Hydrazido complexes prepared by methylation of an anionic end-on bridging dinitrogen dititanium complex.

Here we report stepwise methylation of end-on bridging dinitrogen to a hydrazido ligand to a pentamethylhydrazinium salt, which is mediated by a titanium system with a tripodal aryloxide supporting ligand. The results constitute a synthetic cycle for pentamethylhydrazinium formation from dinitrogen and methyl iodide. We also describe silylation of the dinitrogen complex and carboxylation of the hydrazido complex.

Dinitrogen Functionalization with Carbon Dioxide and Carbon Disulfide Giving Symmetric and Unsymmetric Hydrazido Complexes.

Here we show that a tridentate bis(aryloxide)anilide-ligated titanium/potassium scaffold promotes functionalization of coordinated N2 with CO2 and CS2 through formation of N-C bonds. Treatment of a naphthalene complex with N2 gave an end-on bridging dinitrogen complex featuring a [Ti2 K2 N2 ] core. The dinitrogen complex underwent insertion of CO2 into each Ti-NN bond to afford an N,N'-dicarboxylated hydrazido complex. Stepwise nitrogen-carbon bond formation at coordinated N2 proceeded to afford an unsymmetric hydrazido complex upon sequentially treating the dinitrogen complex with CS2 and CO2 . Addition of Me3 SiCl to the dicarboxylated hydrazido complex resulted in partial silylation of the carboxylate groups but did not lead to removal of the functionalized N2 unit from the metal centers. However, reduction of the dicarboxylated hydrazido complex with potassium naphthalenide afforded an oxo-bridged dinuclear complex along with release of free potassium cyanate.

Lewis Acid-Induced Dinitrogen Cleavage in an Anionic Side-on End-on Bound Dinitrogen Diniobium Hydride Complex.

The side-on end-on dinitrogen hydride complex [{Na(dme)}2{(O3)Nb}2(µ-η1:η2-N2)(µ-H)2] (3-Na, [O3]3- = [(3,5-tBu2-2-O-C6H2)3CH]3-) was observed to undergo facile elimination of H2 and cleavage of the N-N bond in the presence of 9-borabicyclo[3.3.1]nonane (9-BBN), AlMe3, and ZnMe2. Treatment of 3-Na with 9-BBN and ZnMe2 afforded the nitride complex [{K(dme)2}2{(O3)Nb}2(µ-N)2] (2-Na). The reaction of 3-Na with AlMe3 afforded [{Na(dme)}2{(O3)AlMe}2(NbMe2)2(µ-N)2] (5). The nitride complex 2-Na was treated with 9-BBN and AlMe3 to form [{Na(dme)}2{(O3)Nb}(µ-NH)(µ-NBC8H14){Nb(O3C)}] (4) and 5, respectively. Complex 2-Na, 4, and 5 were structurally characterized.

Systematic reductive oligomerization of isocyanides with a vanadium(ii) complex.

Using a V(ii) complex as a reducing reagent, we demonstrate controlled reduction of isocyanides, resulting in decyanation of alkyl isocyanides to form a V(iii) cyanide complex or oligomerization of aryl isocyanides to form trimers and a tetramer. The pathways leading to the trimers involve a divanadium ynediamido intermediate, which further reacts with the third isocyanide molecule to selectively produce a tri(imino)deltate or an indolenine complex, by altering the temperature and stoichiometry.

Autoimmune myelofibrosis associated with systemic lupus erythematosus: a case report.

A 66-year-old woman presented with severe anaemia, thrombocytopenia and lymphopenia. The bone marrow biopsy demonstrated hypocellular marrow with myelofibrosis (MF); there was no evidence of malignancy, but infiltration of peripheral T and B cells were noticed. Magnetic resonance imaging (MRI) revealed that bone marrow of the spine exhibited low signal intensity (SI) with spotty high SI in T1- and T2-weighted images. Because there was evidence of autoimmune abnormality, she had fulfilled the classification criteria for systemic lupus erythematosus (SLE). She was diagnosed with autoimmune myelofibrosis (AIMF) associated with SLE and was treated with corticosteroid. Cytopenia improved after 1 month of corticosteroid therapy. A repeated bone marrow biopsy demonstrated that cellularity had increased and that the amount of reticulin fibre had reduced after treatment. Compared with primary MF, AIMF has generally a favourable prognosis and is often associated with autoimmune diseases, especially SLE. Bone marrow biopsy, but not aspiration, was useful for diagnosing bone marrow fibrosis. Although the association between SLE and MF has been rarely reported, we should pay attention to MF as a possible cause of pancytopenia.

