bluuebunny/crossref_metadata_2025 huggingface dataset:
Tocilizumab in systemic lupus erythematosus: Data on safety, preliminary efficacy, and impact on circulating plasma cells from an open‐label phase I dosage‐escalation study
Authors: Illei Gabor G. , Shirota Yuko , Yarboro Cheryl H. , Daruwalla Jimmy , Tackey Edward , Takada Kazuki , Fleisher Thomas , Balow James E. , Lipsky Peter E.
Published: January 2010

Objective

To assess the safety of interleukin‐6 receptor inhibition and to collect preliminary data on the clinical and immunologic efficacy of tocilizumab in patients with systemic lupus erythematosus (SLE).

Methods

In an open‐label phase I dosage‐escalation study, 16 patients with mild‐to‐moderate disease activity were assigned to receive 1 of 3 doses of tocilizumab given intravenously every other week for 12 weeks (total of 7 infusions): 2 mg/kg in 4 patients, 4 mg/kg in 6 patients, or 8 mg/kg in 6 patients. Patients were then monitored for an additional 8 weeks.

Results

The infusions were well tolerated. Tocilizumab treatment led to dosage‐related decreases in the absolute neutrophil count, with a median decrease of 38% in the 4 mg/kg dosage group and 56% in the 8 mg/kg dosage group. Neutrophil counts returned to normal after cessation of treatment. One patient was withdrawn from the study because of neutropenia. Infections occurred in 11 patients; none was associated with neutropenia. Disease activity showed significant improvement, with a decrease of ≥4 points in the modified Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index score in 8 of the 15 evaluable patients. Arthritis improved in all 7 patients who had arthritis at baseline and resolved in 4 of them. Levels of anti–double‐stranded DNA antibodies decreased by a median of 47% in patients in the 4 mg/kg and 8 mg/kg dosage groups, with a 7.8% decrease in their IgG levels. These changes, together with a significant decrease in the frequency of circulating plasma cells, suggest a specific effect of tocilizumab on autoantibody‐producing cells.

Conclusion

Although neutropenia may limit the maximum dosage of tocilizumab in patients with SLE, the observed clinical and serologic responses are promising and warrant further studies to establish the optimal dosing regimen and efficacy.
Association of the response to tumor necrosis factor antagonists with plasma type I interferon activity and interferon‐β/α ratios in rheumatoid arthritis patients: A post hoc analysis of a predominantly Hispanic cohort
Authors: Mavragani Clio P. , La Dan T. , Stohl William , Crow Mary K.
Published: January 2010

Objective

Despite the substantial clinical efficacy of tumor necrosis factor α (TNFα) antagonist therapy in patients with rheumatoid arthritis (RA), some patients respond poorly to such agents. Since an interferon (IFN) signature is variably expressed among RA patients, we investigated whether plasma type I IFN activity might predict the response to TNF antagonist therapy.

Methods

RA patients (n = 35), the majority of whom were Hispanic, from a single center were evaluated before and after initiation of TNF antagonist therapy. As controls, 12 RA patients from the same center who were not treated with a TNF antagonist were studied. Plasma type I IFN activity was measured using a reporter cell assay, and disease status was assessed using the Disease Activity Score in 28 joints (DAS28). Levels of interleukin‐1 receptor antagonist (IL‐1Ra) were determined in baseline plasma samples using a commercial enzyme‐linked immunosorbent assay. The clinical response was classified according to the European League Against Rheumatism criteria for improvement in RA.

Results

Plasma type I IFN activity at baseline was significantly associated with clinical response (odds ratio 1.36 [95% confidence interval 1.05–1.76], P = 0.020), with high baseline IFN activity associated with a good response. Changes in DAS28 scores were greater among patients with a baseline plasma IFNβ/α ratio >0.8 (indicating elevated plasma IFNβ levels). Consistent with the capacity of IFNβ to induce IL‐1Ra, elevated baseline IL‐1Ra levels were associated with better therapeutic outcomes (odds ratio 1.82 [95% confidence interval 1.1–3.29], P = 0.027).

Conclusion

The plasma type I IFN activity, the IFNβ/α ratio, and the IL‐1Ra level were predictive of the therapeutic response in TNF antagonist–treated RA patients, indicating that these parameters might define clinically meaningful subgroups of RA patients with distinct responses to therapeutic agents.
Clinical features and outcomes in 348 patients with polyarteritis nodosa: A systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French vasculitis study group database
Authors: Pagnoux Christian , Seror Raphaèle , Henegar Corneliu , Mahr Alfred , Cohen Pascal , Le Guern Véronique , Bienvenu Boris , Mouthon Luc , Guillevin Loïc
Published: January 2010

Objective

Previous studies of polyarteritis nodosa (PAN) included patients with microscopic polyangiitis, because these entities were not distinguished prior to the Chapel Hill Consensus Conference (CHCC). This study was undertaken to describe the main characteristics of and long‐term outcomes in patients with well‐characterized PAN diagnoses.

Methods

We conducted a systematic retrospective study of 348 patients who were diagnosed as having PAN between March 1963 and October 2005, were registered in the French Vasculitis Study Group database, and satisfied the American College of Rheumatology and CHCC criteria. Patient characteristics and outcomes were analyzed and compared according to hepatitis B virus (HBV) status.

