bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Cell Precursors and the Pathophysiology of Bone Loss
Authors: BLAIR HARRY C. , CARRINGTON JILL L.
Published: July 2006

Abstract:  In health, changes in bone formation and degradation rates are coupled and adequate cellular resources are available in the bone so that a change in bone formation rate occurs with an opposing change in resorption. On the other hand, the regulation of bone volume, particularly in pathological conditions, is dependent not only on the pathways that mediate terminal pathways of bone cell differentiation, but also on the availability of stem cells for allowing the differentiation to occur. Regulation of cell numbers in stem cell compartments and release of stem cells for differentiation of osteoblast or osteoclast precursors are not well understood, although it is clear that changes in stem cell numbers underlie pathological changes in bone mass. This may include effects of aging, fracture, metastatic disease, and autoimmune diseases on the precursor cell pools available for bone formation and degradation. Increases in osteoclast precursors or decreases in osteoblast precursors are common features of bone‐losing states; increases in precursors may conversely occur during growth or repair processes. Rational therapy based on modifying stem cell populations may, when the processes are better understood, help prevent chronic bone‐losing states and may also be of use in preventing or treating aplastic anemia and related conditions.
Estrogen Regulation of Immune Cell Bone Interactions
Authors: WEITZMANN M. NEALE , PACIFICI ROBERTO
Published: July 2006

Abstract:  Estrogen deficiency is one of the most frequent causes of osteoporosis in women and a possible cause of bone loss and insufficient skeletal development in men. Estrogen deficiency results from menopause but also by a number of conditions, such as stress, excessive physical activity, and low body weight. The mechanism by which estrogen deficiency causes bone loss remains largely unknown. Estrogen deficiency leads to an increase in the immune function, which culminates in an increased production of TNF by activated T cells. TNF increases osteoclast formation and bone resorption both directly and by augmenting the sensitivity of maturing osteoclasts to the essential osteoclastogenic factor RANKL. Increased T cell production of TNF is induced by estrogen deficiency via a complex mechanism mediated by antigen‐presenting cells and involving the cytokines IFN‐γ, IL‐7, and TGF‐β. Herein we review the experimental evidence that suggests that estrogen prevents bone loss by regulating T cell function and immune cell bone interactions.
Autoimmunity and Bone
Authors: SCHWARZ EDWARD M. , LOONEY R. JOHN , DRISSI M. HICHAM , O'KEEFE REGIS J. , BOYCE BRENDAN F. , XING LIANPING , RITCHLIN CHRISTOPHER T.
Published: July 2006

Abstract:  Focal erosions of cartilage and bone, which occur in the joints of patients with autoimmune inflammatory arthritis (i.e., rheumatoid arthritis (RA) and psoriatic arthritis [PsA]), represent the most debilitating and irreversible components of the disease. Over the last decade, seminal breakthroughs in our understanding of the cells and signal transduction pathways central to this process have been elucidated. From this information an established paradigm has been developed to explain focal erosions in which osteoclasts responsible for erosions are derived from bone marrow‐derived myeloid precursors. Using the tumor necrosis factor (TNF) transgenic mouse model of erosive arthritis and anti‐TNF clinical trials with PsA patients, we have demonstrated that systemic TNF induces the migration of CD11b+ osteoclast precursors (OCP) from the bone marrow into peripheral blood. These OCP can then enter the joints in blood vessels, translocate across the receptor activator of NF‐κB ligand (RANKL) rich inflamed synovium, and differentiate into active osteoclasts. In direct contrast to this, systemic lupus erythematosus (SLE) patients appear to have an innate resistance to bone resorption. Our hypothesis to explain this phenomenon is that systemic interferon‐α (IFN‐α) diverts the bone marrow‐derived myeloid precursors away from the osteoclast lineage and stimulates their differentiation into dendritic cells (DC). In support of this model, several labs have used microarray analyses to define the IFN‐induced transcriptome in peripheral blood mononuclear cells (PBMC) from SLE patients. Here we propose the hypothesis that systemic TNF induces osteoclastic differentiation of PBMC in PsA patients that correlates with their erosive disease, and that the innate immune TNF/IFN axis in patients with autoimmune disease dictates their erosive phenotype. To demonstrate this, we injected wild‐type C57B/6 and TNF‐Tg mice with poly I:C, which is known to induce systemic IFN responses, and show its dominant effects on increasing the number of circulating CD11b+/CD11c+ precursor dendritic cells (pDC), concomitant with a dramatic reduction in CD11b+/CD11c− OCP. Thus, systemic factors produced by autoimmunity have a dramatic impact on active myelopoiesis and bone homeostasis.
TSH and Bone Loss
Authors: SUN LI , DAVIES TERRY F. , BLAIR HARRY C. , ABE ETSUKO , ZAIDI MONE
Published: July 2006

Abstract:  We have recently challenged the view that the bone loss associated with hyperthyroidism is solely due to elevated thyroid hormone levels. We find that thyroid‐stimulating hormone (TSH), derived from the anterior pituitary gland, inhibits bone resorption by the osteoclast. Mice haploinsufficient in the TSH receptor show reduced bone density and evidence of enhanced bone resorption in the face of normal thyroid function. In humans, TSH inhibits markers of bone resorption with a single administration, and low TSH levels correlate with increased fracture risk. The evidence that low TSH levels predispose to osteoporosis in hyperthyroidism is discussed in view of the emerging role of pituitary hormones in bone biology.
Advanced Imaging Assessment of Bone Quality
Authors: GENANT HARRY K. , JIANG YEBIN
Published: July 2006