Counterion Dependence of Dinitrogen Activation and Functionalization by a Diniobium Hydride Anion.

We report the synthesis of anionic diniobium hydride complexes with a series of alkali metal cations (Li+ , Na+ , and K+ ) and the counterion dependence of their reactivity with N2 . Exposure of these complexes to N2 initially produces the corresponding side-on end-on N2 complexes, the fate of which depends on the nature of countercations. The lithium derivative undergoes stepwise migratory insertion of the hydride ligands onto the aryloxide units, yielding the end-on bridging N2 complex. For the potassium derivative, the N-N bond cleavage takes place along with H2 elimination to form the nitride complex. Treatment of the side-on end-on N2 complex with Me3 SiCl results in silylation of the terminal N atom and subsequent N-N bond cleavage along with H2 elimination, giving the nitride-imide-bridged diniobium complex.

Synthesis and structures of titanium complexes bearing tetradentate tripodal [O2XC] ligands (X = C, P).

We report the synthesis and structures of titanium complexes supported by tripodal mixed-donor [O2CC] and [O2PC] ligands. Stepwise cyclometallation of a chelating bis(phenoxide) complex led to tetradentate binding of the [O2CC] ligand to the titanium center. Phosphination of a Ti-C bond of the [O2CC] complex afforded the tripodal [O2PC] ligand.

An anionic η2-naphthalene complex of titanium supported by a tripodal [O3C] ligand and its reactions with dinitrogen, anthracene and THF.

We report the synthesis and characterization of a dianionic titanium naphthalene complex supported by a tripodal triaryloxidemethyl ligand, which is a rare example of an η2-coordinated arene complex of low-valent early transition metals. The η2-naphthalene ligand is readily displaced by N2 and anthracene along with the release of free naphthalene, resulting in the formation of the end-on N2 bridging dititanium complex and the anthracene complex, respectively. The naphthalene complex undergoes C-O bond cleavage of THF to produce a 1-oxa-2-titanacyclohexane.

Nitrogen-Carbon Bond Formation by Reactions of a Titanium-Potassium Dinitrogen Complex with Carbon Dioxide, tert-Butyl Isocyanate, and Phenylallene.

Nitrogen-carbon bond-forming reactions at coordinated dinitrogen in a bifunctional titanium-potassium system are reported. A titanium atrane complex with a tris(aryloxide)methyl ligand (1) was treated with two equivalents of potassium naphthalenide under N2 atmosphere to generate a bifunctional complex (2) in which N2 binds end-on to two titanium centers and side-on to three potassium cations. Dinitrogen complex 2 reacted with carbon dioxide, tert-butyl isocyanate, and phenylallene, forming nitrogen-carbon bonds and affording diverse N-functionalized products. The reaction of 2 with CO2 followed by addition of Me3 SiCl resulted in the formation of the starting complex 1 with concomitant release of silylated carboxyl hydrazines while the reaction with two equivalents of tert-butyl isocyanate proceeded by insertion into the Ti-N bonds. Treatment of 2 with phenylallene afforded vinyl-substituted hydrazido complexes.

Synthesis and Structural Characterization of Lithium and Titanium Complexes Bearing a Bulky Aryloxide Ligand Based on a Rigid Fused-Ring s-Hydrindacene Skeleton.

