid), acts as a bidentate ligand. The complexes were characterized by means of electronic (absorption and reflectance) and infrared spectroscopy and magnetic susceptibility measurements. Their thermal behavior was investigated by thermogravimetric and differential thermal analyses. The interest of the investigated system in relation to vanadium detoxification is also discussed.     

A comparison of vanadyl acetylacetonate complexes of N2O heteroscorpionate ligands that vary systematically in donor set

We have successfully prepared a series of vanadyl complexes with N₂O heteroscorpionate ligands and have characterized their cis and trans geometrical isomers both in solution and the solid state. The major difference between the isomers, and between the various oxygen atom donors of the N₂O scorpionate ligands, is in their redox potentials which can span almost a volt for this ostensively similar set of compounds. Such data may be useful in screening vanadium complexes for potential biological activity.     

An insect farnesyl phosphatase homologous to the N-terminal domain of soluble epoxide hydrolase

In insects, farnesyl pyrophosphate (FPP) is converted to juvenile hormone (JH) via a conserved pathway consisting of isoprenoid-derived metabolites. The first step of this pathway is presumed to be hydrolysis of FPP to farnesol in the ring gland. Based on alignment of putative phosphatases from Drosophila melanogaster with the phosphatase domain of soluble epoxide hydrolase, Phos2680 and Phos15739 with conserved phosphatase motifs were identified, cloned and purified. Both D. melanogaster phosphatases hydrolyzed para-nitrophenyl phosphate, however, Phos15739 also hydrolyzed FPP with a K_cat/K_m of 2.1 × 10⁵ M⁻¹ s⁻¹. RT-PCR analysis revealed that Phos15739 was expressed in the ring gland and its expression was correlated with JHIII titer during development of D. melanogaster. N-acetyl-S-geranylgeranyl-l-cysteine was found to be a potent inhibitor of Phos15739 with an IC₅₀ value of 4.4 μM. Thus, our data identify Phos15739 as a FPP phosphatase that likely catalyzes the hydrolysis of FPP to farnesol in D. melanogaster.     

Insulin-enhancing activity of a dinuclear vanadium complex: 5-chloro-salicylaldhyde ethylenediamine oxovanadium(V) and its permeability and cytotoxicity

A new insulin-enhancing oxovanadium complex 5-chloro-salicylaldhyde ethylenediamine oxovanadium (V) ([V₂O₂(μ-O)₂L₂]) has been synthesized. The complex was characterized by a variety of physical methods, including X-ray crystallography. The X-ray diffraction analysis show a dinuclear complex of two six-coordinate vanadium centers doubly bridged by the oxygen atoms of the Schiff base ligand with a V₂O₂ diamond core. The complex was administered intragastrically to STZ-diabetic rats for 2 weeks. The biological activity results show that the complex at the dose of 10.0 and 20.0 mg V kg^− 1, could significantly decrease the blood glucose level and ameliorate impaired glucose tolerance in STZ-diabetic rats. That results suggested that the complex exerts an antidiabetic effect in STZ-diabetic rats. Furthermore, the complex ([V₂O₂(μ-O)₂L₂]) had permeability above 10^− 5 cm/s. The experimental results suggested that the vanadium complex permeates via a passive diffusion mechanism. It was also suggested the complex with salen-type ligands has good lipophilic properties and better oral administration. The cytotoxicity of the complex ([V₂O₂(μ-O)₂L₂]) on Caco-2 cells was measured by a decrease of cell viability using the MTT assay suggesting that the chlorine atom at C4 of complex [V₂O₂(μ-O)₂L₂] increased cytotoxicity for vanadium complexes.     

Aminocarboxylate complexes of vanadium(III): Electronic structure investigation by high-frequency and -field electron paramagnetic resonance spectroscopy

Aminocarboxylate complexes of vanadium(III) are of interest as models for biologically and medicinally relevant forms of this interesting and somewhat neglected ion. The V(III) ion is paramagnetic, but not readily suited to conventional EPR, due to its integer-spin ground state (S = 1) and associated large zero-field splitting (zfs). High-frequency and -field EPR (HFEPR), however, has the ability to study such systems effectively. Three complexes, all previously structurally characterized: Na[V(trdta)] · 3H₂O, Na[V(edta)(H₂O)] · 3H₂O, and [V(nta)(H₂O)₃] · 4H₂O (where trdta stands for trimethylenediamine-N,N,N′,N′-tetraacetate and nta stands for nitrilotriacetate) were studied by HFEPR. All the investigated complexes produced HFEPR responses both in the solid state, and in aqueous solution, but those of [V(nta)(H₂O)₃] · 4H₂O were poorly interpretable. Analysis of multi-frequency HFEPR spectra yielded a set of spin Hamiltonian parameters (including axial and rhombic zfs parameters: D and E, respectively) for these first two complexes as solids: Na[V(trdta)] · 3H₂O: D = 5.60 cm⁻¹, E = 0.85 cm⁻¹, g = 1.95; Na[V(edta)(H₂O)] · 3H₂O: D = 1.4 cm⁻¹, E = 0.14 cm⁻¹, g = 1.97. Spectra in frozen solution yielded similar parameters and showed multiple species in the case of the trdta complex, which are the consequence of the flexibility of this ligand. The EPR spectra obtained in frozen aqueous solution are the first, to our knowledge, of V(III) in solution in general and show the applicability of HFEPR to these systems. In combination with very insightful previous studies of the electronic absorption of these complexes which provided ligand-field parameters, it has been possible to describe the electronic structure of V(III) in [V(trdta)]⁻ and [V(edta)(H₂O)]⁻; the quality of data for [V(nta)(H₂O)₃] does not permit analysis. Qualitatively, six-coordinate V(III) complexes with O,N donor atoms show no electronic absorption band in the NIR region, and exhibit relatively large magnitude zfs (D ? 5 cm⁻¹), while analogous seven-coordinate complexes do have a NIR absorption band and show relatively small magnitude zfs (D < 2 cm⁻¹).