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Sample records for pyrrolidine dithiocarbamate complex

  1. Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity

    SciTech Connect

    Milacic, Vesna; Chen Di; Giovagnini, Lorena; Diez, Alejandro; Fregona, Dolores; Dou, Q. Ping

    2008-08-15

    Zinc and copper are trace elements essential for proper folding, stabilization and catalytic activity of many metalloenzymes in living organisms. However, disturbed zinc and copper homeostasis is reported in many types of cancer. We have previously demonstrated that copper complexes induced proteasome inhibition and apoptosis in cultured human cancer cells. In the current study we hypothesized that zinc complexes could also inhibit the proteasomal chymotrypsin-like activity responsible for subsequent apoptosis induction. We first showed that zinc(II) chloride was able to inhibit the chymotrypsin-like activity of a purified 20S proteasome with an IC{sub 50} value of 13.8 {mu}M, which was less potent than copper(II) chloride (IC{sub 50} 5.3 {mu}M). We then compared the potencies of a pyrrolidine dithiocarbamate (PyDT)-zinc(II) complex and a PyDT-copper(II) complex to inhibit cellular proteasomal activity, suppress proliferation and induce apoptosis in various human breast and prostate cancer cell lines. Consistently, zinc complex was less potent than copper complex in inhibiting the proteasome and inducing apoptosis. Additionally, zinc and copper complexes appear to use somewhat different mechanisms to kill tumor cells. Zinc complexes were able to activate calpain-, but not caspase-3-dependent pathway, while copper complexes were able to induce activation of both proteases. Furthermore, the potencies of these PyDT-metal complexes depend on the nature of metals and also on the ratio of PyDT to the metal ion within the complex, which probably affects their stability and availability for interacting with and inhibiting the proteasome in tumor cells.

  2. Antiviral Effects of Pyrrolidine Dithiocarbamate on Human Rhinoviruses

    PubMed Central

    Gaudernak, Elisabeth; Seipelt, Joachim; Triendl, Andrea; Grassauer, Andreas; Kuechler, Ernst

    2002-01-01

    Human rhinoviruses (HRVs) are the predominant cause of the common cold. The frequency of HRV infections in industrial countries and the lack of effective therapeutical treatment underline the importance of research for new antiviral substances. As viral infections are often accompanied by the generation of oxidative stress inside the infected cells, several redox-active substances were tested as potential antivirals. In the course of these studies it was discovered that pyrrolidine dithiocarbamate (PDTC) is an extremely potent compound against HRV and poliovirus infection in cell culture. Besides the ability to dramatically reduce HRV production by interfering with viral protein expression, PDTC promotes cell survival and abolishes cytopathic effects in infected cells. PDTC also protects cells against poliovirus infection. These effects were highly specific, as several other antioxidants (vitamin C, Trolox, 2-mercaptoethanol, and N-acetyl-l-cysteine) are inactive against HRV infection. Synthesis of HRV proteins and cleavage of eucaryotic initiation factor 4G responsible for host cell shutoff of cellular protein synthesis are severely inhibited in the presence of PDTC. PMID:12021333

  3. The characteristic long-term upregulation of hippocampal NF-κB complex in PTSD-like behavioral stress response is normalized by high-dose corticosterone and pyrrolidine dithiocarbamate administered immediately after exposure.

    PubMed

    Cohen, Hagit; Kozlovsky, Nitsan; Matar, Michael A; Zohar, Joseph; Kaplan, Zeev

    2011-10-01

    Nuclear factor-κB (NF-κB) is a ubiquitously expressed transcription factor for genes involved in cell survival, differentiation, inflammation, and growth. This study examined the role of NF-κB pathway in stress-induced PTSD-like behavioral response patterns in rats. Immunohistochemical technique was used to detect the expression of the NF-κB p50 and p65 subunits, I-κBα, p38, and phospho-p38 in the hippocampal subregions at 7 days after exposure to predator scent stress. Expression of p65 nuclear translocation was quantified by western blot as the level of NF-κB activation. The effects of intraperitoneally administered corticosterone or a selective NF-κB inhibitor (pyrrolidine dithiocarbamate (PDTC)) at 1 h post exposure on behavioral tests (elevated plus-maze and acoustic startle response) were evaluated 7 days later. Hippocampal expressions of those genes were subsequently evaluated. All data were analyzed in relation to individual behavior patterns. Extreme behavioral responder animals displayed significant upregulation of p50 and p65 with concomitant downregulation of I-κBα, p38, and phospho-p38 levels in hippocampal structures compared with minimal behavioral responders and controls. Immediate post-exposure treatment with high-dose corticosterone and PDTC significantly reduced prevalence rates of extreme responders and normalized the expression of those genes. Stress-induced upregulation of NF-κB complex in the hippocampus may contribute to the imbalance between what are normally precisely orchestrated and highly coordinated physiological and behavioral processes, thus associating it with stress-related disorders.

  4. An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis

    PubMed Central

    Kemahli, Eray; Yildiz, Mevlüt; Firat, Tülin; Özyalvaçli, Mehmet Emin; Üyetürk, Uğur; Yilmaz, Burak; Gücük, Adnan

    2016-01-01

    Introduction: The aim of this experimental study was to investigate the histopathological and biochemical effects of pyrrolidine dithiocarbamate, an antioxidant and inhibitor of NF-kβ, on ischemiareperfusion injury in rats. Methods: A total of 21 male Wistar-Albino rats were randomly distributed into three groups as sham group (Group 1), ischemia-reperfusion (I/R) group (Group 2) and I/R with pyrrolidine dithiocarbamate (PDTC) group (Group 3). Left testicles of rats in Groups 2 and 3 underwent testicular torsion of 720° for four hours and 100 mg/kg of PDTC was administered intraperitoneally prior to detorsion in Group 3. An hour after detorsion process, left orchiectomies were performed and 5 ml of intracardiac blood samples were drawn from rats in all three groups. Histopathological examination of testis tissues performed and measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) levels in blood samples were taken. Results: Elevated levels of MDA and decreased SOD activity, together with decreased Johnson tubular biopsy scores consistent with I/R injury were observed in Group 2 (p<0.05). Group 1 and Group 3 were similar in terms of MDA levels, SOD activity, and Johnson scores (p>0.05). Conclusions: Our results indicated that PDTC may have beneficial effects for alleviation of I/R injury in testicular tissue in rats. Understanding the underlying mechanisms and exploration of its diagnostic and therapeutic potential requires further randomized, controlled trials on a larger scale. PMID:27330576

  5. Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction after Endotoxemia in Rats

    PubMed Central

    Kan, Min Hui; Yang, Ting; Fu, Hui Qun; Fan, Long; Wu, Yan; Terrando, Niccolò; Wang, Tian-Long

    2016-01-01

    Systemic inflammation, for example as a result of infection, often contributes to long-term complications. Neuroinflammation and cognitive decline are key hallmarks of several neurological conditions, including advance age. The contribution of systemic inflammation to the central nervous system (CNS) remains not fully understood. Using a model of peripheral endotoxemia with lipopolysaccharide (LPS) we investigated the role of nuclear factor-κB (NF-κB) activity in mediating long-term neuroinflammation and cognitive dysfunction in aged rats. Herein we describe the anti-inflammatory effects of pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor, in modulating systemic cytokines including tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) and CNS markers after LPS exposure in aged rats. In the hippocampus, PDTC not only reduced neuroinflammation by modulating canonical NF-κB activity but also affected IL-1β expression in astrocytes. Parallel effects were observed on behavior and postsynaptic density-95 (PSD95), a marker of synaptic function. Taken together these changes improved acute and long-term cognitive function in aged rats after LPS exposure. PMID:27493629

  6. Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.

    PubMed

    Soerensen, Jonna; Pekcec, Anton; Fuest, Christina; Nickel, Astrid; Potschka, Heidrun

    2009-12-01

    Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.

  7. Short-term pyrrolidine dithiocarbamate administration attenuates cachexia-induced alterations to muscle and liver in ApcMin/+ mice

    PubMed Central

    VanderVeen, Brandon N.; Enos, Reilly T.; Murphy, E. Angela; Carson, James A.

    2016-01-01

    Cancer cachexia is a complex wasting condition characterized by chronic inflammation, disrupted energy metabolism, and severe muscle wasting. While evidence in pre-clinical cancer cachexia models have determined that different systemic inflammatory inhibitors can attenuate several characteristics of cachexia, there is a limited understanding of their effects after cachexia has developed, and whether short-term administration is sufficient to reverse cachexia-induced signaling in distinctive target tissues. Pyrrolidine dithiocarbamate (PDTC) is a thiol compound having anti-inflammatory and antioxidant properties which can inhibit STAT3 and nuclear factor κB (NF-κB) signaling in mice. This study examined the effect of short-term PDTC administration to ApcMin/+ mice on cachexia-induced disruption of skeletal muscle protein turnover and liver metabolic function. At 16 weeks of age ApcMin/+ mice initiating cachexia (7% BW loss) were administered PDTC (10mg/kg bw/d) for 2 weeks. Control ApcMin/+ mice continued to lose body weight during the treatment period, while mice receiving PDTC had no further body weight decrease. PDTC had no effect on either intestinal tumor burden or circulating IL-6. In muscle, PDTC rescued signaling disrupting protein turnover regulation. PDTC suppressed the cachexia induction of STAT3, increased mTORC1 signaling and protein synthesis, and suppressed the induction of Atrogin-1 protein expression. Related to cachectic liver metabolic function, PDTC treatment attenuated glycogen and lipid content depletion independent to the activation of STAT3 and mTORC1 signaling. Overall, these results demonstrate short-term PDTC treatment to cachectic mice attenuated cancer-induced disruptions to muscle and liver signaling, and these changes were independent to altered tumor burden and circulating IL-6. PMID:27449092

  8. Copper uptake is required for pyrrolidine dithiocarbamate-mediated oxidation and protein level increase of p53 in cells.

    PubMed Central

    Furuta, Saori; Ortiz, Fausto; Zhu Sun, Xiu; Wu, Hsiao-Huei; Mason, Andrew; Momand, Jamil

    2002-01-01

    The p53 tumour-suppressor protein is a transcription factor that activates the expression of genes involved in cell cycle arrest, apoptosis and DNA repair. The p53 protein is vulnerable to oxidation at cysteine thiol groups. The metal-chelating dithiocarbamates, pyrrolidine dithiocarbamate (PDTC), diethyldithiocarbamate, ethylene(bis)dithiocarbamate and H(2)O(2) were tested for their oxidative effects on p53 in cultured human breast cancer cells. Only PDTC oxidized p53, although all oxidants tested increased the p53 level. Inductively coupled plasma MS analysis indicated that the addition of 60 microM PDTC increased the cellular copper concentration by 4-fold, which was the highest level of copper accumulated amongst all the oxidants tested. Bathocuproinedisulphonic acid, a membrane-impermeable Cu(I) chelator inhibited the PDTC-mediated copper accumulation. Bathocuproinedisulphonic acid as well as the hydroxyl radical scavenger d-mannitol inhibited the PDTC-dependent increase in p53 protein and oxidation. Our results show that a low level of copper accumulation in the range of 25-40 microg/g of cellular protein increases the steady-state levels of p53. At copper accumulation levels higher than 60 microg/g of cellular protein, p53 is oxidized. These results suggest that p53 is vulnerable to free radical-mediated oxidation at cysteine residues. PMID:11964141

  9. Crystal structure and carrier transport properties of a new 3D mixed-valence Cu(I)-Cu(II) coordination polymer including pyrrolidine dithiocarbamate ligand.

    PubMed

    Okubo, Takashi; Tanaka, Naoya; Kim, Kyung Ho; Anma, Haruho; Seki, Shu; Saeki, Akinori; Maekawa, Masahiko; Kuroda-Sowa, Takayoshi

    2011-03-14

    A novel mixed-valence Cu(i)-Cu(ii) coordination polymer having an infinite three-dimensional (3D) structure, {[Cu(I)(4)Cu(II)(2)Br(4)(Pyr-dtc)(4)]·CHCl(3)}(n) (1) (Pyr-dtc(-) = pyrrolidine dithiocarbamate), has been prepared and structurally characterized via X-ray diffraction. This complex consists of 1D Cu(i)-Br chains and bridging mononuclear copper(ii) units of Cu(II)(Pyr-dtc)(2), which form an infinite 3D network. A magnetic study indicates that this complex includes copper(ii) ions exhibiting a weak antiferromagnetic interaction (θ = -0.086 K) between the unpaired electrons of the copper(ii) ions present in the diamagnetic Cu(i)-Br chains. The carrier transport properties of 1 are investigated using an impedance spectroscopy technique and flash-photolysis time-resolved microwave conductivity measurement (FP-TRMC). The impedance spectroscopy reveals that this complex exhibits intriguing semiconducting properties at a small activation energy (E(a) = 0.29 eV (bulk)). The sum of the mobilities of the negative and positive carriers estimated via FP-TRMC is Σμ∼ 0.4 cm(2) V(-1) s(-1).

  10. Pyrrolidine dithiocarbamate reduces the progression of total kidney volume and cyst enlargement in experimental polycystic kidney disease

    PubMed Central

    Ta, Michelle H. T.; Rao, Padmashree; Korgaonkar, Mayuresh; Foster, Sheryl F.; Peduto, Anthony; Harris, David C. H.; Rangan, Gopala K.

    2014-01-01

    Abstract Heterocyclic dithiocarbamates have anti‐inflammatory and anti‐proliferative effects in rodent models of chronic kidney disease. In this study, we tested the hypothesis that pyrrolidine dithiocarbamate (PDTC) reduces the progression of polycystic kidney disease (PKD). Male Lewis polycystic kidney (LPK) rats (an ortholog of Nek8/NPHP9) received intraperitoneal injections of either saline vehicle or PDTC (40 mg/kg once or twice daily) from postnatal weeks 4 until 11. By serial magnetic resonance imaging at weeks 5 and 10, the relative within‐rat increase in total kidney volume and cyst volume were 1.3‐fold (P =0.01) and 1.4‐fold (P < 0.01) greater, respectively, in LPK + Vehicle compared to the LPK + PDTC(40 mg/kg twice daily) group. At week 11 in LPK rats, PDTC attenuated the increase in kidney weight to body weight ratio by 25% (P < 0.01) and proteinuria by 66% (P < 0.05 vs. LPK + Vehicle) but did not improve renal dysfunction. By quantitative whole‐slide image analysis, PDTC did not alter interstitial CD68+ cell accumulation, interstitial fibrosis, or renal cell proliferation in LPK rats at week 11. The phosphorylated form of the nuclear factor (NF)‐κB subunit, p105, was increased in cystic epithelial cells of LPK rats, but was not altered by PDTC. Moreover, PDTC did not significantly alter nuclear expression of the p50 subunit or NF‐κB (p65)‐DNA binding. Kidney enlargement in LPK rats was resistant to chronic treatment with a proteasome inhibitor, bortezomib. In conclusion, PDTC reduced renal cystic enlargement and proteinuria but lacked anti‐inflammatory effects in LPK rats. PMID:25501440

  11. Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro.

    PubMed

    Ivan, Ana L M; Campanini, Marcela Z; Martinez, Renata M; Ferreira, Vitor S; Steffen, Vinicius S; Vicentini, Fabiana T M C; Vilela, Fernanda M P; Martins, Frederico S; Zarpelon, Ana C; Cunha, Thiago M; Fonseca, Maria J V; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rúbia

    2014-09-05

    Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation-dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibits nuclear factor-κB (NF-κB) activation. In the present study, the mechanisms of PDTC were investigated in cell free oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB-induced NFκB activation in keratinocytes. PDTC presented the ability to scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS), 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical (OH); and also efficiently inhibited iron-dependent and -independent lipid peroxidation as well as chelated iron. In vivo, PDTC treatment significantly decreased UVB-induced skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory cytokine interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also reduced UVB-induced IκB degradation in keratinocytes. These results demonstrate that PDTC presents antioxidant and anti-inflammatory effects in vitro, which line up well with the PDTC inhibition of UVB irradiation-induced skin inflammation and oxidative stress in mice. These data suggest that treatment with PDTC may be a promising approach to reduce UVB irradiation-induced skin damages and merits further pre-clinical and clinical studies.

  12. Pyrrolidine dithiocarbamate attenuates surgery-induced neuroinflammation and cognitive dysfunction possibly via inhibition of nuclear factor κB.

    PubMed

    Zhang, J; Jiang, W; Zuo, Z

    2014-03-07

    Surgery induces learning and memory impairment. Neuroinflammation may contribute to this impairment. Nuclear factor κB (NF-κB) is an important transcription factor to regulate the expression of inflammatory cytokines. We hypothesize that inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC) reduces neuroinflammation and the impairment of learning and memory. To test this hypothesis, four-month-old male Fischer 344 rats were subjected to right carotid exploration under propofol and buprenorphine anesthesia. Some rats received two doses of 50mg/kg PDTC given intraperitoneally 30min before and 6h after the surgery. Rats were tested in the Barnes maze and fear conditioning paradigm begun 6days after the surgery. Expression of various proteins related to inflammation was examined in the hippocampus at 24h or 21days after the surgery. Here, surgery, but not anesthesia alone, had a significant effect on prolonging the time needed to identify the target hole during the training sessions of the Barnes maze. Surgery also increased the time for identifying the target hole in the long-term memory test and decreased context-related learning and memory in fear conditioning test. Also, surgery increased nuclear expression of p65, a NF-κB component, decreased cytoplasmic amount of inhibitor of NF-κB, and increased the expression of interleukin-1β, interleukin-6, ionized calcium binding adaptor molecule 1 and active matrix metalloproteinase 9 (MMP-9). Finally, surgery enhanced IgG extravasation in the hippocampus. These surgical effects were attenuated by PDTC. These results suggest that surgery, but not propofol-based anesthesia, induces neuroinflammation and impairment of learning and memory. PDTC attenuates these effects possibly by inhibiting NF-κB activation and the downstream MMP-9 activity.

  13. Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in bladder ischemia-reperfusion injury in rats.

    PubMed

    Yucel, Mehmet; Kucuk, Aysegul; Bayraktar, Aslihan Cavunt; Tosun, Murat; Yalcinkaya, Soner; Hatipoglu, Namik Kemal; Erkasap, Nilufer; Kavutcu, Mustafa

    2013-10-01

    The aim of the present study was to evaluate the protective effects of the NF-кB inhibition with pyrrolidine-dithiocarbamate (PDTC) in ischemia-reperfusion (I/R) injury in the rat bladder. Twenty-four Sprague-Dawley male rats were divided into three groups. Group I; (n = 8) control, group II; (n = 8) I/R group; group III (n = 8) I/R and PDTC treatment. Superoxide dismutase (SOD), catalase (CAT), and gluatathione-S-transferase (GST) enzymes was studied in bladder tissue. Lipid peroxidation (as TBARS) levels in tissue homogenate were measured with thiobarbituric acid reaction. All the slides were stained with NF-кB, p53 and HSP60 immunohistochemistry for detection genome destruction and tissue stress, respectively. Our results show that the mean TBARS levels were significantly higher in group II (p < 0.05). The TBARS levels were significantly decreased in group III compared with the group II (p < 0.05). CAT, SOD and GST activities were decreased in group II, but these enzymes levels were significantly increased in group III according to the group II (p < 0.05). Under microscopic evaluation NF-кB expression increased significantly in group II compared to the group I (p < 0.05) and then decreased in group III (p < 0.05). HSP60 and p53 expression in group II was increased significantly compared with group I. Under microscopic evaluation we detected that HSP60 and p53 expression was increased significantly in group II compared with group I. In group III PDTC administration was decreased the HSP60 and p53 expression, this difference was statistically significant (p < 0.05). The results of the present study have demonstrated that NF-кB inhibition with PDTC protects and provides beneficial effects on ischemia/reperfusion stress related bladder tissue destruction.

  14. Pyrrolidine dithiocarbamate-induced apoptosis depends on cell type, density, and the presence of Cu(2+) and Zn(2+).

    PubMed

    Erl, W; Weber, C; Hansson, G K

    2000-06-01

    Pyrrolidine dithiocarbamate (PDTC) has been found to induce or inhibit apoptosis in different cell types. Here we show that PDTC dose-dependently reduced the viability of rat smooth muscle cells (rSMC), human fibroblasts, and endothelial cells at low but not at high cell density. Endothelial cells were least sensitive, fibroblasts showed a medium sensitivity, and rSMC showed a high sensitivity to PDTC-mediated cell death. An early reduction in the mitochondrial membrane potential indicated a rapid onset of apoptosis in rSMC. Apoptosis was further confirmed by annexin V staining and DNA fragmentation analysis. Gel shift analysis demonstrated increased nuclear factor (NF)-kappaB activity in high-density rSMC compared with low-density cells. NF-kappaB has recently been shown to regulate the induction of anti-apoptotic proteins. Although PDTC is widely used as an inhibitor for NF-kappaB and a radical scavenger, our data show that PDTC rather enhanced NF-kappaB activity and, alone or in combination with menadione, induced oxygen radical generation. Notably, PDTC failed to reduce rSMC viability in medium without Cu(2+) or Zn(2+), and addition of Cu(2+) or Zn(2+) resulted in a dose-dependent increase in PDTC-induced cell death. Addition of both Cu(2+) and Zn(2+) showed synergistic effects. Our results indicate that the induction of apoptosis by PDTC requires Cu(2+) and Zn(2+) and is dependent on cell type and density. Such differential effects may have implications for studies of PDTC as an anti-atherosclerotic or immunomodulatory drug.

  15. New mono-organotin (IV) dithiocarbamate complexes

    SciTech Connect

    Muthalib, Amirah Faizah Abdul; Baba, Ibrahim

    2014-09-03

    Eighteen new mono-organotin dithiocarbamate compounds derived each nine from methyltin(IV) and phenyltin(IV) reacted using in-situ method with various type of N-dialkylamine together with carbon disulphide with the ratio of 1:3:3. Elemental and gravimetric analysis showed that the general formula of these compounds were RSnCl[S{sub 2}CNR′R″]{sub 2} (R= Ph, CH{sub 3}, R′ = CH{sub 3}, C{sub 2}H{sub 5}, C{sub 7}H{sub 7} and R″ = C{sub 2}H{sub 5}, C{sub 6}H{sub 11}, iC{sub 3}H{sub 7}, C{sub 7}H{sub 7}). These compounds had been characterized by infrared spectroscopy, ultraviolet spectroscopy, {sup 1}H, {sup 13}C NMR spectroscopy and single crystal X-ray crystallography. The infrared spectra of these compounds showed three important peaks indicating the formation of dithiocarbamate compounds, ν(CN), ν(CS) and ν(Sn-S) band which present in the region of 1444–1519, 954–1098 and 318–349 cm{sup −1} respectively. The ultraviolet-visible spectra showed an absorption band for the π - π* transition of NCS group in the range of 253 – 259 nm due to the intramolecular charge transfer of the ligand. The {sup 13}C NMR spectra showed an important shift for δ(N{sup 13}CS{sub 2}) in the range of 196.8 – 201.9 ppm.. Single crystal X-ray diffraction studies showed three new structures with the general formula of PhSnCl[S{sub 2}CN(Et)(i−Pr)]{sub 2}, MeSnCl[S{sub 2}CN(Me)(Cy)]{sub 2} and MeSnCl[S{sub 2}CN(i−Pr)(CH{sub 2}Ph)]{sub 2}. All structures having a distorted octahedral geometry set by CClS{sub 4} donor atom from the two chelating dithiocarbamate ligands.

  16. New mono-organotin (IV) dithiocarbamate complexes

    NASA Astrophysics Data System (ADS)

    Muthalib, Amirah Faizah Abdul; Baba, Ibrahim

    2014-09-01

    Eighteen new mono-organotin dithiocarbamate compounds derived each nine from methyltin(IV) and phenyltin(IV) reacted using in-situ method with various type of N-dialkylamine together with carbon disulphide with the ratio of 1:3:3. Elemental and gravimetric analysis showed that the general formula of these compounds were RSnCl[S2CNR'R″]2 (R= Ph, CH3, R' = CH3, C2H5, C7H7 and R″ = C2H5, C6H11, iC3H7, C7H7). These compounds had been characterized by infrared spectroscopy, ultraviolet spectroscopy, 1H, 13C NMR spectroscopy and single crystal X-ray crystallography. The infrared spectra of these compounds showed three important peaks indicating the formation of dithiocarbamate compounds, ν(CN), ν(CS) and ν(Sn-S) band which present in the region of 1444-1519, 954-1098 and 318-349 cm-1 respectively. The ultraviolet-visible spectra showed an absorption band for the π - π* transition of NCS group in the range of 253 - 259 nm due to the intramolecular charge transfer of the ligand. The 13C NMR spectra showed an important shift for δ(N13CS2) in the range of 196.8 - 201.9 ppm.. Single crystal X-ray diffraction studies showed three new structures with the general formula of PhSnCl[S2CN(Et)(i-Pr)]2, MeSnCl[S2CN(Me)(Cy)]2 and MeSnCl[S2CN(i-Pr)(CH2Ph)]2. All structures having a distorted octahedral geometry set by CClS4 donor atom from the two chelating dithiocarbamate ligands.

  17. Pyrrolidine Dithiocarbamate Inhibits Herpes Simplex Virus 1 and 2 Replication, and Its Activity May Be Mediated through Dysregulation of the Ubiquitin-Proteasome System

    PubMed Central

    Qiu, Min; Chen, Yu; Cheng, Lin; Chu, Ying; Song, Hong-Yong

    2013-01-01

    Pyrrolidine dithiocarbamate (PDTC) is widely used as an antioxidant or an NF-κB inhibitor. It has been reported to inhibit the replication of human rhinoviruses, poliovirus, coxsackievirus, and influenza virus. In this paper, we report that PDTC could inhibit the replication of herpes simplex virus 1 and 2 (HSV-1 and HSV-2). PDTC suppressed the expression of HSV-1 and HSV-2 viral immediate early (IE) and late (membrane protein gD) genes and the production of viral progeny. This antiviral property was mediated by the dithiocarbamate moiety of PDTC and required the presence of Zn2+. Although PDTC could potently block reactive oxygen species (ROS) generation, it was found that this property did not contribute to its anti-HSV activity. PDTC showed no activity in disrupting the mitogen-activated protein kinase (MAPK) pathway activation induced by viral infection that was vital for the virus's propagation. We found that PDTC modulated cellular ubiquitination and, furthermore, influenced HSV-2-induced IκB-α degradation to inhibit NF-κB activation and enhanced PML stability in the nucleus, resulting in the inhibition of viral gene expression. These results suggested that the antiviral activity of PDTC might be mediated by its dysregulation of the cellular ubiquitin-proteasome system (UPS). PMID:23740985

  18. Determination of lead in blood by chelation with ammonium pyrrolidine dithio-carbamate followed by tungsten-coil atomic absorption spectrometry

    NASA Astrophysics Data System (ADS)

    Salido, Arthur; Sanford, Caryn L.; Jones, Bradley T.

    1999-08-01

    An inexpensive, bench-top blood Pb analyzer has been developed. The system is based on tungsten-coil atomic absorption spectrometry. Pb atomization occurs on W-coils extracted from commercially available slide projector bulbs. The system has minimal power requirements: 120 ACV and 15 A. A small, computer-controlled CCD spectrometer is used as the detector. A Pb hollow cathode lamp is used as the source. Blood Pb is chelated with ammonium pyrrolidine dithio-carbamate and extracted into methyl iso-butyl ketone (4-methyl 2-pentanone). Twenty-microliter volumes of the organic phase are deposited on the W-coil, dried at 1.4 A, charred at 2.3 A and atomized at 6.0 A. Graphite furnace atomic absorption spectrometry is used as a comparison for W-coil results. Levels 1-4 of a NIST standard reference material 955b ‘lead in bovine blood’ are used to test accuracy and precision. The analytical figures of merit for the system are: 12-pg instrument detection limit, 24-pg blood detection limit and a characteristic mass of 28 pg.

