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.     

Synthesis, structure and solution chemistry of mixed-ligand oxovanadium(IV) and oxovanadium(V) complexes incorporating tridentate ONO donor hydrazone ligands

In the title family, the ONO donor ligands are the acetylhydrazones of salicylaldehyde (H₂L¹) and 2-hydroxyacetophenone (H₂L²) (general abbreviation, H₂L). The reaction of bis(acetylacetonato)oxovanadium(IV) with a mixture of tridentate H₂L and a bidentate NN donor [e.g., 2,2′-bipyridine(bpy) or 1,10-phenanthroline(phen), hereafter B] ligands in equimolar ratio afforded the tetravalent complexes of the type [V^IVO(L)(B)]; complexes (1)-(4) whereas, if B is replaced by 8-hydroxyquinoline(Hhq) (which is a bidentate ON donor ligand), the above reaction mixture yielded the pentavalent complexes of the type [V^VO(L)(hq)]; complexes (5) and (6). Aerial oxygen is most likely the oxidant (for the oxidation of V^IV → V^V) in the synthesis of pentavalent complexes (5) and (6). [V^IVO(L)(B)] complexes are one electron paramagnetic and display axial EPR spectra, while the [V^VO(L)(hq)] complexes are diamagnetic. The X-ray structure of [V^VO(L²)(hq)] (6) indicates that H₂L² ligand is bonded with the vanadium meridionally in a tridentate dinegative fashion through its phenolic-O, enolic-O and imine-N atoms. The general bond length order is: oxo < phenolato < enolato. The V-O (enolato) bond is longer than V-O (phenolato) bond by ∼0.07 Å and is identical with V-O (carboxylate) bond. ¹H NMR spectrum of (6) in CDCl₃ solution indicates that the binding nature in the solid state is also retained in solution. Complexes (1)-(4) display two ligand-field transitions in the visible region near 820 and 480 nm in DMF solution and exhibit irreversible oxidation peak near +0.60 V versus SCE in DMSO solution, while complexes (5) and (6) exhibit only LMCT band near 535 nm and display quasi-reversible one electron reduction peak near −0.10 V versus SCE in CH₂Cl₂ solution. The VO³⁺-VO²⁺E_1/2 values shift considerably to more negative values when neutral NN donor is replaced by anionic ON donor species and it also provides better VO³⁺ binding via phenolato oxygen. For a given bidentate ligand, E_1/2 increases in the order: (L²)²⁻ < (L¹)²⁻.     

A vanadium-promoted C-N bond cleavage

A C-N bond in one arm of the mixed-valence V^III-V^IV complex bpbp(VOCl₂)(VCl₂), bpbpH = 2,6-bis((N,N-bis-(2-picolyl)amino)methyl)-4-tertbutylphenol, is cleaved in wet acetonitrile solution to give bpa(VOCl₂), bpa = bis(2-methypyridyl)amine, and 2-((N,N-bis-(2-picolyl)amino)methyl)-6-hydroxymethyl-4-tertbutylphenol. The reaction corresponds overall to hydrolysis of a tertiary amine to form a secondary amine and a primary alcohol. The structure of bpa(VOCl₂) was established by X-ray diffraction while 2-((N,N-bis-(2-picolyl)amino)methyl)-6-hydroxymethyl-4-tertbutylphenol was detected by ESI mass spectrometry. The phenol oxygen atom in bpbp(VOCl₂)(VCl₂) is proposed to be non-bridging and this asymmetry is likely to be important for the C-N bond cleavage reaction. A related asymmetrical V^IV complex, [bpbpH(VO)(H₂O)](ClO₄)₂ ·  H₂O, containing bpbp⁻ bound to only one metal ion, has also been characterized by X-ray diffraction. In slightly more basic solution, bpbp(VOCl₂)(VCl₂) is oxidized to the V^IV-V^IV complex [bpbp(VOCl)₂]⁺ and C-N bond cleavage is suppressed.     