Abstract:  Noninvasive and/or nondestructive techniques can provide structural information about bone, beyond simple bone densitometry. While the latter provides important information about osteoporotic fracture risk, many studies indicate that bone mineral density (BMD) only partly explains bone strength. Quantitative assessment of macrostructural characteristics, such as geometry, and microstructural features, such as relative trabecular volume, trabecular spacing, and connectivity, may improve our ability to estimate bone strength. Methods for quantitatively assessing macrostructure include (besides conventional radiographs) dual X ray absorptiometry (DXA) and computed tomography (CT), particularly volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high‐resolution computed tomography (hrCT), microcomputed tomography (micro‐CT), high‐resolution magnetic resonance (hrMR), and micromagnetic resonance (micro‐MR). vQCT, hrCT, and hrMR are generally applicable in vivo; micro‐CT
and micro‐MR are principally applicable in vitro. Despite progress, problems remain. The important balances between spatial resolution and sampling size, or between signal‐to‐noise and radiation dose or acquisition time, need further consideration, as do the complexity and expense of the methods versus their availability and accessibility. Clinically, the challenges for bone imaging include balancing the advantages of simple bone densitometry versus the more complex architectural features of bone, or the deeper research requirements versus the broader clinical needs. The biological differences between the peripheral appendicular skeleton and the central axial skeleton must be further addressed. Finally, the relative merits of these sophisticated imaging techniques must be weighed with respect to their applications as diagnostic procedures, requiring high accuracy or reliability, versus their monitoring applications, requiring high precision or reproducibility.
Future Anti‐Catabolic Therapeutic Targets in Bone Disease
Authors: BOYCE BRENDAN F. , XING LIANPING , YAO ZHENQIANG , SHAKESPEARE WILLIAM C. , WANG YIHAN , METCALF CHESTER A. , SUNDARAMOORTHI RAJI , DALGARNO DAVID C. , IULIUCCI JOHN D. , SAWYER TOMI K.
Published: July 2006

Abstract:  Understanding of the regulation of bone catabolism has advanced significantly over the past two decades with the identification of key enzymes that regulate osteoclast formation, activation, and survival following their knockout in mice or recognition of mutations in humans. This led to the discovery of specific inhibitors of some of these key enzymes as proof‐of‐concept lead compounds or potential clinical candidates for the prevention of osteoporosis and other diseases associated with increased bone resorption. Bisphosphonates have been the major therapeutic agents prescribed for the prevention of bone loss in a variety of pathologic conditions for over 30 years. More potent amino bisphosphonates have increased efficacy than earlier drugs, but side effects such as upper gastrointestinal symptoms and the requirement to take them at least 2 h before food have limited patient compliance. This, coupled with the growing knowledge of the pathways regulating osteoclast function, has driven efforts to identify small molecular lead compounds that could be developed into new therapeutic agents with efficacy that matches or supersedes that of bisphosphonates for the prevention of bone loss. In this article, we review briefly the effects of specific inhibitors of bone resorption that have been developed to date and highlight in a variety of models of increased bone resorption the effects of Src kinase inhibitors that have been targeted to bone to limit potential unwanted side effects on other cells.
Clinical Biophysics: The Promotion of Skeletal Repair by Physical Forces
Authors: AARON ROY K. , CIOMBOR DEBORAH McK. , WANG SHUO , SIMON BRUCE
Published: July 2006

Abstract:  Skeletal tissues respond to the physical demands of their environment by altering the synthesis and organization of the extracellular matrix. These observations have major implications for how physical environmental demands result in the clinical observations of atrophy and hypertrophy, and how manipulation of the physical environment can be used therapeutically to stimulate repair. Electrical stimulation will be considered as a paradigm of how musculoskeletal tissues respond to physical stimuli. A model of demineralized bone matrix‐induced endochondral ossification has been used because it epitomizes the cell biology of endochondral bone formation in a temporally consistent way. We have studied cartilage and bone matrix production, the temporal locus of cell responsiveness, signal dosimetry, and the synthesis of signaling cytokines (TGF‐β) using biochemical, immunohistochemical, and molecular techniques. Exposure to certain electrical environments enhances chondrocyte differentiation reflected as a temporal acceleration and quantitative increase of cartilage extracellular matrix, earlier onset of osteogenesis, and more mature trabecular bone. The cell pool competent to respond resides in the mesenchymal stage. The enhancement in chondrogenesis is associated with an increase in TGF‐β synthesis mediated at least in part by binding of the transcription factor AP‐1 and may be modulated specifically by phosphorylation of JNK. The clinical practice of orthopedics has empirically created a variety of biophysical environments in attempts to optimize skeletal repair. We are beginning to understand the biological effects of biophysical stimulation and are now poised to replace empiricism with treatment paradigms based upon physiologic understandings of dose and biologic response.
Eosinophil Chemotactic Factor‐L (ECF‐L) Enhances Osteoclast Formation by Increasing ICAM‐1 Expression
Authors: PALACIOS VERONICA GARCIA , CHUNG HO YEON , CHOI SUN JIN , KURIHARA NORIYOSHI , LEE JUN WON , EHRLICH LORI A. , COLLINS ROBERT , ROODMAN G. DAVID
Published: July 2006

Abstract:  Eosinophil chemotactic factor‐L (ECF‐L) is a novel stimulator of osteoclast (OCL) formation that acts at the differentiation/fusion stage of OCL formation, and is a cofactor for RANK ligand (RANKL). We examined the effects of ECF‐L on the intracellular signaling pathways utilized by RANKL, and on the expression of ICAM‐1/LFA‐1 to determine its mechanism of action. RAW 264.7 and bone marrow cells were treated with RANKL and/or ECF‐L Fc protein to determine their effect on NF‐κB and AP‐1 activity. ECF‐L by itself only modestly increased NF‐κB binding and JNK activity in RAW 264.7 cells, which were further enhanced by RANKL. In contrast, ECF‐L Fc increased LFA‐1α and ICAM‐1 mRNA levels 1.8‐fold in mouse marrow cultures, and anti‐ICAM‐1 almost completely inhibited OCL formation induced by 10−10 M 1,25‐(OH)2D3, and ECF‐L Fc. Furthermore, ECF‐L Fc did not enhance OCL formation by ICAM‐1 knockout (KO) cells. Increased expression of ICAM‐1 by ECF‐L appears to be critical for its effects on OCL formation.
NFATc1: A Novel Anabolic Therapeutic Target for Osteoporosis
Authors: YEO HYEONJU , MCDONALD JAY M. , ZAYZAFOON MAJD
Published: July 2006