Results

At diagnosis, the mean ± SD age was 51.2 ± 17.3 years. The most frequent findings were general symptoms (93.1%), neurologic manifestations (79%), skin involvement (49.7%), abdominal pain (35.6%), and hypertension (34.8%); 66.2% had renal artery microaneurysms; 70.1% had histologically proven PAN. Patients with HBV‐related PAN (n = 123) had more frequent peripheral neuropathy, abdominal pain, cardiomyopathy, orchitis, and hypertension compared with patients with non–HBV‐related PAN (n = 225). During a mean ± SD followup of 68.3 ± 63.5 months, 76 patients (21.8%) relapsed (63 with non–HBV‐related PAN [28%] versus 13 with HBV‐related PAN [10.6%];P< 0.001); 86 patients (24.7%) died (44 with non–HBV‐related PAN [19.6%] versus 42 with HBV‐related PAN [34.1%];P= 0.003). Five‐year relapse‐free survival rates were 59.4% (95% confidence interval [95% CI] 52.6–67.0) versus 67.0% (95% CI 58.5–76.8) for non–HBV‐related PAN and HBV‐related PAN, respectively. Multivariate analysis retained age >65 years, hypertension, and gastrointestinal manifestations requiring surgery or at least consultation with a surgeon as independent predictors of death, whereas patients with cutaneous manifestations or non–HBV‐related PAN had a higher risk of relapse.

Conclusion

Our findings indicate that the rate of mortality from PAN remains high, especially for the elderly, and relapses do occur, particularly in patients with non–HBV‐related PAN with cutaneous manifestations.
Treatment of polyarteritis nodosa and microscopic polyangiitis without poor‐prognosis factors: A prospective randomized study of one hundred twenty‐four patients
Authors: Ribi Camillo , Cohen Pascal , Pagnoux Christian , Mahr Alfred , Arène Jean‐Pierre , Puéchal Xavier , Carli Philippe , Kyndt Xavier , Le Hello Claire , Letellier Philippe , Cordier Jean‐François , Guillevin Loïc
Published: January 2010

Objective

To assess the efficacy of systemic corticosteroids alone as first‐line treatment of polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA) without poor‐prognosis factors as defined by the Five‐Factors Score (FFS), and to compare the efficacy and safety of azathioprine versus pulse cyclophosphamide as adjunctive immunosuppressive therapy for patients experiencing treatment failure or relapse.

Methods

This prospective, multicenter, therapeutic trial included 124 patients with newly diagnosed PAN or MPA (FFS of 0) treated with corticosteroids alone. At the time of treatment failure or disease relapse, patients were randomized to receive 6 months of therapy with oral azathioprine or 6 pulses of cyclophosphamide. Analyses was performed according to an intent‐to‐treat strategy.

Results

The mean ± SD followup period was 62 ± 33 months. Treatment with corticosteroids alone induced remission in 98 patients; 50 (40%) of these patients had sustained disease remission, 46 (37%) experienced a relapse, and 2 became corticosteroid dependent (daily prednisone dose ≥20 mg). In 26 patients (21%), treatment with corticosteroids alone failed, and 49 patients (40%) required additional immunosuppression. Among the 39 patients randomized, 13 of 19 achieved remission with cyclophosphamide pulses, and 14 of 20 achieved remission with azathioprine. Among all patients, the 1‐year and 5‐year survival rates were 99% and 92%, respectively. Six deaths occurred in the cyclophosphamide‐treated group compared with 2 deaths in the azathioprine‐treated group. Disease‐free survival was significantly lower for patients with MPA than for those with PAN (P = 0.046).

Conclusion

For patients with PAN or MPA with an FFS of 0, overall 5‐year survival was good, but first‐line corticosteroid treatment was able to achieve and maintain remission in only about half of the patients, and 40% of the patients required additional immunosuppressive therapy. Azathioprine or pulse cyclophosphamide was fairly effective for treating corticosteroid‐resistant disease or major relapses.
A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile neurologic, cutaneous, articular syndrome/neonatal‐onset multisystem inflammatory disease: Novel evidence of the role of low‐level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases
Authors: Aróstegui Juan I. , Lopez Saldaña Ma Dolores , Pascal Mariona , Clemente Daniel , Aymerich Marta , Balaguer Francesc , Goel Ajay , Fournier del Castillo Concepción , Rius Josefa , Plaza Susana , López Robledillo Juan Carlos , Juan Manel , Ibañez Mercedes , Yagüe Jordi
Published: January 2010

Objective

Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), also known as neonatal‐onset multisystem inflammatory disease (NOMID), is a severe, early‐onset autoinflammatory disease characterized by an urticaria‐like rash, arthritis/arthropathy, variable neurologic involvement, and dysmorphic features, which usually respond to interleukin‐1 blockade. CINCA/NOMID has been associated with dominant Mendelian inherited NLRP3 mutations. However, conventional sequencing analyses detect true disease‐causing mutations in only ∼55–60% of patients, which suggests the presence of genetic heterogeneity. We undertook the current study to assess the presence of somatic, nongermline NLRP3 mutations in a sporadic case of CINCA/NOMID.

Methods

Clinical data, laboratory results, and information on treatment outcomes were gathered through direct interviews. Exhaustive genetic studies, including Sanger method sequencing, subcloning, restriction fragment length polymorphism assay, and pyrosequencing, were performed.

Results

The patient's CINCA/NOMID was diagnosed based on clinical features (early onset of the disease, urticaria‐like rash, knee arthropathy, and dysmorphic features). The patient has exhibited a successful response to anakinra within the last 28 months. Analysis of NLRP3 identified a novel heterozygous variant (p.D303H) that was detected in ∼30–38% of circulating leukocytes. The absence of this variant in healthy controls and in the patient's parents suggested a de novo true disease‐causing mutation. Additional analyses showed that this novel mutation was present in both leukocyte subpopulations and epithelial cells.

Conclusion

Our findings identify the novel p.D303H NLRP3 variant in a Spanish patient with CINCA/NOMID as a new disease‐causing mutation, which was detected as a somatic, nongermline mutation in hematopoietic and nonhematopoietic cell lineages. Our data provide new insight into the role of low‐level mosaicism in NLRP3 as the pathophysiologic mechanism underlying cryopyrin‐associated periodic syndrome.
Transcriptional profiling and biochemical analysis of mechanically induced cartilaginous tissues in a rat model
Authors: Salisbury Palomares Kristy T. , Gerstenfeld Louis C. , Wigner Nathan A. , Lenburg Marc E. , Einhorn Thomas A. , Morgan Elise F.
Published: January 2010

Objective

To characterize patterns of molecular expression that lead to cartilage formation in vivo in a postnatal setting, by profiling messenger RNA expression across the time course of mechanically induced chondrogenesis.