Synthesis, characterization and anti-diabetic effect of bis[(1-R-imidazolinyl)phenolato]oxovanadium(IV) complexes

The five-coordinate oxovanadium(IV) complexes; [VO(pimin)₂] (1a), [VO(Etpimin)₂] (2) and [VO(EtOHpimin)₂] (3), were prepared by reacting the ligands; 2-(2′-hydroxyphenyl)-1H-imidazoline (piminH), 2-(2′-hydroxyphenyl)-1-ethylimidazoline (EtpiminH) and 2-(2′-hydroxyphenyl)-1-ethanolimidazoline (EtOHpiminH), with VOSO₄. The complexes were characterized by elemental analysis, IR, UV-Vis and cyclic voltammetry. All complexes show VO stretching vibrations between 932 and 987 cm⁻¹. The presence of three d-d transition occurring between 400 and 625 nm and the irreversible oxidation (V^IV → V^V) between 400 and 490 mV confirm the d¹ electronic configuration of the complexes. The solid state structures of [VO(pimin)₂] (1a) and its autoxidation hydrolysis product [VO₂(pimin)(piminH′)] (1b) were determined by single crystal X-ray diffraction. The geometry of [VO(pimin)₂] was found to be intermediate between trigonal bipyramidal and square pyramidal and sits on a crystallographic twofold axis, while the geometry of [VO₂(pimin)(piminH′)] was distorted trigonal bipyramidal. Potentiometric titrations were used to determine the protonation and stability constants for the ligands and oxovanadium(IV) complexes, respectively. The species existing over a biological pH range were also investigated. The in vitro studies indicated that the oxovanadium(IV) complexes were effective in enhancing glucose uptake in the 3T3-L1 adipocytes, C2C12 muscle cells and Chang liver cell lines. In these cell lines, the anti-hyperglycemic effect was equivalent to or surpassed the effect of metformin.     

Ferromagnetic coupling by the spin-polarization mechanism in a trinuclear V triplesalen complex

The first trinuclear vanadium complex [(talen^t-Bu₂)(V^IVO)₃] (1) of a triple tetradentate triplesalen ligand has been synthesized and characterized. The triplesalen ligand (talen^t-Bu₂)^6- provides three salen-like coordination environments bridged in a meta-phenylene arrangement by a phloroglucinol backbone. In the electronic absorption spectrum of 1 all four ligand field transitions are detected below 21 400 cm⁻¹. The region above 23 000 cm⁻¹ is dominated by strong absorption from imine π → π^∗ and ligand-to-ligand CT transitions. The latter may also be described by a combined phenolate-to-vanadium LMCT and vanadium-to-imine MLCT through the empty metal d orbitals in a push-pull type interaction. The temperature-dependent magnetic susceptibility measurements reveal a ferromagnetic coupling of the three V^IVO units in the triplesalen complex with J = +0.44 cm⁻¹. The correlation of the electronic structure to the weakness of the ferromagnetic coupling by the spin-polarization mechanism in the trinuclear VO system is discussed.     

Synthesis, structure, solution chemistry and the electronic effect of para substituents on the vanadium center in a family of mixed-ligand [VO(ONO)(ON)] complexes

Four tridentate dibasic ONO donor hydrazone ligands derived from the condensation of benzoylhydrazine with either 2-hydroxyacetophenone or its para substituted derivatives (H₂L^1-4, general abbreviation H₂L) have been used as primary ligands and 8-hydroxyquinoline (Hhq, a bidentate monobasic ON donor species) has been used as auxiliary ligand. The reaction of [V^IVO(acac)₂] with H₂L in methanol followed by the addition of Hhq in equimolar ratio under aerobic condition afforded the mixed-ligand oxovanadium(V) complexes of the type [V^VO(L)(hq)] (1-4) in excellent yield. The X-ray structure of the compound [V^VO(L⁴)(hq)] (4) indicates that the H₂L⁴ ligand is bonded with vanadium meridionally in a tridentate dinegative fashion through its deprotonated phenolic-O, deprotonated enolic-O and imine-N atoms. The V-O bond length order is: oxo < phenolato < enolato. ¹H NMR spectra of 4 in CDCl₃ solution indicates that it’s solid-state structure is retained in solution. Complexes are diamagnetic and exhibit only ligand to metal charge transfer (LMCT) transition band near 530 nm in CH₂Cl₂ solution in addition to intra-ligand π → π^∗ transition band near 335 nm and they display quasi-reversible one electron reduction peak near − 0.10 V versus SCE in CH₂Cl₂ solution. λ_max (for LMCT transition) and the reduction peak potential values of the complexes are found to be linearly related with the Hammett (σ) constants of the substituents in the aryloxy ring of the hydrazone ligands. λ_max and values show large dependence dλ_max/dσ = 32.54 nm and V, respectively, on the Hammett constant.     