Abstract:  Bone loss and osteoporosis are major public health problems in the elderly. With increasing life expectancy in the United States, the number of people that will develop age‐related bone loss and osteoporosis is expected to rise to over 61 million by 2020. Osteoblast differentiation is a crucial aspect of bone formation and remodeling, a process severely compromised in osteoporosis. Almost all the FDA‐approved treatments for building healthier bones, excluding parathyroid hormone (PTH), do not address the decrease in osteoblast differentiation seen in osteoporosis and rather are designed to target osteoclasts and bone resorption. The purpose of this study is to examine the effects of NFAT inhibition on osteoblast differentiation and to elucidate the mechanism of its action. Here we demonstrate that the inhibition of calcineurin (Cn) by using cyclosporine A (CsA) increases osteoblast differentiation, both in vivo and in vitro. Furthermore, the specific inhibition of NFATc1 by siRNA increased Fra‐2 expression in osteoblasts. Taken together, our results point the way to a novel mechanism to aid in the development of anabolic treatment for osteoporosis.
Does TNF Have Anti‐Osteoclastogenic Actions?
Authors: IQBAL JAMEEL
Published: July 2006

Abstract:  Tumor necrosis factor (TNF) is a pro‐resorption agent that leads to bone degradation. Several mechanisms of action have been proposed to account for these effects: TNF directly inhibits osteoblast differentiation; TNF augments osteoclast formation by inducing stromal cells to increase expression of RANKL and macrophage colony‐stimulating factor (M‐CSF) and decrease that of osteoprotegerin (OPG); and TNF serves to synergize with pathways downstream of RANK to directly increase osteoclast differentiation. All of these actions in sum suggest that TNF dramatically induces osteopenia upon overexpression or injection. However, that the osteopenia seen with TNF is significantly milder than that seen in OPG−/−
animals prompted a reevaluation of existing paradigms on TNF action. The hypothesis that TNF directly enhances osteoclast differentiation was tested by examining the effects of TNF on RANKL‐induced osteoclast formation and marker expression. The data show that TNF decreased RANKL‐induced expression of the osteoclast markers, TRAP and cathepsin K. Furthermore, the addition of 10–60 ng/mL TNF failed to significantly increase RANKL‐induced osteoclast differentiation. Instead, data are presented to suggest that the pro‐osteoclastogenic actions of TNF are mediated through increases in the number of available osteoclast precursors (macrophages).
Pathogenesis of Osteopenia/Osteoporosis Induced by Highly Active Anti‐Retroviral Therapy for AIDS
Authors: PAN GEORGE , YANG ZHEN , BALLINGER SCOTT W. , MCDONALD JAY M.
Published: July 2006

Abstract: The advent of highly active anti‐retroviral therapy (HAART) has dramatically decreased the rate of AIDS‐related mortality and significantly extended the life span of patients with AIDS. A variety of metabolic side effects are associated with these therapies, one of which is metabolic bone disease. A higher prevalence of osteopenia and osteoporosis in HIV‐infected patients receiving anti‐retroviral therapy than in patients not on therapy has now been reported in several studies. Several factors have been demonstrated to influence HIV‐associated decreases in bone mineral density (BMD), including administration of nucleoside reverse transcriptase inhibitors (NRTIs). In this article, discussion will focus on the molecular pathogenesis and treatment of HAART‐associated osteopenia and osteoporosis.
Modeling of Serum C‐Telopeptide Levels with Daily and Monthly Oral Ibandronate in Humans
Authors: ZAIDI MONE , EPSTEIN SOLOMON , FRIEND KEITH
Published: July 2006

Abstract:  A previously validated kinetic‐pharmacodynamic model was applied to changes in a marker of bone resorption (serum C‐telopeptide cross‐links of type I collagen [sCTX]) using data from a large‐scale clinical trial of ibandronate (Monthly Oral iBandronate In LadiEs [MOBILE]). The model showed rapid and significant suppression of sCTX compared to baseline with daily and monthly ibandronate, and gradual recovery of sCTX levels between monthly doses. This modeled, post‐dose oscillatory pattern of sCTX paralleled significant increases in BMD and was associated with an acceptable safety profile for patients in MOBILE, suggesting that the between‐dose recovery of sCTX does not negatively affect the efficacy of once‐monthly ibandronate.
Perfluoroalkylquinones. Synthesis Using Bis(perfluoroalkanoyl) Peroxides, Absorption Bands, and Solubility
Authors: Matsui Masaki , Kondoh Shigeru , Shibata Katsuyoshi , Muramatsu Hiroshige
Published: July 2006

The reactions of 1,4-benzo-, naphtho-, and 9,10-anthraquinones with bis(perfluoroalkanoyl) peroxides gave the corresponding perfluoroalkylated derivatives. Those of 2-methyl- and 2-[4-(chloroanilino)]-1,4-naphthoquinones with bis(oxaperfluoroalkanoyl) peroxides afforded the dichloromethyl and trifluoromethyl derivatives, respectively. Absorption bands of the perfluoroalkylated naphtho- and anthraquinone dyes showed a slight hypsochromic shift. The solubilities of the perfluoroalkylated anthraquinone dyes into hexane were much more higher than those of the non-perfluoroalkylated ones.
Thermochromic Behavior of Polysilanes Concerning the Dependence on the Sequence Length
Authors: Sanji Takanobu , Sakamoto Kenkichi , Sakurai Hideki
Published: July 2006