Methods

Retired breeder Sprague‐Dawley rats underwent a noncritical‐sized transverse femoral osteotomy. Experimental animals (n = 45) were subjected to bending stimulation (60° cyclic motion in the sagittal plane for 15 minutes/day) of the osteotomy gap beginning on day 10 after the operation. Control animals (n = 32) experienced continuous rigid fixation. Messenger RNA isolated on days 10, 17, 24, and 38 after surgery was analyzed using a microarray containing 608 genes involved in skeletal development, tissue differentiation, fracture healing, and mechanotransduction. The glycosaminoglycan (GAG) content in the stimulated tissues was compared with that in native articular cartilage as a means of assessing the progression of chondrogenic development of the tissues.

Results

The majority of the 100 genes that were differentially expressed were up‐regulated in response to mechanical stimulation. Many of these genes are associated with articular cartilage development and maintenance, diarthrodial joint development, cell adhesion, extracellular matrix synthesis, signal transduction, and skeletal development. Quantitative real‐time polymerase chain reaction results were consistent with the microarray findings. The GAG content of the stimulated tissues increased over time and was no different from that of articular cartilage on day 38 after surgery.

Conclusion

Our findings indicate that mechanical stimulation causes up‐regulation of genes that are principally involved in joint cavity morphogenesis and critical to articular cartilage function. Further study of this type of stimulation may identify key signaling events required for postnatal hyaline cartilage formation.
Human single‐chain variable fragment that specifically targets arthritic cartilage
Authors: Hughes Chris , Faurholm Bjarne , Dell'Accio Francesco , Manzo Antonio , Seed Michael , Eltawil Noha , Marrelli Alessandra , Gould David , Subang Christina , Al‐Kashi Adam , De Bari Cosimo , Winyard Paul , Chernajovsky Yuti , Nissim Ahuva
Published: January 2010

Objective

To demonstrate that posttranslational modification of type II collagen (CII) by reactive oxygen species (ROS), which are known to be present in inflamed arthritic joints, can give rise to epitopes specific to damaged cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA) and to establish a proof of concept that antibodies specific to ROS‐modified CII can be used to target therapeutics specifically to inflamed arthritic joints.

Methods

We used a semisynthetic phage display human antibody library to raise single‐chain variable fragments (scFv) specific to ROS‐modified CII. The specificity of anti–ROS‐modified CII scFv to damaged arthritic cartilage was assessed in vitro by immunostaining articular cartilage from RA and OA patients and from normal controls. The in vivo targeting potential was tested using mice with antigen‐induced arthritis, in which localization of anti–ROS‐modified CII scFv in the joints was determined. The therapeutic effect of anti–ROS‐modified CII scFv fused to soluble murine tumor necrosis factor receptor II–Fc fusion protein (mTNFRII‐Fc) was also investigated.

Results

The anti–ROS‐modified CII scFv bound to damaged arthritic cartilage from patients with RA and OA but not to normal preserved cartilage. When systemically administered to arthritic mice, the anti–ROS‐modified CII accumulated selectively at the inflamed joints. Importantly, when fused to mTNFRII‐Fc, it significantly reduced inflammation in arthritic mice, as compared with the effects of mTNFRII‐Fc alone or of mTNFRII‐Fc fused to an irrelevant scFv.

Conclusion

Our findings indicate that biologic therapeutics can be targeted specifically to arthritic joints and suggest a new approach for the development of novel treatments of arthritis.
Deletion of either CD55 or CD97 ameliorates arthritis in mouse models
Authors: Hoek Robert M. , de Launay Daphne , Kop Else N. , Yilmaz‐Elis A. Seda , Lin Feng , Reedquist Kris A. , Verbeek J. Sjef , Medof M. Edward , Tak Paul P. , Hamann Jörg
Published: January 2010

Objective

CD55 (decay‐accelerating factor) is best known for its role in the negative regulation of the complement system. Indeed, lack of this molecule leads to disease aggravation in many autoimmune disease models. However, CD55 is abundantly present on fibroblast‐like synoviocytes and is also a ligand of the adhesion‐class heptahelical receptor CD97, which is expressed by infiltrating macrophages. Treatment with antibodies to CD97 ameliorates the collagen‐induced model of rheumatoid arthritis (RA) in DBA/1 mice, but the net contribution of CD55 is unknown. This study was undertaken to investigate the role of CD55 in experimental RA.

Methods

Arthritis was induced in wild‐type, CD55−/−, and CD97−/− mice using collagen‐induced and K/BxN serum–transfer models. Incidence of arthritis was monitored over time, and disease activity was assessed by clinical and immunohistochemical evaluation.

Results

In contrast to observations in many inflammatory disease models, lack of CD55 resulted in decreased arthritis in experimental models of RA. Consistent with the previously reported effects of anti‐CD97 antibody treatment, CD97−/− mice had reduced arthritis activity compared with wild‐type controls.