  19. Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor κB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis

    PubMed Central

    Xu, Min; Wang, Kun-Ning; Wu, Kai; Wang, Xing-Peng

    2015-01-01

    Background/Aims To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor κB (NF-κB), as well as to determine the relationship between TLR4 and NF-κB in ANP pathogenesis. Methods A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-κB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor α, interleukin (IL)-1β, and IL-6 were measured by reverse transcription polymerase chain reaction. Results The expressions of TLR4, NF-κB, and cytokine (NF-κB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-κB, and cytokine genes in the pancreatic tissue. Conclusions The expressions of TLR4 and NF-κB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-κB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes. PMID:25287011

  20. Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia

    PubMed Central

    Francioli, Cyril; Wang, Xingyu; Parapanov, Roumen; Abdelnour, Etienne; Lugrin, Jérôme; Gronchi, Fabrizio; Perentes, Jean; Eckert, Philippe; Ris, Hans-Beat; Piquilloud, Lise

    2017-01-01

    Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation. PMID:28323904

  1. Polynuclear transition metal complexes with thiocarbohydrazide and dithiocarbamates

    NASA Astrophysics Data System (ADS)

    Siddiqi, K. S.; Khan, Sadaf; Nami, Shahab A. A.; El-ajaily, M. M.

    2007-07-01

    Sn(tch) 2{MCl 2} 2 was prepared from the precursor Sn(tch) 2 and MCl 2. It was subsequently allowed to react with diethyldithiocarbamate which yielded the trinuclear complexes of the type Sn(tch) 2{M 2(dtc) 4}, where tch = thiocarbohydrazide, M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and dtc = diethyldithiocarbamate. They were characterized on the basis of microanalytical, thermal (TGA/DSC), spectral (IR, UV-vis, EPR, 1H NMR) studies, conductivity measurement and magnetic moment data. On the basis of spectral data a tetrahedral geometry has been proposed for the halide complexes, Sn(tch) 2{MCl 2} 2 except for Cu(II) which exhibits a square planar coordination although the transition metal ion in Sn(tch) 2{M 2(dtc) 4} achieves an octahedral geometry where the dithiocarbamato moiety acts as a symmetrical bidentate ligand. The bidentate nature has been established by the appearance of a sharp single ν(C-S) around 1000 cm -1. A downfield shift observed in NH a and NH b protons on moving from Sn(tch) 2 to Sn(tch) 2{MCl 2} 2 is due to the drift of electrons toward metal atoms. A two-step pyrolysis has been observed in the Sn(tch) 2{MCl 2} 2 complexes while their dithiocarbamato derivatives exhibit a three-stage degradation pattern. Finally, the in vitro antibacterial activity of Sn(tch) 2{M 2(dtc) 4} and the mononuclear Sn(tch) 2 has been carried out on bacterial strains Escherichia coli and Salmonella typhi. The compounds were found to be active against the test organisms. The activity of the complexes is enhanced with increasing concentration. The maximum activity in both the strains was achieved by cobalt(II) dithiocarbamate complex. Minimum activity was found for Sn(tch) 2 which generally increases with the introduction of transition metal ion in the complex.

  2. Spectral, thermal and in vitro antimicrobial studies of cyclohexylamine- N-dithiocarbamate transition metal complexes

    NASA Astrophysics Data System (ADS)

    Mamba, Saul M.; Mishra, Ajay K.; Mamba, Bhekie B.; Njobeh, Patrik B.; Dutton, Mike F.; Fosso-Kankeu, Elvis

    2010-10-01

    Transition metal complexes of the type [M(L) 2] and those containing monodentate phosphines of the type [M(L) 2(PPh 3)] {M = Ni, Co, Cu and Zn; L = cyclohexylamine- N-dithiocarbamate; PPh 3 = triphenylphosphine} have been synthesized. The complexes were characterized using IR, UV-vis, NMR spectroscopy, and thermal analysis (TGA). The 1H NMR, 13C NMR and 31P NMR showed the expected signals for the dithiocarbamate and triphenylphosphine moieties. The spectral studies in all compounds revealed that the coordination of metals occurs via the sulphur atom of the dithiocarbamate ligand in a bidentate fashion. Thermal behavior of the complexes showed that the complexes were more stable than their parent ligands. The ligand moiety is lost in the first step and the rest of the organic moiety decomposes in the subsequent steps. Furthermore, the ligand and their metal complexes were screened in vitro for their antibacterial activity against Escherichia coli, Staphylococcus aureus, Salmonella typhi, Enterococcus faecalis, Pseudomonas aeruginosa and Bacillus cereus and antifungal activities against Aspergillus flavus, Aspergillus carbonarius, Aspergillus niger and Aspergillus fumigatus. The metal complexes exhibited higher antimicrobial activity than the parent ligands. Generally, the zinc complexes were effective against the growth of bacteria with Zn(L) 2 displaying broad spectrum bacteriocidal activity at concentrations of 50 μg/mL; and Ni(L) 2 was more effective against the growth of fungi at concentrations of 100-400 μg/mL under laboratory conditions.

  3. Synthesis and structural characterization of new dithiocarbamate complexes from Sb(III) and Bi(III)

    SciTech Connect

    Jamaluddin, Nur Amirah; Baba, Ibrahim

    2013-11-27

    Twenty new antimony and bismuth dithiocarbamate complexes which employed ten different type of amines have been successfully synthesized. The synthesized complexes with metal to dithiocarbamate ratio at 1:3. Elemental analysis of the complexes gave the general formula of MCl[S{sub 2}CNR’R”]{sub 2} where M = Sb(III), Bi(III); R’ = methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, benzyl; R” = ethanol, methyl, ethyl, propyl, isopropyl, cyclohexyl, benzyl. The complexes were analysed by IR and NMR spectroscopy. The crystal structure of five-coordinated antimony (III) complex have been determined by X-ray single crystal diffraction. Single crystal X-ray diffraction studies on SbCl[S{sub 2}CN(C{sub 4}H{sub 9})(C{sub 2}H{sub 5})]{sub 2} adopted a triclinic system with a space group P1 with a = 10.0141(8) Å, b = 10.1394(7) Å, c = 11.8665(9) Å, α = 67.960°, β =87.616°, γ = 80.172°.

  4. An analytical method for hydrogeochemical surveys: Inductively coupled plasma-atomic emission spectrometry after using enrichment coprecipitation with cobalt and ammonium pyrrolidine dithiocarbamate

    USGS Publications Warehouse

    Hopkins, D.M.

    1991-01-01

    Trace metals that are commonly associated with mineralization were concentrated and separated from natural water by coprecipitation with ammonium pyrollidine dithiocarbamate (APDC) and cobalt and determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The method is useful in hydrogeochemical surveys because it permits preconcentration near the sample sites, and selected metals are preserved shortly after the samples are collected. The procedure is relatively simple: (1) a liter of water is filtered; (2) the pH is adjusted; (3) Co chloride and APDC are added to coprecipitate the trace metals; and (4) later, the precipitate is filtered, dissolved, and diluted to 10 ml for a 100-fold concentration enrichment of the separated metals. Sb(III), As(III), Cd, Cr, Cu, Fe, Pb, Mo, Ni, Ag, V, and Zn can then be determined simultaneously by ICP-AES. In an experiment designed to measure the coprecipitation efficiency, Sb(III), Cd and Ag were recovered at 70 to 75% of their original concentration. The remaining metals were recovered at 85 to 100% of their original concentrations, however. The range for the lower limits of determination for the metals after preconcentration is 0.1 to 3.0 ??g/l. The precision of the method was evaluated by replicate analyses of a Colorado creek water and two simulated water samples. The accuracy of the method was estimated using a water reference standard (SRM 1643a) certified by the U.S. National Bureau of Standards. In addition, the method was evaluated by analyzing groundwater samples collected near a porphyry copper deposit in Arizona and by analyzing meltwater from glacier-covered areas favorable for mineralization in south-central Alaska. The results for the ICP-AES analyses compared favorably with those obtained using the sequential technique of GFAAS on the acidified but unconcentrated water samples. ICP-AES analysis of trace-metal preconcentrates for hydrogeochemical surveys is more efficient than GFAAS because a

  5. Phosphinogold(I) Dithiocarbamate Complexes: Effect of the Nature of Phosphine Ligand on Anticancer Properties

    PubMed Central

    2015-01-01

    The reactions of potassium salts of the dithiocarbamates L {where L = pyrazolyldithiocarbamate (L1), 3,5-dimethylpyrazolyldithiocarbamate (L2), or indazolyldithiocarbamate (L3)} with the gold precursors [AuCl(PPh3)], [Au2Cl2(dppe)], [Au2Cl2(dppp)], or [Au2Cl2(dpph)] lead to the new gold(I) complexes [AuL(PPh3)] (1–3), [Au2L2(dppe)] (4–6), [(Au2L2)(dppp)] (7–9), and [Au2(L)2(dpph)] (10–12) {where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, and dpph = 1,6-bis(diphenylphosphino)hexane}. These gold compounds were characterized by a combination of NMR and infrared spectroscopy, microanalysis, and mass spectrometry; and in selected cases by single-crystal X-ray crystallography. Compounds 4–6, which have dppe ligands, are unstable in solution for prolonged periods, with 4 readily transforming to the Au18 cluster [Au18S8(dppe)6]Cl2 (4a) in dichloromethane. Compounds 1–3 and 7–12 are all active against human cervical epithelioid carcinoma (HeLa) cells, but the most active compounds are 10 and 11, with IC50 values of 0.51 μM and 0.14 μM, respectively. Compounds 10 and 11 are more selective toward HeLa cells than they are toward normal cells, with selectivities of 25.0 and 70.5, respectively. Further tests, utilizing the 60-cell-line Developmental Therapeutics Program at the National Cancer Institute (U.S.A.), showed 10 and 11 to be active against nine other types of cancers. PMID:24476103

  6. Phase-transformation-induced twinning of an iron(III) calix[4]pyrrolidine complex.

    PubMed

    Journot, Guillaume; Neier, Reinhard; Stoeckli-Evans, Helen

    2014-07-01

    The title compound, tetrachlorido-1κCl;2κ(3)Cl-(2,2,7,7,12,12,17,17-octamethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1(3,6).1(8,11).1(13,16)]tetracosane-1κ(4)N,N',N'',N''')-μ2-oxido-diiron(III), [Fe2Cl4O(C28H52N4)], undergoes a slow phase transformation at ca 173 K from monoclinic space group P2(1)/n, denoted form (I), to the maximal non-isomorphic subgroup, triclinic space group P1, denoted form (II), which is accompanied by nonmerohedral twinning [twin fractions of 0.693 (4) and 0.307 (4)]. The transformation was found to be reversible, as on raising the temperature the crystal reverted to monoclinic form (I). In the asymmetric unit of form (I), Z' = 1, while in form (II), Z' = 2, with a very small reduction (ca 1.8%) in the unit-cell volume. The two independent molecules (A and B) in form (II) are related by a pseudo-twofold screw axis along the b axis. The molecular overlay of molecule A on molecule B has an r.m.s. deviation of 0.353 Å, with the largest distance between two equivalent atoms being 1.202 Å. The reaction of calix[4]pyrrolidine, the fully reduced form of meso-octamethylporphyrinogen, with FeCl3 gave a red-brown solid that was recrystallized from ethanol in air, resulting in the formation of the title compound. In both forms, (I) and (II), the Fe(III) atoms are coordinated to the macrocyclic ligand and have distorted octahedral FeN4OCl coordination spheres. These Fe(III) atoms lie out of the mean plane of the four N atoms, displaced towards the O atom of the [OFeCl3] unit by 0.2265 (5) Å in form (I), and by 0.2210 (14) and 0.2089 (14) Å, respectively, in the two independent molecules (A and B) of form (II). The geometry of the [OFeCl3] units are similar, with each Fe(III) atom having a tetrahedral coordination sphere. The NH H atoms are directed below the planes of the macrocycles and are hydrogen bonded to the coordinated Cl(-) ions. There are also intramolecular C-H···Cl hydrogen bonds present in both (I) and (II

  7. Mixed Ligand Complexes of N-Methyl-N-phenyl Dithiocarbamate: Synthesis, Characterisation, Antifungal Activity, and Solvent Extraction Studies of the Ligand

    PubMed Central

    Ekennia, Anthony C.; Onwudiwe, Damian C.; Ume, Cyril; Ebenso, Eno E.

    2015-01-01

    A series of mixed ligand dithiocarbamate complexes with a general formula [ML2(py)2], where M = Mn(II), Co(II), Ni(II), and Cu(II), py = pyridine, and L = N-methyl-N-phenyl dithiocarbamate have been prepared and characterised by elemental analysis, FTIR and Uv spectroscopy, magnetic moment, and thermogravimetric and conductance analysis. The infrared spectra showed that symmetrical bidentate coordination occurred with the dithiocarbamate moiety through the sulfur atoms, while neutral monodentate coordination occurred through the nitrogen atom for the pyridine molecule in the complexes. The electronic spectra, elemental analysis, and magnetic moment results proved that the complexes adopted octahedral geometry. The conductance measurement showed that the complexes are nonelectrolytes proving their nonionic nature. The compounds were screened for three human pathogenic fungi: Aspergillus flavus, Aspergillus niger, and Candida albicans. The cobalt complex showed the best antifungal activity among the test compounds. Liquid-liquid extractive abilities of the ligand towards copper and nickel ions in different solvent media were investigated. The ligand showed a strong binding affinity towards the metals ions with an extractive efficiency of about 99%. PMID:26543441

  8. Tris dithiocarbamate of Co(III) complexes: Synthesis, characterization, thermal decomposition studies and experimental and theoretical studies on their crystal structures

    NASA Astrophysics Data System (ADS)

    Sonia, Ayyavoo Sait; Bhaskaran, Ramalingam

    2017-04-01

    New homoleptic complexes of the form [Co(L1)3] & [Co(L2)3] where L1 = (ethylaminoethanol dithiocarbamate) 1 and L2 = (methylaminoethanol dithiocarbamate) 2 have been prepared and characterized by elemental analysis, IR, UV-visible absorption spectra, Cyclic voltammetry,1H and C13 NMR. The thermal properties were studied using a simultaneous thermal analyzer, and showed two main steps of decomposition. In addition, structures for 1 and 2 have been elucidated by X-ray crystallography. The single-crystal X-ray analysis for both the complexes showed distorted octahedral geometry. The optimized molecular structure, natural bond orbital analysis, electrostatic potential map, HOMO-LUMO energies, molecular properties, and atomic charges of these molecules have been studied by performing DFT/B3LYP/6-31G(d,p) level of theory in gas phase.

  9. Technetium-99m nitrido dithiocarbamate complex with lateral ester groups: A potential agent for cerebral perfusion. Direct labeling and kinetic results in baboons

    SciTech Connect

    Bottlaender, M.; Bourguignon, M.; Maziere, M.

    1994-05-01

    Previous studies have shown that technetium-99m-nitrido (TcN) complexes of ester derivatives of dithiocarbamate cross the brain-blood barrier and one term of this class, namely the complex formed with sarcosine methyl ester dithiocarbamate (TcN-PR13) is retained in the brain of Cynomolgus monkeys. However these compounds were obtained through an in situ esterification of preformed TcN dicarboxylic derivative. We have been able to synthesize one term of this class of ligands, the sarcosine methylester dithiocarbamate, by reacting sarcosine with thionyl chloride in methanol to give the sarcosine methyl ester, which was reacted with carbon disulfide and NaOH in methanol to give the sodium salt of the dithiocarbamate derivative which was isolated as an oil. The corresponding TcN complex was obtained with a radiochemical purity greater than 96% by a kit method. The complex was injected in baboons and its radioactive distribution compared to that obtained with Tc-HMPAO. Blood and plasma kinetics were calculated from arterial sampling whereas tissue kinetics (brain, lungs) were obtained by ROI`s analysis. The values of the half-life in the blood were comparable for the two tracers, although the absolute activity was about 20% lower for TcN-PR13. The brain uptake of TcN-PR13 was 10% lower than that observed for Tc-HMPAO, and remained stable during 2 hours. TcN-PR13 displayed lower lung uptake and faster clearance from this organ than Tc-HMPAO. Brain/Lung ratios were 1.11 and 1.65 at 30 and 60 min for TcN-PR13 compared to 0.93 and 0.99 at the same time for Tc-HMPAO.

  10. Thermal Studies of Zn(II), Cd(II) and Hg(II) Complexes of Some N-Alkyl-N-Phenyl-Dithiocarbamates

    PubMed Central

    Onwudiwe, Damian C.; Ajibade, Peter A.

    2012-01-01

    The thermal decomposition of Zn(II), Cd(II) and Hg(II) complexes of N-ethyl-N-phenyl and N-butyl-N-phenyl dithiocarbamates have been studied using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The products of the decomposition, at two different temperatures, were further characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The results show that while the zinc and cadmium complexes undergo decomposition to form metal sulphides, and further undergo oxidation forming metal oxides as final products, the mercury complexes gave unstable volatiles as the final product. PMID:22949811

  11. DNA Binding and Antitumor Activity of α-Diimineplatinum(II) and Palladium(II) Dithiocarbamate Complexes

    PubMed Central

    Mansouri-Torshizi, Hassan; Saeidifar, Maryam; Khosravi, Fatemeh; Divsalar, Adeleh; Saboury, Ali Akbar; Hassani, Fatemeh

    2011-01-01

    The two water-soluble designed platinum(II) complex, [Pt(Oct-dtc)(bpy)]NO3 (Oct-dtc = Octyldithiocarbamate and bpy = 2,2′ -bipyridine) and palladium(II) complex, [Pd(Oct-dtc)(bpy)]NO3, have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR, 1H NMR, and electronic spectra studies. Studies of antitumor activity of these complexes against human cell tumor lines (K562) have been carried out. They show Ic50 values lower than that of cisplatin. The complexes have been investigated for their interaction with calf thymus DNA (CT-DNA) by utilizing the electronic absorption spectroscopy, fluorescence spectra, and ethidium bromide displacement and gel filtration techniques. Both of these water-soluble complexes bound cooperatively and intercalatively to the CT-DNA at very low concentrations. Several binding and thermodynamic parameters are also described. PMID:22110410

  12. Spectrophotometric determination of ferbam [iron(III) dimethyl dithiocarbamate] in commercial sample and wheat grains after extraction of its bathophenanthroline tetraphenylborate complex into molten naphthalene.

    PubMed

    Malik, A K; Rao, A L

    2000-09-01

    A procedure has been developed for the determination of iron(III) dimethyldithiocarbamate by converting it into a iron(III)-bathophenanthroline-tetraphenylborate complex, which was then extracted into molten naphthalene, and the absorbance was measured at 534 nm against a reagent blank. Beer's law is obeyed over the concentration range 0.4-20 microg mL(-)(1) in final solution. The method is sensitive and highly selective and is applied for the determination of ferbam in a commercial sample, in mixtures with various dithiocarbamates (ziram, zineb, maneb, etc.), and from wheat grains.

  13. Synthesis and spectral studies on Pb(II) dithiocarbamate complexes containing benzyl and furfuryl groups and their use as precursors for PbS nanoparticles.

    PubMed

    Sathiyaraj, Ethiraj; Thirumaran, Subbiah

    2012-11-01

    Nine lead bis(dithiocarbamate) complexes based on benzyl and furfuryl groups have been prepared. The complexes were characterized using IR and NMR spectroscopy. All the complexes showed the expected signals in (1)H and (13)C NMR spectra associated with the dithiocarbamate ligands. IR and (13)C NMR spectral studies indicate that the S(2)CN double bond character increases with increase in length of alkyl chain bonded to nitrogen atom. Bis(N-benzyl-N-(2-phenylethyl)dithiocarbamato-S,S')lead(II) (3) and bis(N-furfuryl-N-(2-phenylethyl)dithiocarbamato-S,S')lead(II) (4) have been used as single source precursors for the synthesis of ethylenediamine capped PbS nanoparticles. Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), FTIR, UV-vis and fluorescence spectroscopy have been used to characterize the as-prepared lead sulfide nanoparticles. The PXRD measurements suggest that PbS nanoparticles are single phase with face-centered-cubic structure.

  14. Synthesis and spectral studies on Pb(II) dithiocarbamate complexes containing benzyl and furfuryl groups and their use as precursors for PbS nanoparticles

    NASA Astrophysics Data System (ADS)

    Sathiyaraj, Ethiraj; Thirumaran, Subbiah

    2012-11-01

    Nine lead bis(dithiocarbamate) complexes based on benzyl and furfuryl groups have been prepared. The complexes were characterized using IR and NMR spectroscopy. All the complexes showed the expected signals in 1H and 13C NMR spectra associated with the dithiocarbamate ligands. IR and 13C NMR spectral studies indicate that the S2Cpdbdtd N double bond character increases with increase in length of alkyl chain bonded to nitrogen atom. Bis(N-benzyl-N-(2-phenylethyl)dithiocarbamato-S,S')lead(II) (3) and bis(N-furfuryl-N-(2-phenylethyl)dithiocarbamato-S,S')lead(II) (4) have been used as single source precursors for the synthesis of ethylenediamine capped PbS nanoparticles. Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), FTIR, UV-vis and fluorescence spectroscopy have been used to characterize the as-prepared lead sulfide nanoparticles. The PXRD measurements suggest that PbS nanoparticles are single phase with face-centered-cubic structure.

  15. Synthesis, characterization and antibacterial study of cyclometalated rhodium(III) complex containing dithiocarbamate

    NASA Astrophysics Data System (ADS)

    Mansouri, Ghobad; Heidarizadi, Fateme; Naghipour, Ali; Notash, Behrouz

    2016-10-01

    The novel cyclometalated Rh(III) complex, [Rh(phpy)2(SˆS)], Where phpy is 2-phenylpyridine and (SˆS) is diethyldithiocarbamate, has been prepared and characterized by elemental analysis, IR, 13C and 1H NMR, electronic absorption and Fluorescence spectroscopies, cyclic voltammetry, and X-ray crystallography. The crystal structure of [Rh(phpy)2(SˆS)] shows that the coordination geometry around the Rh(III) is a distorted octahedron, with bite angles of 71.19-81.04° for all three bidentate ligands. Electrochemical analysis by cyclic voltammetry reveals irreversible redox behavior of the rhodium centre. Antibacterial activity of the complex has also been studied by agar disc diffusion method against three Gram-negative bacteria (Pseudomonas aeroginosa, Salmonella typhi and Escherichia coli) and two Gram-positive bacteria (Staphylococcus aureus and Corynebacterium renale).

  16. DFT calculations in the assignment of solid-state NMR and crystal structure elucidation of a lanthanum(iii) complex with dithiocarbamate and phenanthroline.

    PubMed

    Gowda, Vasantha; Laitinen, Risto S; Telkki, Ville-Veikko; Larsson, Anna-Carin; Antzutkin, Oleg N; Lantto, Perttu

    2016-12-06

    The molecular, crystal, and electronic structures as well as spectroscopic properties of a mononuclear heteroleptic lanthanum(iii) complex with diethyldithiocarbamate and 1,10-phenanthroline ligands (3 : 1) were studied by solid-state (13)C and (15)N cross-polarisation (CP) magic-angle-spinning (MAS) NMR, X-ray diffraction (XRD), and first principles density functional theory (DFT) calculations. A substantially different powder XRD pattern and (13)C and (15)N CP-MAS NMR spectra indicated that the title compound is not isostructural to the previously reported analogous rare earth complexes with the space group P21/n. Both (13)C and (15)N CP-MAS NMR revealed the presence of six structurally different dithiocarbamate groups in the asymmetric unit cell, implying a non-centrosymmetric packing arrangement of molecules. This was supported by single-crystal X-ray crystallography showing that the title compound crystallised in the triclinic space group P1[combining macron]. In addition, the crystal structure also revealed that one of the dithiocarbamate ligands has a conformational disorder. NMR chemical shift calculations employing the periodic gauge including projector augmented wave (GIPAW) approach supported the assignment of the experimental (13)C and (15)N NMR spectra. However, the best correspondences were obtained with the structure where the atomic positions in the X-ray unit cell were optimised at the DFT level. The roles of the scalar and spin-orbit relativistic effects on NMR shielding were investigated using the zeroth-order regular approximation (ZORA) method with the outcome that already the scalar relativistic level qualitatively reproduces the experimental chemical shifts. The electronic properties of the complex were evaluated based on the results of the natural bond orbital (NBO) and topology of the electron density analyses. Overall, we apply a multidisciplinary approach acquiring comprehensive information about the solid-state structure and the

  17. Dithiocarbamate toxicity - An appraisal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dithiocarbamates are used as agricultural pesticides and general biocides in a variety of applications. However, acute or chronic exposure to these chemicals can produce neurotoxicity, developmental deformities, endocrine disruption, hypersensitivity, and metabolic dysfunctions in animals and human...

  18. Theoretical investigations of the structures and electronic spectra of Zn(II) and Ni(II) complexes with cyclohexylamine-N-dithiocarbamate

    NASA Astrophysics Data System (ADS)

    Yu, Xiaohan; Wang, Na; He, Hongqing; Wang, Li

    2014-03-01

    The ground-state structures of two ligands cyclohexylamine-N-dithiocarbamate (L) and PPh3 and four complexes [Zn(L)2] (A), [Ni(L)2] (B), [Zn(L)2PPh3] (C), and [Ni(L)2PPh3] (D) are optimized by M06, B3LYP, and B3PW91 methods with the same mixed basis set. As compared with the experimental data of other complexes containing the Ni-P bond, the result obtained by M06/6-31+G(d)-LANL2DZ method is finally regarded as accurate and reliable for this project. Based on the optimized geometries, the compositions of molecular orbitals are analyzed and the absorption spectra are simulated. When one more ligand PPh3 is coordinated, the lowest-lying transition energy presents red-shift; while it shows blue-shift when the metal coordination center change from Ni to Zn with the same ligands. The detailed transition characters related with the absorption spectrum are assigned. In all the key transitions, it is hard to find the contribution from Zn atom. On the contrary, the d orbital of Ni atom contributes a lot for the HOMO and LUMO of complexes B and D. Consequently, the transition characters of Zn(II) and Ni(II) complexes are different.

  19. Separation of heavy metal from water samples--The study of the synthesis of complex compounds of heavy metal with dithiocarbamates.

    PubMed

    Kane, Sonila; Lazo, Pranvera; Ylli, Fatos; Stafilov, Trajce; Qarri, Flora; Marku, Elda

    2016-01-01

    The toxicity and persistence of heavy metal (HM) ions may cause several problems to marine organisms and human beings. For this reason, it is growing the interest in the chemistry of sulphur donor ligands such as dithiocarbamates (DDTC), due to their applications particularly in analytical chemistry sciences. The aim of this work has been the study of heavy metal complexes with DDTC and their application in separation techniques for the preconcentration and/or removing of heavy metals from the water solutions or the water ecosystems prior to their analysis. The HM-DDTC complexes were prepared and characterized by elemental analysis, FTIR and UV-Vis spectroscopic methods. The elemental analysis and the yield of the synthesis (97.5-99.9%) revealed a good purity of the complexes. High values of complex formation yields of HM-DDTC complexes is an important parameter for quantitatively removing/and or preconcentration of heavy metal ions from water solution even at low concentration of heavy metals. Significant differences founded between the characteristic parameters of UV/Vis (λmax and ϵmax) and FTIR absorption spectra of the parent DDTC and HM-DDTC complexes revealed the complex formation. The presence of the peaks at the visible spectral zone is important to M(nd(10-m))-L electron charge transfer of the new complexes. The (C=N) (1450-1500 cm(-1)) and the un-splitting (C-S) band (950-1002 cm(-1)) in HM-DDTC FTIR spectra are important to the identification of their bidentate mode (HM[S2CNC4H10]2). The total CHCl3 extraction of trace level heavy metals from water samples after their complex formation with DDTC is reported in this article.