Poly(dihexylsilane) and poly(dibutylsilane) having a wide range of molecular weights were prepared by the photodegradation of the corresponding high-molecular-weight polymers. These polymers showed characteristic thermochromism. Thus, the absorption maximum observed for both polymers at around room temperature disappeared and generated a new band at longer wavelengths at low temperature. The transition temperatures (Tc) (at which the intensities of these two absorption bands become equal) of these polymers were apparently proportional to the inverse of the number-average molecular weight () until the polysilanes reach a certain value of molecular weight. Beyond that value, the transition temperature was no longer dependent on the molecular weight. The thermochromic transition temperature also depended on the size of the alkyl substituents. These results have been satisfactorily explained by a model of the thermochromism based on a cooperative transition between the ordered trans and gauche states for poly(dialkylsilane)s.
Reaction Mechanism of the Pyrolysis of Polycarbosilane and Polycarbosilazane as Ceramic Precursors
Authors: Narisawa Masaki , Shimoda Manabu , Okamura Kiyohito , Sugimoto Masaki , Seguchi Tadao
Published: July 2006

The pyrolytic processes of polycarbosilane (PCS) to silicon carbide and of polycarbosilazane (PCSZ) to silicon carbonitride were studied by gas analysis, electron spin resonance (ESR), and X-ray diffraction. On the progress of conversion from organic polymers to ceramics above 800 K, decomposition gases like CH4 and H2 evolved, and free radicals as the intermediate active species in the chemical reactions were detected during the pyrolysis. The gas yield and the radical concentration profile against pyrolysis temperature indicated that there were several steps in the pyrolysis of PCS and PCSZ. At the last step in the pyrolysis of PCS, the microcrystals of β-SiC began to precipitate, while the microcrystals of β-SiC and Si3N4 precipitated in the pyrolysis of PCSZ.
Di(phenoxo)-bridged Dinuclear Mn2(II,II) and Mn2(II,III) Complexes of Macrocyclic Ligands: Structure, Properties, and Catalase-Like Function
Authors: Wada Hisae , Motoda Ken-ichiro , Ohba Masaaki , Sakiyama Hiroshi , Matsumoto Naohide , Okawa Hisashi
Published: July 2006

Dinuclear Mn2(II,II) complexes [Mn2(Lm,n)(RCOO)2] ((m,n) = (2,3), (2,4), (3,3); R = CH3, C6H5) have been prepared where (Lm,n)2− denotes dinucleating macrocycles with two 2,6-bis(iminomethyl)-4-methylphenolate entities combined through two lateral chains, –(CH2)m– and –(CH2)n–, at the imino nitrogens. The complex [Mn2(L3,3)(CH3COO)2] crystallizes in the monoclinic space group P21/n with a = 18.795(5), b = 7.608(2), c = 10.081(1) Å, β = 92.89(2)°, V = 1439.7 Å3, and Z = 2. The refinement converges with R = 6.38 and Rw = 9.63% based on 2727 reflections with |Fo| ≥ 3σ(|Fo|). A pair of Mn(II) ions are bridged by the two phenolic oxygens with a Mn–Mn separation of 3.367(1) Å. An acetate group coordinates bidentately to each Mn(II) to afford a six-coordinate geometry about the metal ion. The oxidation of [Mn2(L3,3)(CH3COO)2] with Br2 forms a mixed-valence Mn2(II,III) complex [Mn2(L3,3)(CH3COO)Br2]·H2O. The Mn2(II,II) and Mn2(II,III) complexes show catalytic activity for decomposing H2O2 in DMF or DMSO. The involvement of the Mn2(II,III)/Mn2(II,IV) cycle in the catalytic process is inferred based on visible and ESR spectroscopic studies of the reaction mixture.
Diorganotin(IV) Dialkoxyphosphinothioates: Synthesis and Characterization
Authors: Mokal Vijaya B , Jain Vimal K
Published: July 2006

Diorganotin(IV) dialkoxyphosphinothioates of the general formula, [R2Sn{OSP(OR′)2}2] (R = Me, Et, Prn, Bun, But; R′ = Me, Prn or Bun), [R2Sn(Cl){OSP(OR′)2}] (R = Me or But; R′ = Prn or Bun), ([R2Sn{OSP(OR′)2}]2O)2 (R = Me, Prn; R′ = Prn) and [But2Sn(μ-OH){OSP(OR′)2}]2 (R′ = Me or Prn) have been synthesized. All of the complexes were characterized by elemental analyses as well as IR and multinuclear NMR (1H, 13C, 31P, and 119Sn) spectroscopy. The stereochemistry of these complexes is discussed based on the NMR data.
Reductive Carbonylation of gem-Dihalogenocyclopropanes by Pentacarbonyliron(0) in the Presence of Sodium Methoxide
Authors: Reyne Françoise , Waegell Bernard , Brun Pierre
Published: July 2006

The reaction of gem-dihalogenocyclopropanes derivatives with (tetracarbonyl)(methoxycarbonylato)ferrate(I−) has been investigated; gem-dibromocyclopropanes and gem-chlorobromocyclopropane derivatives are reduced and carbonylated. It could be shown that a bromo ester such as methyl 1-bromo-2-phenylcyclopropanecarboxylate is an intermediate in the transformation of 1,1-dibromo-2-phenylcyclopropane into methyl cis- and trans-2-phenylcyclopropanecarboxylates and dimethyl 2-phenyl-1,1-cyclopropanedicarboxylate.
Hypervalent Iodine Oxidation of Flavanones: A New Synthesis of Methyl 2-Aryl-2,3-dihydrobenzofuran-3-carboxylates by 1,2-Aryl Shift
Authors: Prakash Om , Tanwar Madan P
Published: July 2006

Flavanones (1), on oxidation with (diacetoxyiodo)benzene-sulfuric acid (DIB–H2SO4) or (hydroxy)tosyloxy)iodo)benzene (HTIB) in trimethyl orthoformate, undergo facile ring contraction by 1,2-aryl shift, thereby yielding methyl 2-aryl-2,3-dihydrobenzofuran-3-carboxylates (4) as major products (40—80%). cis-3-Methoxyflavanones (5) and flavones (3) are the minor products formed in variable ratios.
Catalytic Decomposition of Dinitrogen Oxide over Perovskite-Related Mixed Oxides
Authors: Wang Jie , Yasuda Hiroyuki , Inumaru Kei , Misono Makoto
Published: July 2006