Conclusion

Our findings indicate that the lack of CD55 or CD97 in 2 different models of arthritis increases resistance to the disease. These findings provide insight into a role for CD55 interaction with CD97 in the pathogenesis of RA and suggest that therapeutic strategies that disrupt CD55/CD97 may be clinically beneficial.
Maps on the basis of the Arts & Humanities Citation Index: The journals Leonardo and Art Journal versus “digital humanities” as a topic
Authors: Leydesdorff Loet , Salah Alkim Almila Akdag
Published: January 2010

The possibilities of using the Arts & Humanities Citation Index (A&HCI) for journal mapping have not been sufficiently recognized because of the absence of a Journal Citations Report (JCR) for this database. A quasi‐JCR for the A&HCI (2008) was constructed from the data contained in the Web of Science and is used for the evaluation of two journals as examples: Leonardo and Art Journal. The maps on the basis of the aggregated journal–journal citations within this domain can be compared with maps including references to journals in the Science Citation Index and Social Science Citation Index. Art journals are cited by (social) science journals more than by other art journals, but these journals draw upon one another in terms of their own references. This cultural impact in terms of being cited is not found when documents with a topic such as “digital humanities” are analyzed. This community of practice functions more as an intellectual organizer than a journal.
Voltammetry in Room Temperature Ionic Liquids: Comparisons and Contrasts with Conventional Electrochemical Solvents.
Authors: Barrosse‐Antle L. E. , Bond A. M. , Compton R. G. , O'Mahony A. M. , Rogers E. I. , Silvester D. S.
Published: January 2010

The recent literature is surveyed to explore the nature of voltammetry in room temperature ionic liquids. The extent of similarities with conventional electrochemical solvents is reported and some surprising differences are noted.
Multianalyte Electrochemical Biosensor Based on Aptamer‐ and Nanoparticle‐Integrated Bio‐Barcode Amplification
Authors: Li Xuemei , Xia Jianping , Li Wei , Zhang Shusheng
Published: January 2010

In the present work, a signal‐on electrochemical sensing strategy for the simultaneous detection of adenosine and thrombin is developed based on switching structures of aptamers. An Au electrode as the sensing surface is modified with two kinds of thiolated capture probes complementary to the linker DNA that contains either an adenosine aptamer or thrombin aptamer. The capture probes hybridize with their corresponding linker DNA, which has prehybridized with the reporter DNA loaded onto the gold nanoparticles (AuNPs). The AuNP contained two kinds of bio‐barcode DNA: one is complementary to the linker DNA (reporter), whereas the other is not (signal) and is tagged with different metal sulfide nanoparticles. Thus a “sandwich‐type” sensing interface is fabricated for adenosine and thrombin. With the introduction of adenosine and thrombin, the aptamer parts bind with their targets and fold to form the complex structures. As a result, the bio‐barcoded AuNPs are released into solution. The metal sulfide nanoparticles are measured by anodic stripping voltammetry (ASV), and the concentrations of adenosine and thrombin are proportional to the signal of either metal ion. With the dual amplification of the bio‐barcoded AuNP and the preconcentration of metal ions through ASV technology, detection limits as low as 6.6×10−12 M for adenosine and 1.0×10−12 M for thrombin are achieved. The sensor exhibits excellent selectivity and detectability in biological samples.
Pyridyl‐Substituted Corrole Isomers: Synthesis and their Regulation to G‐quadruplex Structures
Authors: Ma Heng , Zhang Ming , Zhang Dan , Huang Rong , Zhao Yang , Yang Hao , Liu Yijing , Weng Xiaocheng , Zhou Yangyang , Deng Minggang , Xu Liang , Zhou Xiang
Published: January 2010

G‐quadruplex DNA plays an important role in the potential therapeutic target for the design and development of anticancer drugs. As various G‐quadruplex sequences in the promoter regions or telomeres can form different secondary structural modes and display a diversity of biology functions, variant G‐quadruplex interactive agents may be necessary to cure different disease by differentiating variant types of G‐quadruplexes. We synthesize five cationic methylpyridylium corroles and compare the interactions of corroles with different types of G‐quadruplexes such as cmyc, htelo, and bcl2 by using surface plasmon resonance. Because of the importance of human telomere G‐quadruplex DNA, we focus on the biological properties of the interactions between human telomere G‐quadruplex DNA and corrole isomers using CD, Tm, PCR‐stop (PCR= polymerase chain reaction), and polymerase‐stop assay, which demonstrate the excellent ability of the corrole to induce and stabilize the G‐quadruplex. This study provides the first experimental insight into how selectivity might be achieved for different G‐quadruplexes by a single group of methylpyridylium corrole isomers that may be optimized for potential selective cancer therapy.
Concentration Dependent Transformation of Oligopeptide based Nanovesicles to Nanotubes and an Application of Nanovesicles
Authors: Naskar Jishu , Banerjee Arindam
Published: January 2010

The concentration dependent transformation of an oligopeptide nanostructure from nanovesicles to nanotubes at neutral pH is presented. The oligopeptide Acp‐Tyr‐Glu (Acp: 6‐aminohexanoic acid) forms nanovesicles at a concentration of 6.9 mg mL−1. At a concentration of 2.3 mg mL−1 these vesicular structures completely disappear and nanotubular structures are observed. We have also successfully optimized an intermediate concentration (3.4 mg mL−1) where an ordered array of fused vesicular structures are formed, which actually leads to the transition from nanovesicles to nanotubes. These vesicular structures are very much sensitive toward metal ions and pH. Biocompatible calcium ions and high pH (10.7) can trigger the rupturing of these nanovesicles. One important property of these nanovesicular structures is the encapsulation of a potent anticancer drug doxorubicin, which can also be released in the presence of calcium ions promising a future use of these nanovesicles as vehicles for carrying biologically important molecules.
Functionalized Carbon Nanomaterials Derived from Carbohydrates
Authors: Jagadeesan Dinesh , Eswaramoorthy Muthusamy
Published: January 2010