Effects of decavanadate and insulin enhancing vanadium compounds on glucose uptake in isolated rat adipocytes

The effects of different vanadium compounds namely pyridine-2,6-dicarboxylatedioxovanadium(V) (V5-dipic), bis(maltolato) oxovanadium(IV) (BMOV) and amavadine, and oligovanadates namely metavanadate and decavanadate were analysed on basal and insulin stimulated glucose uptake in rat adipocytes. Decavanadate (50 μM), manifest a higher increases (6-fold) on glucose uptake compared with basal, followed by BMOV (1 mM) and metavanadate (1 mM) solutions (3-fold) whereas V5 dipic and amavadine had no effect. Decavanadate (100 μM) also shows the highest insulin like activity when compared with the others compounds studied. In the presence of insulin (10 nM), only decavanadate increases (50%) the glucose uptake when compared with insulin stimulated glucose uptake whereas BMOV and metavanadate, had no effect and V5 dipic and amavadine prevent the stimulation to about half of the basal value. Decavanadate is also able to reduce or eradicate the suppressor effect caused by dexamethasone on glucose uptake at the level of the adipocytes. Altogether, vanadium compounds and oligovanadates with several structures and coordination spheres reveal different effects on glucose uptake in rat primary adipocytes.     

DNA cleavage activity of VO(acac)2 and derivatives

The DNA cleavage activity of several β-diketonate vanadyl complexes is examined. Vanadyl acetylacetonate, V^IVO(acac)₂, 1, shows a remarkable activity in degrading plasmid DNA in the absence of any activating agents, air and photoirradiation. The cleaving activity of several related complexes V^IVO(hd)₂ (2, Hhd = 3,5-heptanedione), V^IVO(acac-NH₂)₂ (3, Hacac-NH₂ = acetoacetamide) and V^IVO(acac-NMe₂)₂ (4, Hacac-NMe₂ = N,N-dimethylacetoacetamide) is also evaluated. It is shown that 2 exhibits an activity similar to 1, while 3 and 4 are much less efficient cleaving agents. The different activity of the complexes is related to their stability towards hydrolysis in aqueous solution, which follows the order 1∼2 ? 3∼4. The nature of the pH buffer was also found to be determinant in the nuclease activity of 1 and 2. In a phosphate buffered medium DNA cleavage by these agents is much more efficient than in tris, hepes, mes or mops buffers. The reaction seems to take place through a mixed mechanism, involving the formation of reactive oxygen species (ROS), namely OH radicals, and possibly also direct cleavage at phosphodiester linkages induced by the vanadium complexes.     

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.     

Synthesis, crystal structure and magnetism of a new mixed germanium-polyoxovanadate cluster