The bulky aryl alcohols, (Rind)OH (1) [Rind = EMind (a) and Eind (b)], based on the rigid fused-ring 1,1,3,3,5,5,7,7-octa-R-substituted s-hydrindacene skeleton were prepared by the reaction of (Rind)Li with nitrobenzene followed by protonation. The treatment of 1 with (n)BuLi affords the lithium aryloxide dimers [(Rind)OLi(THF)]2 (2) or trimers [(Rind)OLi]3 (3), depending on the employed solvents (THF = tetrahydrofuran). The salt metathesis reaction of [(EMind)OLi(THF)]2 (2a) with TiCl4(THF)2 leads to the formation of the mononuclear diamagnetic mono- and bis(aryloxide) Ti(IV) complexes, [(EMind)O]TiCl3(THF) (4a) and [(EMind)O]2TiCl2 (5a). We also isolated a trace amount of the tris(aryloxide) Ti(IV) complex, [(EMind)O]3TiCl (6a). The reaction between 2a and TiCl3(THF)3 resulted in the isolation of the mononuclear paramagnetic mono- and bis(aryloxide) Ti(III) complexes, [(EMind)O]TiCl2(THF)2 (7a) and [(EMind)O]2TiCl(THF)2 (8a). The discrete monomeric structures of the titanium complexes 4a, 5a, 6a, 7a, and 8a were determined by X-ray crystallography.

Synthesis and reactions of a zirconium naphthalene complex bearing a tetraanionic C-capped triaryloxide ligand.

Treatment of [(O3C)Zr(thf)3] (1; [O3C]4- = [(3,5-tBu2-2-OC6H2)3C]4-) with 2 equiv. of potassium naphthalenide in DME produced [{K(dme)}2(O3C)Zr(C10H8)] (2), in which the [(O3C)Zr] fragment is η4-bound to one ring of the naphthalene ligand. Complex 2 underwent facile exchange with free naphthalene, and addition of anthracene into a solution of 2 resulted in clean formation of an anthracene complex [{K2(dme)3}(O3C)Zr(C14H10)] (3). The reaction of 2 with an excess of Me3SiN3 involves generation of an imide intermediate via extrusion of N2 and Si-N bond cleavage, and an amide complex [{K(thf)2}(O3C)Zr{N(SiMe3)2}(thf)] (4) was isolated. Analogously, treatment of 2 with mesityl azide (MesN3) followed by addition of Me3SiN3 afforded [{K(thf)2}(O3C)Zr{N(Mes)(SiMe3)}(thf)] (5). Hydrogenation of 2 provided a hydride-bridged dizirconium complex [{K(thf)2}3{(O3C)Zr}2(µ-H)3] (6) along with tetralin. The solid-state structures of 2, 4, and 5 were established by single-crystal X-ray diffraction studies.

Zirconium Hydride Complex Supported by a Tetradentate Carbon-Centered Tripodal Tris(aryloxide) Ligand: Synthesis, Structure, and Reactivity.

A dizirconium trihydride complex supported by a tetradentate carbon-centered tris(aryloxide) ligand [{Na(dme)}3{(O3C)Zr}2(µ-H)3] (2; [O3C] = [(3,5-(t)Bu2-2-O-C6H2)3C](4-)) was prepared by reacting [(O3C)Zr(thf)3] (1) with NaBHEt3 in toluene. Exposure of 2 in THF to CO2 (1 atm) resulted in facile insertion of CO2 into Zr-H bonds, yielding a formate complex [{Na(thf)2}3{(O3C)Zr}2(µ-O2CH)3] (3). Treatment of 2 with P4 in toluene led to formation of [Na(thf)5][{Na(thf)2}2{(O3C)Zr}2(µ-P3)] (4) and PH3, in which hydrogenation of P4 took place. Complex 2 reacted with Me3SiN3 to afford an azide-bridged cyclotrimer [{Na(thf)2}{(O3C)ZrN3(thf)}]3 (5) with concomitant liberation of Me3SiH. The molecular structures of these complexes 2-5 have been determined by X-ray diffraction analyses.

[Some case reports which suggest correlation between biologics and leprosy, Mini-symposium on problems on leprosy].