  20. New bipyridine gold(III) dithiocarbamate-containing complexes exerted a potent anticancer activity against cisplatin-resistant cancer cells independent of p53 status

    PubMed Central

    Altaf, Muhammad; Monim-ul-Mehboob, Muhammad; Kawde, Abdel-Nasser; Corona, Giuseppe; Larcher, Roberto; Ogasawara, Marcia; Casagrande, Naike; Celegato, Marta; Borghese, Cinzia; Siddik, Zahid H.; Aldinucci, Donatella; Isab, Anvarhusein A.

    2017-01-01

    We synthesized, characterized and tested in a panel of cancer cell lines, nine new bipyridine gold(III) dithiocarbamate-containing complexes. In vitro studies demonstrated that compounds 1, 2, 4, 5, 7 and 8 were the most cytotoxic in prostate, breast, ovarian cancer cell lines and in Hodgkin lymphoma cells with IC50 values lower than the reference drug cisplatin. The most active compound 1 was more active than cisplatin in ovarian (A2780cis and 2780CP-16) and breast cancer cisplatin-resistant cells. Compound 1 determined an alteration of the cellular redox homeostasis leading to increased ROS levels, a decrease in the mitochondrial membrane potential, cytochrome-c release from the mitochondria and activation of caspases 9 and 3. The ROS scavenger NAC suppressed ROS generation and rescued cells from damage. Compound 1 resulted more active in tumor cells than in normal human Mesenchymal stromal cells. Gold compounds were active independent of p53 status: exerted cytotoxic effects on a panel of non-small cell lung cancer cell lines with different p53 status and in the ovarian A2780 model where the p53 was knocked out. In conclusion, these promising results strongly indicate the need for further preclinical evaluation to test the clinical potential of these new gold(III) complexes. PMID:27888799

  1. Nitrogen substituent polarity influences dithiocarbamate-mediated lipid oxidation, nerve copper accumulation, and myelin injury.

    PubMed

    Valentine, Holly L; Viquez, Olga M; Amarnath, Kalyani; Amarnath, Venkataraman; Zyskowski, Justin; Kassa, Endalkachew N; Valentine, William M

    2009-01-01

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture, and medicine, with new applications being investigated. Past studies have suggested that the neurotoxicity of some dithiocarbamates may result from copper accumulation, protein oxidative damage, and lipid oxidation. The polarity of a dithiocarbamate's nitrogen substituents influences the lipophilicity of the copper complexes that it generates and thus potentially determines its ability to promote copper accumulation within nerve and induce myelin injury. In the current study, a series of dithiocarbamate-copper complexes differing in their lipophilicity were evaluated for their relative abilities to promote lipid peroxidation determined by malondialdehyde levels generated in an ethyl arachidonate oil-in-water emulsion. In a second component of this study, rats were exposed to either N,N-diethyldithiocarbamate or sarcosine dithiocarbamate; both generated dithiocarbamate-copper complexes that were lipid- and water-soluble, respectively. Following the exposures, brain, tibial nerve, spinal cord, and liver tissue copper levels were measured by inductively coupled mass spectroscopy to assess the relative abilities of these two dithiocarbamates to promote copper accumulation. Peripheral nerve injury was evaluated using grip strengths, nerve conduction velocities, and morphologic changes at the light microscope level. Additionally, the protein expression levels of glutathione transferase alpha and heme-oxygenase-1 in nerve were determined, and the quantity of protein carbonyls was measured to assess levels of oxidative stress and injury. The data provided evidence that dithiocarbamate-copper complexes are redox active and that the ability of dithiocarbamate complexes to promote lipid peroxidation is correlated to the lipophilicity of the complex. Consistent with neurotoxicity requiring the formation of a lipid-soluble copper complex, significant increases in copper accumulation, oxidative

  2. Nitrogen Substituent Polarity Influences Dithiocarbamate-Mediated Lipid Oxidation, Nerve Copper Accumulation, and Myelin Injury

    PubMed Central

    Valentine, Holly L.; Viquez, Olga M.; Amarnath, Kalyani; Amarnath, Venkataraman; Zyskowski, Justin; Kassa, Endalkachew N.; Valentine, William M.

    2009-01-01

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture, and medicine, with new applications being investigated. Past studies have suggested that the neurotoxicity of some dithiocarbamates may result from copper accumulation, protein oxidative damage, and lipid oxidation. The polarity of a dithiocarbamate’s nitrogen substituents influences the lipophilicity of the copper complexes it generates and thus potentially determines its ability to promote copper accumulation within nerve and induce myelin injury. In the current study, a series of dithiocarbamate-copper complexes differing in their lipophilicity were evaluated for their relative abilities to promote lipid peroxidation determined by malondialdehyde levels generated in an ethyl arachidonate oil-in-water emulsion. In a second component of this study, rats were exposed to either N,N-diethyldithiocarbamate or sarcosine dithiocarbamate; both generate dithiocarbamate-copper complexes that are lipid and water soluble, respectively. Following the exposures, brain, tibial nerve, spinal cord and liver tissue copper levels were measured by inductively coupled mass spectroscopy to assess the relative abilities of these two dithiocarbamates to promote copper accumulation. Peripheral nerve injury was evaluated using grip strengths, nerve conduction velocities and morphologic changes at the light microscope level. Additionally, the protein expression levels of glutathione transferase alpha and heme-oxygenase-1 in nerve were determined and the quantity of protein carbonyls measured to assess levels of oxidative stress and injury. The data provide evidence that dithiocarbamate-copper complexes are redox active; and that the ability of dithiocarbamate complexes to promote lipid peroxidation is correlated to the lipophilicity of the complex. Consistent with neurotoxicity requiring the formation of a lipid soluble copper complex, significant increases in copper accumulation, oxidative stress and myelin

  3. Synthesis Characterization and Biological Activities of Coordination Compounds of 4-Hydroxy-3-nitro-2H-chromen-2-one and Its Aminoethanoic Acid and Pyrrolidine-2-carboxylic Acid Mixed Ligand Complexes

    PubMed Central

    Akinkunmi, Ezekiel; Obuotor, Efere; Olawuni, Idowu; Isabirye, David; Jordaan, Johan

    2017-01-01

    Coordination compounds of 4-hydroxy-3-nitro-2H-chromen-2-one and their mixed ligand complexes with aminoethanoic acid and pyrrolidine-2-carboxylic acid were synthesized by the reaction of Cu(II) and Zn(II) salts in molar ratio 1 : 2 for the coumarin complexes and 1 : 1 : 1 for the mixed ligand complexes, in basic media. The compounds formed were characterized using infrared, Uv-vis spectrophotometric analyses, mass spectrometry, magnetic susceptibility measurements, and EDX analyses. It was concluded that 4-hydroxy-3-nitro-2H-chromen-2-one coordinated as a monobasic ligand for all the complexes; it also coordinated via the carbonyl moiety in the case of the Cu(II) mixed ligand complexes. Similarly it was proposed that the amino acids also coordinated in a bidentate fashion via their amino nitrogen and carboxylate oxygen atoms. The synthesized compounds were screened for their antimicrobial and cytotoxic activities. The complexes exhibited marginal antimicrobial activity but good cytotoxic activity. PMID:28270743

  4. Synthesis, characterisation and biological aspects of copper(II) dithiocarbamate complexes, [Cu{S2CNR(CH2CH2OH)}2], (R = Me, Et, Pr and CH2CH2OH)

    NASA Astrophysics Data System (ADS)

    de Lima, Geraldo M.; Menezes, Daniele C.; Cavalcanti, Camila A.; dos Santos, Jaqueline A. F.; Ferreira, Isabella P.; Paniago, Eucler B.; Wardell, James L.; Wardell, Solange M. S. V.; Krambrock, Klaus; Mendes, Isolda C.; Beraldo, Heloisa

    2011-03-01

    Cu(II) dithiocarbamates, [Cu{S2CNR(CH2CH2OH)}2], R = Me (1), Et (2), Pr (3) and CH2CH2OH (4), have been prepared from HNR(CH2CH2OH) (R = Me, Et, Pr and CH2CH2OH), CS2 and Cu(OAc)2. Characterisation of the complexes were generally achieved by infrared and EPR spectroscopies and, in addition, for (2) and (3), by X-ray crystallography at 120 K. Complex (2) crystallises as a Cu-S linked dimer, in which the CH2CH2OH groups have a cis arrangement in each monomer but are trans to those in the other monomer partner. On the other hand complex (3) exists in the solid state in the form of two similar and independent centrosymmetric monomers. The weak antiferromagnetic coupling, present in similar complexes, was absent in complexes (1)-(3). The in vitro activity of (1)-(4) was investigated against colonies of Candida albicans, Sthaphyloccocus aureus and Pseudomonas aeruginosa. They all displayed MIC (minimal inhibitory concentration) values against C. albicans close to those found for Fluconazole. All complexes were inert towards Gram-negative or Gram-positive bacteria, S. aureus and P. auruginosa, respectively.

  5. One-step synthesis of dithiocarbamates from metal powders

    NASA Technical Reports Server (NTRS)

    Hepp, Aloysius F.; Hehemann, David G.; Duraj, Stan A.; Clark, Eric B.; Eckles, William E.; Fanwick, Phillip E.

    1994-01-01

    Neutral metal dithiocarbamate complexes (M(NR2CS2)X) are well-known precursors to metal sulfides, a class of materials with numerous technological applications. We are involved in a research effort to prepare new precursors to metal sulfides using simple, reproducible synthetic procedures. We describe the results of our synthetic and characterization studies for M = Fe, Co, Ni, Cu. and In. For example, treatment of metallic indium with tetramethylthiuram disulfide (tmtd) in 4-methylpyridine (4-Mepy) at 25 deg C produces a new homoleptic indium (III) dithiocarbamate, In(N(CH3)2CS2)3(I), in yields of over 60 percent. The indium (III) dithiocarbamate was characterized by X-ray crystallography; (I) exists in the solid state as discrete distorted-octahedral molecules. Compound (I) crystallizes in the P1bar (No. 2) space group with lattice parameters: a = 9.282(1) A, b = 10.081(1) A, c = 12.502 A, alpha = 73.91(1) deg, beta = 70.21(1) deg, gamma = 85.8(1)deg, and Z = 2. X-ray diffraction and mass spectral data were used to characterize the products of the analogous reactions with Fe, Co, Ni, and Cu. We discuss both use of dithiocarbamates as precursors and our approach to their preparation.

  6. Synthesis, characterization and anticancer activity of a Cd(II) complex with in situ formation of (E)-1-(5-chloro-2-hydroxy-benzylideneamino)-pyrrolidin-2-one ligand

    NASA Astrophysics Data System (ADS)

    Huang, Qiu-Ying; Zheng, Ze-Bao; Diao, Yun-Peng

    2015-05-01

    A new complex of Cd(II) with (E)-1-(5-chloro-2-hydroxybenzylideneamino)-pyrrolidin-2-one [Cd(L)2ṡ2DMF] was synthesized and characterized by elemental analysis, IR, TG and single-crystal X-ray diffraction. Where the HL ligand is formed in situ by the intramolecular nucleophilic substitution of (E)-N‧-(5-chloro-2-hydroxybenzyli-dene)-4-(quinolin-8-yloxy)butanehydrazide (H2L‧). The cadmium(II) ion is hexacoordinated by two tridentate L- ligands and giving a distorted octahedral coordination geometry. A cytotoxicity of [Cd(L)2ṡ2DMF] against liver (SMMC-7721) and cervical (HeLa) cancer cells have been studied. The results revealed that this cadmium(II) complex exhibited an effective and selective anticancer activity against HeLa over SMMC-7721 cell line with IC50 of 1.54 ± 0.25 and 31.02 ± 3.76 μmol/dm-3.

  7. Lanthanum(III) and praseodymium(III) derivatives with dithiocarbamates derived from alpha-amino acids.

    PubMed

    Rai, Anita; Sengupta, Soumitra K; Pandey, Om P

    2006-06-01

    Lanthanum(III) and praseodymium(III) complexes with dithiocarbamates have been synthesized by the reactions of lanthanum(III) and praseodymium(III) chloride with barium dithiocarbamate and complexes of type [LnCl(L)H2O]n have been obtained (where Ln=La(III) or Pr(III); L=barium salt of dithiocarbamate derived from glycine, L-leucine, L-valine, DL-alanine). The complexes have been characterized by elemental analysis, molar conductance, electronic absorption and fluorescence, infrared, far infrared, 1H NMR spectral studies. The presence of coordinated water molecule is inferred from thermogravimetric analysis which indicates the loss of one water molecule at 150-170 degrees C. The oscillator strength, Judd-Ofelt intensity parameter, stimulated emission cross-section, etc. have been obtained for different transitions of Pr3+.

  8. Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

    PubMed Central

    Martínez-Martínez, S; Gómez del Arco, P; Armesilla, A L; Aramburu, J; Luo, C; Rao, A; Redondo, J M

    1997-01-01

    Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants. PMID:9343406

  9. PRACTICAL SYNTHESIS OF AROMATIC DITHIOCARBAMATES

    PubMed Central

    Padungros, Panuwat; Wei, Alexander

    2015-01-01

    GRAPHICAL ABSTRACT Oxidation-sensitive N,N-diaryl dithiocarbamates (DTCs) are synthesized in good yields by the generation of metal amide salts from N-benzoyl precursors, followed by addition of CS2. para-Substituted diphenylamines are prepared by electrophilic aromatic substitution of diphenylbenzamide and saponification. Deacylation of electron-rich species such as bis(p-dimethylaminophenyl)benzamide is challenging because of the oxidative sensitivity of the anionic intermediate but could be achieved in good yield by using n-BuLi to generate a hemiaminal adduct, prior to acidification. The N,N-diaryl DTCs are stable as alkali salts and can be used to produce densely packed monolayers on gold surfaces. PMID:25999616

  10. Synthesis, DFT Calculation, and Antimicrobial Studies of Novel Zn(II), Co(II), Cu(II), and Mn(II) Heteroleptic Complexes Containing Benzoylacetone and Dithiocarbamate

    PubMed Central

    Ekennia, Anthony C.; Onwudiwe, Damian C.; Olasunkanmi, Lukman O.; Osowole, Aderoju A.; Ebenso, Eno E.

    2015-01-01

    Heteroleptic complexes of zinc(II), copper(II), manganese(II), and cobalt(II) of the types [MLL′(H2O)2]·nH2O and [MLL′]·nH2O have been synthesized using sodium N-methyl-N-phenyldithiocarbamate (L) and benzoylacetone (L′). The metal complexes were characterized by elemental analysis, electrical conductance, magnetic susceptibility, infrared (IR), and UV-visible spectroscopic studies. The electrical conductance measurements revealed the nonelectrolytic nature of the synthesized complexes. The results of the elemental analyses, magnetic susceptibility measurements, and electronic spectra inferred that the Zn(II) complex adopted a four-coordinate geometry while the Co(II), Cu(II), and Mn(II) complexes assumed octahedral geometries. The IR spectra showed that the metal ions coordinated with the ligands via the S- and O-donor atoms. The geometry, electronic, and thermodynamic parameters of the complexes were obtained from density functional theory (DFT) calculations. The spin density distributions, relative strength of H–bonds, and thermodynamic parameters revealed that the order of stability of the metal complexes is Mn < Co < Cu > Zn. The agar diffusion methods were used to study the antimicrobial activity of the complexes against two Gram positive bacteria (S. aureus and S. pneumoniae), one Gram negative bacterium (E. coli), and two fungi organisms (A. niger and A. candida) and the complexes showed a broad spectrum of activities against the microbes. PMID:26681931

  11. 40 CFR 721.10314 - Dialkyl dithiocarbamate esters (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Dialkyl dithiocarbamate esters... Specific Chemical Substances § 721.10314 Dialkyl dithiocarbamate esters (generic). (a) Chemical substance... dialkyl dithiocarbamate esters (PMNs P-02-778, P-02-779, and P-02-780) are subject to reporting under...

  12. 40 CFR 721.10314 - Dialkyl dithiocarbamate esters (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Dialkyl dithiocarbamate esters... Specific Chemical Substances § 721.10314 Dialkyl dithiocarbamate esters (generic). (a) Chemical substance... dialkyl dithiocarbamate esters (PMNs P-02-778, P-02-779, and P-02-780) are subject to reporting under...

  13. 40 CFR 721.10314 - Dialkyl dithiocarbamate esters (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Dialkyl dithiocarbamate esters... Specific Chemical Substances § 721.10314 Dialkyl dithiocarbamate esters (generic). (a) Chemical substance... dialkyl dithiocarbamate esters (PMNs P-02-778, P-02-779, and P-02-780) are subject to reporting under...

  14. Improving the developability profile of pyrrolidine progesterone receptor partial agonists

    SciTech Connect

    Kallander, Lara S.; Washburn, David G.; Hoang, Tram H.; Frazee, James S.; Stoy, Patrick; Johnson, Latisha; Lu, Qing; Hammond, Marlys; Barton, Linda S.; Patterson, Jaclyn R.; Azzarano, Leonard M.; Nagilla, Rakesh; Madauss, Kevin P.; Williams, Shawn P.; Stewart, Eugene L.; Duraiswami, Chaya; Grygielko, Eugene T.; Xu, Xiaoping; Laping, Nicholas J.; Bray, Jeffrey D.; Thompson, Scott K.

    2010-09-17

    The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

  15. Preparation of 1,5-disubstituted pyrrolidin-2-ones.

    PubMed

    Katritzky, A R; Mehta, S; He, H Y; Cui, X

    2000-07-14

    1,5-Disubstituted pyrrolidin-2-ones 18a-g, 19a-h, and 20a-f were synthesized in good to excellent yields via the nucleophilic substitution of 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-2-ones 9 with allylsilanes, organozinc reagents, and phosphorus compounds. Compounds 9 and 5-(benzotriazol-2-yl)-1-substituted-pyrrolidin-2-one isomers 10 are readily prepared in total 70-84% yields from 2, 5-dimethoxy-2,5-dihydrofuran (7), primary amines 8, and benzotriazole; 9 and 10 react identically with nucleophiles.

  16. Synthesis, Structure, Characterization, and Decomposition of Nickel Dithiocarbamates: Effect of Precursor Structure and Processing Conditions on Solid-State Products

    NASA Technical Reports Server (NTRS)

    Hepp, Aloysius F.; Kulis, Michael J.; McNatt, Jeremiah S.; Duffy, Norman V.; Hoops, Michael D.; Gorse, Elizabeth; Fanwick, Philip E.; Masnovi, John; Cowen, Jonathan E.; Dominey, Raymond N.

    2016-01-01

    Single-crystal X-ray structures of four nickel dithiocarbamate complexes, the homoleptic mixed-organic bis-dithiocarbamates Ni[S2CN(isopropyl)(benzyl)]2, Ni[S2CN(ethyl)(n-butyl)]2, and Ni[S2CN(phenyl)(benzyl)]2, as well as the heteroleptic mixed-ligand complex NiCl[P(phenyl)3][(S2CN(phenyl)(benzyl)], were determined. Synthetic, spectroscopic, structural, thermal, and sulfide materials studies are discussed in light of prior literature. The spectroscopic results are routine. A slightly distorted square-planar nickel coordination environment was observed for all four complexes. The organic residues adopt conformations to minimize steric interactions. Steric effects also may determine puckering, if any, about the nickel and nitrogen atoms, both of which are planar or nearly so. A trans-influence affects the Ni-S bond distances. Nitrogen atoms interact with the CS2 carbons with a bond order of about 1.5, and the other substituents on nitrogen display transoid conformations. There are no strong intermolecular interactions, consistent with prior observations of the volatility of nickel dithiocarbamate complexes. Thermogravimetric analysis of the homoleptic species under inert atmosphere is consistent with production of 1:1 nickel sulfide phases. Thermolysis of nickel dithiocarbamates under flowing nitrogen produced hexagonal or -NiS as the major phase; thermolysis under flowing forming gas produced millerite (-NiS) at 300 C, godlevskite (Ni9S8) at 325 and 350 C, and heazlewoodite (Ni3S2) at 400 and 450 C. Failure to exclude oxygen results in production of nickel oxide. Nickel sulfide phases produced seem to be primarily influenced by processing conditions, in agreement with prior literature. Nickel dithiocarbamate complexes demonstrate significant promise to serve as single-source precursors to nickel sulfides, a quite interesting family of materials with numerous potential applications.

  17. Self assembled homodinuclear dithiocarbamates: One pot synthesis and spectral characterization

    NASA Astrophysics Data System (ADS)

    Nami, Shahab A. A.; Husain, Ahmad; Ullah, Irfan

    2014-01-01

    Several self assembled homodinuclear complexes of the type [M2(Ldtc)2·4H2O] derived from quadridentate ligand (Ldtc), where Ldtc = 2-aminobenzoylhydrazidebis(dithiocarbamate) and M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) have been reported. The in situ procedure gives high yield with the formation of single product as evident by TLC and various other physicochemical techniques. Elemental analysis, TGA, 1H NMR, 13C NMR, ESI mass spectrometry, EPR, UV-vis. and IR spectroscopy were used to characterize the homodinuclear complexes. The spectroscopic evidences and room temperature magnetic moment values suggest that all the complexes have octahedral geometry around the transition metal atom. A symmetrical bidentate coordination of the dithiocarbamato moiety has been observed in all the complexes. The energy-minimized structure of the molecule also showed that each metal atom acquires a distorted octahedral geometry. The complexes exhibit a three-step thermolytic pattern and are non-electrolyte in nature.

  18. Measurements of the solubility of metal dithiocarbamates in supercritical carbon dioxide

    SciTech Connect

    Bartle, K.D.; Cowey, C.M.; Burford, M.D.; Clifford, A.A.

    1996-10-01

    Heavy metal contamination of the environmental has been traditionally analyzed by acid digestion and organic solvent extraction methods. However, recently supercritical fluids such as carbon dioxide have been investigated as a potentially more rapid and environmentally friendly extraction procedure for metal recovery. Direct extraction of metal ions by pure supercritical carbon dioxide has previously proved ineffective as charge neutralization of the ion using a ligand is required to significantly enhance the solute solvent interactions. Commercial chelating agents such as dithiocarbamates have been extensively used in both conventional and supercritical extractions for the recovery of a wide range of heavy metal. Initial studies using diethldithiocarbamate metal complexes at low supercritical temperatures (50 {degrees}C) and pressure (100 atm.) Showed poor solubility (1x10{sup {minus}6}mol dm{sup 3}) in supercritical carbon dioxide. In this study, the solubility of Pb, Cd, Fe, Zn, and Cu dithiocarbamates were measures at both high and low supercritical fluid temperatures and pressures and a significant increase in the solubility of the metal complexes (e.g. two orders of magnitude) was achieved using 100 {degrees}C, 350 atm supercritical carbon dioxide. Increasing the alkyl chain length of the dithiocarbamate ligand was also investigated and it was shown that as the hydrocarbon content of the ligand increased and became more non-polar in nature the solubility of the corresponding metal complex increased. The results from the solubility study will be subsequently used to assists in the optimization of methods used for the extraction of metals in environmental samples.

  19. Potent pyrrolidine- and piperidine-based BACE-1 inhibitors

    SciTech Connect

    Iserloh, U.; Wu, Y.; Cumming, J.N.; Pan, J.; Wang, L.Y.; Stamford, A.W.; Kennedy, M.E.; Kuvelkar, R.; Chen, X.; Parker, E.M.; Strickland, C.; Voigt, J.

    2008-08-18

    Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. The discovery and development of novel BACE-1 inhibitors incorporating a cyclic amine scaffold is described.

  20. Transition metal ferrocenyl dithiocarbamates functionalized dye-sensitized solar cells with hydroxy as an anchoring group

    NASA Astrophysics Data System (ADS)

    Yadav, Reena; Waghadkar, Yogesh; Kociok-Köhn, Gabriele; Kumar, Abhinav; Rane, Sunit B.; Chauhan, Ratna

    2016-12-01

    Three new transition-metal dithiocarbamates involving ferrocene (Fc), namely [Co(FcCH2EtOHdtc)3] (Co), [M(FcCH2EtOHdtc)2] M = Ni (Ni), Cu (Cu) (EtOHdtc = N-ethanol dithiocarbamate), have been synthesized and characterized by microanalyses, FTIR, 1H and 13C NMR spectroscopies and single crystal X-ray diffraction technique. The peak broadening in the 1H spectrum of the copper complex indicates the paramagnetic behavior of this compound. The observed single quasi-reversible cyclic voltammograms for the complexes indicate the stabilization of a metal center (except copper) other than Fe in their characteristic oxidation state. These complexes have been used as photo-sensitizer in dye-sensitized solar cells which indicates that Co displays the best photosensitization property with an overall conversion efficiency of 3.25 ± 0.04%. The low cell efficiency of Ni and Cu complexes may be due to slow regeneration of the dye by iodine/iodide redox couple followed by charge injection into TiO2.

  1. Spectroscopic and structural study of novel interaction product of pyrrolidine-2-thione with molecular iodine. Presumable mechanisms of oxidation

    NASA Astrophysics Data System (ADS)

    Chernov'yants, Margarita S.; Burykin, Igor V.; Starikova, Zoya A.; Tereznikov, Alexander Yu.; Kolesnikova, Tatiana S.

    2013-09-01

    Synthesis, spectroscopic and structural characterization of novel interaction product of pyrrolidine-2-thione with molecular iodine is reported. The ability of pyrrolidine-2-thione to form the outer-sphere charge-transfer complex C4H7NS·I2 with iodine molecule in dilute chloroform solution has been studied by UV/vis spectroscopy. Oxidative desulfurization promotes ring fusion of two pyrrolidine-2-thione molecules. The product of iodine induced oxidative desulfurization has been studied by X-ray diffraction method. The crystal structure of the reaction product is formed by 5-(2-thioxopyrrolidine-1-yl)-3,4-dihydro-2H-pyrrolium (C8H13N2S+) cations and pentaiodide anions I5-, which are linked by the intermolecular I⋯Hsbnd C and I⋯C close contacts. The angular pentaiodide anions can be considered as structures formed by coordination of two iodine molecules to the iodide ion (type 1) or by the coordination of iodine molecule to the triiodide ion (type 2).

  2. INHIBITORY ACTION OF DITHIOCARBAMATES ON ENZYMES OF ANIMAL TISSUES

    DTIC Science & Technology

    these compounds on the oxidative phase of intermediary carbohydrate metabolism. All of the compounds were effective inhibitors of the tricarboxylic...oxidase, and succinic dehydrogenase. The salts of dithiocarbamic acid were effective inhibitors of these enzymatic reactions in vivo but the disulfide...cytochrome c and inhibited tyrosinase activity in vitro. The results of this investigation suggest that the acute mammalian toxicity of the

  3. Trisubstituted 2-trifluoromethyl pyrrolidines via catalytic asymmetric Michael addition/reductive cyclization.

    PubMed

    Corbett, Michael T; Xu, Qihai; Johnson, Jeffrey S

    2014-05-02

    The stereoselective synthesis of trisubstituted 2-trifluoromethyl pyrrolidines by asymmetric Michael addition/hydrogenative cyclization is described. The direct organocatalytic addition of 1,1,1-trifluoromethylketones to nitroolefins proceeds under mild reaction conditions and low catalyst loadings to provide Michael adducts in high yield with excellent diastereo- and enantioselectivity. Catalytic hydrogenation of the Michael adducts stereoselectively generates 2-trifluoromethylated pyrrolidines bearing three contiguous stereocenters. A stereospecific route to epimeric 2-trifluoromethyl pyrrolidines from a common intermediate is described.

