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.

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.

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.

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.

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.

[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.

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.

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.

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.

[Guidelines for the treatment of Hansen's disease in Japan (third edition)].

ad hoc committee of Japanese Leprosy Association recommends revised standard treatment protocol of leprosy in Japan, which is a modification of World Health Organization's multidrug therapy (WHO/MDT, 2010). For paucibacillary (PB) leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough. However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment seems insufficient. Thus, (A) For MB with bacterial index (BI) > 3 before treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is necessary. When BI becomes negative and active lesion is lost within 2 years, no maintenance therapy is necessary. When BI is still positive, one year of MDT/MB is added (3 years in total), followed by maintenance therapy by dapsone and clofazimine until BI negativity and loss of active lesions. (B) For MB with BI < 3 or fresh MB (less than 6 months after the onset of the disease) with BI > 3, 1 year treatment by MDT/MB is necessary. When BI becomes negative and active lesion is lost within one year, no maintenance therapy is necessary. When BI is still positive or active lesion is remaining, additional therapy with MDT/MB for one more year is recommended. Brief summary of diagnosis, purpose of therapy, character of drugs, and prevention of deformity is also described.

Rare sugar D-allose suppresses gibberellin signaling through hexokinase-dependent pathway in Oryza sativa L.

One of the rare sugars, D-allose, which is the epimer of D-glucose at C3, has an inhibitory effect on rice growth, but the molecular mechanisms of the growth inhibition by D-allose were unknown. The growth inhibition caused by D-allose was prevented by treatment with hexokinase inhibitors, D-mannoheptulose and N-acetyl-D-glucosamine. Furthermore, the Arabidopsis glucose-insensitive2 (gin2) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1, showed a D-allose-insensitive phenotype. D-Allose strongly inhibited the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of α-amylase in embryo-less half rice seeds. The growth of the slender rice1 (slr1) mutant, which exhibits a constitutive gibberellin-responsive phenotype, was also inhibited by D-allose, and the growth inhibition of the slr1 mutant by D-allose was also prevented by D-mannoheptulose treatment. The expressions of gibberellin-responsive genes were down-regulated by D-allose treatment, and the down-regulations of gibberellin-responsive genes were also prevented by D-mannoheptulose treatment. These findings reveal that D-allose inhibits the gibberellin-signaling through a hexokinase-dependent pathway.

[Japanese guideline on thalidomide usage in the management of erythema nodosum leprosum].

Treatment of erythema nodosum leprosum (ENL, type 2 reaction) using thalidomide provides effective alternative choice to steroid therapy. Yet, the Japanese National Health Insurance approves thalidomide prescription only for the treatment of multiple myeloma under the Thalidomide Education and Risk Management System (TERMS). Benefit of thalidomide therapy for patients with ENL is already an established fact based on various reports from other countries, but limited experiences and standards in Japan have hindered application of the medication to our patients. This led us to compose a local guideline. Based on and following the TERMS, we suggest starting thalidomide from 50-100 mg/day and then onwards adjusting the dose according to the symptoms of each patient, not to exceed the maximum recommended dose of 300 mg/day, for the treatment of ENL.

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.

A rare sugar, d-allose, confers resistance to rice bacterial blight with upregulation of defense-related genes in Oryza sativa.

We investigated responses of rice plant to three rare sugars, d-altrose, d-sorbose, and d-allose, due to establishment of mass production methods for these rare sugars. Root growth and shoot growth were significantly inhibited by d-allose but not by the other rare sugars. A large-scale gene expression analysis using a rice microarray revealed that d-allose treatment causes a high upregulation of many defense-related, pathogenesis-related (PR) protein genes in rice. The PR protein genes were not upregulated by other rare sugars. Furthermore, d-allose treatment of rice plants conferred limited resistance of the rice against the pathogen Xanthomonas oryzae pv. oryzae but the other tested sugars did not. These results indicate that d-allose has a growth inhibitory effect but might prove to be a candidate elicitor for reducing disease development in rice.

Syntheses and characterization of new nickel coordination polymers with 4,4'-dipyridylsulfide. Dynamic rearrangements of one-dimensional chains responding to external stimuli: temperature variation and guest releases/re-inclusions.

Crystal structures and dynamic rearrangements of one-dimensional coordination polymers with 4,4'-dipyridylsulfide (dps) have been studied. Reaction of Ni(NO(3))(2)·6H(2)O with dps in EtOH yielded [Ni(dps)(2)(NO(3))(2)] ·EtOH (1), which had channels filled with guest EtOH molecules among the four Ni(dps)(2) chains. This coordination polymer reversibly transformed the channel structure responding to temperature variations. Immersion of 1 in m-xylene released guest EtOH molecules to yield a guest-free coordination polymer [Ni(dps)(2)(NO(3))(2)] (2a), which was also obtained by treatment of Ni(NO(3))(2)·6H(2)O with dps in MeOH. On the other hand, removal of the guest molecules from 1 upon heating at 130 °C under reduced pressure produced a guest-free coordination polymer [Ni(dps)(2)(NO(3))(2)] (2b). Although the 2a and 2b guest-free coordination polymers have the same formula, they showed differences in the assembled structures of the one-dimensional chains. Exposure of 2b to EtOH vapor reproduced 1, while 2a did not convert to 1 in a similar reaction. Reaction of Ni(NO(3))(2)·6H(2)O with dps in acetone provided [Ni(dps)(NO(3))(2)(H(2)O)] ·Me(2)CO (4) with no channel structure. When MeOH or acetone was used as a reaction solvent, the [Ni(dps)(2)(NO(3))(2)] · (guest molecule) type coordination polymer, which was observed in 1, was not formed. Nevertheless, the reaction of Ni(NO(3))(2)·6H(2)O with dps in MeOH/acetone mixed solution produced [Ni(dps)(2)(NO(3))(2)]·0.5(MeOH·acetone) (5), which has an isostructural Ni-dps framework to 1.

[Two cases of leprosy related conditions and relevant issues on medical services for ex-leprosy patients who live in communities in Japan].

In Japan people affected by leprosy who were forced to admit to national leprosy sanatoria under leprosy prevention/segregation law (1953) have ever been promoted to return to live in community, after destruction of the law in 1996. In this paper two cases are shown with some comments who had already been discharged from leprosy sanatoria and came late to OPD of National Suruga Sanatorium for consultations of their leprosy related conditions. One case is a 60 year-old male who developed squamous cell carcinoma (SCC) from chronic planter ulcer. The other is a 69 year-old female who developed relapse after more than 20 years BI negativity. In these cases, periods until consultation to our clinic were one year and five months, and five years and five months respectively. One reason is that there is no follow-up system of leprosy related conditions for ex-patients in current medical service of Japan. Another reason may be that patients hesitated to consult local doctors for their leprosy related conditions. Since national leprosy sanatoria will come to be closed in near future, services should be available for leprosy related conditions, such as prevention of disability (POD), prevention of worsening disability (POWD), early detection of relapse and leprosy reaction, in general medical service of Japan.