A new germanium-polyoxovanadate, (H₃aep)₄[V₁₄Ge₈O₅₀]·2(aep)·13H₂O (1), has been synthesized under solvothermal conditions applying GeO₂, NH₄VO₃, Cu(NO₃)₂·3H₂O and an aqueous solution of 1-(2-aminoethyl)-piperazine (aep, C₆H₁₈N₃) in the temperature range from 110 to 150 °C. The compound crystallizes in the non-centrosymmetric tetragonal space group P-42₁c with a = 17.193(1) Å, c = 16.501(1) Å, V = 4877.9(5) Å³ and Z = 2. The structure consists of isolated spherical [V^IV₁₄Ge^IV₈O₅₀]¹²⁻ cluster anions and protonated amine molecules as counterions. The cluster anion can be viewed as a derivative of the [V₁₈O₄₂] archetype by replacing four VO₅ pyramids by four Ge₂O₇ units. The latter are formed by corner-sharing of two [GeO₄]⁴⁻ tetrahedra. At temperatures above 150 °C the compound (H₂pip)₄(Hpip)₄[V^IV₁₄Ge^IV₈O₅₀(H₂O)] (2) (pip = piperazine, C₄N₂H₁₀) is formed and during the reaction Cu²⁺ is reduced to elemental copper. This redox reaction is essential for the formation of 2. The crystal water molecules in the structure of 1 are emitted at low temperatures. The magnetic properties are dominated by strong intra-cluster antiferromagnetic coupling and the strongest exchange between edge- and corner-sharing VO₅ square pyramids results in an eight-membered spin ring to which two three-membered spin bridges are joined. The magnetic susceptibility data suggest that even at the low temperature of 2 K several multiplet states are still significantly populated.     

A fresh look into VO(salen) chemistry: synthesis, spectroscopy, electrochemistry and crystal structure of [VO(salen)(H2O)]Br · 0.5 CH3CN

The reaction of V^IVO(salen) with [Et₄N][SnBr₃] in air proceeds via an initial reduction to give a [V^III (salen)]⁺ intermediate, which is then oxidised to dark green [V^VO(salen)(H₂O)]Br, 1. As determined by X-ray crystallography, 1 in the solid state contains hexacoordinate vanadium. ⁵¹V NMR spectra indicate that dissociation of the aqua ligand occurs to give a pentacoordinated [V^VO(salen)] cation in methanol-d₄ solution, while in DMSO-d₆ solutions, coordination of the solvent occurs to give [V^VO(salen)(DMSO-d₆)]⁺. The colour of 1 can be accounted for by O_oxo → V^V and phenolate → V^V LMCTs. Results from this study have led to the re-assignment of LMCTs and V-N and V-O_phenolate stretching frequencies in the IR spectrum. Cyclic voltammetry of 1 indicates three redox processes. The first is typical of [VO(salen)]/[VO(salen)]⁺ couple and the other two are bromide oxidations.     

Synthesis, characterization, and protein tyrosine phosphatases inhibition activities of oxovanadium(IV) complexes with Schiff base and polypyridyl derivatives

Seven new mixed-ligand vanadyl complexes, [V^IVO(5-Br-SAA)(NN)] and [V^IVO(2-OH-NAA)(NN)] (1-7) (5-Br-SAA for 5-bromosalicylidene anthranilic acid, 2-OH-NAA for 2-hydroxy-1-naphthaldehyde anthranilic acid and NN for N,N′-donor heterocyclic base, namely, 2,2′-bipyridine (bpy, 1 and 5), 1,10-phenanthroline (phen, 2 and 6), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3 and 7), dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 4)), were synthesized and characterized. X-ray crystal structure of [V^IVO(5-Br-SAA)(phen)] revealed a distorted octahedral geometry with the Schiff base ligand coordinated in a tridentate ONO-fashion and the phenanthroline ligand in a bidentate fashion. Density-functional theory (DFT) calculations suggest a similar structure and the same coordination mode for all the other oxovanadium complexes synthesized. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of protein tyrosine phosphatase 1B (PTP1B), with IC₅₀ values approximately 41-75 nM. Kinetics assays suggest that the complexes inhibit PTP1B in a competitive manner. Notably, they had moderate selectivity of PTP1B over T-cell protein tyrosine phosphatase (TCPTP) (about 2-fold) and good selectivity over Src homology phosphatase 1 (SHP-1) (about 4∼7-fold). Thus, these mixed-ligand complexes represent a promising class of PTP1B inhibitors for future development as anti-diabetic agents.     