  4. The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel.

    PubMed

    Li, Ping; Zhu, Jin; Kong, Qingya; Jiang, Baifeng; Wan, Xia; Yue, Jinfeng; Li, Min; Jiang, Hualiang; Li, Jian; Gao, Zhaobing

    2013-06-07

    Mancozeb (manganese/zinc ethylene bis-dithiocarbamate) is an organometallic fungicide that has been associated with human neurotoxicity and neurodegeneration. In a high-throughput screen for modulators of KCNQ2 channel, a fundamental player modulating neuronal excitability, Mancozeb, was found to significantly potentiate KCNQ2 activity. Mancozeb was validated electrophysiologically as a KCNQ2 activator with an EC50 value of 0.92±0.23μM. Further examination showed that manganese but not zinc ethylene bis-dithiocarbamate is the active component for the positive modulation effects. In addition, the compounds are effective when the metal ions are substituted by iron but lack potentiation activity when the metal ions are substituted by sodium, signifying the importance of the metal ion. However, the iron (Fe(3+)) alone, organic ligands alone or the mixture of iron with the organic ligand did not show any potentiation effect, suggesting as the active ingredient is a specific complex rather than two separate additive or synergistic components. Our study suggests that potentiation on KCNQ2 potassium channels might be the possible mechanism of Mancozeb toxicity in the nervous system.

  5. Sediment washing by EDTA and its reclamation by sodium polyamidoamine-multi dithiocarbamate.

    PubMed

    Deng, Tianlin; Zhang, Bingru; Li, Fengting; Jin, Luyao

    2017-02-01

    Sodium polyamidoamine-multi dithiocarbamate (PAMAM-DTC) is a kind of heavy metals capturing agent, containing functional groups of dithiocarbamate that could strongly chelate heavy metals. In this paper, it was applied to precipitate heavy metal ions from meal-EDTA and reclaim EDTA during sediment washing process. The extracting performance of fresh EDTA was studied as a function of EDTA concentration, liquid/sediment (L/S), pH, and extraction time. Then the EDTA effluents were treated with PAMAM-DTC, Na2S and sodium diethyldithiocarbamate (DDTC) to compare their effectiveness on capturing metals from metal-EDTA complexes. Four divalent heavy metals were investigated (Pb, Cd, Cu, Zn). PAMAM-DTC shows much better performance. Pb, Cd and Cu could almost be precipitated completely by PAMAM-DTC under the dosage of 350 mg L(-1), while Zn could be only partly precipitated which may due to its failure in competition with the other three metal ions on chelation with PAMAM-DTC. The reclaimed EDTA was reused in three cycles of sediment washing, and the amount of heavy metals extracted just slightly decreased in each cycle.

  6. Asymmetric Synthesis of α-Trifluoromethyl Pyrrolidines through Organocatalyzed 1,3-Dipolar Cycloaddition Reaction.

    PubMed

    Dong, Zhenghao; Zhu, Yuanyuan; Li, Boyu; Wang, Cui; Yan, Wenjin; Wang, Kairong; Wang, Rui

    2017-02-28

    The optically active α-trifluoromethyl pyrrolidines have been achieved through organocatalyzed 1, 3-dipolar cycloaddition reaction firstly. With diphenyl- prolinol trimethylsilyl ether as catalyst and in the presence of 3, 5-dinitrobenzoic acid, the reaction of trifluoroethylamine-derived ketimine with 2-enals gave α-trifluoro-methyl pyrrolidines bearing three contiguous stereogenic centers in excellent diastereoselectivies, stereoselectivities and yields.

  7. Synthesis of Enantioenriched Pyrrolidines via Gold-Catalyzed Tandem Cycloisomerization/Hydrogenation of Chiral Homopropargyl Sulfonamides.

    PubMed

    Yu, Yong-Fei; Shu, Chao; Tan, Tong-De; Li, Long; Rafique, Shahid; Ye, Long-Wu

    2016-10-07

    A novel gold-catalyzed tandem cycloisomerization/hydrogenation of chiral homopropargyl sulfonamides has been developed. Various enantioenriched pyrrolidines can be obtained in excellent yields and excellent enantioselectivities by combination of chiral tert-butylsulfinimine chemistry with gold catalysis. Importantly, this represents the first example of a pyrrolidine synthesis from homopropargyl sulfonamide.

  8. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    PubMed

    Talaat, Roba; El-Sayed, Waheba; Agwa, Hussein S; Gamal-Eldeen, Amira M; Moawia, Shaden; Zahran, Magdy A H

    2015-08-05

    Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself.

  9. Effects of mancozeb and other dithiocarbamate fungicides on Saccharomyces cerevisiae: the role of mitochondrial petite mutants in dithiocarbamate tolerance.

    PubMed

    Casalone, E; Bonelli, E; Polsinelli, M

    2010-11-01

    Saccharomyces cerevisiae as model system was used to evaluate the occurrence of resistant mutants and adaptation mechanism to mancozeb (MZ), a widespread fungicide of the dithiocarbamate class with a broad spectrum of action and multiple cell targets. We were unable to isolate mutants resistant to inhibitory concentration of MZ but found an unusually large number of mitochondrial defective petite mutants among cells incubated in the presence of subinhibitory MZ concentration. Similar results were obtained with two other dithiocarbamate fungicides. Comparison of wild type and petite mutants showed that the latter were more resistant to toxic effects of MZ, highlighting the role of mitochondria in MZ-tolerance. The data suggest that petite cells, arising by exposure to sub-inhibitory MZ concentration, are not induced by fungicides but are spontaneous mutants already present in the population before the contact with the fungicide.

  10. Pyrrolidine synthesis via palladium-catalyzed trimethylenemethane cycloaddition and related studies

    SciTech Connect

    Marrs, C.M.

    1992-01-01

    The palladium catalyzed trimethylenemethane cycloaddition has been extended to the synthesis of pyrrolidines and azepines. In contrast to previous attempts with N-alkyl and N-aryl imine, successful cycloadditions were recorded with several aromatic and aliphatic electron-deficient imines. Sulfonimines were found to be excellent acceptors, yielding pyrrolidine cycloadducts in excellent yields. Aromatic sulfonimines were observed to undergo cycloaddition very rapidly at or below room temperature. Some aliphatic nitrimine and N-phenyl, C-carbalkoxy imines were also found to be useful acceptors. Azepines were obtained from the cycloaddition of cisoid lockeed [alpha],[beta] unsaturated sulfonimines. In order to support the cycloaddition studies, a novel synthetic method was developed for the synthesis of sulfonimines. bis(Toluene-sulfonylimido)tellurium, Te(=N-Ts)[sub 2], generated from tellurium metal and anhydrous chloramine-t, was found to convert both aromatic and aliphatic aldehydes into the corresponding sulfonimines. Chiral ligands were examined in this cyclization and an enantiomeric excess of 35% was achieved with Hayashi's bidentate ferrocenyl ligand (BPFA). In support of this effort, the total synthesis of [+-] nicotine was accomplished in seven steps starting from pyridine 3-carboxaldehyde using these methodologies in order to verify the enantiomeric excess. Finally, the trimethylenemethane cycloaddition was examined with tropone irontricarbonyl complex. A novel [5+3] cycloaddition was observed to proceed in good yield, which upon decomplexation from the iron tricarbonyl moiety yielded the tricyclo[3.2.0] system. The scope and generality were briefly examined. Extended Huekel calculations were performed in order to help rationalize the unexpected regiochemistry.

  11. Dithiocarbamate Self-Assembled Monolayers as Efficient Surface Modifiers for Low Work Function Noble Metals.

    PubMed

    Meyer, Dominik; Schäfer, Tobias; Schulz, Philip; Jung, Sebastian; Rittich, Julia; Mokros, Daniel; Segger, Ingolf; Maercks, Franziska; Effertz, Christian; Mazzarello, Riccardo; Wuttig, Matthias

    2016-09-06

    Tuning the work function of the electrode is one of the crucial steps to improve charge extraction in organic electronic devices. Here, we show that N,N-dialkyl dithiocarbamates (DTC) can be effectively employed to produce low work function noble metal electrodes. Work functions between 3.1 and 3.5 eV are observed for all metals investigated (Cu, Ag, and Au). Ultraviolet photoemission spectroscopy (UPS) reveals a maximum decrease in work function by 2.1 eV as compared to the bare metal surface. Electronic structure calculations elucidate how the complex interplay between intrinsic dipoles and dipoles induced by bond formation generates such large work function shifts. Subsequently, we quantify the improvement in contact resistance of organic thin film transistor devices with DTC coated source and drain electrodes. These findings demonstrate that DTC molecules can be employed as universal surface modifiers to produce stable electrodes for electron injection in high performance hybrid organic optoelectronics.

  12. Dithiocarbamate Self-Assembled Monolayers as Efficient Surface Modifiers for Low Work Function Noble Metals

    SciTech Connect

    Meyer, Dominik; Schäfer, Tobias; Schulz, Philip; Jung, Sebastian; Rittich, Julia; Mokros, Daniel; Segger, Ingolf; Maercks, Franziska; Effertz, Christian; Mazzarello, Riccardo; Wuttig, Matthias

    2016-09-06

    Tuning the work function of the electrode is one of the crucial steps to improve charge extraction in organic electronic devices. Here, we show that N,N-dialkyl dithiocarbamates (DTC) can be effectively employed to produce low work function noble metal electrodes. Work functions between 3.1 and 3.5 eV are observed for all metals investigated (Cu, Ag, and Au). Ultraviolet photoemission spectroscopy (UPS) reveals a maximum decrease in work function by 2.1 eV as compared to the bare metal surface. Electronic structure calculations elucidate how the complex interplay between intrinsic dipoles and dipoles induced by bond formation generates such large work function shifts. Subsequently, we quantify the improvement in contact resistance of organic thin film transistor devices with DTC coated source and drain electrodes. These findings demonstrate that DTC molecules can be employed as universal surface modifiers to produce stable electrodes for electron injection in high performance hybrid organic optoelectronics.

  13. A modular synthesis of dithiocarbamate pendant unnatural α-amino acids

    EPA Science Inventory

    Unnatural α-amino acids containing dithiocarbamate side chains were synthesized by a one-pot reaction of in-situ generated dithiocarbamate anions with sulfamidates. A wide range of these anions participated in the highly regio- and stereo-selective ring opening of sulfamidates to...

  14. μ-η2:η2-Peroxido-bis­[nitratodioxido­bis(pyrrolidin-2-one)uranium(VI)

    PubMed Central

    Takao, Koichiro; Ikeda, Yasuhisa

    2010-01-01

    In the crystal structure of the title compound, [U2(NO3)2O4(O2)(C4H7NO)4], two UO2 2+ ions are connected by a μ-η2:η2-O2 unit. The O2 unit shows ‘side-on’ coordination to both U atoms. An inversion center is located at the midpoint of the O—O bond in the O2 unit, affording a centrosymmetrically expanded dimeric structure. The U—O(axial) bond lengths are 1.777 (4) Å and 1.784 (4) Å, indicating that the oxidation state of U is exclusively 6+, i.e., UO2 2+. Furthermore, the O—O distance is 1.492 (8) Å, which is typical of peroxide, O2 2–. The U atom is eight-coordinated in a hexa­gonal-bipyramidal geometry. The coordinating atoms of the nitrate and pyrrolidine-2-one ligands and the μ-η2:η2-O2 2– unit are located in the equatorial plane and form an irregular hexa­gon. An inter­molecular hydrogen bond is found between N—H of the pyrrolidine-2-one ligand and the coordinating O of the same ligand in a neighboring complex. A second inter­molecular hydrogen bond is found between the N—H of the other pyrrolidine-2-one ligand and one of the uranyl oxido atoms. PMID:21579030

  15. Method of removing nitrogen monoxide from a nitrogen monoxide-containing gas using a water-soluble iron ion-dithiocarbamate, xanthate or thioxanthate

    DOEpatents

    Liu, D. Kwok-Keung; Chang, Shih-Ger

    1987-08-25

    The present invention relates to a method of removing of nitrogen monoxide from a nitrogen monoxide-containing gas which method comprises contacting a nitrogen oxide-containing gas with an aqueous solution of water soluble organic compound-iron ion chelate complex. The NO absorption efficiency of ferrous urea-dithiocarbamate and ferrous diethanolamine-xanthate as a function of time, oxygen content and solution ph is presented. 3 figs., 1 tab.

  16. Iron- and cobalt-catalyzed arylation of azetidines, pyrrolidines, and piperidines with Grignard reagents.

    PubMed

    Barré, Baptiste; Gonnard, Laurine; Campagne, Rémy; Reymond, Sébastien; Marin, Julien; Ciapetti, Paola; Brellier, Marie; Guérinot, Amandine; Cossy, Janine

    2014-12-05

    Iron- and cobalt-catalyzed cross-couplings between iodo-azetidines, -pyrrolidines, -piperidines, and Grignard reagents are disclosed. The reaction is efficient, cheap, chemoselective and tolerates a large variety of (hetero)aryl Grignard reagents.

  17. Comparative effects of N,N-disubstituted dithiocarbamates and dimercaptosuccinate on mobilization of methylmercury in mice

    SciTech Connect

    Gale, G.R.; Atkins, L.M.; Smith, A.B.; Walker, E.M. Jr.; Jones, M.M.

    1984-07-01

    Diethyldithiocarbamate (DDTC) and five of its N,N-disubstituted analogs were compared with dimercaptosuccinate (DMSA) for effectiveness in mobilizing and promoting excretion of methylmercury (MeHg) following administration of a sublethal dose of MeHg labeled with Me203Hg. The previously reported effectiveness of DMSA was confirmed. Of the dithiocarbamates assessed, only di(carboxymethyl)-dithiocarbamate (DCDC) was active in mobilizing MeHg, and its activity on a molar dose basis was less than that of DMSA. The disparate structural requirements of dithiocarbamates as antagonists of MeHg and of cadmium were discussed.

  18. Detection and quantification of dithiocarbamate pesticides by Surface Enhanced Raman Spectroscopy (SERS)

    NASA Astrophysics Data System (ADS)

    Saute, Benjamin Calvin

    Dithiocarbamates are a subclass of carbamate pesticides that are widely used as insecticidal agents on food crops in the US and abroad. Quantitative determination of trace quantities of dithiocarbamates is necessary in order to mitigate potential human exposure via pesticide residues left on inadequately washed food items as well as groundwater contamination from agricultural runoff. The focus of this research is on the development and optimization of a Surface Enhanced Raman Spectroscopy (SERS) based analytical technique for the quantitative determination of trace amounts of dithiocarbamate pesticides in different matrices. Gold nanoparticles of different shapes and sizes will be investigated to determine the suitability of these materials as SERS active substrates for the trace analysis of dithiocarbamate pesticides. Analytical sensitivity will be evaluated by determining the limits of detection using established statistical methods.

  19. Antitumor effect of sonodynamically activated pyrrolidine tris-acid fullerene

    NASA Astrophysics Data System (ADS)

    Iwase, Yumiko; Nishi, Koji; Fujimori, Junya; Fukai, Toshio; Yumita, Nagahiko; Ikeda, Toshihiko; Chen, Fu-shin; Momose, Yasunori; Umemura, Shin-ichiro

    2016-07-01

    In this study, the sonodynamically induced antitumor effect of pyrrolidine tris-acid fullerene (PTF) was investigated. Sonodynamically induced antitumor effects of PTF by focused ultrasound were investigated using isolated sarcoma-180 cells and mice bearing ectopically-implanted colon 26 carcinoma. Cell damage induced by ultrasonic exposure was enhanced by 5-fold in the presence of 80 µM PTF. The combined treatment of ultrasound and PTF suppressed the growth of the implanted colon 26 carcinoma. Ultrasonically induced 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (4oxoTEMPO) production in the presence and absence of PTF was assessed, and it was shown that 80 µM PTF enhanced 4oxoTEMPO production as measured by ESR spectroscopy. Histidine, a reactive oxygen scavenger, significantly reduced cell damage and 4oxoTEMPO generation caused by ultrasonic exposure in the presence of PTF. These results suggest that singlet oxygen is likely to be involved in the ultrasonically induced cell damage enhanced by PTF.

  20. Synthesis, characterization, structural and biological aspects of copper(II) dithiocarbamate complexes - Part II, [Cu{S2CN(Me)(R1)}2], [Cu{S2CN(Me)(R2)}2] and [Cu{S2CN(R3)(R4)}2] {R1 = CH2CH(OMe)2, R2 = 2-methyl-1,3-dioxolane, R3 = CH2(CH2)2NCHPhOCH2Ph and R4 = CH2CH2OH}

    NASA Astrophysics Data System (ADS)

    Ferreira, Isabella P.; de Lima, Geraldo M.; Paniago, Eucler B.; Takahashi, Jacqueline A.; Krambrock, Klaus; Pinheiro, Carlos B.; Wardell, James L.; Visentin, Lorenzo C.

    2013-09-01

    Three new copper(II) dithiocarbamates (DTC), [Cu{S2CN(Me)(R1)}2] (1), [Cu{S2CN(Me)(R2)}2] (2) and [Cu{S2CN(R3)(R4)}2] (3) with R1 = CH2CH(OMe)2, R2 = 2-methyl-1,3-dioxolane, R3 = CH2(CH2)2NCHPhOCH2Ph and R4 = CH2CH2OH, have been synthesized and characterized by different spectroscopic techniques. Complexes (1) and (2) display typical EPR spectra for separated Cu(II) centers, and the spectrum of (3) is characteristic of two magnetically coupled Cu(II) ions with S = 1. The X-ray crystallographic determination has shown that complexes (1) and (2) crystallise in the triclinic and monoclinic systems. In addition both complexes are monomers in which the geometry at each Cu(II) is square planar. The in vitro antimicrobial activity of the sodium salts of ligands, and of the Cu(II)-DTC complexes have been screened against Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Penicillium citrinum and Curvularia senegalensis, as well as Gram positive and Gram negative bacteria. Finally, the toxic effects of complexes (1)-(3) were performed using Chlorella vulgaris.

  1. Interactions of nitric oxide with copper(II) dithiocarbamates in aqueous solution.

    PubMed

    Díaz, Alicia; Ortiz, Mayreli; Sánchez, Ileana; Cao, Roberto; Mederos, Alfredo; Sanchiz, Joaquin; Brito, Felipe

    2003-07-01

    This is the first report on the formation of air-stable copper nitrosyl complexes. The interaction of nitric oxide, NO, with Cu(DTC)(2).3H(2)O (DTC: dithiocarbamate) and was studied in aqueous solution at pH 7.4 and 293 K. The stability constants were determined from UV-Vis data, using LETAGROP program. The high values obtained, log beta(1)=9.743(5) and log beta(2)=15.44(2) for Cu(ProDTC)(2)-NO, (ProDTC=L-prolinedithiocarbamate) and log beta(1)=8.723(5) and log beta(2)=11.45(2) for Cu(MorDTC)(2)-NO system, (MorDTC=morpholyldithiocarbamate), indicate the formation of two stable nitrosyl complexes, Cu(DTC)(2)NO and Cu(DTC)(2)(NO)(2). Coordinated NO is neither affected by the presence of air nor when the solution is purged with Ar. Cu(MorDTC)(2)NO.3H(2)O was isolated in the solid state and its nuNO (IR) band at 1682 cm(-1), but affected by temperature variations over 333 K.

  2. Dual platinum and pyrrolidine catalysis in the direct alkylation of allylic alcohols: selective synthesis of monoallylation products.

    PubMed

    Shibuya, Ryozo; Lin, Lu; Nakahara, Yasuhito; Mashima, Kazushi; Ohshima, Takashi

    2014-04-22

    A dual platinum- and pyrrolidine-catalyzed direct allylic alkylation of allylic alcohols with various active methylene compounds to produce products with high monoallylation selectivity was developed. The use of pyrrolidine and acetic acid was essential, not only for preventing undesirable side reactions, but also for obtaining high monoallylation selectivity.

  3. Prediction on the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase based on gene expression programming.

    PubMed

    Li, Yuqin; You, Guirong; Jia, Baoxiu; Si, Hongzong; Yao, Xiaojun

    2014-01-01

    Quantitative structure-activity relationships (QSAR) were developed to predict the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase via heuristic method (HM) and gene expression programming (GEP). The descriptors of 33 pyrrolidine derivatives were calculated by the software CODESSA, which can calculate quantum chemical, topological, geometrical, constitutional, and electrostatic descriptors. HM was also used for the preselection of 5 appropriate molecular descriptors. Linear and nonlinear QSAR models were developed based on the HM and GEP separately and two prediction models lead to a good correlation coefficient (R (2)) of 0.93 and 0.94. The two QSAR models are useful in predicting the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase during the discovery of new anticancer drugs and providing theory information for studying the new drugs.

  4. A chiral benzoylthiourea-pyrrolidine catalyst for the highly enantioselective Michael addition of ketones to chalcones.

    PubMed

    Ban, Shu-Rong; Zhu, Xi-Xia; Zhang, Zhi-Ping; Li, Qing-Shan

    2014-06-01

    A benzoylthiourea-pyrrolidine catalyst was developed for the asymmetric Michael addition of ketones to chalcones. The corresponding products were obtained in high yields with high level of diastereoselectivities (up to 99:1 dr) and high level of enantioselectivities (up to 94% ee) under mild conditions.

  5. Stereoselective access to heteroarylmethylene-substituted pyrrolidines: fully organocatalytic Mannich-hydroamination reactions.

    PubMed

    Jean, Alexandre; Blanchet, Jérôme; Rouden, Jacques; Maddaluno, Jacques; De Paolis, Michaël

    2013-02-25

    A one-pot sequence of organocatalytic transformations delivers heteroarylmethylene-substituted pyrrolidines with high stereo- and enantioselectivity. A Mannich coupling of N-heteroarylalkyne aldehydes with aldimine and an original metal-free hydroamination of the resulting adducts are the key transformations of the process delivering highly functionalized molecules with high potential for synthetic applications.

  6. Design, structural and spectroscopic elucidation, and the in vitro biological activities of new diorganotin dithiocarbamates.

    PubMed

    Ferreira, Isabella P; de Lima, Geraldo M; Paniago, Eucler B; Rocha, Willian R; Takahashi, Jacqueline A; Pinheiro, Carlos B; Ardisson, José D

    2012-12-01

    The reaction of 2,2-dimethoxy-N-methylethyllamine or 2-methyl-1,3-dioxolane with CS(2) in alkaline media produced two novel dithiocarbamate salts. Subsequent reactions with organotin halides yielded six new complexes: [SnMe(2){S(2)CNR(R(1))(2)}(2)] (1), [Sn(n-Bu)(2){S(2)CNR(R(1))(2)}(2)] (2), [SnPh(2){S(2)CNR(R(1))(2)}(2)] (3), [SnMe(2){S(2)CNR(R(2))(2)}(2)] (4), [Sn(n-Bu)(2){S(2)CNR(R(2))(2)}(2)] (5), [SnPh(2){S(2)CNR(R(2))(2)}(2)] (6), where R = methyl, R(1) = CH(2)CH(OMe)(2), and R(2) = 2-methyl-1,3-dioxolane. All compounds were identified in terms of infrared, (1)H and (13)C NMR, and the complexes were also characterized using (119)Sn NMR, (119)Sn Mössbauer and X-ray crystallography. The biological activity of all derivatives has been screened in terms of IC(90) and IC(50) against Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Penicillium citrinum, Curvularia senegalensis, Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Streptococcus sanguinis, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, and Pseudomonas aeruginosa and the results correlated well with a performed study of structure-activity relationship (SAR). Complexes (3), (5) and (6) displayed the best IC(90) and IC(50) in the presence of the fungi, greater than that of miconazole, used as control drug.

  7. Effects of substituted dithiocarbamates on distribution and excretion of inorganic mercury in mice

    SciTech Connect

    Gale, G.R.; Atkins, L.M.; Smith, A.B.; Jones, M.M.

    1985-02-01

    Diethyldithiocarbamate (DDTC) and six of its N,N-disubstituted congeners were evaluated for their relative efficacies in mobilizing and promoting excretion of mercury (Hg/sup + +/) using mice which had been given /sup 203/Hg/sup + +/; D-penicillamine (PEN) was used as a positive control compound. While none was as effective as PEN when compared on a molar dose basis, significant activity as assessed by reduction of whole body /sup 203/Hg burden, was observed following treatment with three of the analogs. The order of effectiveness was PEN greater than N-methyl-N-dithiocarboxyglucamine (MDCG) greater than di(carboxymethyl)dithiocarbamate (DCDC) greater than di(hydroxyethyl)dithiocarbamate (DHDC).

  8. Toxic Epidermal Necrolysis After Exposure to Dithiocarbamate Fungicide Mancozeb.

    PubMed

    Zakharov, Sergey; Csomor, Jan; Urbanek, Petr; Pelclova, Daniela

    2016-01-01

    Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disease with high mortality. Dithiocarbamates (DTC) are organosulphur compounds widely used in agriculture, industry and households. We report a case of TEN after exposure to mancozeb in fungicide. A 48-year-old 75 kg b.w. man was admitted with fever and generalized skin/mucous lesions after application of fungicide in a home garden. The patient had necrotic desquamation of gastrointestinal/respiratory tract mucosa, ocular lesion and skin epidermolysis of 90% of body surface. The laboratory findings included elevation of inflammatory parameters, hyperglycaemia, increased urea, creatinine, liver enzymes, hypoalbuminemia and electrolyte disturbances. The treatment included supportive care, management of fluid/electrolyte requirements, analgesics and enteral nutrition. Skin lesions were treated with occlusive non-adhesive biological wound dressings. Due to the proof of Acinetobacter, Escherichia coli and Escherichia faecalis from skin swabs, a combination of meropenem with amikacin was administered. During the next 2 weeks, complete re-epithelialization of skin lesions occurred, mucosal lesions healed and the laboratory parameters returned to normal. The patient was discharged on day 42. TEN is a rare condition that is generally caused by medications. Nevertheless, high attention should be paid to the cases of occupational or household exposure to DTC fungicides widely used in agriculture and home gardens because of their ability to cause TEN after skin and inhalation exposure. Greater emphasis on the hazardous properties of these products is necessary to ensure non-professional users are aware of the necessity of protective clothing during mixing, loading, application and early re-entry into treated fields.

  9. Microglia activation and cell death in response to diethyl-dithiocarbamate acute administration.

    PubMed

    Zucconi, Gigliola Grassi; Laurenzi, Maria Assunta; Semprevivo, Massimo; Torni, Federica; Lindgren, Jan Ake; Marinucci, Eva

    2002-04-29

    An increasing body of evidence suggests a role for activated microglia in the pathogenesis of neurodegenerative disorders. Hence, it would be useful to have a better understanding of the significance of microglial activation for neuronal damage. Unfortunately, most models of microglial activation use invasive or long-lasting insults, which make it difficult to evaluate the role played by microglia. We have instead developed a model for microglial activation by using brief exposure to the widely available neurotoxin diethyl-dithiocarbamate (DDTC). Despite evidence for the neurotoxic nature of this substance, microglia involvement has not been hitherto investigated. After acute i.p. administration of DDTC at two different doses, microglia were already activated in selected areas of the rat brain (hippocampal dentate gyrus, entorhinal-pyriform cortex and hypothalamus) after 1 hour, reaching a peak at 3-6 hours and subsided within 6-48 hours, depending on the brain region. Microglia activation was associated with interleukin-1 beta immunopositivity between 3 and 6 hours and with up-regulation of major histocompatibility complex class II expression between 24 and 48 hours. No significant changes in astrocyte immunostaining were detected between 6 hours and 6 days. The TUNEL procedure revealed the death of a limited number of cells in the above-mentioned structures that peaked at 6h and then declined rapidly. Cell death was detected in sites with major, minor, or no microglial activation, indicating that these two events can occur concomitantly or independently. The study shows that the administration of DDTC provides a useful model for studying the implications of region-specific reactivity of microglia and its differential interaction with neuronal damage.