The catalytic decomposition of dinitrogen oxide (N2O) was carried out over La2−xSrxCuO4 (x = 0—1), LaMO3 (M = Cr, Mn, Fe, Co, and Ni) and La2MO4 (M = Co, Ni, and Cu) mixed oxides with perovskite and perovskite-related structure. The reaction rate at the steady state was first-order in the partial pressure of N2O, with reversible inhibition of oxygen. The initial rate was enhanced by pretreatment in helium at 1073 K, but decreased gradually due to irreversible inhibition of oxygen formed by the reaction, while the rate increased with time when the catalyst was pretreated in oxygen. A good correlation between the catalytic activity and the average oxidation number of copper (AON) was observed for La2−xSrxCuO4 and was explained by a Cu2+/Cu3+ redox mechanism. The catalytic activity for a series of LaMO3 and La2MO4 showed a one peak pattern with Co at the peak. These trends in catalytic activity are similar in general to those for NO decomposition.
Multiplex Proton-Transfer and Electron-Transfer Natures Based on the 2,2′-Bi-1H-imidazole System. I. Acid Dissociation Constants and Redox Properties in Solution
Authors: Akutagawa Tomoyuki , Saito Gunzi
Published: July 2006

The 2,2′-bi-1H-imidazole (H2BIM) derivatives were studied from the point of the interplay of proton-transfer (PT) and electron (charge)-transfer (CT) interactions. Seven new states among the speculated 25 independent species were identified based on the study of their redox and acid dissociation properties. Isoelectronic substitution of four sulfur atoms of the dication state of tetrathiafulvalene (TTF2+) by four imino groups was found to increase the stability of the dication state 2,2′-bi-1H-imidazolium (H4BIM2+) with aromatic 6π–6π character. The high PT character of H3BIM+ (2-(2-1H-imidazolyl)-1H-imidazolium) and H4BIM2+ compared with that of the corresponding hydroquinone system was clearly observed. The on-site Coulomb repulsion energy for electron-transfer (U1CT) was evaluated for various π-electron acceptor and donor systems. It was found that the U1CT values decrease linearly with increasing the length of a molecule, which can divide the molecular systems into two classifications, i.e. electron acceptors and dications. The on-site Coulomb repulsion energy for two-step proton-transfer processes (U1PT) was newly defined and evaluated for the H2BIM, H4BIM2+, hydroquinone (H2Q), and bis(4-hydroxyphenyl) disulfide (HPDS) systems. The U1PT values become constant above a certain molecular length (rc). Below rc the U1PT values increase linearly with decreasing the distance r regardless of Würster and Weitz structures, approximately. The H2BIM (H4BIM2+) system has large U1PT values in comparison with the H2Q and HPDS systems.
Structure of Clusters in Ethanol–Water Binary Solutions Studied by Mass Spectrometry and X-Ray Diffraction
Authors: Matsumoto Masaki , Nishi Nobuyuki , Furusawa Toshiya , Saita Masaru , Takamuku Toshiyuki , Yamagami Motoyuki , Yamaguchi Toshio
Published: July 2006

The structure of clusters in ethanol–water binary solutions at xE (ethanol mole fraction) ≥ 0.2 was investigated by the mass-spectrometric analysis of clusters isolated from liquid droplets and X-ray diffraction measurements of the intact solution. The average number of water molecules (Na) of the ethanol m-mer hydrates (5 < m < 15) in the mixtures at 0.2 ≤ xE ≤ 0.8 was found to be expressed by a function of the water mole fraction (xw), Na = {(m/4.2) − 1}2 (xw + 0.85), suggesting that the fundamental structure of ethanol polymer-hydrates is invariable in this region. An inflection point of Na was found at xE ≈ 0.2. The radial distribution functions (RDFs) from X-ray measurements demonstrated a decrease of linear hydrogen bonds at 2.8 Å with increasing xE, while keeping the strongest peak at 4.8 Å for 0.4 ≤ xE ≤ 1.0. On the basis of a composition analysis of the mass spectra and the concentration dependence of RDFs, we propose the most likely model of ethanol–water binary clusters formed in the region 0.2 ≤ xE ≤ 0.8.
Characterization of Enantiomeric Pairs of Optically Active 10-P-5 Phosphoranes with Asymmetry Only at Phosphorus
Authors: Kojima Satoshi , Kajiyama Kazumasa , Akiba Kin-ya
Published: July 2006

Diastereomeric phosphoranes (o-OC(CF3)2C6H4)2P*CH2CO2-(−)-menthyl (3-RP and 3-SP) of which absolute stereochemistry was determined were treated with LiAlH4 to give (o-OC(CF3)2C6H4)2P*CH2CH2OH (4-RP and 4-SP) as the first optically active pair of enantiomeric phosphoranes of rigid stereochemistry with asymmetry only upon the pentacoordinate phosphorus atom. The high enantiomeric purities of the alcohols were confirmed by converting them to their (+)-MTPA esters. Furthermore, when diastereomeric phosphoranes (o-OC(CF3)2C6H4)2P*CH2NHC*HCH3Ph (10-RP and 10-SP) of which absolute stereochemistry was also determined were treated with MeLi the first optically active pair of enantiomeric P–H phosphoranes (o-OC(CF3)2C6H4)2P*H (2-RP and 2-SP) with asymmetry only upon the pentacoordinate phosphorus atom could be obtained. The high enantiomeric purities of the P–H phosphoranes were confirmed by converting each of them to their corresponding (−)-menthyl esters 3-RP and 3-SP.
Spectroscopic and Conductometric Studies of Lanthanide Soaps
Authors: Mehrotra Krishna N , Shukla Rajeev K , Chauhan Mithlesh
Published: July 2006