Vanadium chemistry and biochemistry of relevance for use of vanadium compounds as antidiabetic agents

The stability of 11 vanadium compounds is tested under physiological conditions and in administration fluids. Several compounds including those currently used as insulin-mimetic agents in animal and human studies are stable upon dissolution in distilled water but lack such stability in distilled water at pH7. Complex lability may result in decomposition at neutral pH and thus may compromise the effectiveness of these compounds as therapeutic agents; Even well characterized vanadium compounds are surprisingly labile. Sufficiently stable complexes such as the VEDTA complex will only slowly reduce, however, none of the vanadium compounds currently used as insulin-mimetic agents show the high stability of the VEDTA complex. Both the bis(maltolato)oxovanadium(IV) and peroxovanadium complexes extend the insulin-mimetic action of vanadate in reducing cellular environments probably by increased lifetimes under physiological conditions and/or by decomposing to other insulin mimetic compounds. For example, treatment with two equivalents of glutathione or other thiols the (dipicolinato)peroxovanadate(V) forms 9dipicolinato)oxovanadate(V) and vanadate, which are both insulin-mimetic vanadium(V) compounds and can continue to act. The reactivity of vanadate under physiological conditions effects a multitude of biological responses. Other vanadium complexes may mimic insulin but not induce similar responses if the vanadate formation is blocked or reduced. We conclude that three properties, stability, lability and redox chemistry are critical to prolong the half-life of the insulin-mimetic form of vanadium compounds under physiological conditions and should all be considered in development of vanadium-based oral insulin-mimetic agents.Abbreviations ADP adenosine 5-diphosphate - ATP adenosine 5-triphosphate - ADP-V adenosine 5-diphosphate-vanadate - bpV bis(peroxo)oxovanadium(V) - (bpV)2 bis(peroxo)oxovanadium(V) dimer - bpVpic bis(peroxo)picolinatooxovanadate(V) - ¹³C carbon-13 - EDTA ethylenediaminetetraacetic acid - EPR electron paramagnetic resonance - EXSY exchange spectroscopy - ¹H proton - HSG glutathione - NAD -nicotinamide adenine dinucleotide - NADP -nicotinamide adenine dinucleotide phosphate - NADV -nicotinamide adenine dinucleotide vanadate - NMR nuclear magnetic resonance (also referred to as magnetic resonance imaging) - pVdipic (dipicolinato)peroxovanadate(V) - Vcit (citrato)dioxovanadate(V) - VEDTA (ethylenediaminetetraacetato)dioxovanadate(V) - Vmalto bis(maltolato)-oxovanadium(IV) - Voxal bis(oxalato)dioxovanadate(V) - ⁵¹V vanadium-51 - V₁ vanadate monomer - V₂ vanadate dimer - V₄ vanadate tetramer - V₅ vanadate pentamer - UV-vis spectroscopy ultraviolet-visible spectroscopy     

Synthesis of soluble coordination polymer nanoparticles using room-temperature ionic liquid

We report a new family of soluble cyano-bridged coordination polymer nanoparticles M₃[Cr(CN)₆]₂/[BMIM][BF₄] (where M²⁺ = Ni, Mn, V^IVO; BMIM = 1-butyl-3-methylimidazolium). These nanoparticles of ca. 6 nm were synthesised in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate, which acts both as a stabilizing agent and a solvent. The magnetic properties of frozen colloids containing the nanoparticles show that the relaxation of magnetisation is strongly influenced by interparticle interactions leading to the appearance of spin-glass-like dynamics in these systems.     