A tremendous growth in the field of carbon nanomaterials has led to the emergence of carbon nanotubes, fullerenes, mesoporous carbon and more recently graphene. Some of these materials have found applications in electronics, sensors, catalysis, drug delivery, composites, and so forth. The high temperatures and hydrocarbon precursors involved in their synthesis usually yield highly inert graphitic surfaces. As some of the applications require functionalization of their inert graphitic surface with groups like COOH, OH, and NH2, treatment of these materials in oxidizing agents and concentrated acids become inevitable. More recent works have involved using precursors like carbohydrates to produce carbon nanostructures rich in functional groups in a single‐step under hydrothermal conditions. These carbon nanostructures have already found many applications in composites, drug delivery, materials synthesis, and Li ion batteries. The review aims to highlight some of the recent developments in the application of carbohydrate derived carbon nanostructures and also provide an outlook of their future prospects.
A Sub‐50‐nm Monosized Superparamagnetic Fe3O4@SiO2T2‐Weighted MRI Contrast Agent: Highly Reproducible Synthesis of Uniform Single‐Loaded Core–Shell Nanostructures
Authors: Chen Feng , Bu Wenbo , Chen Yu , Fan Yuchi , He Qianjun , Zhu Min , Liu Xiaohang , Zhou Liangping , Zhang Shengjian , Peng Weijun , Shi Jianlin
Published: January 2010

Oleic acid stabilized superparamagnetic iron oxide nanoparticles (SPION) were selected as the cores for fabrication of sub‐50‐nm monodisperse single‐loaded SPION@SiO2 core–shell nanostructures. Parameters that influence the formation of SPION@SiO2 in the water‐in‐oil reverse microemulsion system have been systematically investigated. The sufficiently high concentration of well‐dispersed SPION, together with an appropriately low injection rate of tetraethoxysilane, were found to be the keys to efficiently prevent the homogeneous nucleation of silica and obtain a high‐quality single‐loaded core–shell nanocomposite. A more detailed mechanism for incorporating oleic acid capped inorganic functional nanoparticles into silica is proposed on the basis of previous reports and our new experimental results. Finally, the as‐synthesized SPION@SiO2 nanospheres are exploited as an MRI‐enhanced contrast agent, and their contrast effect in solution is tested by using a clinical MRI instrument.
Formation of α‐Lithio Siloles from Silylated 1,4‐Dilithio‐1,3‐Butadienes: Mechanism and Applications
Authors: Luo Qian , Wang Chao , Gu Li , Zhang Wen‐Xiong , Xi Zhenfeng
Published: January 2010

A full account of a useful transformation from silylated 1,4‐dilithio‐1,3‐butadienes to α‐lithio siloles is described. These lithio siloles formed by this procedure are general, in terms of substitution patterns and synthetic methods, affording diversified silole derivatives. Notably, some structurally complex molecules, such as bridged bis‐silole compounds, have been synthesized easily and successfully by applying our protocol. The structure of the α‐lithio silole, which adopts a dimeric fashion through two lithium bridges, was confirmed by X‐ray analysis. Furthermore, a possible mechanism of the skeleton rearrangements via E/Z isomerization of 1‐silyl‐1‐lithio alkene and nucleophilic attack on silicon is proposed, and is also proved by experimental investigations.
Stereospecific Construction of Chiral Tertiary and Quaternary Carbon by Nucleophilic Cyclopropanation with Bis(iodozincio)methane
Authors: Nomura Kenichi , Matsubara Seijiro
Published: January 2010

The reaction of a ketone having a leaving group at the α‐position, such as α,β‐epoxy ketone or α‐sulfonyloxy ketone, with bis(iodozincio)methane affords a zinc alkoxide of cyclopropanol. The reaction proceeds by nucleophilic addition of the dizinc to the carbonyl group and a sequential intramolecular nucleophilic substitution of the introduced iodozinciomethyl group to the adjacent electrophilic carbon that has a leaving group. When an optically active α,β‐epoxy ketone or α‐sulfonyloxy ketone is treated with the dizinc, a zinc alkoxide of cyclopropanol having a chiral tertiary or quaternary carbon in the cyclopropane ring is obtained, and the obtained zinc alkoxide of cyclopropanol acts as a chiral homoenolate. When it is treated with an electrophile in the presence of copper cyanide, it gives an optically active α‐tertiary or ‐quaternary ketone that retains high optical purity.
Synthesis and Characterization of Water‐Soluble Conjugated Glycopolymer for Fluorescent Sensing of Concanavalin A
Authors: Shi Jianbing , Cai Liping , Pu Kan‐Yi , Liu Bin
Published: January 2010

A neutral polyfluorene derivative that contains 20 mol % 2,1,3‐benzothiadiazole (BT) is synthesized by Suzuki cross‐coupling polymerization. A cationic conjugated polymer A and an α‐mannose‐bearing polymer B are subsequently obtained through different post‐polymerization methods. As a result of the charged pendant groups or sugar‐bearing groups attached to the polymer side chains, both A and B show good water‐solubility. The titration of Concanavalin A (Con A) into polymer aqueous solution leads to different fluorescent responses for polymers A and B. Polymer A does not show any obvious fluorescence change upon interaction with Con A, whereas polymer B shows fluorescence increase in BT emission intensity when Con A is added. This is because of the specific interaction between α‐mannose and Con A, which induces polymer aggregation, and then facilitates energy transfer from the phenylene–fluorene segments to the BT units. A practical calibration curve ranging from 1 nM to 250 nM is obtained by correlating the changes in BT emission intensity with Con A concentration. The advantage of polymer B‐based Con A macromolecular probe is that it shows signal increase upon Con A recognition, which is significantly different from other conjugated polymer‐based fluorescence quenching assays.
Redox Multifunctionality in a Series of PtII Dithiolene Complexes of a Tetrathiafulvalene‐Based Diphosphine Ligand
Authors: Lee Su‐Kyung , Shin Kyong‐Soon , Noh Dong‐Youn , Jeannin Olivier , Barrière Frédéric , Bergamini Jean‐François , Fourmigué Marc
Published: January 2010