  10. Synthesis, Characterization, and Processing of Copper, Indium, and Gallium Dithiocarbamates for Energy Conversion Applications

    NASA Technical Reports Server (NTRS)

    Duraj, S. A.; Duffy, N. V.; Hepp, A. F.; Cowen, J. E.; Hoops, M. D.; Brothrs, S. M.; Baird, M. J.; Fanwick, P. E.; Harris, J. D.; Jin, M. H.-C.

    2009-01-01

    Ten dithiocarbamate complexes of indium(III) and gallium(III) have been prepared and characterized by elemental analysis, infrared spectra and melting point. Each complex was decomposed thermally and its decomposition products separated and identified with the combination of gas chromatography/mass spectrometry. Their potential utility as photovoltaic materials precursors was assessed. Bis(dibenzyldithiocarbamato)- and bis(diethyldithiocarbamato)copper(II), Cu(S2CN(CH2C6H5)2)2 and Cu(S2CN(C2H5)2)2 respectively, have also been examined for their suitability as precursors for copper sulfides for the fabrication of photovoltaic materials. Each complex was decomposed thermally and the products analyzed by GC/MS, TGA and FTIR. The dibenzyl derivative complex decomposed at a lower temperature (225-320 C) to yield CuS as the product. The diethyl derivative complex decomposed at a higher temperature (260-325 C) to yield Cu2S. No Cu containing fragments were noted in the mass spectra. Unusual recombination fragments were observed in the mass spectra of the diethyl derivative. Tris(bis(phenylmethyl)carbamodithioato-S,S'), commonly referred to as tris(N,N-dibenzyldithiocarbamato)indium(III), In(S2CNBz2)3, was synthesized and characterized by single crystal X-ray crystallography. The compound crystallizes in the triclinic space group P1(bar) with two molecules per unit cell. The material was further characterized using a novel analytical system employing the combined powers of thermogravimetric analysis, gas chromatography/mass spectrometry, and Fourier transform infrared (FT-IR) spectroscopy to investigate its potential use as a precursor for the chemical vapor deposition (CVD) of thin film materials for photovoltaic applications. Upon heating, the material thermally decomposes to release CS2 and benzyl moieties in to the gas phase, resulting in bulk In2S3. Preliminary spray CVD experiments indicate that In(S2CNBz2)3 decomposed on a Cu substrate reacts to produce

  11. Expanding The Scope Of Oligo-pyrrolinone-pyrrolidines As Protein-protein Interface Mimics

    PubMed Central

    Raghuraman, Arjun; Xin, Dongyue; Perez, Lisa M.; Burgess, Kevin

    2013-01-01

    Oligo-pyrrolinone-pyrrolidines (generic structure 1) have the potential to interfere with protein-protein interactions (PPIs), but to reduce this to practice it is necessary to be able to synthesize these structures with a variety of different side-chains corresponding to genetically encoded proteins. This paper describes expansion of the synthetic scope of 1, the difficulties encountered in this process, particularly issues with epimerization and slow coupling rates, and methods to overcome them. Finally, spectroscopic and physicochemical properties as well as proteolytic stabilities of molecules in this series were measured; these data highlight the suitability of oligo-pyrrolinone-pyrrolidines for the development of pharmacological probes or pharmaceutical leads. PMID:23654284

  12. Facile access to unnatural dipeptide-alcohols based on cis-2,5-disubstituted pyrrolidines.

    PubMed

    Jia, Yan-Yan; Li, Xiao-Ye; Wang, Ping-An; Wen, Ai-Dong

    2015-02-11

    Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(-)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, 1H- and 13C-NMR spectroscopy. These unnatural dipeptide-alcohols can act as building blocks for peptidomimetics.

  13. Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors.

    PubMed

    Bannwart, Linda M; Carter, David S; Cai, Hai-Ying; Choy, Jason C; Greenhouse, Robert; Jaime-Figueroa, Saul; Iyer, Pravin S; Lin, Clara J; Lee, Eun Kyung; Lucas, Matthew C; Lynch, Stephen M; Madera, Ann Marie; Moore, Amy; Ozboya, Kerem; Raptova, Lubica; Roetz, Ralf; Schoenfeld, Ryan C; Stein, Karin Ann; Steiner, Sandra; Villa, Marzia; Weikert, Robert J; Zhai, Yansheng

    2008-12-01

    A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p.

  14. Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists

    SciTech Connect

    Thompson, Scott K.; Washburn, David G.; Frazee, James S.; Madauss, Kevin P.; Hoang, Tram H.; Lapinski, Leahann; Grygielko, Eugene T.; Glace, Lindsay E.; Trizna, Walter; Williams, Shawn P.; Duraiswami, Chaya; Bray, Jeffrey D.; Laping, Nicholas J.

    2010-09-03

    Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the progesterone receptor, and one of these analogs was shown to be efficacious upon oral dosing in the OVX rat model of estrogen opposition.

  15. Total reflection X-ray fluorescence trace mercury determination by trapping complexation: Application in advanced oxidation technologies

    NASA Astrophysics Data System (ADS)

    Custo, Graciela; Litter, Marta I.; Rodríguez, Diana; Vázquez, Cristina

    2006-11-01

    It is well known that Hg species cause high noxious effects on the health of living organisms even at very low levels (5 μg/L). Quantification of this element is an analytical challenge due to the peculiar physicochemical properties of all Hg species. The regulation of the maximal allowable Hg concentration led to search for sensitive methods for its determination. Total reflection X-ray fluorescence is a proved instrumental analytical tool for the determination of trace elements. In this work, the use of total reflection X-ray fluorescence for Hg quantification is investigated. However, experimental determination by total reflection X-ray fluorescence requires depositing a small volume of sample on the reflector and evaporation of the solvent until dryness to form a thin film. Because of volatilization of several Hg forms, a procedure to capture these volatile species in liquid samples by using complexing agents is proposed. Acetate, oxalic acid, ethylenediaminetetracetic acid and ammonium pyrrolidine-dithiocarbamate were assayed for trapping the analytes into the solution during the preparation of the sample and onto the reflector during total reflection X-ray fluorescence measurements. The proposed method was applied to evaluate Hg concentration during TiO 2-heterogeneous photocatalysis, one of the most known advanced oxidation technologies. Advanced oxidation technologies are processes for the treatment of effluents in waters and air that involve the generation of very active oxidative and reductive species. In heterogeneous photocatalysis, Hg is transformed to several species under ultraviolet illumination in the presence of titanium dioxide. Total reflection X-ray fluorescence was demonstrated to be applicable in following the extent of the heterogeneous photocatalysis reaction by determining non-transformed Hg in the remaining solution.

  16. Development of new portable miniaturize solid phase microextraction of silver-APDC complex using micropipette tip in-syringe system couple with electrothermal atomic absorption spectrometry

    NASA Astrophysics Data System (ADS)

    Naeemullah; Kazi, Tasneem Gul; Afridi, Hassan Imran; Shah, Faheem; Arain, Sadaf Sadia; Arain, Salma Aslam; Panhwar, Abdul Haleem; Arain, Mariam Shahzadi; Samoon, Muhammad Kashif

    2016-02-01

    An innovative and simple miniaturized solid phase microextraction (M-SPME) method, was developed for preconcentration and determination of silver(I) in the fresh and waste water samples. For M-SPME, a micropipette tip packed with activated carbon cloth (ACC) as sorbent, in a syringe system. The size, morphology and elemental composition of ACC before and after adsorption of analyte have been characterized by scanning electron microscopy and energy dispersive spectroscopy. The sample solution treated with a complexing reagent, ammonium pyrrolidine dithiocarbamate (APDC), was drawn into the syringe filled with ACC and dispensed manually for 2 to 10 aspirating/dispensing cycle. Then the Ag- complex sorbed on the ACC in micropipette was quantitatively eluted by drawing and dispensing of different concentrations of acids for 2 to 5 aspirating/dispensing cycles. The extracted Ag ions with modifier were injected directly into the electrothermal atomic absorption spectrometry for analysis. The influence of different variables on the extraction efficiency, including the concentration of ligand, pH, sample volume, eluent type, concentration and volume was investigated. Validity and accuracy of the developed method was checked by the standard addition method. Reliability of the proposed methodology was checked by the relative standard deviation (%RSD), which was found to be < 5%. Under the optimized experimental variables, the limits of detection (LOD) and enhancement factors (EF), were obtained to be 0.86 ng L- 1 and 120, respectively. The proposed method was successfully applied for the determination of trace levels of silver ions in fresh and waste water samples.

  17. ACE inhibitors hypothesis generation for selective design, synthesis and biological evaluation of 3-mercapto-2-methyl-propanoyl-pyrrolidine-3-imine derivatives as antihypertensive agents.

    PubMed

    Ismail, Mohamed A H; Nabil Aboul-Enein, M; Abouzid, Khaled A M; Abou El Ella, Dalal A; Ismail, Nasser S M

    2009-05-15

    A series of new 3-mercapto-2-methyl-propanoyl-pyrrolidine derivatives (V, VIa-e) were designed. A new validated ACE inhibitors pharmacophore model (hypothesis) was generated for the first time in this research from the biologically active (frozen) conformation of Lisinopril-Human ACE complex that was downloaded from PDB, using stepwise technique of CATALYST modules. The molecular modeling compare-fit study of the designed molecules (V, VIa-e), with such ACE inhibitors hypothesis was fulfilled, and several compounds showed significant high simulation fit values. The compounds with high fit values were synthesized and biologically evaluated in vivo as hypotensive agents. It appears that the in vivo hypotensive activity of compounds V, VIa, VIb, and VIe was consistent with their molecular modeling results, and compound VIe showed the highest activity in comparison to Captopril.

  18. Importance of the nature of α-substituents in pyrrolidine organocatalysts in asymmetric Michael additions.

    PubMed

    Patil, Mahendra P; Sharma, Akhilesh K; Sunoj, Raghavan B

    2010-11-05

    The fundamental factors contributing toward the stereoselectivity in organocatalyzed asymmetric Michael reaction between aldehydes (propanal and 3-phenyl propanal) and methyl vinyl ketone (MVK) are established by using density functional theory methods. Three of the most commonly employed α-substituted pyrrolidine organocatalysts are examined. Several key stereochemical modes of addition between (i) a model enamine or (ii) pyrrolidine enamines derived from aldehydes and secondary amine to MVK are examined. Among these possibilities, the addition of (E)-enamine to cis-MVK is found to have a lower activation barrier. The stereochemical outcome of the reaction is reported on the basis of the relative energies between pertinent diastereomeric transition states. Moderate selectivity is predicted for the reaction involving pyrrolidine catalysts I and II, which carry relatively less bulky α-substituents dimethylmethoxymethyl and diphenylmethyl, respectively. On the other hand, high selectivity is computed in the case of catalyst III having a sufficiently large α-substituent (diarylmethoxymethyl or diphenylprolinol methyl ether). The enantiomeric excess in the case of 3-phenyl propanal is found to be much higher as compared to that with unsubstituted propanal, suggesting potential for improvement in stereoselectivity by substrate modifications. The computed enantiomeric excess is found to be in reasonable agreement with the reported experimental stereoselectivities. A detailed investigation on the geometries of the crucial transition states reveals that apart from steric interactions between the α-substituent and MVK, various other factors such as orbital interactions and weak stabilizing hydrogen-bonding interactions play a vital role in stereoselectivity. The results serve to establish the importance of cumulative effects of various stabilizing and destabilizing interactions at the transition state as responsible for the stereochemical outcome of the reaction. The

  19. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone: A potent, selective, orally active dipeptidyl peptidase IV inhibitor

    SciTech Connect

    Ammirati, Mark J.; Andrews, Kim M.; Boyer, David D.; Brodeur, Anne M.; Danley, Dennis E.; Doran, Shawn D.; Hulin, Bernard; Liu, Shenping; McPherson, R. Kirk; Orena, Stephen J.; Parker, Janice C.; Polivkova, Jana; Qiu, Xiayang; Soglia, Carolyn B.; Treadway, Judith L.; VanVolkenburg, Maria A.; Wilder, Donald C.; Piotrowski, David W.; Pfizer

    2010-10-01

    A series of 4-substituted proline amides was synthesized and evaluated as inhibitors of dipeptidyl pepdidase IV for the treatment of type 2 diabetes. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone (5) emerged as a potent (IC{sub 50} = 13 nM) and selective compound, with high oral bioavailability in preclinical species and low plasma protein binding. Compound 5, PF-00734200, was selected for development as a potential new treatment for type 2 diabetes.

  20. Squaramide-catalysed asymmetric cascade aza-Michael/Michael addition reaction for the synthesis of chiral trisubstituted pyrrolidines.

    PubMed

    Zhao, Bo-Liang; Lin, Ye; Yan, Hao-Hao; Du, Da-Ming

    2015-12-14

    A bifunctional squaramide catalysed aza-Michael/Michael cascade reaction between nitroalkenes and tosylaminomethyl enones or enoates has been developed. This organocatalytic cascade reaction provides easy access to highly functionalized chiral pyrrolidines with a broad substrate scope, giving the desired products in good yields (up to 99%) with good diastereoselectivities (up to 91 : 9 dr) and excellent enantioselectivities (up to >99% ee) under mild conditions. This protocol provides a straightforward entry to highly functionalized chiral trisubstituted pyrrolidine derivatives from simple starting materials.

  1. Dithiocarbamate fungicides increase intracellular Zn(2+) levels by increasing influx of Zn(2+) in rat thymic lymphocytes.

    PubMed

    Kanemoto-Kataoka, Yumiko; Oyama, Tomohiro M; Ishibashi, Hitoshi; Oyama, Yasuo

    2015-07-25

    Dithiocarbamate fungicides are used as alternative antifouling agents to highly toxic organotin antifouling agents, such as tri-n-butyltin and triphenyltin. There are some concerns regarding their environmental and health risks. It has been shown that tri-n-butyltin increases intracellular Zn(2+) levels of mammalian lymphocytes. Therefore, we examined the effects of dithiocarbamate fungicides (Ziram, Thiram, and Zineb) on rat thymic lymphocytes using a flow-cytometric technique to elucidate how these fungicides affect intracellular Zn(2+) levels. We further determined whether the agents increase intracellular Zn(2+) and/or Ca(2+), because both Zn(2+) and Ca(2+) are intracellular signals in lymphocytes, and excessive increases in their intracellular concentrations can have adverse effects. Dithiocarbamate fungicides increased intracellular Zn(2+) levels, without affecting intracellular Ca(2+) levels. Ziram was the most potent compound, increasing intracellular Zn(2+) levels via Zn(2+) influx. Ziram (1μM) greatly decreased the cellular nonprotein thiol content, and Zn(2+) chelators attenuated the Ziram-induced decrease. Ziram increased the population of annexin V-positive cells in a Zn(2+)-dependent manner. Therefore, we propose that dithiocarbamate fungicides induce Zn(2+) influx, resulting in an excessive elevation of intracellular Zn(2+) levels, leading to the induction of apoptosis. This study gives a basic insight into the mechanisms of dithiocarbamate fungicide-induced adverse events.

  2. Synthesis of polyhydroxylated piperidine and pyrrolidine peptidomimetics via one-pot sequential lactam reduction/Joullié-Ugi reaction.

    PubMed

    Szcześniak, Piotr; Maziarz, Elżbieta; Stecko, Sebastian; Furman, Bartłomiej

    2015-04-03

    A direct approach to the synthesis of polyhydroxylated piperidine and pyrrolidine peptidomimetics is described. The presented strategy is based on one-pot reduction of sugar-derived lactams with Schwartz's reagent followed by a multicomponent Ugi-Joullié reaction.

  3. Speciation of AsIII and AsV in fruit juices by dispersive liquid–liquid microextraction and hydride generation-atomic fluorescence spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new procedure was developed to speciate and quantify As(III) and As(V) in fruit juices. At pH 3.0, As(III) and ammonium pyrrolidine dithiocarbamate (APDC) formed a complex, which was extracted into carbon tetrachloride by dispersive liquid–liquid microextraction (DLLME) and subsequently quantified...

  4. Design, synthesis and SAR studies of GABA uptake inhibitors derived from 2-substituted pyrrolidine-2-yl-acetic acids.

    PubMed

    Steffan, Tobias; Renukappa-Gutke, Thejavathi; Höfner, Georg; Wanner, Klaus T

    2015-03-15

    In this paper, we disclose the design and synthesis of a series of 2-substituted pyrrolidine-2-yl-acetic acid as core structures and the N-arylalkyl derivatives thereof as potential GABA transport inhibitors. The 2-position in the side chain of pyrrolidine-2-yl-acetic acid derivatives was substituted with alkyl, hydroxy and amino groups to modulate the activity and selectivity to mGAT1 and mGAT4 proteins. SAR studies of the compounds performed for the four mouse GABA transporter proteins (mGAT1-mGAT4) implied significant potencies and subtype selectivities for 2-hydroxy-2-pyrrolidine-2-yl-acetic acid derivatives. The racemate rac-(u)-13c exhibited the highest potency (pIC50 5.67) at and selectivity for mGAT1 in GABA uptake assays. In fact, the potency of rac-(u)-13c at hGAT-1 (pIC50 6.14) was even higher than its potency at mGAT1. These uptake results for rac-(u)-13c are in line with the binding affinities to the aforesaid proteins mGAT1 (pKi 6.99) and hGAT-1 (pKi 7.18) determined by MS Binding Assay based on NO711 as marker quantified by LC-ESI-MS-MS analysis. Interestingly, the 2-hydroxy-2-pyrrolidine-2-yl-acetic acid rac-(u)-13d containing 2-{[tris(4-methoxyphenyl)]methoxy} ethyl group at the nitrogen atom of the pyrrolidine ring showed high potency at mGAT4 and a comparatively better selectivity for this protein (>15 against mGAT3) than the well known mGAT4 uptake inhibitor (S)-SNAP-5114.

  5. Removal of mercury species with dithiocarbamate-anchored polymer/organosmectite composites.

    PubMed

    Say, Ridvan; Birlik, Ebru; Erdemgil, Zerrin; Denizli, Adil; Ersöz, Arzu

    2008-02-11

    Mercury is one of the most toxic heavy metals found in solid and liquid waste disposed by chloro-alkali, paint, paper/pulp, battery, pharmaceutical, oil refinery and mining companies. Any form of mercury introduced to nature through any means is converted into a more toxic form such as methylmercury chloride (as produced by aquatic organisms) which usually accumulates in the tissue of fish and birds. The primary aim of this study was to investigate performance of dithiocarbamate-anchored polymer/organosmectite composites as sorbents for removal of mercury from aqueous solution. The modified smectite nanocomposites then were reacted with carbondisulfide to incorporate dithiocarbamate functional groups into the nanolayer of the organoclay. These dithiocarbamate-anchored composites were used for the removal of mercury species [Hg(II), CH(3)Hg(I) and C(6)H(5)Hg(I)]. Mercury adsorption was found to be dependent on the solution pH, mercury concentration and the type of mercury species to be adsorbed. The maximum adsorption capacities were equal to 157.3 mg g(-1) (782.5 micromol g(-1)) for Hg(II); 214.6 mg g(-1) (993.9 micromol g(-1)) for CH(3)Hg(I); 90.3 mg g(-1) (325 micromol g(-1)) for C(6)H(5)Hg(I). The competitive adsorption capacities (i.e. adsorption capacities based on solutions containing all three mercuric ions) are 7.7 mg g(-l) (38.3 micromol g(-1)), 9.2 mg g(-l) (42.6 micromol g(-1)) and 12.7 mg g(-1) (45.7 micromol g(-1)) for Hg(II), CH(3)Hg(I) and C(6)H(5)Hg(I), respectively, at 10 ppm initial concentration. The adsorption capacities on molar basis were in order of C(6)H(5)Hg(I)>CH(3)Hg(I)>Hg(II).

  6. The effects of a pyrrolidine functional group on the magnetic properties of N@C 60

    NASA Astrophysics Data System (ADS)

    Zhang, Jinying; Morton, John J. L.; Sambrook, Mark R.; Porfyrakis, Kyriakos; Ardavan, Arzhang; Briggs, G. Andrew D.

    2006-12-01

    A new stable pyrrolidine functionalized fullerene derivative, C 69H 10N 2O 2, has been synthesized, purified by high performance liquid chromatography, and characterized by MALDI mass spectrometry, UV-vis spectroscopy, Fourier transform infrared, 1H and 13C nuclear magnetic resonance. The magnetic properties of the analogous endohedral species have been studied by both continuous wave (CW) and pulsed EPR. CW-EPR spectra indicated an anisotropic hyperfine interaction and a permanent zero-field-splitting (ZFS). Both CW and pulsed EPR showed the ZFS parameter Deff to be around 17 MHz. Pulsed EPR revealed a biexponential decay in both T 1 and T 2, yielding a molecular tumbling correlation time τc of 31.4 ± 2.5 ps.

  7. Feasible Management of Southern Corn Leaf Blight via Induction of Systemic Resistance by Bacillus cereus C1L in Combination with Reduced Use of Dithiocarbamate Fungicides

    PubMed Central

    Lai, Yi-Ru; Lin, Pei-Yu; Chen, Chao-Ying; Huang, Chien-Jui

    2016-01-01

    Dithiocarbamate fungicides such as maneb and mancozeb are widely used nonsystemic protectant fungicides to control various plant fungal diseases. Dithiocarbamate fungicides should be frequently applied to achieve optimal efficacy of disease control and avoid either decline in effectiveness or wash-off from leaf surface. Dithiocarbamates are of low resistance risk but have the potential to cause human neurological diseases. The objective of this study was to develop a strategy to effectively control plant disease with reduced use of dithiocarbamtes. Southern corn leaf blight was the model pathosystem for the investigation. When corn plants were drench-treated with Bacillus cereus C1L, a rhizobacterium able to induce systemic resistance in corn plants against southern leaf blight, frequency of spraying dithiocarbamate fungicides could be decreased. The treatment of B. cereus C1L was able to protect maize from southern leaf blight while residues of dithiocarbamates on leaf surface were too low to provide sufficient protection. On the other hand, frequent sprays of mancozeb slightly but significantly reduced growth of corn plants under natural conditions. In contrast, application of B. cereus C1L can significantly promote growth of corn plants whether sprayed with mancozeb or not. Our results provide the information that plant disease can be well controlled by rhizobacteria-mediated induced systemic resistance in combination with reduced but appropriate application of dithiocarbamate fungicides just before a heavy infection period. An appropriate use of rhizobacteria can enhance plant growth and help plants overcome negative effects caused by dithiocarbamates. PMID:27721698

  8. Feasible Management of Southern Corn Leaf Blight via Induction of Systemic Resistance by Bacillus cereus C1L in Combination with Reduced Use of Dithiocarbamate Fungicides.

    PubMed

    Lai, Yi-Ru; Lin, Pei-Yu; Chen, Chao-Ying; Huang, Chien-Jui

    2016-10-01

    Dithiocarbamate fungicides such as maneb and mancozeb are widely used nonsystemic protectant fungicides to control various plant fungal diseases. Dithiocarbamate fungicides should be frequently applied to achieve optimal efficacy of disease control and avoid either decline in effectiveness or wash-off from leaf surface. Dithiocarbamates are of low resistance risk but have the potential to cause human neurological diseases. The objective of this study was to develop a strategy to effectively control plant disease with reduced use of dithiocarbamtes. Southern corn leaf blight was the model pathosystem for the investigation. When corn plants were drench-treated with Bacillus cereus C1L, a rhizobacterium able to induce systemic resistance in corn plants against southern leaf blight, frequency of spraying dithiocarbamate fungicides could be decreased. The treatment of B. cereus C1L was able to protect maize from southern leaf blight while residues of dithiocarbamates on leaf surface were too low to provide sufficient protection. On the other hand, frequent sprays of mancozeb slightly but significantly reduced growth of corn plants under natural conditions. In contrast, application of B. cereus C1L can significantly promote growth of corn plants whether sprayed with mancozeb or not. Our results provide the information that plant disease can be well controlled by rhizobacteria-mediated induced systemic resistance in combination with reduced but appropriate application of dithiocarbamate fungicides just before a heavy infection period. An appropriate use of rhizobacteria can enhance plant growth and help plants overcome negative effects caused by dithiocarbamates.

  9. Toxicity of the dithiocarbamate fungicide mancozeb to the nontarget soil nematode, Caenorhabditis elegans.

    PubMed

    Easton, A; Guven, K; de Pomerai, D I

    2001-01-01

    We have previously shown that the dithiocarbamate fungicide, Mancozeb, strongly induces lacZ reporter expression from an endogenous heat-shock promoter (hsp16) in the PC72 transgenic strain of the nematode Caenorhabditis elegans. Such evidence of organismal stress, in a nontarget species at subapplication concentrations, was much less apparent for the related fungicide, Maneb, which only weakly induced reporter expression. We now show that reporter induction by Mancozeb is marginal (<60%) after a few hours' exposure, but increases substantially (to almost 10-fold) after overnight exposure. In conjunction with our previous results using intermediate exposure periods, this suggests that the factor limiting reporter responses is likely to be a slow rate of uptake and/or metabolism of the fungicide. We confirm that a potentially toxic metabolite of dithiocarbamate fungicides, namely ethylenethiourea (ETU), has minimal toxicity toward C. elegans, even after prolonged exposure at high concentrations. We demonstrate that exposure to Mancozeb (but not ETU) significantly inhibits larval growth in C. elegans, although this parameter is not markedly more sensitive than reporter induction as a toxicological endpoint. Finally, we have used two-dimensional electrophoresis to show that high concentrations of both Maneb and Mancozeb drastically simplify the protein spot profile compared with controls. However, only in the latter case is there evidence of novel proteins being induced. Both fungicides appear toxic to C. elegans, but only Mancozeb induces a strong heat-shock response.

  10. Quantum chemical study of a derivative of 3-substituted dithiocarbamic flavanone

    NASA Astrophysics Data System (ADS)

    Gosav, Steluta; Paduraru, Nicoleta; Maftei, Dan; Birsa, Mihail Lucian; Praisler, Mirela

    2017-02-01

    The aim of this work is to characterize a quite novel 3-dithiocarbamic flavonoid by vibrational spectroscopy in conjunction with Density Functional Theory (DFT) calculations. Quantum mechanics calculations of energies, geometries and vibrational wavenumbers in the ground state were carried out by using hybrid functional B3LYP with 6-311G(d,p) as basis set. The results indicate a remarkable agreement between the calculated molecular geometries, as well as vibrational frequencies, and the corresponding experimental data. In addition, a complete assignment of all the absorption bands present in the vibrational spectrum has been performed. In order to assess its chemical potential, quantum molecular descriptors characterizing the interactions between the 3-dithiocarbamic flavonoid and its biological receptors have been computed. The frontier molecular orbitals and the HOMO-LUMO energy gap have been used in order to explain the way in which the new molecule can interact with other species and to characterize its molecular chemical stability/reactivity. The molecular electrostatic potential (MEP) map, computed in order to identify the sites of the studied flavonoid that are most likely to interact with electrophilic and nucleophilic species, is discussed.