The vanadyl (VO2+) chelate bis(acetylacetonato)oxovanadium(IV) potentiates tyrosine phosphorylation of the insulin receptor

We have compared the insulin-like activity of bis(acetylacetonato)oxovanadium(IV) [VO(acac)₂], bis(maltolato)oxovanadium(IV) [VO(malto)₂], and bis(1-N-oxide-pyridine-2-thiolato)oxovanadium(IV) [VO(OPT)₂] in differentiated 3T3-L1 adipocytes. The insulin-like influence of VO(malto)₂ and VO(OPT)₂ was decreased compared with that of VO(acac)₂. Also, serum albumin enhanced the insulin-like activity of all three chelates more than serum transferrin. Each of the three VO²⁺ chelates increased the tyrosine phosphorylation of proteins in response to insulin, including the β-subunit of the insulin receptor (IRβ) and the insulin receptor substrate-1 (IRS1). However, VO(acac)₂ exhibited the greatest synergism with insulin and was therefore further investigated. Treatment of 3T3-L1 adipocytes with 0.25 mM VO(acac)₂ in the presence of 0.25 mM serum albumin synergistically increased glycogen accumulation stimulated by 0.1 and 1 nM insulin, and increased the phosphorylation of IRβ, IRS1, protein kinase B, and glycogen synthase kinase-3β. Wortmannin suppressed all of these classical insulin-signaling activities exerted by VO(acac)₂ or insulin, except for tyrosine phosphorylation of IRβ and IRS1. Additionally, VO(acac)₂ enhanced insulin signaling and metabolic action in insulin-resistant 3T3-L1 adipocytes. Cumulatively, these results provide evidence that VO(acac)₂ exerts its insulin-enhancing properties by directly potentiating the tyrosine phosphorylation of the insulin receptor, resulting in the initiation of insulin metabolic signaling cascades in 3T3-L1 adipocytes.     

Investigation of the insulin-like properties of zinc(II) complexes of 3-hydroxy-4-pyridinones: identification of a compound with glucose lowering effect in STZ-induced type I diabetic animals

Results from an investigation in an in vivo model of STZ-induced diabetic rats demonstrate that compound bis(1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate)zinc(II), Zn(dmpp)₂, significantly lowers the blood glucose levels of individuals, thus showing evidence of glucose lowering activity.The compound was selected from a set of eight zinc(II) complexes of 3-hydroxy-4-pyridinones with diverse lipophilicity that were prepared and characterized in our laboratory. Assessment of insulin-like activity of the complexes was firstly performed in vitro by measuring the inhibition of FFA release in isolated rat adipocytes. The results indicate that compounds bis(2-methyl-3-hydroxy-4-pyridinonate)zinc(II), Zn(mpp)₂ and Zn(dmpp)₂ display significantly higher activity than that of the respective positive control thus suggesting its selection for in vivo tests.Safety evaluation of the active zinc(II) compounds was performed in freshly isolated rat hepatocytes. The results support that cell viability is not significantly different from the control set after 1 and 2 h of incubation with both zinc(II) 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.     

Two dumbbell-like polyoxometalates constructed from capped molybdovanadate and transition metal complexes

Self assembly of NaVO₃, Na₂MoO₄·2H₂O and NiCl₂·6H₂O with the assistance of organic liginds under hydrothermal conditions results in two molybdovanadates [Ni(enMe)₂]₄{[Ni(enMe)₂(H₂O)]₂[Ni(enMe)₂][(V^VMo^VI₈V₄^IVO₄₀)(V^IVO)₂]₂}·10H₂O (1) and [Ni(enMe)₂]₅{[Ni(enMe)₂]₂[(V^VMo^VI₄Mo^V₄V₄^IVO₄₀)(V^IVO)₄]₂}·2H₂O (2), (enMe = 1,2-diaminopropane), which have been characterized by single crystal X-ray diffraction analysis, IR spectroscopy, and elemental analysis. Both of the two compounds exhibit dumbbell-like structures constructed from capped polyoxomolybdovanadates and [Ni(enMe)₂]²⁺ complexes. Polyoxoxanion 1 is composed of two bicapped Keggin-type anions [(V^VMo₈V₄^IVO₄₀)(V^IVO)₂]⁷⁻, one [Ni(enMe)₂]²⁺ bridging fragment and two decorated nickel(II) complexes. Polyxoxanion 2 consists of two tetracapped molybdenum-vanadium polyoxoanions [(V^VMo^VI₄Mo^V₄V₄^IVO₄₀)(V^IVO)₄]⁷⁻, one [Ni(enMe)₂]²⁺ bridging fragment and a nickel(II) decorated fragment. Polyxoxanions 1 and 2 are further linked to form three-dimensional supramolecular networks through extensive hydrogen bonding interactions. In addition, photocatalysis properties of these two compounds have been investigated.     