The redox‐active and chelating diphosphine, 3,4‐dimethyl‐3′,4′‐bis(diphenylphosphino)‐tetrathiafulvalene, denoted as P2, is engaged in a series of platinum complexes, [(P2)Pt(dithiolene)], with different dithiolate ligands, such as 1,2‐benzenedithiolate (bdt), 1,3‐dithiole‐2‐thione‐4,5‐dithiolate (dmit), and 5,6‐dihydro‐1,4‐dithiin‐2,3‐dithiolate (dddt). The complexes are structurally characterized by X‐ray diffraction, together with a model compound derived from bis(diphenylphosphino)ethane, namely, [(dppe)Pt(dddt)]. Four successive reversible electron‐transfer processes are found for the [(P2)Pt(dddt)] complex, associated with the two covalently linked but electronically uncoupled electrophores, that is, the TTF core and the platinum dithiolene moiety. The assignments of the different redox processes to either one or the other electrophore is made thanks to the electrochemical properties of the model compound [(dppe)Pt(dddt)] lacking the TTF redox core, and with the help of theoretical calculations (DFT) to understand the nature and energy of the frontier orbitals of the [(P2)Pt(dithiolene)] complexes in their different oxidation states. The first oxidation of the highly electron‐rich [(P2)Pt(dddt)] complex can be unambiguously assigned to the redox process affecting the Pt(dddt) moiety rather than the TTF core, a rare example in the coordination chemistry of tetrathiafulvalenes acting as ligands.
Platinum‐Catalyzed Multi‐Step Reaction of Propargyl Alcohols with N‐Heteroaromatics
Authors: Bhuvaneswari Sivakolundu , Jeganmohan Masilamani , Cheng Chien‐Hong
Published: January 2010

N‐Methyl indole reacts with but‐2‐yn‐1‐ol in the presence of PtCl2 in MeOH giving indole derivatives having a substituted 3‐oxobutyl group at the 3‐position in good yield. Under the reaction conditions, various substituted indoles and substituted propargyl alcohols are successfully involved in the reaction giving the corresponding addition products in good to moderate yields. The catalytic reaction can be further extended to N‐phenyl pyrrole. In the present multi‐step reaction, PtCl2 likely plays dual roles: as the catalyst for the rearrangement of propargyl alcohols to the corresponding alkenyl ketones and as the catalyst for the addition of indoles to the alkenyl ketones. Experimental evidence is provided to support the proposed mechanism.
An Efficient and Convenient Synthesis of Ethyl 1‐(4‐Methoxyphenyl)‐5‐phenyl‐1H‐1,2,3‐triazole‐4‐carboxylate
Authors: Chen Jung‐Hsuan , Liu Shuan‐Ru , Chen Kwunmin
Published: January 2010

The “click chemistry” of using organic azides and terminal alkynes is arguably the most efficient and straightforward route to the synthesis of 1,2,3‐triazoles. In this paper, an alternative and direct access to ethyl 1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐1,2,3‐triazole‐4‐carboxylate is described. Treatment of ethyl diazoacetate with 4‐methoxyaniline derived aryl imines in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene provided fully substituted 1,2,3‐triazoles in good to high chemical yields. The base‐mediated reaction tolerates various substituted phenyl imines as well as ethyl diazoacetate or the more bulky diazoacetamide. A reasonable mechanism is proposed that involves the addition of an imine nitrogen atom to the terminal nitrogen atom of the diazo compound, followed by aromatization to give the 1,2,3‐triazole. The presence of the 4‐carboxy group is advantageous as it can be easily transformed into other functional groups.
Synthesis of N‐Arylated 1,2‐Dihydroheteroaromatics Through the Three‐Component Reaction of Arynes with N‐Heteroaromatics and Terminal Alkynes or Ketones
Authors: Jeganmohan Masilamani , Bhuvaneswari Sivakolundu , Cheng Chien‐Hong
Published: January 2010

The reaction of benzynes with N‐heteroaromatics including quinolines, isoquinolines, and pyridines and various terminal alkynes or ketones with an α‐hydrogen in the presence of KF and 18‐crown‐6 in THF at room temperature for 8 h gave various N‐arylated 1,2‐dihydroheteroaromatics in good to moderate yields. Some of these product structures are found in various naturally occurring and biologically active heterocyclic compounds. The reaction involves an unusual multiple construction of new CC, CN, and CH bonds and the cleavage of a CH bond in one pot. It is likely that the three‐component coupling proceeds through the nucleophilic addition of quinoline to benzyne, which generates a zwitterionic species. The latter then attracts a proton from terminal alkyne (or ketone) to generate an N‐arylated quinolinium cation and an acetylide anion. Further reaction of these two ions provides the final substituted 1,2‐dihydroquinolines. In the reaction, the terminal alkyne acts first as a proton donor and then as a nucleophile. The application of a three‐component coupling reaction product, 1,2‐dihydro‐2‐pyridinyl alkyne in a stereospecific [4+2] Diels–Alder cycloaddition reaction with N‐phenyl maleimide to give an isoquinuclidine derivative, an important core present in various natural products, is demonstrated.
Vesicle Formation from an Amphiphilic Porphyrin Derivative at the Air–Water Interface
Authors: Ghosh Amrita , Choudhury Sipra , Das Amitava
Published: January 2010

A tetraphenyl porphyrin derivative with two C16 alkyl chains covalently bound to each of the four peripheral phenyl rings through ether linkages formed multilayer clusters or vesicles at the air–water surface. More interestingly, spherical vesicles were also formed when deposited on appropriate solid surfaces, and these vesicles were stable even in dry conditions. Various microscopic images of the cast film deposited on a mica surface confirmed closed‐ended nanotube/nanorod‐type formation with necking and bulging. These narrow tubes are proposed to be intermediates for the formation of vesicles by fission at either side of the bulge. Such vesicular formation is not common when either cast or Langmuir–Blodgett films were deposited on a solid surface.
Phase‐Transfer‐Catalyzed Asymmetric Alkylation of α‐Benzoyloxy‐β‐keto Esters: Stereoselective Construction of Congested 2,3‐Dihydroxycarboxylic Acid Esters
Authors: Hashimoto Takuya , Sasaki Keigo , Fukumoto Kazuhiro , Murase Yuichi , Abe Naoyuki , Ooi Takashi , Maruoka Keiji
Published: January 2010