  11. Masked thiol sugars: chemical behavior and synthetic applications of S-glycopyranosyl-N-monoalkyl dithiocarbamates.

    PubMed

    Megia-Fernandez, Alicia; de la Torre-Gonzalez, Diego; Parada-Aliste, Jose; Lopez-Jaramillo, Francisco Javier; Hernandez-Mateo, Fernando; Santoyo-Gonzalez, Francisco

    2014-02-01

    The chemical behavior of S-glycopyranosyl-N-monoalkyl dithiocarbamates (DTCs) as masked 1-glycosyl thiols, easily prepared by the nucleophilic displacement of 1-halo sugars with dithiocarbamate salts of primary amines, has been studied and synthetically exploited. This behavior relies on the abstraction of the proton of the carbamate functionality that allows controlled access to thiolate sugar intermediates. The basic character of the DTC salts used as reagents leads to thiolates that evolve in situ to symmetrical diglycosyldisulfides (DGDSs) when long reaction times are allowed. Alternatively, controlled unmasking of the thiolate function can be efficiently attained by treatment with an external base of isolated anomeric glycosyl DTCs, the formation of which is prevalent when using short reaction times. In this manner, a second methodology for the preparation of symmetrical DGDSs and a chemical protocol for the S-glycosylation of any electrophilic substrate are established. The applications of this last strategy for the preparation of thioglycosyl vinyl sulfones, thiodisaccharides, and S-linked homo- and heterodivalent neoglycoconjugates are described as a proof-of-concept of the great potential of the sugar DTCs in any chemical scenario in which the covalent attachment of a thiol sugar is required. The evaluation of the biological functionality of some divalent sulfurated sugar systems is also described.

  12. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    PubMed

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.

  13. Rapid discovery of potent α-fucosidase inhibitors by in situ screening of a library of (pyrrolidin-2-yl)triazoles.

    PubMed

    Elías-Rodríguez, Pilar; Moreno-Clavijo, Elena; Carmona, Ana T; Moreno-Vargas, Antonio J; Robina, Inmaculada

    2014-08-21

    The synthesis of a small library of (pyrrolidin-2-yl)triazoles via copper catalysed cycloaddition of an alkynyl iminocyclopentitol and a set of commercial and synthetic azides has been achieved. The in situ screening for the activity towards α-fucosidase of the resulting triazoles has allowed the identification of one of the most potent and selective pyrrolidine derived inhibitors of this enzyme (Ki = 4 nM).

  14. Design and synthesis of 2-(3-alkylaminophenyl)-6-(pyrrolidin-1-yl)quinolin-4-ones as potent antitumor agents.

    PubMed

    Huang, Shih-Ming; Cheng, Yung-Yi; Chen, Ming-Hua; Huang, Chi-Hung; Huang, Li-Jiau; Hsu, Mei-Hua; Kuo, Sheng-Chu; Lee, Kuo-Hsiung

    2013-02-01

    2-(3-Alkylaminophenyl)-6-(pyrrolidin-1-yl)quinolin-4-ones 1-3 were synthesized and screened for anti-proliferative activity against three human cancer cell lines, as well as the normal cell line Detroit 551. All of the synthesized target compounds 1-3 demonstrated potent cytotoxic activity against the cancer cell lines, but weak inhibitory activity toward the normal cell line. 2-(3-Methyl aminophenyl)-6-(pyrrolidin-1-yl)quinolin-4-one (1), one of the potent compounds in vitro, was also tested in an in vivo Hep3B xenograft nude mice model, and its significant anticancer activity was reconfirmed. Therefore, compound 1 merits further investigation as an antitumor clinical trial candidate and potential anticancer agent.

  15. Highly enantioselective Michael addition of cyclohexanone to nitroolefins catalyzed by pyrrolidine-based bifunctional benzoylthiourea in water.

    PubMed

    Wang, Zhen-Yu; Ban, Shu-Rong; Yang, Meng-Chen; Li, Qing-Shan

    2016-11-01

    Organocatalysis and aqueous reactions are identified as the focus of the greening of chemistry. Combining these two strategies effectively remains an interesting challenge in organic synthesis. Herein, we used pyrrolidine-based benzoylthiourea 1c to catalyze the asymmetric Michael addition of cyclohexanone to various nitroolefins in water to afford the corresponding compounds in moderate to good yields, and with excellent diastereoselectivities (up to >99:1 dr) and enantioselectivities (up to 99% ee).

  16. Dithiocarbamates have a common toxic effect on zebrafish body axis formation

    SciTech Connect

    Tilton, Fred; La Du, Jane K.; Vue, Meng; Alzarban, Noor; Tanguay, Robert L. . E-mail: Robert.Tanguay@oregonstate.edu

    2006-10-01

    We previously determined that the dithiocarbamate pesticide sodium metam (NaM) and its active ingredient methylisothiocyanate (MITC) were developmentally toxic causing notochord distortions in the zebrafish. In this study, developing zebrafish were exposed to isothiocyanates (ITCs), dithiocarbamates (DTCs) and several degradation products to determine the teratogenic relationship of these chemical classes at the molecular level. All dithiocarbamates tested elicited notochord distortions with notochord NOELs from <4 to 40 ppb, while none of the ITCs caused notochord distortions with the exception of MITC. Carbon disulfide (CS{sub 2}), a common DTC degradate, also caused distortions at concentrations >200 times the DTCs. Whole mount in situ hybridization of developmental markers for collagen (collagen2a1), muscle (myoD), and body axis formation (no tail) was perturbed well after cessation of treatment with pyrolidine-DTC (PDTC), dimethyl-DTC (DMDTC), NaM, MITC, and CS{sub 2}. Therefore, distinct albeit related chemical classes share a common toxic effect on zebrafish notochord development. To test the responsiveness of the distortion to metal perturbation, five metal chelators and 2 metals were studied. The membrane permeable copper chelator neocuproine (NCu) was found to cause notochord distortions similar to DTC-related molecules. DMDTC and NCu treated animals were protected with copper, and collagen 2a1 and no tail gene expression patterns were identical to controls in these animals. PDTC, NaM, MITC, and CS{sub 2} were not responsive to copper indicating that the chelation of metals is not the primary means by which these molecules elicit their developmental toxicity. Embryos treated with DMDTC, NaM, and NCu were rescued by adding triciaine (MS-222) which abolishes the spontaneous muscle contractions that begin at 18 hpf. In these animals, only collagen 2a1 expression showed a similar pattern to the other notochord distorting molecules. This indicates that the

  17. Mechanism of action of some acrylophenones, quinolines and dithiocarbamate as potent, non-detergent spermicidal agents.

    PubMed

    Maikhuri, J P; Dwivedi, A K; Dhar, J D; Setty, B S; Gupta, G

    2003-05-01

    Some suitably substituted acrylophenones, quinolines and dithiocarbamate were synthesized as new generation, non-detergent spermicides and were studied for their mechanism of action in comparison with various known spermicides belonging to several different classes of chemical compound. Nonoxynol-9, benzalkonium chloride, Sapindus saponins, verapamil, emetine and tartaric acid were used as reference molecules to study the effect of new spermicides on human sperm motility parameters (using computer-assisted semen analyzer), plasma membrane integrity, lipid peroxidation and defense system against reactive oxygen species (ROS). Results have indicated that sperm plasma membrane remains the primary site of action of most of the spermicides, though the effect may be predominantly on the physiological integrity rather than the structural integrity in case of the new compounds. Lipid peroxidation may play an important role in disrupting sperm membrane physiology that may or may not be accompanied with a detrimental effect on the defense system of the human spermatozoa against the ROS.

  18. Tunable diastereoselection of biased rigid systems by Lewis acid induced conformational effects: a rationalization of the vinylation of cyclic nitrones en route to polyhydroxylated pyrrolidines.

    PubMed

    Delso, Ignacio; Marca, Eduardo; Mannucci, Vanni; Tejero, Tomás; Goti, Andrea; Merino, Pedro

    2010-08-23

    The diastereofacial selection in addition reactions to biased rigid systems can be modulated by the action of Lewis acids. As an example, the stereoselectivity of the nucleophilic addition of vinyl magnesium bromide (VMB) to cyclic nitrones in the presence of diethylaluminum chloride (DEAC) shows a strong dependence on the temperature and the carbon substituent adjacent at the reaction center; it is remarkable that whereas a high selectivity is obtained at higher temperatures, in the presence of DEAC, a trend to invert the stereochemical course of the reaction is observed at lower temperatures, provided the substituent at C3 of the pyrrolidine ring allows delivery of the vinyl moiety. This behavior and difference in selectivity is to be attributed to the high conformational barriers of the intermediate nitrone-DEAC-VMB complex. A clear inversion of the selectivity is observed at -78 degrees C for the reaction of the nitrone protected as an O-methyl derivative. The present study provides a rationalization for the stereocontrolled addition of nucleophiles to rigid systems (cyclic nitrones).

  19. Computer-Aided Design of Orally Bioavailable Pyrrolidine Carboxamide Inhibitors of Enoyl-Acyl Carrier Protein Reductase of Mycobacterium tuberculosis with Favorable Pharmacokinetic Profiles

    PubMed Central

    Kouassi, Affiba Florance; Kone, Mawa; Keita, Melalie; Esmel, Akori; Megnassan, Eugene; N’Guessan, Yao Thomas; Frecer, Vladimir; Miertus, Stanislav

    2015-01-01

    We have carried out a computational structure-based design of new potent pyrrolidine carboxamide (PCAMs) inhibitors of enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis (MTb). Three-dimensional (3D) models of InhA-PCAMx complexes were prepared by in situ modification of the crystal structure of InhA-PCAM1 (Protein Data Bank (PDB) entry code: 4U0J), the reference compound of a training set of 20 PCAMs with known experimental inhibitory potencies (IC50exp). First, we built a gas phase quantitative structure-activity relationships (QSAR) model, linearly correlating the computed enthalpy of the InhA-PCAM complex formation and the IC50exp. Further, taking into account the solvent effect and loss of inhibitor entropy upon enzyme binding led to a QSAR model with a superior linear correlation between computed Gibbs free energies (ΔΔGcom) of InhA-PCAM complex formation and IC50exp (pIC50exp = −0.1552·ΔΔGcom + 5.0448, R2 = 0.94), which was further validated with a 3D-QSAR pharmacophore model generation (PH4). Structural information from the models guided us in designing of a virtual combinatorial library (VL) of more than 17 million PCAMs. The VL was adsorption, distribution, metabolism and excretion (ADME) focused and reduced down to 1.6 million drug like orally bioavailable analogues and PH4 in silico screened to identify new potent PCAMs with predicted IC50pre reaching up to 5 nM. Combining molecular modeling and PH4 in silico screening of the VL resulted in the proposed novel potent antituberculotic agent candidates with favorable pharmacokinetic profiles. PMID:26703572

  20. Computer-Aided Design of Orally Bioavailable Pyrrolidine Carboxamide Inhibitors of Enoyl-Acyl Carrier Protein Reductase of Mycobacterium tuberculosis with Favorable Pharmacokinetic Profiles.

    PubMed

    Kouassi, Affiba Florance; Kone, Mawa; Keita, Melalie; Esmel, Akori; Megnassan, Eugene; N'Guessan, Yao Thomas; Frecer, Vladimir; Miertus, Stanislav

    2015-12-12

    We have carried out a computational structure-based design of new potent pyrrolidine carboxamide (PCAMs) inhibitors of enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis (MTb). Three-dimensional (3D) models of InhA-PCAMx complexes were prepared by in situ modification of the crystal structure of InhA-PCAM1 (Protein Data Bank (PDB) entry code: 4U0J), the reference compound of a training set of 20 PCAMs with known experimental inhibitory potencies (IC50(exp)). First, we built a gas phase quantitative structure-activity relationships (QSAR) model, linearly correlating the computed enthalpy of the InhA-PCAM complex formation and the IC50(exp). Further, taking into account the solvent effect and loss of inhibitor entropy upon enzyme binding led to a QSAR model with a superior linear correlation between computed Gibbs free energies (ΔΔGcom) of InhA-PCAM complex formation and IC50(exp) (pIC50(exp) = -0.1552·ΔΔGcom + 5.0448, R² = 0.94), which was further validated with a 3D-QSAR pharmacophore model generation (PH4). Structural information from the models guided us in designing of a virtual combinatorial library (VL) of more than 17 million PCAMs. The VL was adsorption, distribution, metabolism and excretion (ADME) focused and reduced down to 1.6 million drug like orally bioavailable analogues and PH4 in silico screened to identify new potent PCAMs with predicted IC50(pre) reaching up to 5 nM. Combining molecular modeling and PH4 in silico screening of the VL resulted in the proposed novel potent antituberculotic agent candidates with favorable pharmacokinetic profiles.

  1. Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers.

    PubMed

    Wallach, Jason; Kavanagh, Pierce V; McLaughlin, Gavin; Morris, Noreen; Power, John D; Elliott, Simon P; Mercier, Marion S; Lodge, David; Morris, Hamilton; Dempster, Nicola M; Brandt, Simon D

    2015-05-01

    Substances with the diphenylethylamine nucleus represent a recent addition to the product catalog of dissociative agents sold as 'research chemicals' on the Internet. Diphenidine, i.e. 1-(1,2-diphenylethyl)piperidine (1,2-DEP), is such an example but detailed analytical data are less abundant. The present study describes the synthesis of diphenidine and its most obvious isomer, 1-(2,2-diphenylethyl)piperidine (2,2-DEP), in order to assess the ability to differentiate between them. Preparation and characterization were also extended to the two corresponding pyrrolidine analogues 1-(1,2-diphenylethyl)- and 1-(2,2-diphenylethyl)pyrrolidine, respectively. Analytical characterizations included high-resolution electrospray mass spectrometry (HR-ESI-MS), liquid chromatography ESI-MS/MS, gas chromatography ion trap electron and chemical ionization MS, nuclear magnetic resonance spectroscopy (NMR) and infrared spectroscopy. Differentiation between the two isomeric pairs was possible under GC-(EI/CI)-MS conditions and included the formation of distinct iminium ions, such as m/z 174 for 1,2-DEP and m/z 98 for 2,2-DEP, respectively. The pyrrolidine counterparts demonstrated similar phenomena including the expected mass difference of 14 Da due to the lack of one methylene unit in the ring. Two samples obtained from an Internet vendor provided confirmation that diphenidine was present in both samples, concurring with the product label. Finally, it was confirmed that diphenidine (30 μM) reduced N-methyl-D-aspartate-mediated field excitatory postsynaptic potentials (NMDA-fEPSPs) to a similar extent to that of ketamine (30 μM) when using rat hippocampal slices. The appearance of 1,2- diphenylethylamines appears to reflect the exploration of alternatives to arylcyclohexylamine-type substances, such as methoxetamine, PCP and PCPy-based analogues that also show NMDA receptor activity as demonstrated here for diphenidine.

  2. Enantio- and diastereoselective Michael addition reactions of unmodified aldehydes and ketones with nitroolefins catalyzed by a pyrrolidine sulfonamide.

    PubMed

    Wang, Jian; Li, Hao; Lou, Bihshow; Zu, Liansuo; Guo, Hua; Wang, Wei

    2006-05-24

    Chiral (S)-pyrrolidine trifluoromethanesulfonamide has been shown to serve as an effective catalyst for direct Michael addition reactions of aldehydes and ketones with nitroolefins. A wide range of aldehydes and ketones as Michael donors and nitroolefins as acceptors participate in the process, which proceeds with high levels of enantioselectivity (up to 99 % ee) and diastereoselectivity (up to 50:1 d.r.). The methodology has been employed successfully in an efficient synthesis of the potent H(3) agonist Sch 50917. In addition, a practical three-step procedure for the preparation of (S)-pyrrolidine trifluoromethanesulfonamide has been developed. The high levels of stereochemical control attending Michael addition reactions catalyzed by this pyrrolidine sulfonamide, have been investigated by using ab initio and density functional methods. Transition state structures for the rate-limiting C--C bond-forming step, corresponding to re- and si-face addition to the reactive conformation of the key enamine intermediates have been calculated. Analysis of these structures indicates that hydrogen bonding plays an important role in catalysis and that the energy barrier for si-face attack in reactions of aldehydes to form 2R,3S products is lower than that for the re-face attack leading to 2S,3R products. In contrast, the energy barrier for re-face addition is lower than that for si-face addition in reactions of ketones. The computational results, which are in good agreement with the experimental observations, are discussed in the context of the stereochemical course of these Michael addition reactions.

  3. Metal-free oxysulfenylation of alkenes with 1-(arylthio)pyrrolidine-2,5-diones and alcohols.

    PubMed

    Yu, Jipan; Gao, Chang; Song, Zhixuan; Yang, Haijun; Fu, Hua

    2015-05-07

    β-Alkoxy sulfides are widely used as versatile building blocks in organic synthesis. Therefore, it is highly desirable to develop a convenient and efficient method for oxysulfenylation of alkenes. In this communication, an easy and efficient metal-free approach to β-alkoxy sulfides has been developed. The protocol uses readily available 1-(arylthio)pyrrolidine-2,5-diones and alcohols as the oxysulfenylating agents, chloroform as the solvent, and no ligand, additive and exclusion of air were required. Therefore, the present method provides a useful strategy for synthesis of β-alkoxy sulfides.

  4. Enantiodivergent Synthesis of (+)- and (-)-Pyrrolidine 197B: Synthesis of trans-2,5-Disubstituted Pyrrolidines by Intramolecular Hydroamination.

    PubMed

    Pérez, Sixto J; Purino, Martín A; Cruz, Daniel A; López-Soria, Juan M; Carballo, Rubén M; Ramírez, Miguel A; Fernández, Israel; Martín, Víctor S; Padrón, Juan I

    2016-10-17

    A highly efficient, diastereoselective, iron(III)-catalyzed intramolecular hydroamination/cyclization reaction involving α-substituted amino alkenes is described. Thus, enantiopure trans-2,5-disubstituted pyrrolidines and trans-5-substituted proline derivatives were synthesized by means of a combination of enantiopure starting materials, easily available from l-α-amino acids, with sustainable metal catalysts such as iron(III) salts. The scope of this methodology is highlighted in an enantiodivergent approach to the synthesis of both (+)- and (-)-pyrrolidine 197B alkaloids from l-glutamic acid. In addition, a computational study was carried out to gain insight into the complete diastereoselectivity of the transformation.

  5. Enantioselective Formal [3 + 1 + 1] Cycloaddition Reaction by Ru(II)/Iminium Cocatalysis for Construction of Multisubstituted Pyrrolidines.

    PubMed

    Li, Mingfeng; Chu, Rui; Chen, Jianghui; Wu, Xiang; Zhao, Yun; Liu, Shunying; Hu, Wenhao

    2017-03-01

    A Ru(II)/iminium cocatalyzed asymmetric formal [3 + 1 + 1] cycloaddition reaction of diazoacetophenones, anilines, and enals is disclosed to construct multisubstituted pyrrolidines in one step with excellent diastereoselectivity and enantioselectivity. The reaction mechanism was postulated as a successful trapping of Ru(II)-associated ammonium ylides via a selective 1,4-addition to chiral amine activated enals followed by a tandem aza-aldol process. The control experiments and theoretical density functional theory investigation revealed that the reversible NaOAc-facilitated aza-aldol process led to the diastereomeric conversion to provide a stable product.

  6. Structure-based drug design of pyrrolidine-1, 2-dicarboxamides as a novel series of orally bioavailable factor Xa inhibitors.

    PubMed

    Van Huis, Chad A; Bigge, Christopher F; Casimiro-Garcia, Agustin; Cody, Wayne L; Dudley, Danette A; Filipski, Kevin J; Heemstra, Ronald J; Kohrt, Jeffrey T; Narasimhan, Lakshmi S; Schaum, Robert P; Zhang, Erli; Bryant, John W; Haarer, Staci; Janiczek, Nancy; Leadley, Robert J; McClanahan, Thomas; Thomas Peterson, J; Welch, Kathleen M; Edmunds, Jeremy J

    2007-06-01

    A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor Xa inhibitors using structure-based drug design. This series consisted of a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline scaffold (1, IC(50) = 18 nM). Optimization of the initial hit resulted in an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) = 0.38 nM), which was shown to be efficacious in a canine electrolytic model of thrombosis with minimal bleeding.

  7. Crystal structure of 1-{4-hy-droxy-3-[(pyrrolidin-1-yl)meth-yl]phen-yl}-3-phenyl-prop-2-en-1-one.

    PubMed

    Aydın, Abdullah; Akkurt, Mehmet; Gul, Halise Inci; Yerdelen, Kadir Ozden; Celik, Raziye Catak

    2016-05-01

    In the title compound, C20H21NO2, the pyrrolidine ring adopts an envelope conformation with the N atom at the flap position. The central benzene ring makes dihedral angles of 21.39 (10) and 80.10 (15)° with the phenyl ring and the mean plane of the pyrrolidine ring, respectively. The mol-ecular conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond, which closes an S(6) ring. A weak C-H⋯π inter-action is observed in the crystal.

  8. Pyrrolidine analogs of lobelane: Relationship of affinity for the dihydrotetrabenazine binding site with function of the vesicular monoamine transporter 2 (VMAT2)

    PubMed Central

    Vartak, Ashish P.; Nickell, Justin R.; Chagkutip, Jaturaporn; Dwoskin, Linda P.; Crooks, Peter A.

    2013-01-01

    Ring size reduction of the central piperidine ring of lobelane yielded pyrrolidine analogs that showed marked inconsistencies in their ability to bind to the dihydrotetrabenazine (DTBZ) binding site on the vesicular monoamine transporter-2 (VMAT2) and their ability to inhibit VMAT2 function. The structure activity relationships indicate that structural modification within the pyrrolidine series resulted in analogs that interact with two different sites, i.e., the DTBZ binding site and an alternative site on VMAT2 to inhibit transporter function. PMID:19691331

  9. Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit.

    PubMed

    Backes, Bradley J; Longenecker, Kenton; Hamilton, Gregory L; Stewart, Kent; Lai, Chunqiu; Kopecka, Hana; von Geldern, Thomas W; Madar, David J; Pei, Zhonghua; Lubben, Thomas H; Zinker, Bradley A; Tian, Zhenping; Ballaron, Stephen J; Stashko, Michael A; Mika, Amanda K; Beno, David W A; Kempf-Grote, Anita J; Black-Schaefer, Candace; Sham, Hing L; Trevillyan, James M

    2007-04-01

    A novel series of pyrrolidine-constrained phenethylamines were developed as dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2 diabetes. The cyclohexene ring of lead-like screening hit 5 was replaced with a pyrrolidine to enable parallel chemistry, and protein co-crystal structural data guided the optimization of N-substituents. Employing this strategy, a >400x improvement in potency over the initial hit was realized in rapid fashion. Optimized compounds are potent and selective inhibitors with excellent pharmacokinetic profiles. Compound 30 was efficacious in vivo, lowering blood glucose in ZDF rats that were allowed to feed freely on a mixed meal.

  10. Dithiocarbamates are teratogenic to developing zebrafish through inhibition of lysyl oxidase activity

    SciTech Connect

    Boxtel, Antonius L. van; Kamstra, Jorke H.; Fluitsma, Donna M.; Legler, Juliette

    2010-04-15

    Dithiocarbamates (DTCs) are a class of compounds that are extensively used in agriculture as pesticides. As such, humans and wildlife are undoubtedly exposed to these chemicals. Although DTCs are thought to be relatively safe due to their short half lives, it is well established that they are teratogenic to vertebrates, especially to fish. In zebrafish, these teratogenic effects are characterized by distorted notochord development and shortened anterior to posterior axis. DTCs are known copper (Cu) chelators but this does not fully explain the observed teratogenic effects. We show here that DTCs cause malformations in zebrafish that highly resemble teratogenic effects observed by direct inhibition of a group of cuproenzymes termed lysyl oxidases (LOX). Additionally, we demonstrate that partial knockdown of three LOX genes, lox, loxl1 and loxl5b, sensitizes the developing embryo to DTC exposure. Finally, we show that DTCs directly inhibit zebrafish LOX activity in an ex vivo amine oxidase assay. Taken together, these results provide the first evidence that DTC induced teratogenic effects are, at least in part, caused by direct inhibition of LOX activity.

  11. Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents.

    PubMed

    Tan, Yee Seng; Ooi, Kah Kooi; Ang, Kok Pian; Akim, Abdah Md; Cheah, Yoke-Kqueen; Halim, Siti Nadiah Abdul; Seng, Hoi-Ling; Tiekink, Edward R T

    2015-09-01

    In the solid state each of three binuclear zinc dithiocarbamates bearing hydroxyethyl groups, {Zn[S2CN(R)CH2CH2OH]2}2 for R = iPr (1), CH2CH2OH (2), and Me (3), and an all alkyl species, [Zn(S2CNEt2)2]2 (4), features a centrosymmetric {ZnSCS}2 core with a step topology; both 1 and 3 were isolated as monohydrates. All compounds were broadly cytotoxic, specifically against human cancer cell lines compared with normal cells, with greater potency than cisplatin. Notably, some selectivity were indicated with 2 being the most potent against human ovarian carcinoma cells (cisA2780), and 4 being more cytotoxic toward multidrug resistant human breast carcinoma cells (MCF-7R), human colon adenocarcinoma cells (HT-29), and human lung adenocarcinoma epithelial cells (A549). Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis in HT-29 cells is demonstrated via both extrinsic and intrinsic pathways. Compounds 2-4 activate the p53 gene while 1 activates both p53 and p73. Cell cycle arrest at the S and G2/M phases correlates with inhibition of HT-29 cell growth. Cell invasion is also inhibited by 1-4 which is correlated with down-regulation of NF-κB.

  12. Triazole-dithiocarbamate based, selective LSD1 inactivators inhibit gastric cancer cell growth, invasion and migration

    PubMed Central

    Ma, Jin-Lian; Xu, Rui-Min; Zi, Xiaolin; Lv, Wen-Lei; Wang, Meng-Meng; Ye, Xian-Wei; Zhu, Shun; Mobley, David; Zhu, Yan-Yan; Wang, Jun-Wei; Li, Jin-Feng; Wang, Zhi-Ru; Zhao, Wen; Liu, Hong-Min

    2013-01-01

    Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression. The up-regulated LSD1's expression has been reported in several malignant tumors. In the current study, we designed and synthesized five series of 1, 2, 3-triazole-dithiocarbamate hybrids and screened their inhibitory activity toward LSD1. We found that some of these compounds, especially compound 26, exhibited the most specific and robust inhibition of LSD1. Interestingly, compound 26 also showed potent and selective cytotoxicity against LSD1 overexpressing gastric cancer cell lines MGC-803 and HGC-27, as well as marked inhibition of cell migration and invasion, compared to 2-PCPA. Furthermore, compound 26 effectively reduced the tumor growth bared by human gastric cancer cells in vivo with no signs of adverse side effects. These findings suggested that compound 26 deserves further investigation as a lead compound in the treatment of LSD1 overexpressing gastric cancer. PMID:24131029

  13. Dithiocarbamate-modified starch derivatives with high heavy metal adsorption performance.

    PubMed

    Xiang, Bo; Fan, Wen; Yi, Xiaowei; Wang, Zuohua; Gao, Feng; Li, Yijiu; Gu, Hongbo

    2016-01-20

    In this work, three types of dithiocarbamate (DTC)-modified starch derivatives including DTC starch (DTCS), DTC enzymolysis starch (DTCES) and DTC mesoporous starch (DTCMS) were developed, which showed the significant heavy metal adsorption performance. The adsorption ability of these three DTC modified starch derivatives followed the sequences: DTCMS>DTCES>DTCS. In single metal aqueous solutions, the uptake amount of heavy metal ions onto the modified starches obeyed the orders: Cu(II)>Ni(II)>Cr(VI)>Zn(II)>Pb(II). The adsorption mechanism was proved by the chelating between DTC groups and heavy metal ions through the pH effect measurements. A monolayer adsorption of Langmuir isotherm model for the adsorption of Cu(II) onto DTCMS was well fitted rather than the multilayer adsorption of Freundlich isotherm model. The adsorption kinetics of Cu(II) onto starch derivatives was found to be fit well with the pseudo-second-order model. Additionally, in the presence of EDTA, the adsorption ability and uptake amount of heavy metal ions onto these three DTC modified starch derivatives is identical with the results obtained in the absence of EDTA.