Preparation, crystal structures and spectroscopic properties of novel [MCl3 − n(P)3 + n] (M = Co, Rh; n = 0, 1, 2 or 3) series of complexes containing tripodal tridentate phosphine, 1,1,1-tris(dimethylphosphinomethyl)ethane

Cobalt(III) and rhodium(III) complexes of the series of [M^IIICl_3 − n(P)_3 + n]ⁿ⁺ (M = Co or Rh; n = 0, 1, 2 or 3) have been prepared with the use of 1,1,1-tris(dimethylphosphinomethyl)ethane (tdmme) and mono- or didentate phosphines. The single-crystal X-ray analyses of both series of complexes revealed that the M-P and M-Cl bond lengths were dependent primarily on the strong trans influence of the phosphines, and secondarily on the steric congestion around the metal center resulting from the coordination of several phosphine groups. In fact, the M-P(tdmme) bonds became longer in the order of [MCl₃(tdmme)] < [MCl₂(tdmme)(PMe₃)]⁺ < [MCl(tdmme)(dmpe)]²⁺ (dmpe = 1,2-bis(dimethylphosphino)ethane) < [M(tdmme)₂]³⁺ for both Co^III and Rh^III series of complexes, while the M-Cl bond lengths were shortened in this order (except for [M(tdmme)₂]³⁺). Such a steric congestion around the metal center can also account for the structural and spectroscopic characteristics of the series of complexes, [MCl(tdmme)(dmpm, dmpe or dmpp)]²⁺ (dmpm = bis(dimethylphosphino)methane, dmpp = 1,3-bis(dimethylphosphino)propane). The X-ray analysis for [CoCl(tdmme)(dmpm or dmpe)](BF₄)₂ showed that all Co-P bonds in the dmpm complex were shorter by 0.03-0.04 Å than those in the dmpe complex. Furthermore, the first d-d transition energy of the Co^III complexes and the ¹J_Rh-P(tdmme) coupling constants observed for the Rh^III complexes indicated an unusual order in the coordination bond strengths of the didentate diphosphines, i.e., dmpm > dmpe > dmpp.     

Synthesis and spectral investigation of manganese(II), cadmium(II) and oxovanadium(IV) complexes with 2,6-diacetylpyridine bis(2-aminobenzoylhydrazone): Crystal structure of manganese(II) and cadmium(II) complexes

The chelating behavior of 2,6-diacetylpyridine bis(2-aminobenzoylhydrazone) (H₂dapa) towards manganese(II), cadmium(II) and oxovanadium(IV) ions has been studied by elemental analyses, conductance measurements, magnetic properties and spectral (IR, ¹H NMR, UV-Vis and EPR) studies. The IR spectral studies suggest the pentadentate nature of the ligand with pyridine nitrogen, two azomethine nitrogens and two carbonyl oxygen atoms as the ligating sites. Six coordinate structure for [VO(H₂dapa)]SO₄ · H₂O and seven coordinate structures for [Mn(H₂dapa)(Cl)(H₂O)]Cl · 2H₂O and [Cd(H₂dapa)Cl₂] · H₂O complexes have been proposed. Pentagonal bipyramidal geometry for [Mn(H₂dapa)(Cl)(H₂O)]Cl · 2H₂O and [Cd(H₂dapa)(Cl₂)] · H₂O complexes was confirmed by single crystal analysis. The X-band EPR spectra of the oxovanadium(IV) and manganese(II) complexes in the polycrystalline state at room (300 K) and also at liquid nitrogen temperature (77 K) were recorded and their salient features are reported.