Biologics are relatively new drugs developed through modern monoclonal antibody techniques and became more familiar to some disease treatments such as Rheumatoid arthritis, psoriasis, ankylosing spondylitis, ulcerative colitis, malignant lymphoma, SLE and lupus nephritis. Some case reports shows development of leprosy during/after biolo- gics treatment and success treatment of ENL with biologics. Collection of reports was done through web search by using document retrieval engine such as Pub-med and ProQuest. 7 cases of development of leprosy with biologics and 2 cases of ENL treatment with biologics and they were reported in the mini-symposium of Annual academic meeting of Japan Leprosy association. The widespread use of biologics reminds us of development of some infectious diseases as a side-effect and leprosy might be one of them. Because number of the reports was still very limited, we cannot go to further discussion at this moment. Accu- mulation of reported cases will lead the detailed information about correlation between biologics and leprosy, either on effectiveness or on adverse ones.

Nitrogen atom transfer from a dinitrogen-derived vanadium nitride complex to carbon monoxide and isocyanide.

Reduction of [(ONO)V(THF)] with KH under an N2 atmosphere cleaves the N≡N bond to afford a bis(µ-nitride) V(IV) dimer. This complex is oxidized to generate a V(V) nitride. The reactions of the V(V) nitride with carbon monoxide and isocyanide led to formation of cyanate and carbodiimide complexes. Following treatment of the cyanate complex with alkyne produces an alkyne adduct along with the release of potassium cyanate. Dissolution of the alkyne adduct in THF regenerates the starting complex [(ONO)V(THF)], thereby closing a synthetic cycle for conversion of N2 and CO into [NCO](-).

Methylene-linked anilide-bis(aryloxide) ligands: lithium, sodium, potassium, chromium(III), and vanadium(III) ligation.

The anilide-bis(aryloxide) proligands H3[ONO(R)] (where H3[ONO(R)] = 2,6-(3-R(1)-5-R(2)-2-hydroxybenzyl)-4-tert-butyl-N-tolyl-aniline; H3[ONO(tBu)], R(1) = (t)Bu, R(2) = Me; H3[ONO(Me)], R(1) = Me, R(2) = (t)Bu; H3[ONO(Me2)], R(1) = R(2) = Me) were synthesized from 2-bromo-5-tert-butyl-isophthalic acid dimethyl ester in three steps in multigram scale. The ligand precursor H3[ONO(tBu)] was readily doubly and triply deprotonated with alkali metal reagents to generate the related derivatives M2[H(ONO(tBu))] and M3[ONO(tBu)] (M = Li, Na, K). The extent of ligand deprotonation is observed to depend on the choice of deprotonating reagents and solvents. Transmetalation reaction of the trilithium derivative Li3[ONO(tBu)] with MCl3(THF)3 (M = Cr, V; THF = tetrahydrofuran) afforded [(ONO(tBu))CrCl(THF){Li(THF)}] (5) and [(ONO(tBu))V(THF)] (6). The vanadium complex 6 reacted readily with 2-butyne, styrene oxide, and mesityl azide, yielding [(ONO(tBu))V(η(2)-MeCCMe)] (7), [(ONO(tBu))V(O)] (8), and [(ONO(tBu))V(NMes)] (9), respectively. The solid-state structures of H3[ONO(tBu)] and metal complexes were determined by X-ray crystallography. The [ONO(tBu)] ligand adopts a u-shaped structure in solution and solid state.

[Effectiveness of thalidomide for erythema nodosum leprosum (ENL): retrospective study of 20 Japanese cases in National Sanatrium Oku-Komyoen].