Highly enantioselective phase‐transfer‐catalyzed alkylation of tert‐butyl 2‐benzoyloxy‐3‐oxobutanoate was realized by the use of an N‐spiro chiral quaternary ammonium salt, as a complementary approach to the asymmetric hydroxylation of α‐alkyl‐β‐keto esters. The synthetic utility of the alkylated compounds is highlighted by the diastereoselective reduction and alkylation of the remaining ketone moiety to give various enantiomerically enriched congested 2,3‐dihydroxycarboxylic acid esters.
RhII‐Catalyzed Reaction of α‐Diazocarbonyl Compounds Bearing β‐Trichloroacetylamino Substituent: CH Insertion versus 1,2‐H Shift
Authors: Zhang Zhenhua , Shi Weifeng , Zhang Jian , Zhang Bo , Liu Bingge , Liu Yiyang , Fan Bo , Xiao Fengping , Xu Feng , Wang Jianbo
Published: January 2010

The RhII‐carbene reaction is dramatically affected by the neighboring substituents. If the neighboring substituent is an OH group, a1,2‐H shift is the exclusive pathway. If it is an OAc group, a 1,2‐acetoxy migration is observed. If it is p‐toluenesulfonyl group, 1,3 and 1,5‐CH insertion are the major pathways, and the 1,2‐H shift is completely suppressed. If the adjacent substituent is a trichloroacetyl amino group, 1,5‐CH insertion competes with the 1,2‐hydride shift, and no 1,3‐CH insertion can be observed. Both electronic and steric factors are responsible for the switching of the RhII‐carbene reaction pathway. The highly stereoselective 1,5‐CH insertions in RhII‐catalyzed reaction of α‐diazocarbonyl compounds, bearing β‐trichloroacetylamino substituent, can be utilized as a novel way to synthesize five‐membered cyclic β‐amino acid derivatives.
Controllable Synthesis and Optical Properties of Connected Zinc Oxide Nanoparticles
Authors: Wu Wei , Xiao Xiangheng , Peng Tangchao , Jiang Changzhong
Published: January 2010

Connected zinc oxide (ZnO) nanoparticles are successfully synthesized by a simple solution‐based chemical route that uses evaporation and concentration technology. The influences of processing parameters, especially the evaporation and concentration time on the size and morphology of the nanoparticles, have been investigated by transmission electron microscopy (TEM) and high‐resolution TEM (HRTEM). The structure and optical properties are systematically characterized by X‐ray diffraction (XRD), UV/Vis spectrophotometery, and fluorescence spectroscopy (FL). It is found that the average diameter and morphology are strongly affected by the evaporation and concentration time. Additionally, the formation mechanism of the nanoparticles is also discussed. The studies revealed that the evaporation and concentration are important aggregation or nucleation processes for ZnO growth, which leads to the macro‐differences in morphology. These results provide some insight into the growth mechanism of ZnO nanostructures. The synthetic strategy developed in this study may also be extended to the preparation of other nanomaterials and promising applications in various fields of nanotechnology.
Oxidative Dissolution of Silver Nanoparticles by Biologically Relevant Oxidants: A Kinetic and Mechanistic Study
Authors: Ho Chi‐Ming , Yau Sammi King‐Woon , Lok Chun‐Nam , So Man‐Ho , Che Chi‐Ming
Published: January 2010

The oxidative dissolution of silver nanoparticles (AgNPs) plays an important role in the synthesis of well‐defined nanostructured materials, and may be responsible for their activities in biological systems. In this study, we use stopped‐flow spectrophotometry to investigate the kinetics and mechanism of the oxidative dissolution of AgNPs by H2O2 in quasi‐physiological conditions. Our results show that the reaction is first order with respect to both [Ag0] and [H2O2], and parallel pathways that involve the oxidation of H2O2 and HO2− are proposed. The order of the reaction is independent of the size of the AgNPs (≈5–20 nm). The rate of dissolution increases with increasing pH from 6.0 to 8.5. At 298 K and I=0.1 M, the value of kb is five orders of magnitude higher than that of ka (where ka and kb are the rate constants for the oxidative dissolution of AgNPs by H2O2 and HO2−, respectively). In addition, the effects of surface coating and the presence of halide ions on the dissolution rates are investigated. A possible mechanism for the oxidative dissolution of AgNPs by H2O2 is proposed. We further demonstrate that the toxicities of AgNPs in both bacteria and mammalian cells are enhanced in the presence of H2O2, thereby highlighting the biological relevance of investigating the oxidative dissolution of AgNPs.
Mechanistic Insights into Selectivity Control for Heterogeneous Olefin Oxidation: Styrene Oxidation on Au(111)
Authors: Quiller Ryan G. , Liu Xiaoying , Friend Cynthia M.
Published: January 2010

We demonstrate that intermolecular interactions, controlled by both oxygen and styrene coverage, alter reaction selectivity for styrene oxidation on oxygen‐covered Au(111). Several partial oxidation products are formed—styrene oxide, acetophenone, benzoic acid, benzeneacetic acid, and phenylketene—in competition with combustion. The maximum ratio of the yields of styrene oxide to the total CO2 produced is obtained for the maximum styrene coverage for the first two layers (0.28 ML) adsorbed on Au(111) precovered with 0.2 ML of O. Furthermore, our reactivity and infrared studies support a mechanism whereby styrene oxidation proceeds via two oxametallacycle intermediates which, under oxygen‐lean conditions, lead to the formation of styrene oxide, acetophenone, and phenylketene. Benzoate, identified on the basis of infrared reflection absorption spectroscopy, is converted into benzoic acid during temperature‐programmed reaction. These results demonstrate the ability to tune the epoxidation selectivity using reactant coverages and provide important mechanistic insight into styrene oxidation reactions.
Synthesis and Rearrangement of Stable NHC→Silylene Adducts and Their Unique Reactivity towards Cyclohexylisocyanide
Authors: Xiong Yun , Yao Shenglai , Driess Matthias
Published: January 2010