Infrared spectral studies of lanthanide soaps (octanoates of cerium, didymium, neodymium, and samarium) reveal that fatty acids exist with a dimeric-type structure through hydrogen bonding between two molecules of fatty acids, whereas the metal-to-oxygen bonds in these soaps have an ionic character. The X-ray diffraction results confirm that these soaps have a double-layer structure with molecular axes slightly inclined to the basal plane. The premicellar association and the formation of micelles in lanthanide soap solutions have been investigated by conductometric measurements in a nonaqueous medium. The molar conductance at infinite dilution, the degree of ionization and the ionization constant have been evaluated. The results show that these soaps behave as weak electrolytes in dilute solutions.
Effect of Counterions on the Surface Adsorption and Volume Behavior of Micelle-Forming Local Anesthetics
Authors: Matsuki Hitoshi , Yamanaka Michio , Kaneshina Shoji
Published: July 2006

The surface tension and densities of aqueous solutions of micelle-forming local anesthetic dibucaine and tetracaine salts having different halide ions as counterions from each other (dibucaine hydrochloride (DC·HCl), hydrobromide (DC·HBr) and hydroiodide (DC·HI), and tetracaine hydrochloride (TC·HCl) and hydrobromide (TC·HBr)) were measured as a function of the molality at 298.15 K under atmospheric pressure. The thermodynamic quantities of adsorption and volume for the anesthetics were evaluated numerically based on the experimental results. The surface densities of the anesthetics increased in the order of chloride, bromide, and iodide salts. This behavior may result from differences in the degree of three factors, that is, a hydration interaction between water molecules and counterions, the counterion distribution in the surface-adsorbed film, and ion-pair formation in the adsorbed film between anesthetic cations and counterions. It was further shown from the surface pressure vs. area per adsorbed molecule curves that the adsorbed films of the anesthetics undergo a phase transition from a gaseous state to an expanded state at low concentrations. On the other hand, the volumes of micelle formation for DC·HCl and DC·HBr have been found to be almost equal to each other. This fact means that the effect of these halide counterions on the volume of micelle formation is considerably small in contrast to the results of surface adsorption.
Pressure-Induced Phase Transition in the 1,2,4,5-Tetrabromobenzene Crystal
Authors: Shimizu Fumio , Suzuki Yoshio , Mitarai Keiko , Fujino Mitsuyo , Kawano Hiroshi , Nibu Yoshinori , Shimada Hiroko , Shimada Ryoichi
Published: July 2006

The effects of pressure on the frequencies and band structures of the Raman active inter- and intramolecular vibrations of the 1,2,4,5-tetrabromobenzene crystal were studied under hydrostatic pressures upto 5 GPa at 300 K in a gasketed diamond anvil cell. Changes of the Raman frequencies and band structures of the inter- and intramolecular vibrations induced by pressure suggest that the phase transition takes place under about 0.7 GPa. Comparison of the pressure-induced frequency shifts of the inter- and intramolecular vibrations of the 1,2,4,5-tetrabromobenzene crystal with the frequency shifts observed in the 1,2,4,5-tetrachlorobenzene crystal indicates that the repulsive force between bromine atoms belonging to the adjacent molecules is fairly stronger than the force between chlorine atoms.
Ultraviolet Photoelectron Spectroscopy of Alkaline-Metal Doped Polyacetylene
Authors: Miyamae Takayuki , Kamiya Koji , Hasegawa Shinji , Seki Kazuhiko , Tanaka Chizuko , Tanaka Jiro
Published: July 2006

Sodium- and potassium-doped highly conducting polyacetylenes were studied by ultraviolet photoelectron spectroscopy (UPS) using synchrotron radiation. Upon doping, the UPS spectra immediately show a large shift toward the higher binding energy side relative to EF. At intermediate doping level, a new state is created in the empty energy gap region. The gap state in the UPS spectra is assigned to the charged soliton band. This is the first direct observation of emission from the charged soliton state in doped polyacetylene. At heavily doped level, the quasi-metallic density of states is found just below the Fermi level and the broadening of the UPS spectra occurs at the regions of C 2p and C 2s levels. However, no finite density of states was observed at the Fermi level in the case of unoriented polyacetylene. This result is in contrast to the case of oriented polyacetylene doped with perchlorate, where the existence of a finite density of states at EF is reported. The spectral shape of UPS near the Fermi level is in accordance with Tomonaga–Luttinger liquid model of strong electron correlated system. Ab initio molecular orbital calculations taking account of nearest-neighbor chain effect gives a good description of the UPS for all the C 2s, C 2pσ, and C 2pπ bands.
Synthesis and Characterization of Hybrid Porphyrin Dimers and Halogenated Porphyrin Dimers
Authors: Iida Kouji , Nango Mamoru , Okada Kenichi , Hikita Masaya , Matsuura Mitsutaka , Kurihara Takayuki , Tajima Takeharu , Hattori Ayako , Ishikawa Shinichi , Yamashita Keiji , Tsuda Kazuichi , Kurono Yukihisa
Published: July 2006

Zinc hybrid porphyrin dimer(ZnTTP-C2-H2PFPP, ZnTTP-C2-H2TTP, ZnPFPP-C2-H2PFPP, and ZnPFPP-C2-H2TTP) and manganese (III) halogenated porphyrin dimers (MnPFPP-C2-MnPFPP, MnPFPP-C2-MnDCPP, and MnDCPP-C2-MnDCPP) covalently bridged by an ethylene moiety () were synthesized and characterized by UV-vis spectra, fluorescence spectra, and cyclic voltammograms. These porphyrin dimers could be embedded into the lipid bilayers of a liposomal membrane. The redox potential of the manganese complex for the halogenated porphyrin dimers increased with increasing of halogen portions on the porphyrin rings. An efficient energy transfer of the excited singlet state in the covalently-linked zinc hybrid dimers from zinc porphyrin to a free base porphyrin was observed, depending on the porphyrin structure. Furthermore, the manganese halogenated porphyrin dimers acted as catalysts of transmembrane electron transfer; such activity depends on the steric effect of halogen portions on the porphyrin ring.
A Novel Dehydrative Ring-Transformation of 1-Alkyl-3-aroylpyrrolidines into 1-Alkyl-2-aryl-3-methylpyrroles
Authors: Mataka Shuntaro , Kitagawa Hirohisa , Tsukinoki Takehito , Tashiro Masashi , Takahashi Kazufumi , Kamata Kichinosuke
Published: July 2006