  14. Oxidation of dithiocarbamates to yield N-nitrosamines by water disinfection oxidants.

    PubMed

    Padhye, Lokesh P; Kim, Jae-Hong; Huang, Ching-Hua

    2013-02-01

    Two most commonly used dithiocarbamate (DTC) pesticides, dimethyldithiocarbamate (DMDTC) and diethyldithiocarbamate (DEDTC), were examined in this study to evaluate their potential to form nitrosamines when in contact with various water disinfection oxidants. Results show that DTCs can serve as nitrosamine precursors, by release of secondary amines through hydrolysis or through reactions with oxidants. The reactions of DTCs with monochloramine and ozone were found to be particularly problematic in the risk of generating nitrosamines, though all four tested oxidants, including free chlorine and chlorine dioxide, formed nitrosamines. NDEA yield from DEDTC was lower, by different degrees, than NDMA yield from DMDTC for all four oxidants, which was attributed to the steric hindrance associated with bulkier reaction intermediate that are more difficult to be further oxidized to form nitrosamine. The yield of nitrosamines increased with the oxidant dosage for both monochloramination and ozonation of DTCs. Results for nitrosamine formation from DTCs at varying pH were found to be consistent with the pH trend of nitrosamine formation from ozonation and monochloramination of secondary amines. Kinetic study results and identification and quantification of reaction products suggest that the DTCs were not significant direct precursors of nitrosamines during monochloramination or ozonation, but rather nitrosamines formed were primarily from reaction of oxidants with the amine which may be generated either through hydrolysis or through oxidation of DTCs.

  15. The effects of the endocrine disruptors dithiocarbamates on the mammalian ovary with particular regard to mancozeb.

    PubMed

    Cecconi, Sandra; Paro, Rita; Rossi, Gianna; Macchiarelli, Guido

    2007-01-01

    Many human-made chemicals are called endocrine disruptors (EDs) because they have the potential to disrupt endocrine functions in exposed organisms. Many EDs can disrupt hormonal homeostasis by interfering with hormone receptor recognition, binding and activation, while others act by still unknown mechanisms. Among the EDs specifically affecting the female reproductive system, those with steroidogenic/antisteroidogenic effects have been extensively studied and the mechanisms of toxicity clarified also at molecular level. For many others, information is restricted to few epidemiological data and in vivo/in vitro experiments with animal models. This is the case of the dithiocarbamates, and in particular of the fungicide mancozeb, an ethylenedithiocarbamate widely used to protect fruit and vegetables, ginseng included, because of its low acute toxicity in humans. Although the mechanism(s) by which mancozeb may specifically act on female reproductive organs are largely unknown, data on experimental animals in vivo have demonstrated that the fungicide can induce several disturbances on estrus cycle. When used in vitro at concentrations considered too low to cause human health injuries, the fungicide impairs mouse embryo development and meiotic spindle assembly. The possibility that the female germ cell (the oocyte) could be a specific target of mancozeb suggests a role for this fungicide as probable inductor of infertility also in exposed human populations.

  16. Pyrrolidine and Piperidine Formation Via Copper(II) Carboxylate Promoted Intramolecular Carboamination of Unactivated Olefins: Diastereoselectivity and Mechanism

    PubMed Central

    Sherman, Eric S.; Fuller, Peter H.; Kasi, Dhanalakshmi; Chemler, Sherry R.

    2008-01-01

    An expanded substrate scope and in depth analysis of the reaction mechanism of the copper(II) carboxylate promoted intramolecular carboamination of unactivated alkenes is described. This method provides access to N-functionalized pyrrolidines and piperidines. Both aromatic and aliphatic γ- and δ-alkenyl N-arylsulfonamides undergo the oxidative cyclization reaction efficiently. N-Benzoyl-2-allylaniline also underwent the oxidative cyclization. The terminal olefin substrates examined were more reactive than those with internal olefins, and the latter terminated in elimination rather than carbon-carbon bond formation. The efficiency of the reaction was enhanced by the use of more organic soluble copper(II) carboxylate salts, copper(II) neodecanoate in particular. The reaction times were reduced by the use of microwave heating. High levels of diastereoselectivity were observed in the synthesis of 2,5-disubstituted pyrrolidines, wherein the cis substitution pattern predominates. The mechanism of the reaction is discussed in the context of the observed reactivity and in comparison to analogous reactions promoted by other reagents and conditions. Our evidence supports a mechanism wherein the N-C bond is formed via intramolecular syn aminocupration and the C-C bond is formed via intramolecular addition of a primary carbon radical to an aromatic ring. PMID:17428100

  17. Pharmacokinetics and metabolism of N-(2-hydroxyethyl)-2,5-[14C]-pyrrolidine (HEP, Epolamine) in male healthy volunteers.

    PubMed

    Giachetti, C; Assandri, A; Mautone, G; Tajana, E; Palumbo, B; Palumbo, R

    1996-01-01

    N-(2-hydroxyethyl)-pyrrolidine (HEP, Epolamine) is a strong base used to salify organic acids of pharmaceutical interest in order to improve their solubility in water. Diclofenac-HEP (Flector) is the first example of an epolamine salt of a drug. In this study, [14C]-HEP was administered by oral route (300 mg, about 50 microCi/subject) to 3 volunteers with the aim to investigate its plasma profile and to calculate the relevant pharmacokinetic parameters. The experimental data correlated with a two-compartment pharmacokinetic model. Total radioactivity in urine and faeces was also measured. The radioactivity was excreted preferentially by the faecal route (about 65% of the dose administered in the 0-72 h collection interval). Urinary excretion accounted for about 30% of the dose and occurred very rapidly (about 22% of the dose was in the 0-8 h collection interval). Metabolic investigations were carried out on urine samples. TLC analysis with radioscan detector indicated a main radioactive zone, accounting for about 98% of the radioactivity in the plate. After scraping off and purification of the radioactive areas, the compound isolated (Met I) was analysed by gas chromatography-mass spectrometry with electron-impact ionization process. The structure of the metabolite was postulated to be pyrrolidine N-oxide.

  18. 1-(5-Bromo-4-phenyl-1,3-thia­zol-2-yl)pyrrolidin-2-one

    PubMed Central

    Ghabbour, Hazem A.; Kadi, Adnan A.; El-Subbagh, Hussein I.; Chia, Tze Shyang; Fun, Hoong-Kun

    2012-01-01

    The asymmetric unit of the title compound, C13H11BrN2OS, consists of two crystallographically independent mol­ecules (A and B). In each mol­ecule, the pyrrolidine ring adopts an envelope conformation with a methyl­ene C atom as the flap atom. In mol­ecule A, the central thia­zole ring makes a dihedral angle of 36.69 (11)° with the adjacent phenyl ring, whereas the corresponding angle is 36.85 (12)° in mol­ecule B. The pyrrolidine ring is slightly twisted from the thia­zole ring, with C—N—C—N torsion angles of 4.8 (3) and 3.0 (4)° in mol­ecules A and B, respectively. In the crystal, C—H⋯π and π–π [centroid-to-centroid distance = 3.7539 (14) Å] inter­actions are observed. The crystal studied was a pseudo-merohedral twin with twin law (-100 0-10 101) and a refined component ratio of 0.7188 (5):0.2812 (5). PMID:22719524

  19. Validation of a GC-MS method for the estimation of dithiocarbamate fungicide residues and safety evaluation of mancozeb in fruits and vegetables.

    PubMed

    Mujawar, Sumaiyya; Utture, Sagar C; Fonseca, Eddie; Matarrita, Jessie; Banerjee, Kaushik

    2014-05-01

    A sensitive and rugged residue analysis method was validated for the estimation of dithiocarbamate fungicides in a variety of fruit and vegetable matrices. The sample preparation method involved reaction of dithiocarbamates with Tin(II) chloride in aqueous HCl. The CS2 produced was absorbed into an isooctane layer and estimated by GC-MS selected ion monitoring. Limit of quantification (LOQ) was ⩽40μgkg(-1) for grape, green chilli, tomato, potato, brinjal, pineapple and chayote and the recoveries were within 75-104% (RSD<15% at LOQ). The method could be satisfactorily applied for analysis of real world samples. Dissipation of mancozeb, the most-used dithiocarbamate fungicide, in field followed first+first order kinetics with pre-harvest intervals of 2 and 4days in brinjal, 7 and 10days in grapes and 0day in chilli at single and double dose of agricultural applications. Cooking practices were effective for removal of mancozeb residues from vegetables.

  20. Phosphine-Catalyzed Enantioselective [2+4] Cycloaddition to Synthesize Pyrrolidin-2-one Fused Dihydropyrans Using α-Substituted Allenoates as C2 Synthons.

    PubMed

    Wang, Chang; Jia, Hao; Zhang, Cheng; Gao, Zhenzhen; Zhou, Leijie; Yuan, Chunhao; Xiao, Yumei; Guo, Hongchao

    2017-01-06

    A bifunctional phosphine-catalyzed highly enantioselective [2+4] cycloaddition of α-substituted allenoates with (E)-1-benzyl-4-olefinicpyrrolidine-2,3-diones has been achieved, giving pyrrolidin-2-one fused dihydropyran derivatives in moderate to good yields with excellent enantioselectivities (up to 98% ee). This reaction provides a useful catalytic asymmetric access to dihydropyran structural motifs.

  1. Extraction of haptens from solid products and their delivery to the skin, exemplified by dithiocarbamates from rubber gloves.

    PubMed

    Bergendorff, O; Persson, C; Hansson, C

    2005-07-01

    Allergic contact dermatitis is often caused by solid products such as rubber gloves. Patch testing with the product as is often gives negative results. Extraction of the haptens into an organic solvent is commonly performed to achieve a more correct investigation. The technique used for extraction of haptens from solid materials is only sporadically described. In this study, we investigated and optimized the yields of dithiocarbamates obtained by extraction from rubber gloves. The influence of solvent, extraction time and the procedures for extraction are evaluated. The delivery of zinc dibutyldithiocarbamate from the patch test preparation to the skin is determined.

  2. Study of sulfur adlayers on Au(1 1 1) from basic hydrolysis of piperazine bis(dithiocarbamate) sodium salt

    NASA Astrophysics Data System (ADS)

    Martínez, Javier A.; Valenzuela, José; Hernandez-Tamargo, Carlos E.; Cao-Milán, Roberto; Herrera, José A.; Díaz, Jesús A.; Farías, Mario H.; Mikosch, Hans; Hernández, Mayra P.

    2015-08-01

    Sulfur adlayers on Au(1 1 1) were obtained after the interaction of a gold substrate with an alkaline solution of piperazine bis(dithiocarbamate) sodium salt. Characterization of the sulfur modified gold surface was performed by means of X-Ray Photoelectron Spectroscopy (XPS), Scanning Tunneling Microscopy (STM) and Density Functional Theory (DFT) calculations. XPS signals indicated the presence of S-Au bonds, monomeric and polymeric sulfur, and absence of nitrogen and sodium. Images from STM showed the formation of quasi-rectangular octomers in coexistence with another phase. A DFT model using the arrangement of sulfur dimers on the Au(1 1 1) surface effectively reproduced the experimental STM images.

  3. Molecular Mechanisms of Allosteric Inhibition of Brain Glycogen Phosphorylase by Neurotoxic Dithiocarbamate Chemicals.

    PubMed

    Mathieu, Cécile; Bui, Linh-Chi; Petit, Emile; Haddad, Iman; Agbulut, Onnik; Vinh, Joelle; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2017-02-03

    Dithiocarbamates (DTCs) are important industrial chemicals used extensively as pesticides and in a variety of therapeutic applications. However, they have also been associated with neurotoxic effects and in particular with the development of Parkinson-like neuropathy. Although different pathways and enzymes (such as ubiquitin ligases or the proteasome) have been identified as potential targets of DTCs in the brain, the molecular mechanisms underlying their neurotoxicity remain poorly understood. There is increasing evidence that alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. Interestingly, recent studies with N,N-diethyldithiocarbamate suggest that brain glycogen phosphorylase (bGP) and glycogen metabolism could be altered by DTCs. Here, we provide molecular and mechanistic evidence that bGP is a target of DTCs. To examine this system, we first tested thiram, a DTC pesticide known to display neurotoxic effects, observing that it can react rapidly with bGP and readily inhibits its glycogenolytic activity (kinact = 1.4 × 10(5) m(-1) s(-1)). Using cysteine chemical labeling, mass spectrometry, and site-directed mutagenesis approaches, we show that thiram (and certain of its metabolites) alters the activity of bGP through the formation of an intramolecular disulfide bond (Cys(318)-Cys(326)), known to act as a redox switch that precludes the allosteric activation of bGP by AMP. Given the key role of glycogen metabolism in brain functions and neurodegeneration, impairment of the glycogenolytic activity of bGP by DTCs such as thiram may be a new mechanism by which certain DTCs exert their neurotoxic effects.

  4. Complexity.

    PubMed

    Gómez-Hernández, J Jaime

    2006-01-01

    It is difficult to define complexity in modeling. Complexity is often associated with uncertainty since modeling uncertainty is an intrinsically difficult task. However, modeling uncertainty does not require, necessarily, complex models, in the sense of a model requiring an unmanageable number of degrees of freedom to characterize the aquifer. The relationship between complexity, uncertainty, heterogeneity, and stochastic modeling is not simple. Aquifer models should be able to quantify the uncertainty of their predictions, which can be done using stochastic models that produce heterogeneous realizations of aquifer parameters. This is the type of complexity addressed in this article.

  5. Enantioselective Construction of Pyrrolidines by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of Trimethylenemethane with Imines

    PubMed Central

    Trost, Barry M.; Silverman, Steven M.

    2012-01-01

    A protocol for the enantioselective [3+2] cycloaddition of trimethylenemethane (TMM) with imines has been developed. Central to this effort were the novel phosphoramidite ligands developed in our laboratories. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of imine acceptors to provide the corresponding pyrrolidine cycloadducts with excellent yields and selectivities. Use of a bis-2-naphthyl phosphoramidite allowed the successful cycloaddition of the parent TMM with N-Boc imines, and has further permitted the reaction of substituted donors with N-tosyl aldimines and ketimines in high regio-, diastereo-, and enantioselectivity. Use of a diphenylazetidine ligand allows the complimentary synthesis of the exocyclic nitrile product shown, and we demonstrate control of the regioselectivity of the product based on manipulation of the reaction parameters. PMID:22309214

  6. Structure sensitive normal coordinate analysis of metal-diethyldithiocarbamate - complexes

    NASA Astrophysics Data System (ADS)

    Mikosch, H.; Bauer, G.; Kellner, R.; Trendafilova, N. S.; St. Nikolov, G.

    1986-03-01

    Symmetry changes in the course of dissolution are assumed to produce frequency shifts in molecular spectra of N, N-Disubstituted Dithiocarbamates. Using (mass-weighted) cartesian coordinates it is possible to calculate eigenvalues both for the site- and the molecular symmetry. Calculated shifts for Cu- and Zn- complexes are of the same order of magnitude as experimental results and calculation of frequencies even for assumed structures is possible.

  7. Dietary exposure assessment of Danish consumers to dithiocarbamate residues in food: a comparison of the deterministic and probabilistic approach.

    PubMed

    Jensen, B H; Andersen, J H; Petersen, A; Christensen, T

    2008-06-01

    Probabilistic and deterministic estimates of the acute and chronic exposure of the Danish populations to dithiocarbamate residues were performed. The Monte Carlo Risk Assessment programme (MCRA 4.0) was used for the probabilistic risk assessment. Food consumption data were obtained from the nationwide dietary survey conducted in 2000--02. Residue data for 5721 samples from the monitoring programme conducted in the period 1998--2003 were used for dithiocarbamates, which had been determined as carbon disulphide. Contributions from 26 commodities were included in the calculations. Using the probabilistic approach, the daily acute intakes at the 99.9% percentile for adults and children were 11.2 and 28.2 microg kg(-1) body weight day(-1), representing 5.6% and 14.1% of the ARfD for maneb, respectively. When comparing the point estimate approach with the probabilistic approach, the outcome of the point estimate calculations was generally higher or comparable with the outcome of the probabilistic approach at the 99.9 percentile (consumers only). The chronic exposures for adults and children were 0.35 and 0.76 microg kg(-1) body weight day(-1) at the 99.9 percentile, representing 0.7% and 1.5%, respectively, of the acceptable daily intake for mancozeb and maneb at 50 microg kg(-1) body weight.

  8. Synthesis of a novel silica-supported dithiocarbamate adsorbent and its properties for the removal of heavy metal ions.

    PubMed

    Bai, Lan; Hu, Huiping; Fu, Weng; Wan, Jia; Cheng, Xiliang; Zhuge, Lei; Xiong, Lei; Chen, Qiyuan

    2011-11-15

    Silica-supported dithiocarbamate adsorbent (Si-DTC) was synthesized by anchoring the chelating agent of macromolecular dithiocarbamate (MDTC) to the chloro-functionalized silica matrix (SiCl), as a new adsorbent for adsorption of Pb(II), Cd(II), Cu(II) and Hg(II) from aqueous solution. The surface characterization was performed by FT-IR, XPS, SEM and elemental analysis indicating that the modification of the silica surface was successfully performed. The effects of media pH, adsorption time, initial metal ion concentration and adsorption temperature on adsorption capacity of the adsorbent had been investigated. Experimental data were exploited for kinetic and thermodynamic evaluations related to the adsorption processes. The characteristics of the adsorption process were evaluated by using the Langmuir, Freundlich and Dubinin-Radushkevich (D-R) adsorption isotherms and adsorption capacities were found to be 0.34 mmol g(-1), 0.36 mmol g(-1), 0.32 mmol g(-1) and 0.40 mmol g(-1) for Pb(II), Cd(II), Cu(II) and Hg(II), respectively. The adsorption mechanism of Hg(II) onto Si-DTC is quite different from that of Pb(II), Cd(II) or Cu(II) onto Si-DTC, which is demonstrated by the XPS and FT-IR results.

  9. Biomimetic synthesis of highly biocompatible gold nanoparticles with amino acid-dithiocarbamate as a precursor for SERS imaging

    NASA Astrophysics Data System (ADS)

    Li, Li; Liu, Jianbo; Yang, Xiaohai; Huang, Jin; He, Dinggeng; Guo, Xi; Wan, Lan; He, Xiaoxiao; Wang, Kemin

    2016-03-01

    Amino acid-dithiocarbamate (amino acid-DTC) was developed as both the reductant and ligand stabilizer for biomimetic synthesis of gold nanoparticles (AuNPs), which served as an excellent surface-enhanced Raman scattering (SERS) contrast nanoprobe for cell imaging. Glycine (Gly), glutamic acid (Glu), and histidine (His) with different isoelectric points were chosen as representative amino acid candidates to synthesize corresponding amino acid-DTC compounds through mixing with carbon disulfide (CS2), respectively. The pyrogenic decomposition of amino acid-DTC initiated the reduction synthesis of AuNPs, and the strong coordinating dithiocarbamate group of amino acid-DTC served as a stabilizer that grafted onto the surface of the AuNPs, which rendered the as-prepared nanoparticles a negative surface charge and high colloidal stability. MTT cell viability assay demonstrated that the biomimetic AuNPs possessed neglectful toxicity to the human hepatoma cell, which guaranteed them good biocompatibility for biomedical application. Meanwhile, the biomimetic AuNPs showed a strong SERS effect with an enhancement factor of 9.8 × 105 for the sensing of Rhodamine 6G, and two distinct Raman peaks located at 1363 and 1509 cm-1 could be clearly observed in the cell-imaging experiments. Therefore, biomimetic AuNPs can be explored as an excellent SERS contrast nanoprobe for biomedical imaging, and the amino acid-DTC mediated synthesis of the AuNPs has a great potential in bio-engineering and biomedical imaging applications.

  10. Crystal structure of methyl 3'-benzamido-4'-(4-meth-oxy-phen-yl)-1'-methyl-spiro-[indeno-[1,2-b]quinoxaline-11,2'-pyrrolidine]-3'-carboxyl-ate.

    PubMed

    Chandralekha, Kuppan; Sureshbabu, Adukamparai Rajukrishnan; Gavaskar, Deivasigamani; Lakshmi, Srinivasakannan

    2016-09-01

    In the title compound, C35H30N4O3, the spiro C atom connects the five-membered pyrrolidine ring and the indeno-quinoxaline ring system. The pyrrolidine ring adopts a twist conformation. An intra-molecular N-H⋯N inter-action between the amino group and the pyrazine ring is observed. In the crystal, mol-ecules are linked by a pairs of C-H⋯O hydrogen bonds, forming inversion dimers.

  11. Hydrido copper clusters supported by dithiocarbamates: oxidative hydride removal and neutron diffraction analysis of [Cu7(H){S2C(aza-15-crown-5)}6].

    PubMed

    Liao, Ping-Kuei; Fang, Ching-Shiang; Edwards, Alison J; Kahlal, Samia; Saillard, Jean-Yves; Liu, C W

    2012-06-18

    Reactions of Cu(I) salts with Na(S(2)CR) (R = N(n)Pr(2), NEt(2), aza-15-crown-5), and (Bu(4)N)(BH(4)) in an 8:6:1 ratio in CH(3)CN solution at room temperature yield the monocationic hydride-centered octanuclear Cu(I) clusters, [Cu(8)(H){S(2)CR}(6)](PF(6)) (R = N(n)Pr(2), 1(H); NEt(2), 2(H); aza-15-crown-5, 3(H)). Further reactions of [Cu(8)(H){S(2)CR}(6)](PF(6)) with 1 equiv of (Bu(4)N)(BH(4)) produced neutral heptanuclear copper clusters, [Cu(7)(H){S(2)CR}(6)] (R = N(n)Pr(2), 4(H); NEt(2), 5(H); aza-15-crown-5, 6(H)) and clusters 4-6 can also be generated from the reaction of Cu(BF(4))(2), Na(S(2)CR), and (Bu(4)N)(BH(4)) in a 7:6:8 molar ratio in CH(3)CN. Reformation of cationic Cu(I)(8) clusters by adding 1 equiv of Cu(I) salt to the neutral Cu(7) clusters in solution is observed. Intriguingly, the central hydride in [Cu(8)(H){S(2)CN(n)Pr(2)}(6)](PF(6)) can be oxidatively removed as H(2) by Ce(NO(3))(6)(2-) to yield [Cu(II)(S(2)CN(n)Pr(2))(2)] exploiting the redox-tolerant nature of dithiocarbamates. Regeneration of hydride-centered octanuclear copper clusters from the [Cu(II)(S(2)CN(n)Pr(2))(2)] can be achieved by reaction with Cu(I) ions and borohydride. The hydride release and regeneration of Cu(I)(8) was monitored by UV-visible titration experiments. To our knowledge, this is the first time that hydride encapsulated within a copper cluster can be released as H(2) via chemical means. All complexes have been fully characterized by (1)H NMR, FT-IR, UV-vis, and elemental analysis, and molecular structures of 1(H), 2(H), and 6(H) were clearly established by single-crystal X-ray diffraction. Both 1(H) and 2(H) exhibit a tetracapped tetrahedral Cu(8) skeleton, which is inscribed within a S(12) icosahedron constituted by six dialkyl dithiocarbamate ligands in a tetrametallic-tetraconnective (μ(2), μ(2)) bonding mode. The copper framework of 6(H) is a tricapped distorted tetrahedron in which the four-coordinate hydride is demonstrated to occupy the central site by

  12. Spiro[pyrrolidine-3, 3´-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification

    NASA Astrophysics Data System (ADS)

    Hati, Santanu; Tripathy, Sayantan; Dutta, Pratip Kumar; Agarwal, Rahul; Srinivasan, Ramprasad; Singh, Ashutosh; Singh, Shailja; Sen, Subhabrata

    2016-08-01

    The spiro[pyrrolidine-3, 3´-oxindole] moiety is present as a core in number of alkaloids with substantial biological activities. Here in we report design and synthesis of a library of compounds bearing spiro[pyrrolidine-3, 3´-oxindole] motifs that demonstrated exceptional inhibitory activity against the proliferation of MCF-7 breast cancer cells. The synthesis involved a one pot Pictet Spengler-Oxidative ring contraction of tryptamine to the desired scaffolds and occurred in 1:1 THF and water with catalytic trifluoroacetic acid and stoichiometric N-bromosuccinimide as an oxidant. Phenotypic profiling indicated that these molecules induce apoptotic cell death in MCF-7 cells. Target deconvolution with most potent compound 5l from the library, using chemical proteomics indicated histone deacetylase 2 (HDAC2) and prohibitin 2 as the potential cellular binding partners. Molecular docking of 5l with HDAC2 provided insights pertinent to putative binding interactions.

  13. Spiro[pyrrolidine-3, 3´-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification

    PubMed Central

    Hati, Santanu; Tripathy, Sayantan; Dutta, Pratip Kumar; Agarwal, Rahul; Srinivasan, Ramprasad; Singh, Ashutosh; Singh, Shailja; Sen, Subhabrata

    2016-01-01

    The spiro[pyrrolidine-3, 3´-oxindole] moiety is present as a core in number of alkaloids with substantial biological activities. Here in we report design and synthesis of a library of compounds bearing spiro[pyrrolidine-3, 3´-oxindole] motifs that demonstrated exceptional inhibitory activity against the proliferation of MCF-7 breast cancer cells. The synthesis involved a one pot Pictet Spengler-Oxidative ring contraction of tryptamine to the desired scaffolds and occurred in 1:1 THF and water with catalytic trifluoroacetic acid and stoichiometric N-bromosuccinimide as an oxidant. Phenotypic profiling indicated that these molecules induce apoptotic cell death in MCF-7 cells. Target deconvolution with most potent compound 5l from the library, using chemical proteomics indicated histone deacetylase 2 (HDAC2) and prohibitin 2 as the potential cellular binding partners. Molecular docking of 5l with HDAC2 provided insights pertinent to putative binding interactions. PMID:27573798

  14. Variation of the Molecular Conformation, Shape, and Cavity Size in Dinuclear Metalla-Macrocycles Containing Hetero-Ditopic Dithiocarbamate-Carboxylate Ligands from a Homologous Series of N-Substituted Amino Acids.