The syntheses and reactivity of the two N‐heterocyclic carbene (NHC)→ silylene complexes 2 and 4 have been investigated. The latter are easily accessible by reaction of the zwitterionic, N‐heterocyclic silylene LSi: 1 [L=Ar‐N‐C(=CH2)CHC(Me)‐N‐Ar, Ar=2,6‐iPr2C6H3] with 1,3,4,5‐tetramethylimidazol‐2‐ylidene and 1,3‐diisopropyl‐4,5‐dimethylimidazol‐2‐ylidene, respectively. While compound 2 undergoes facile rearrangement above −20 °C to give the unsymmetrical N‐heterocyclic silylcarbene 3, the derivative 4 remains unchanged even after boiling in benzene. The remarkable reactivity of 3 and 4 towards cyclohexylisocyanide has been examined which leads in a unique series of CH, SiH, and CN bond activations to the new triaminosilanes 5 and 6, respectively. The novel compounds 3, 4, 5, and 6 were fully characterized by 1H, 13C, and 29Si NMR spectroscopy, EI‐MS, elemental analysis, and single‐crystal X‐ray diffraction.
1‐Alkynylphosphines and Their Derivatives as Key Starting Materials in Creating New Phosphines
Authors: Kondoh Azusa , Yorimitsu Hideki , Oshima Koichiro
Published: January 2010

This Focus Review summarizes transformations of 1‐alkynylphosphines and their derivatives directed toward the synthesis of new phosphines. Owing to the importance of organophosphines as ligands for transition metal catalysts, development of efficient methods for the synthesis of new phosphines is quite important. 1‐Alkynylphosphines and their derivatives have been emerging as useful precursors for the creation of new phosphines. Chemical modifications of the carbon–carbon triple bonds, including nucleophilic addition and cycloaddition, lead to a wide range of new useful phosphines that are otherwise difficult to synthesize.
Binding of Multivalent Anionic Porphyrins to V3 Loop Fragments of an HIV‐1 Envelope and Their Antiviral Activity
Authors: Watanabe Kenji , Negi Shigeru , Sugiura Yukio , Kiriyama Akiko , Honbo Akino , Iga Katsumi , Kodama Eiichi N. , Naitoh Takeshi , Matsuoka Masao , Kano Koji
Published: January 2010

Interactions of multivalent anionic porphyrins and their iron(III) complexes with cationic peptides, V3Ba‐L and V3IIIB, which correspond to those of the V3 loop regions of the gp120 envelope proteins of the HIV‐1Ba‐L and HIV‐1IIIB strains, respectively, are studied by UV/Vis, circular dichroism, 1H NMR, and EPR spectroscopy, a microcalorimetric titration method, and anti‐HIV assays. Tetrakis(3,5‐dicarboxylatophenyl)porphyrin (P1), tetrakis[4‐(3,5‐dicarboxylatophenylmethoxy)phenyl]porphyrin (P2), and their ferric complexes (FeIIIP1 and FeIIIP2) were used as the multivalent anionic porphyrins. P1 and FeIIIP1 formed stable complexes with both V3 peptides (binding constant K>106 M−1) through combined electrostatic and van der Waals interactions. Coordination of the His residues in V3Ba‐L to the iron center of FeIIIP1 also played an important role in the complex stabilization. As P2 and FeIIIP2 form self‐aggregates in aqueous solution even at low concentrations, detailed analysis of their interactions with the V3 peptides could not be performed. To ascertain whether the results obtained in the model system are applicable to a real biological system, anti‐HIV‐1BA‐L and HIV‐1IIIB activity of the porphyrins is examined by multiple nuclear activation of a galactosidase indicator (MAGI) and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays. There is little correlation between chemical analysis and actual anti‐HIV activity, and the size rather than the number of the anionic groups of the porphyrin is important for anti‐HIV activity. All the porphyrins show high selectivity, low cytotoxicity, and high viral activity. FeIIIP1 and FeIIIP2 are used for the pharmacokinetic study. Half‐lives of these iron porphyrins in serum of male Wistar rats are around 4 to 6 h owing to strong interaction of these porphyrins with serum albumin.
1,4‐Butanediol as a Reducing Agent in Transfer Hydrogenation Reactions
Authors: Maytum Hannah C. , Francos Javier , Whatrup David J. , Williams Jonathan M. J.
Published: January 2010

1,4‐Butanediol is able to deliver two equivalents of H2 in hydrogen‐transfer reactions to ketones, imines, and alkenes. Unlike simple alcohols, which establish equilibrium in the reduction of ketones, 1,4‐butanediol acts essentially irreversibly owing to the formation of butyrolactone, which acts as a thermodynamic sink. It is therefore not necessary to use 1,4‐butanediol in great excess in order to achieve reduction reactions. In addition, allylic alcohols are reduced to saturated alcohols through an isomerization/reduction sequence using a ruthenium catalyst with 1,4‐butanediol as the reducing agent. Imines and alkenes are also reduced under similar conditions.
Platelet Graphite Nanofibers for Electrochemical Sensing and Biosensing: The Influence of Graphene Sheet Orientation
Authors: Ambrosi Adriano , Sasaki Toshio , Pumera Martin
Published: January 2010

Here, we demonstrate that platelet graphite nanofibers (PGNFs) exhibit fast heterogeneous electron‐transfer rates for a wide variety of compounds such as FeCl3, ferrocyanide, dopamine, uric acid, ascorbic acid, and the reduced form of β‐nicotinamide adenine dinucleotide. The electrochemical properties of PGNFs are superior to those of multiwalled carbon nanotubes (MWCNTs) or graphite microparticles (GMPs). Transmission electron microscopy and Raman spectroscopy reveal that this arises from the unique graphene sheet orientation of such platelet nanofibers, which accounts for their unparalleled high ratio of graphene edge planes versus basal planes.