When heated in an alcoholic solvent, such as ethylene glycol or butanol, 4-substituted 3-aroyl-1-alkylpyrrolidines, which are readily accessible via the condensation of an amino acid, paraformaldehyde, and 3-substituted 1-ary-2-propen-1-one, afforded 4-substituted 1-alkyl-2-aryl-3-methylpyrrole derivatives in good yields. The ring-transformation of 3,4-dibenzoyl-1-methyl-2-phenylpyrrolidine occurred in two directions, giving the corresponding 3-benzyl- and 3-methylpyrrole derivative. Also, bicyclic pyrroles, such as 1H,3H-pyrrolo[1,2-c]thiazole, 2,3-dihydro-1H-pyrrolizine, and 5,6,7,8-tetrahydroindolizine, were prepared by the ring-transformation of bicyclic aroylpyrrolidines obtained from the corresponding cyclic amino acids. A mechanism for the ring-transformation is proposed.
Novel C5-Substituted 2′-Deoxyuridine Derivatives Bearing Amino-Linker Arms: Synthesis, Incorporation into Oligodeoxyribonucleotides, and Their Hybridization Properties
Authors: Ozaki Hiroaki , Nakamura Akiko , Arai Midori , Endo Masakazu , Sawai Hiroaki
Published: July 2006

2′-Deoxyuridine derivatives bearing several kinds of amino-linker arms at C5 position were synthesized from 5-(methoxycarbonylmethyl)-2′-deoxyuridine and ethylenediamine, 1,6-hexanediamine, or tris(2-aminoethyl)amine. The modified nucleosides were incorporated into oligodeoxyribonucleotides at one or three positions in place of thymidine residues. The thermal stability of the duplexes was investigated. Three incorporations of ethylenediamine or tris(2-aminoethyl)amine at the C5-position increase the duplex stability. The amino-linker arm affected the stability of the duplexes depending on the number of amino groups in the linker arm and the length of the arm. The linker arm improved the nuclease resistance at 5′-side phosphodiester linkage of the modified nucleoside in oligodeoxyribonucleotides.
A Membrane Protein Model: Polypeptides with Four α-Helix Bundle Structure on 5,10,15,20-Tetrakis[2-(carboxymethoxy)phenyl]porphyrin
Authors: Arai Toru , Kobata Keisuke , Mihara Hisakazu , Fujimoto Tsutomu , Nishino Norikazu
Published: July 2006

A novel template for the polypeptide–porphyrin hybrid, 5,10,15,20-tetrakis[2-(ethoxycarbonylmethoxy)phenyl]porphyrin (2) was synthesized in 17% yield. Four protected carboxyl groups are installed in 2 at the ortho-phenyl groups as the anchoring points, to which the N-termini of the polypeptides can be linked after the hydrolysis. Thus, 2 is a new analog of the porphyrin template tetrakis[2-(methoxycarbonyl)phenyl]porphyrin. The atropisomerization of 2 was much more rapid than that of tetrakis[2-(methoxycarbonyl)phenyl]porphyrin: At 353 K, 2 reached their equilibrium within 15 min. Such atropisomeric flexibility of 2 allows the self-organization of the α-helical peptide segments which are connected to 2. After the hydrolyses of the ethyl ester groups of 2, four α-helical 21-peptides, H–(–Gln–Leu–Leu–Gln–Ala–Leu–Ala–)3–NHCH2CH2OH were combined through the amide bonds to yield a new polypeptide–porphyrin hybrid (12). The polypeptide moieties of 12 showed typical α-helix profiles on circular dichroism measurements in methanol–water (3/1, v/v) and in Tris·HCl buffer solution. Thus, the four α-helix polypeptides are considered to fold into a bundle structure on the porphyrin template through the hydrophobic interaction. The circular dichroism spectrum of 12 in methanol showed an induced Cotton effect at the porphyrin region, and the CD band was symmetrically split. The hybrid (12) was also successfully incorporated into the egg yolk lecithin membrane almost quantitatively. When the molar ratio of egg yolk lecithin/12 was 500/1, the α-helix structure of the peptide segments in 12 was completely retained in the vesicles.
Manganese(III)-Mediated Oxidative Radical Cyclization 2. Reaction of 1,1,ω,ω-Tetraarylsubstituted Terminal Alkadienes with Malonamide or Acetoacetamide
Authors: Nishino Hiroshi , Hashimoto Hideaki , Korp James D , Kurosawa Kazu
Published: July 2006

The oxidation of 1,1,6,6-tetraaryl-1,5-hexadienes with manganese(III) acetate in the presence of malonamide gave two types of 5-exo cyclization products, 1-carbamoyl-8-diarylmethylene-3-azabicyclo[3.3.0]octan-2-ones and 3,10-dioxatricyclo[6.3.0.01,5]undecane-2,11-diones, in good to moderate yields. Similar reactions of 1,1,5,5-tetraaryl-1,4-pentadienes or 1,1,7,7-tetraaryl-1,6-heptadienes with malonamide yielded only complex mixtures, except for the formation of a small amount of 3,11-dioxatricyclo[7.3.0.01,5]dodecane-2,12-dione. On the other hand, 1,1,5,5-tetraaryl-1,4-pentadienes reacted with acetoacetamide in the presence of manganese(III) acetate to afford 3-carbamoyl-2-methyl-4-(2-propenyl)-4,5-dihydrofurans and 1,4-pentadienes substituted at the 3-position with acetoacetamide. A similar reaction of 1,1,6,6-tetraaryl-1,5-hexadienes with acetoacetamide gave 8-[acetoxy(diaryl)methyl]-3-oxabicyclo[3.3.0]octan-2-ones, 1-acetyl-8-diarylmethylene-3-azabicyclo[3.3.0]octan-2-ones, and 4-(3-butenyl)-3-carbamoyl-2-methyl-4,5-dihydrofurans. The selectivity of the inter- and intramolecular cyclizations containing the carboxamide moiety of malonamide or acetoacetamide is discussed.
Studies of the Selective O-Alkylation and Dealkylation of Flavonoids. XVIII. A Convenient Method for Synthesizing 3,5,6,7-Tetrahydroxyflavones
Authors: Horie Tokunaru , Kobayashi Takashi , Kawamura Yasuhiko , Yoshida Isao , Tominaga Hideaki , Yamashita Kazuyo
Published: July 2006