Thalidomide is a TNF-alpha inhibitor and has been administrated for erythema nodosum leprosum (ENL, Type II leprosy reaction) which is one of leprosy reactions and can cause serious illness to patients oflepromatous pole among the immune spectrum. Twenty live cases (at May, 2011) were identified to whom thalidomide had been administrated since 1978 for their ENL reactions. Data were collected from their clinical records in order to evaluate the usage and effectiveness of thalidomide in National Sanatorium Oku-Komyoen, Okayama, Setouchi-city, Japan. Individual data includes bacillary index (BI), total dose, average daily dose, maximum daily dose, minimum daily dose, methods of thalidomide administration and change of symptoms of ENL. Results: No adverse effect was found among 20 cases. Average daily dose of 20 cases was 19 mg. Regarding to the maximum daily dose, in 3 cases (15%) more than 100 mg, in 3 cases (15%) 50 mg, and in 14 cases (70%) less than 40 mg was administrated. Dose was gradually tapered in most cases. From clinical records, thalidomide was found effective for ENL in 19 cases and clinicians concerned were trying to adjust the proper dose of the drug carefully depending on the current symptoms, because there was no guideline of thalidomide administration for ENL. This data suggests that even less than 50-100 mg as the initial daily dose was still effective, though 50-100 mg daily dose is recommended in the current guideline of Japan (2011) and more dose had been administrated in USA and India.

Synthesis of titanium and zirconium complexes supported by a p-terphenoxide ligand and their reactions with N2, CO2 and CS2.

The synthesis, characterization and reactions of a series of titanium and zirconium complexes that incorporate a p-terphenolate ligand are described.

The rare sugar D-allose acts as a triggering molecule of rice defence via ROS generation.

Only D-allose, among various rare monosaccharides tested, induced resistance to Xanthomonas oryzae pv. oryzae in susceptible rice leaves with defence responses: reactive oxygen species, lesion mimic formation, and PR-protein gene expression. These responses were suppressed by ascorbic acid or diphenylene iodonium. Transgenic rice plants overexpressing OsrbohC, encoding NADPH oxidase, were enhanced in sensitivity to D-allose. D-Allose-mediated defence responses were suppressed by the presence of a hexokinase inhibitor. 6-Deoxy-D-allose, a structural derivative of D-allose unable to be phosphorylated, did not confer resistance. Transgenic rice plants expressing Escherichia coli AlsK encoding D-allose kinase to increase D-allose 6-phosphate synthesis were more sensitive to D-allose, but E. coli AlsI encoding D-allose 6-phosphate isomerase expression to decrease D-allose 6-phosphate reduced sensitivity. A D-glucose 6-phosphate dehydrogenase-defective mutant was also less sensitive, and OsG6PDH1 complementation restored full sensitivity. These results reveal that a monosaccharide, D-allose, induces rice resistance to X. oryzae pv. oryzae by activating NADPH oxidase through the activity of D-glucose 6-phosphate dehydrogenase, initiated by hexokinase-mediated conversion of D-allose to D-allose 6-phosphate, and treatment with D-allose might prove to be useful for reducing disease development in rice.

Phosphorylation of D-allose by hexokinase involved in regulation of OsABF1 expression for growth inhibition in Oryza sativa L.

We previously reported that a rare sugar D-allose, which is the D-glucose epimer at C3, inhibits the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of α-amylase in embryo-less half seeds in rice (Fukumoto et al. 2011). D-Allose suppresses expressions of gibberellin-responsive genes downstream of SLR1 protein in the gibberellin-signaling through hexokinase (HXK)-dependent pathway. In this study, we discovered that D-allose induced expression of ABA-related genes including OsNCED1-3 and OsABA8ox1-3 in rice. Interestingly, D-allose also up-regulated expression of OsABF1, encoding a conserved bZIP transcription factor in ABA signaling, in rice. The D-allose-induced expression of OsABF1 was diminished by a hexokinase inhibitor, D-mannoheptulose (MNH). Consistently, D-allose also inhibited Arabidopsis growth, but failed to trigger growth retardation in the glucose-insensitive2 (gin2) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1. D-Allose activated AtABI5 expression in transgenic gin2 over-expressing wild-type AtHXK1 but not in gin2 over-expressing the catalytic mutant AtHXK1(S177A), indicating that the D-allose phosphorylation by HXK to D-allose 6-phosphate (A6P) is the first step for the up-regulation of AtABI5 gene expression as well as D-allose-induced growth inhibition. Moreover, overexpression of OsABF1 showed increased sensitivity to D-allose in rice. These findings indicated that the phosphorylation of D-allose at C6 by hexokinase is essential and OsABF1 is involved in the signal transduction for D-allose-induced growth inhibition.