In the demethylation of 6-hydroxy-3,4′,7-trimethoxy-5-(tosyloxy)flavone with anhydrous aluminum bromide, the 5-tosyloxyl group was eliminated with bromination to give 8-bromo-3,6,7-trihydroxy-4′-methoxyflavone as the main product. When anhydrous aluminum chloride was used in the demethylation of the acetate, the 5-tosyloxyl group was cleaved prior to the demethylation to give 5,6,7-trihydroxy-3,4′-dimethoxyflavone. Demethylation of 6-hydroxy-4′,5,7-trimethoxy-3-(tosyloxy)flavone and its acetate with the bromide or chloride afforded the 5,6,7-trihydroxyflavone without the cleavage of the 3-tosyloxyl group, but was not suitable for the general synthesis of the 3,5,6,7-tetrahydroxyflavones because of the difficulty in removing the protecting group. Consequently, it was found that the direct demethylation of 3,6-dihydroxy-5,7-dimethoxyflavones with anhydrous aluminum chloride–sodium iodide in acetonitrile was the most useful general method for synthesizing 3,5,6,7-tetrahydroxyflavones. Additionally, the reported structures of two natural flavones were revised.
Calorimetric and 195Pt NMR Studies on Aromatic Ring Stacking between Nucleotides and Platinum DNA Intercalators
Authors: Odani Akira , Sekiguchi Tetsuo , Okada Hisashi , Ishiguro Shin-ichi , Yamauchi Osamu
Published: July 2006

Calorimetric and spectroscopic investigations have been carried out on the stacking interactions between nucleosides or nucleotides (NMP) and platinum DNA intercalators and other planar platinum(II) complexes with heteroaromatic ligands (L). Pt(L)(diamine) (L = 1,10-phenathroline (phen), its methyl and nitro derivatives, 2,2′-bipyridine; diamine = ethylenediamine (en), L-2,3-diaminopropionate) reacts with NMP (=adenosine 5′-monophosphate (AMP), guanosine 5′-monophosphate (GMP), inosine 5′-monophosphate (IMP), cytidine 5′ -monophosphate (CMP); nicotinamide adenine dinucleotide (NAD), adenosine, cytidine) to give the Pt(L)(diamine)–(NMP)n adducts (n = 1, 2) with log K1 = 1.63—3.00 and log K2 = 1.47—2.51 at 25 °C at ionic strength = 0.1 mol dm−3 (NaCl). The 1 : 1 adduct formation mainly depends on the enthalpy change ΔH1° = −6.5 — −26.2 kJ mol−1, and the entropy change (ΔS1° = −38—20 J mol−1 K−1) makes a negative or small contribution. 1H NMR upfield shifts observed for the Pt(phen)(en)–NMP systems have substantiated the presence of stacked adducts in dilute aqueous solution, whereas diquat, a dicationic organic molecule, did not cause appreciable shifts, and hence the adduct formation was negligible. NAD was found to interact with Pt(phen)(en) through the adenine moiety. 195Pt NMR signals of Pt(phen)(en) in water suffered downfield shifts upon addition of NMP, the Δδ1 values being in the order NAD ≥ AMP ≈ GMP > IMP. This indicates that stacking causes an electron density decrease of the Pt(II) center. Linear relationships have been detected between the ΣΔHn° values and the absorption coefficients εn of the difference spectra in the charge transfer region and between ΣΔHn° and 195Pt NMR shift differences Δδn. These observations serve as evidence for the electronic effects of stacking interactions on the stacked rings and the central Pt(II) ion.
High Resolution Solid State NMR in Liquid. IV. 1H NMR Study of Terephthalic Acid Nano-Particles
Authors: Satoh Naoki , Naito Akira , Kimura Keisaku
Published: July 2006

High-resolution 1H NMR spectra of terephthalic acid (TPA) ultrafine particles (UFP’s) were obtained under the conditions of rapid Brownian motion of UFP’s in liquid CCl4 (UFP-NMR method). Six signals were resolved in the range of 6.85 to 7.65 ppm with respect to an tetramethylsilane. These were assigned to aromatic protons, even though only a single signal at 8.15 ppm was obtained from molecular dispersion of TPA in acetone. TPA-UFP dispersions were prepared by a vacuum evaporation technique combined with a cold matrix-isolation method. Particle sizes obtained were ca. 15 nm by a dynamic laser scattering method. The results from UFP-NMR method are discussed in conjunction with those from solid state 1H NMR via a CRAMPS method and with a conventional liquid state NMR of TPA.
Study of the Reaction of Benzoyl Chloride and Sodium Dicarboxylate under Inverse Phase Transfer Catalysis
Authors: Wang Maw-Ling , Ou Chin-Chou , Jwo Jing-Jer
Published: July 2006

The reaction of benzoyl chloride (PhCOCl) and sodium dicarboxylate (R(COONa)2) catalyzed by an inverse-phase-transfer catalyst (IPTC) in the two-phase medium H2O/CH2Cl2 was investigated. Pyridine 1-oxide (PNO) was used as the inverse-phase-transfer catalyst. Ten dicarboxylates, namely oxalate, malonate, maleate, succinate, adipate, nonanedioate, fumarate, phthalate, isophthalate, and terephthalate, were selected for study. In general, the observed mixed products included mono- and bis(benzoyloxycarbonyl) compounds, benzoic anhydride and benzoic acid, depending on the molecular structure of the dicarboxylate ion. Dicarboxylates of four types were classified according to distribution of products. The reaction rate is strongly affected by PhCOCl and R(COONa)2 due to their influence on the distribution of PNO in the organic phase. A mechanistic interpretation of the experimental data is presented.