    PubMed

    Torres-Huerta, Aaron; Cruz-Huerta, Jorge; Höpfl, Herbert; Hernández-Vázquez, Luis G; Escalante-García, Jaime; Jiménez-Sánchez, Arturo; Santillan, Rosa; Hernández-Ahuactzi, Irán F; Sánchez, Mario

    2016-12-05

    A homologous series of dithiocarbamate ligands derived from N-substituted amino acids was reacted with different diorganotin dichlorides to give 18 diorganotin complexes. Spectroscopic and mass spectrometric analysis evidenced the formation of assemblies with six-coordinate tin atoms embedded in skewed-trapezoidal bipyramidal coordination environments of composition C2SnS2O2. Single-crystal X-ray diffraction analysis for three of the compounds revealed a one-dimensional polymeric structure for the complex with the ligand derived from 5-aminopentanoic acid, which through further intermolecular Sn···O interactions generated an overall two-dimensional coordination polymer containing 40-membered hexanuclear tin macrocycles. On the contrary, the ligands derived from 6-aminohexanoic and 8-aminooctanoic acid provided the expected 22- and 26-membered dinuclear macrocyclic structures. Density functional theory calculations for a representative series of macrocyclic complexes of composition [Me2SnLx]2 with Lx = ¯S2CN(Me)-(CH2)x-COO¯ (x = 3-12) enabled a detailed analysis of the variations in the molecular conformation, shape, and cavity size of the macrocycles in dependence of the aliphatic spacer. Because of odd-even effects, the difunctional ligands can adopt either a curved or a twisted-pincer shape, while the SnSxO4-x (x = 0-4) moieties can act either as linear or angular tectons with varying connectivity angles.

  15. Synthesis and characterization of the novel fluorescent prolyl oligopeptidase inhibitor 4-fluoresceinthiocarbamoyl-6-aminocaproyl-L-prolyl-2(S)-(hydroxyacetyl)pyrrolidine.

    PubMed

    Venäläinen, Jarkko I; Wallén, Erik A A; Poso, Antti; García-Horsman, J Arturo; Männistö, Pekka T

    2005-11-17

    The synthesis and characterization of the first fluorescent prolyl oligopeptidase inhibitor 4-fluoresceinthiocarbamoyl-6-aminocaproyl-L-prolyl-2(S)-(hydroxyacetyl)pyrrolidine is described. This compound has an IC50 value of 0.83 nM and a dissociation half-life of 160 min, and its fluorescence signal is detectable using standard filters for fluorescein. These properties make this compound a suitable probe for visualizing prolyl oligopeptidase in various applications.

  16. Synthesis of Pyrrolidines and Pyrrolizidines with α-Pseudoquaternary Centers by Copper-Catalyzed Condensation of α-Diazodicarbonyl Compounds and Aryl γ-Lactams.

    PubMed

    Goudedranche, Sébastien; Besnard, Céline; Egger, Léo; Lacour, Jérôme

    2016-10-24

    N-aryl γ-lactams react intermolecularly with acceptor-acceptor diazo reagents, usually dicarbonyl compounds, in a copper-catalyzed process to yield functionalized pyrrolidines with α-pseudoquaternary centers. As 1,2-acyl or -phosphoryl migration is preferred, single regioisomers are obtained. Furthermore, in the presence of a Lewis acid, subsequent Friedel-Crafts reactions yield tricyclic pyrrolizidines in excellent yields (90-96 %) and diastereoselectivities (up to >20:1).

  17. Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734 821 Pyrrolidine Bis-piperazines

    PubMed Central

    2015-01-01

    The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17 340 to 4 879 681 compounds) for analgesia directly in the mouse tail withdrawal model. The “all X” mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using the Comprehensive Laboratory Animal Monitoring System (CLAMS). The TPI-1954 library is a pyrrolidine bis-piperazine and totals 738 192 compounds. This library has 26 functionalities at the first three positions of diversity made up of 28 392 compounds each (26 × 26 × 42) and 42 functionalities at the fourth made up of 19 915 compounds each (26 × 26 × 26). The 120 resulting mixtures representing each of the variable four positions were screened directly in vivo in the mouse 55 °C warm-water tail-withdrawal assay (ip administration). The 120 samples were then ranked in terms of their antinociceptive activity. The synthesis of 54 individual compounds was then carried out. Nine of the individual compounds produced dose-dependent antinociception equivalent to morphine. In practical terms what this means is that one would not expect multiexponential increases in activity as we move from the all-X mixture, to the positional scanning libraries, to the individual compounds. Actually because of the systematic formatting one would typically anticipate steady increases in activity as the complexity of the mixtures is reduced. This is in fact what we see in the current study. One of the final individual compounds identified, TPI 2213-17, lacked significant

  18. Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734,821 Pyrrolidine Bis-piperazines.

    PubMed

    Houghten, Richard A; Ganno, Michelle L; McLaughlin, Jay P; Dooley, Colette T; Eans, Shainnel O; Santos, Radleigh G; LaVoi, Travis; Nefzi, Adel; Welmaker, Greg; Giulianotti, Marc A; Toll, Lawrence

    2016-01-11

    The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17,340 to 4,879,681 compounds) for analgesia directly in the mouse tail withdrawal model. The "all X" mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using the Comprehensive Laboratory Animal Monitoring System (CLAMS). The TPI-1954 library is a pyrrolidine bis-piperazine and totals 738,192 compounds. This library has 26 functionalities at the first three positions of diversity made up of 28,392 compounds each (26 × 26 × 42) and 42 functionalities at the fourth made up of 19,915 compounds each (26 × 26 × 26). The 120 resulting mixtures representing each of the variable four positions were screened directly in vivo in the mouse 55 °C warm-water tail-withdrawal assay (ip administration). The 120 samples were then ranked in terms of their antinociceptive activity. The synthesis of 54 individual compounds was then carried out. Nine of the individual compounds produced dose-dependent antinociception equivalent to morphine. In practical terms what this means is that one would not expect multiexponential increases in activity as we move from the all-X mixture, to the positional scanning libraries, to the individual compounds. Actually because of the systematic formatting one would typically anticipate steady increases in activity as the complexity of the mixtures is reduced. This is in fact what we see in the current study. One of the final individual compounds identified, TPI 2213-17, lacked significant respiratory

  19. Design, synthesis and antiproliferative activity studies of novel 1,2,3-triazole-dithiocarbamate-urea hybrids.

    PubMed

    Duan, Ying-Chao; Zheng, Yi-Chao; Li, Xiao-Chen; Wang, Meng-Meng; Ye, Xian-Wei; Guan, Yuan-Yuan; Liu, Gai-Zhi; Zheng, Jia-Xin; Liu, Hong-Min

    2013-06-01

    A series of novel 1,2,3-triazole-dithiocarbamate-urea hybrids were designed, synthesized and their antiproliferative activities against four selected human cancer cell lines were evaluated. The results showed that a number of the hybrids exhibited potent activity in selected human cancer cell lines. Among them, compounds 27 and 34 showed broad spectrum anticancer activity with IC50 values ranging from 1.62 to 20.84 μM and 0.76 to 13.55 μM, respectively. Interestingly, compounds 27 and 34, being very potent against MGC-803 cells, exhibited no significant cytotoxicity against normal human embryonic kidney cells at up to 55 μM and 70 μM, respectively. Evidences of cell cycle arrest and apoptosis induction were obtained for the most effective compounds 27 and 34 by means of flow cytometry and microscopic techniques.

  20. Visual Identification of Light-Driven Breakage of the Silver-Dithiocarbamate Bond by Single Plasmonic Nanoprobes

    PubMed Central

    Gao, Peng Fei; Yuan, Bin Fang; Gao, Ming Xuan; Li, Rong Sheng; Ma, Jun; Zou, Hong Yan; Li, Yuan Fang; Li, Ming; Huang, Cheng Zhi

    2015-01-01

    Insight into the nature of metal-sulfur bond, a meaningful one in life science, interface chemistry and organometallic chemistry, is interesting but challenging. By utilizing the localized surface plasmon resonance properties of silver nanoparticles, herein we visually identified the photosensitivity of silver-dithiocarbamate (Ag-DTC) bond by using dark field microscopic imaging (iDFM) technique at single nanoparticle level. It was found that the breakage of Ag-DTC bond could be accelerated effectively by light irradiation, followed by a pH-dependent horizontal or vertical degradation of the DTC molecules, in which an indispensable preoxidation process of the silver was at first disclosed. These findings suggest a visualization strategy at single plasmonic nanoparticle level which can be excellently applied to explore new stimulus-triggered reactions, and might also open a new way to understand traditional organic reaction mechanisms. PMID:26493773

  1. CS(2) blinds in Brassica crops: false positive results in the dithiocarbamate residue analysis by the acid digestion method.

    PubMed

    Perz, R C; van Lishaut, H; Schwack, W

    2000-03-01

    Various members of the Brassicaceae family (cauliflower, savoy cabbage, red cabbage, turnip-rooted cabbage) grown without any application of pesticides were analyzed according to the acid digestion method commonly used for the determination of dithiocarbamate fungicide residues. Depending on postharvest treatments, high non-anthropogenic CS(2) values up to 4 mg/kg were found in some cases, especially in frozen raw cabbage samples, exceeding maximum residue limits. To explore phytogenic CS(2) occurrences, two model substances (phenylisothiocyanate and methyl tryptaminedithiocarbamate) representing natural mustard oils and brassinines, respectively, were analyzed for their acid hydrolysis decomposition products. In both cases, COS was found generally, but CS(2) was readily formed during acid digestion, too, when sulfides were present. The results obtained clearly demonstrate that CS(2) values determined by using the acid digestion method of crops rich in secondary metabolism sulfur compounds have to be interpreted carefully.

  2. Effect of additives on Hg2+ reduction and precipitation inhibited by sodium dithiocarbamate in simulated flue gas desulfurization solutions.

    PubMed

    Lu, Rongjie; Hou, Jiaai; Xu, Jiang; Tang, Tingmei; Xu, Xinhua

    2011-11-30

    Mercury (II) (Hg(2+)) ion can be reduced by aqueous S(IV) (sulfite and/or bisulfite) species, which leads to elemental mercury (Hg(0)) emissions in wet flue gas desulfurization (FGD) systems. Numerous reports have demonstrated the high trapping efficiency of sodium dithiocarbamate over heavy metals. In this paper, a novel sodium dithiocarbamate, DTCR, was utilized as a precipitator to control Hg(2+) reduction and Hg(0) emission against S(IV) in FGD solutions. Results indicated that Hg(2+) reduction efficiency decreased dramatically while precipitation rate peaked at around 91.0% in consistence with the increment of DTCR dosage. Initial pH and temperature had great inhibitory effects on Hg(2+) reduction: the Hg(2+) removal rate gradually increased and reached a plateau along with the increment of temperature and initial pH value. Chloride played a key role in Hg(2+) reduction and precipitation reactions. When Cl(-) concentration increased from 0 to 150 mM, Hg(2+) removal rate dropped from 93.84% to 86.05%, and the Hg(2+) reduction rate remained at a low level (<7.8%). SO(4)(2-), NO(3)(-) and other common metal ions would affect the efficiency of Hg(2+) reduction and precipitation reactions in the simulated desulfurization solutions: Hg(2+) removal rate could always be above 90%, while Hg(2+) reduction rate was maintained at below 10%. The predominance of DTCR over aqueous S(IV), indicated by the results above, has wide industrial applications in FGD systems.

  3. Biomimetic synthesis of highly biocompatible gold nanoparticles with amino acid-dithiocarbamate as a precursor for SERS imaging.

    PubMed

    Li, Li; Liu, Jianbo; Yang, Xiaohai; Huang, Jin; He, Dinggeng; Guo, Xi; Wan, Lan; He, Xiaoxiao; Wang, Kemin

    2016-03-11

    Amino acid-dithiocarbamate (amino acid-DTC) was developed as both the reductant and ligand stabilizer for biomimetic synthesis of gold nanoparticles (AuNPs), which served as an excellent surface-enhanced Raman scattering (SERS) contrast nanoprobe for cell imaging. Glycine (Gly), glutamic acid (Glu), and histidine (His) with different isoelectric points were chosen as representative amino acid candidates to synthesize corresponding amino acid-DTC compounds through mixing with carbon disulfide (CS2), respectively. The pyrogenic decomposition of amino acid-DTC initiated the reduction synthesis of AuNPs, and the strong coordinating dithiocarbamate group of amino acid-DTC served as a stabilizer that grafted onto the surface of the AuNPs, which rendered the as-prepared nanoparticles a negative surface charge and high colloidal stability. MTT cell viability assay demonstrated that the biomimetic AuNPs possessed neglectful toxicity to the human hepatoma cell, which guaranteed them good biocompatibility for biomedical application. Meanwhile, the biomimetic AuNPs showed a strong SERS effect with an enhancement factor of 9.8 × 10(5) for the sensing of Rhodamine 6G, and two distinct Raman peaks located at 1363 and 1509 cm(-1) could be clearly observed in the cell-imaging experiments. Therefore, biomimetic AuNPs can be explored as an excellent SERS contrast nanoprobe for biomedical imaging, and the amino acid-DTC mediated synthesis of the AuNPs has a great potential in bio-engineering and biomedical imaging applications.

  4. Low polydispersity (N-ethyl pyrrolidine methacrylamide-co-1-vinylimidazole) linear oligomers for gene therapy applications.

    PubMed

    Velasco, D; Réthoré, G; Newland, B; Parra, J; Elvira, C; Pandit, A; Rojo, L; San Román, J

    2012-11-01

    Nonviral methods for gene delivery are becoming ever more prevalent along with the need to design new vectors that are highly effective, stable in biological fluids, inexpensive, and facile to produce. Here, we synthesize our previously reported monomer N-ethyl pyrrolidine methacrylamide (EPA) and evaluate its effectiveness in gene vector applications when copolymerized with 1-vinylimidazole (VI). A range of these novel linear cationic copolymers were synthesized via free radical polymerization with low molecular weights (oligomers) and low polydispersities showing two pK(a) values as the two co-monomers are cationic. DNA-polymer polyplexes had average sizes between 100 and 250nm and zeta-potentials between 10 and 25mV, and a strong dependence of composition on the size on the zeta-potential was observed. The cytotoxicity of the homopolymers, oligomers, and polyplexes toward human fibroblasts and 3T3 mouse fibroblasts was evaluated using the MTT and AlamarBlue™ assays, proving that formulations could be made with toxicity as low as low molecular weight linear poly (dimethylaminoethyl methacrylate) (PDMAEMA). The transfection capability of the polyplexes measured using the G-luciferase marker gene far superseded PDMAEMA when evaluated in biological conditions. Furthermore, blood compatibility studies showed that these new oligomers exhibit no significant hemolysis or platelet activation above PBS controls. These new EPA based oligomers with low toxicity and ease of scalability show high transfection abilities in serum conditions, and blood compatibility showing its potential for systemic gene delivery applications.

  5. Synthesis of first ever 4-quinolone-3-carboxylic acid-appended spirooxindole-pyrrolidine derivatives and their biological applications.

    PubMed

    Arasakumar, Thangaraj; Mathusalini, Sadasivam; Ata, Athar; Shankar, Ramasamy; Gopalan, Subashini; Lakshmi, Krishnasamy; Sakthivel, Pandiyarajan; Mohan, Palathurai Subramaniam

    2017-02-01

    A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including [Formula: see text], [Formula: see text], 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a-r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f [Formula: see text] showed significant cytotoxic activity compared to the standard drug doxorubicin [Formula: see text].

  6. Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1.

    PubMed

    Wróbel, Martyna Z; Chodkowski, Andrzej; Herold, Franciszek; Gomółka, Anna; Kleps, Jerzy; Mazurek, Aleksander P; Pluciński, Franciszek; Mazurek, Andrzej; Nowak, Gabriel; Siwek, Agata; Stachowicz, Katarzyna; Sławińska, Anna; Wolak, Małgorzata; Szewczyk, Bernadeta; Satała, Grzegorz; Bojarski, Andrzej J; Turło, Jadwiga

    2013-05-01

    A series of 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives was synthesized and their biological activity was evaluated. The chemical structures of the newly prepared compounds were confirmed by (1)H NMR, (13)C NMR and ESI-HRMS spectra data. All tested compounds proved to be potent 5-HT1A receptor and serotonin transporter protein (SERT) ligands. Among them, compounds 15, 18, 19 and 30 showed significant affinity for 5-HT1A and SERT. Computer docking simulations carried out for compounds 15, 31 and 32 to models of 5-HT1A receptor and SERT confirm the results of biological tests. Due to high affinity for the 5-HT1A receptor and moderate affinity for SERT, compounds 31, 32, 35, and 37 were evaluated for their affinity for D2L, 5-HT6, 5-HT7 and 5-HT2A receptors. In vivo tests, in turn, resulted in determining the functional activity of compounds 15, 18, 19 and 30 to the 5-HT1A receptor. The results of these tests indicate that all of the ligands possess properties characteristic of 5-HT1A receptor agonists.

  7. ToF-SIMS analysis of anti-fretting films generated on the surface of ball bearings containing dithiocarbamate and dithiophosphate grease additives

    NASA Astrophysics Data System (ADS)

    Duque, Ricardo G.; Wang, Zhiyu; Duell, Dave; Fowler, David E.

    2004-06-01

    During transport of hard drives from the factory to the end customer, vibrations can induce small repetitive displacements of the ball bearings giving rise to fretting corrosion at the metal surfaces. On the other hand, it has been found that some particular types of grease additives can form thin layers on steel surfaces and thus protect against fretting corrosion. ToF-SIMS has been used to study the chemical nature of layers formed on bearing surfaces containing greases with dithiocarbamates, dithiophosphates, and metal sulfonate additives. In cases where fretting was prevented, the presence of MoS 2-, FeS - and ion fragments containing Mo-Fe-S - were observed, whereas none of these ions were detected on the surfaces of fretted bearings. Finally, it is inferred that the action of metal sulfonates may have an antagonist effect on the anti-fretting activity of the dithiocarbamate and dithiophosphate compounds studied.

  8. Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways.

    PubMed

    Fu, Dong-Jun; Zhang, Li; Song, Jian; Mao, Ruo-Wang; Zhao, Ruo-Han; Liu, Ying-Chao; Hou, Yu-Hui; Li, Jia-Huan; Yang, Jia-Jia; Jin, Cheng-Yun; Li, Ping; Zi, Xiao-Lin; Liu, Hong-Min; Zhang, Sai-Yang; Zhang, Yan-Bing

    2017-02-15

    A series of novel formononetin-dithiocarbamate derivatives were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell line (MGC-803, EC-109, PC-3). The first structure-activity relationship (SAR) for this formononetin-dithiocarbamate scaffold is explored in this report with evaluation of 14 variants of the structural class. Among these analogues, tert-butyl 4-(((3-((3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)propyl)thio)carbonothioyl)piperazine-1-carboxylate (8i) showed the best inhibitory activity against PC-3 cells (IC50 = 1.97 μM). Cellular mechanism studies elucidated 8i arrests cell cycle at G1 phase and regulates the expression of G1 checkpoint-related proteins in concentration-dependent manners. Furthermore, 8i could inhibit cell growth via MAPK signaling pathway and inhibit migration via Wnt pathway in PC-3 cells.

  9. RECOVERY OF URANIUM BY CYCLOALKYLDITHIO-CARBAMATE COMPLEXING

    DOEpatents

    Neville, O.K.

    1959-06-30

    The separation of uranium-233 from an aqueous nitric acid solution of neutron irradiated thorium by selectively complexing the uranium is described. The separation is carried out by contacting the thorium solution with a non- aromatic organic dithiocarbamate selected from the group which consists of alkali and alkaline earth cycloalkyldithiocarbamates and recovering the resulting uranyl cycloalkyldithiocarbamate complex by organic solvent extraction such as with methyl ethyl ketone. The complexed uranium may be stripped from the separated organic phase by scrubbing with one normal nitric acid solution.

  10. Determination of dithiocarbamate pesticides in occupational hygiene sampling devices using the isooctane method and comparison with an automatic thermal desorption (ATD) method.

    PubMed

    Coldwell, Matthew R; Pengelly, Ian; Rimmer, Duncan A

    2003-01-10

    Two new methods for the determination of dithiocarbamate pesticides in occupational hygiene sampling devices are described. Dithiocarbamate spiked occupational hygiene sampling devices, consisting of glass fibre (GF/A) filters, cotton pads, cotton gloves and disposable overalls, were reduced under acidic conditions and the CS2 evolved as a decomposition product was extracted into isooctane. The isooctane was then analysed using gas chromatography with mass spectrometry, for CS2, which provided a quantitative result for dithiocarbamates. Recoveries obtained were generally within a 70-110% range and reproducibilities better than 15% RSD were typically achieved. The method has been successfully applied to samples collected during occupational exposure surveys. A second method employing automatic thermal desorption-gas chromatography-mass spectrometry (ATD-GC-MS) has also been developed and applied to the direct analysis of GF/A (airborne) samples. The method relies on the thermal degradation of dithiocarbamates to release CS2, which is used to quantify the analytes. Thiram spiked GF/A filters gave an average recovery of 107% with an RSD of 4%. The performance of the two analytical methods were directly compared by analysing sub-portions of GF/A filters collected during a survey to evaluate occupational exposures to thiram during seed treatment operations. Both methods performed well for the analysis of airborne (GF/A) samples and produced results in good agreement. ATD-GC-MS is the preferred method for studies involving GF/A (airborne) samples only. Because of the wider applicability of the isooctane method for other sampling devices, it is the preferred choice when carrying out surveys which require a dermal as well as respirable exposure assessment.

  11. Construction of Fused Pyrrolidines and β-Lactones by Carbene-Catalyzed C-N, C-C, and C-O Bond Formations.

    PubMed

    Wu, Xingxing; Hao, Lin; Zhang, Yuexia; Rakesh, Maiti; Reddi, Rambabu N; Yang, Song; Song, Bao-An; Chi, Yonggui Robin

    2017-03-15

    A carbene-catalyzed intermolecular C-N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused β-lactones, is disclosed. The nitrogen-containing bicyclic β-lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene-catalyzed asymmetric carbon-heteroatom bond-forming reactions.

  12. Efficient iodine catalyzed three components domino reaction for the synthesis of 1-((phenylthio)(phenyl)methyl)pyrrolidin-2-one derivatives possessing anticancer activities.

    PubMed

    Ramachandran, Gunasekar; Karthikeyan, Natesan S; Giridharan, Periyasamy; Sathiyanarayanan, Kulathu I

    2012-07-28

    A simple and efficient three components domino reaction of γ-butyrolactam (2-pyrrolidinone), aromatic aldehyde and substituted thiophenol catalyzed by elemental iodine resulted in the formation of 1-((phenylthio)(phenyl)methyl)pyrrolidin-2-one derivatives. The stability of the synthesized analogues was evaluated in stimulated gastric fluid (SGF) and bovine serum albumin (BSA). In vitro anticancer activity was investigated in the low micromolar range and a few analogues were found to possess good activity. This current protocol provides several advantages like shorter reaction time, excellent yield and convenient work-up.

  13. Crystal structure of 1-{4-hy­droxy-3-[(pyrrolidin-1-yl)meth­yl]phen­yl}-3-phenyl­prop-2-en-1-one

    PubMed Central

    Aydın, Abdullah; Akkurt, Mehmet; Gul, Halise Inci; Yerdelen, Kadir Ozden; Celik, Raziye Catak

    2016-01-01

    In the title compound, C20H21NO2, the pyrrolidine ring adopts an envelope conformation with the N atom at the flap position. The central benzene ring makes dihedral angles of 21.39 (10) and 80.10 (15)° with the phenyl ring and the mean plane of the pyrrolidine ring, respectively. The mol­ecular conformation is stabilized by an intra­molecular O—H⋯N hydrogen bond, which closes an S(6) ring. A weak C—H⋯π inter­action is observed in the crystal. PMID:27308021

  14. 2-Trimethylsilylethanesulfonyl (SES) versus tosyl (Ts) protecting group in the preparation of nitrogen-containing five-membered rings. A novel route for the synthesis of substituted pyrrolines and pyrrolidines.

    PubMed

    Declerck, Valérie; Allouchi, Hassan; Martinez, Jean; Lamaty, Frédéric

    2007-02-16

    The 2-trimethylsilylethanesulfonyl (or SES) protecting group was compared to the tosyl (Ts) group in the preparation of a nitrogen-containing five-membered ring obtained by the aza-Baylis-Hillman/alkylation/RCM route. While deprotection of Ts-protected pyrrolines gave only pyrroles, deprotection of the same SES-protected compounds gave either pyrroles or free amine pyrrolines depending on the deprotection conditions. The SES-protected pyrrolines were hydrogenated to yield pyrrolidines with an excellent diastereoselectivity. Free amine pyrrolidines were obtained by HF-mediated deprotection of the SES group.

  15. Exposure to Mn/Zn ethylene-bis-dithiocarbamate and glyphosate pesticides leads to neurodegeneration in Caenorhabditis elegans.

    PubMed

    Negga, Rekek; Rudd, David A; Davis, Nathan S; Justice, Amanda N; Hatfield, Holly E; Valente, Ana L; Fields, Anthony S; Fitsanakis, Vanessa A

    2011-06-01

    Epidemiological evidence suggests positive correlations between pesticide usage and the incidence of Parkinson's disease (PD). To further explore this relationship, we used wild type (N2) Caenorhabditis elegans (C. elegans) to test the following hypothesis: Exposure to a glyphosate-containing herbicide (TD) and/or a manganese/zinc ethylene-bis-dithiocarbamate-containing fungicide (MZ) may lead to neurotoxicity. We exposed N2 worms to varying concentrations of TD or MZ for 30 min (acute) or 24h (chronic). To replicate agricultural usage, a third population was exposed to TD (acute) followed by MZ (acute). For acute TD exposure, the LC(50)=8.0% (r(2)=0.6890), while the chronic LC(50)=5.7% (r(2)=0.9433). Acute MZ exposure led to an LC(50)=0.22% (r(2)=0.5093), and chronic LC(50)=0.50% (r(2)=0.9733). The combined treatment for TD+MZ yielded an LC(50)=12.5% (r(2)=0.6367). Further studies in NW1229 worms, a pan-neuronally green fluorescent protein (GFP) tagged strain, indicated a statistically significant (p<0.05) and dose-dependent reduction in green pixel number in neurons of treated worms following each paradigm. This reduction of pixel number was accompanied by visual neurodegeneration in photomicrographs. For the dual treatment, Bliss analysis suggested synergistic interactions. Taken together, these data suggest neuronal degeneration occurs in C. elegans following treatment with environmentally relevant concentrations of TD or MZ.

  16. Primary risk assessment of dimethyldithiocarbamate, a dithiocarbamate fungicide metabolite, based on their probabilistic concentrations in a coastal environment.

    PubMed

    Hano, Takeshi; Ito, Katsutoshi; Mochida, Kazuhiko; Ohkubo, Nobuyuki; Kono, Kumiko; Onduka, Toshimitsu; Ito, Mana; Ichihashi, Hideki; Fujii, Kazunori; Tanaka, Hiroyuki

    2015-07-01

    The primary ecological risk of dimethyldithiocarbamate (DMDC), a dithiocarbamate fungicide (DTC) metabolite, was evaluated based on their probabilistic environmental concentration distributions (ECDs) in the coastal environment, Hiroshima Bay, Japan. And their behavior and temporal trends was further considered. This is the first report of the identification of DMDC from environmental seawater and sediment samples. DMDC concentrations in bottom seawater were substantially higher than those in surface seawater, which are associated with the leachability from sediments in bottom seawaters, and with photodegradation in surface seawaters. Furthermore, seasonal risks are dominated by higher concentrations from April to June, indicating temporal variation in the risk to exposed species. Hierarchical Bayesian analysis offered DMDC ECD medians and range (5th to 95th percentiles) of 0.85 ng L(-1) (0.029, 22), 12 ng L(-1) (3.2, 48) and 110 ng kg dry(-1) (9.5, 1200) in surface seawater, bottom seawater and sediment, respectively. Considering that DMDC and DTCs have similar toxicological potential to aquatic organisms, the occurrence of the compound in water is likely to be of biological relevance. In summary, this work provides the first demonstration that the ecological risk of DMDC and its derived DTCs in Hiroshima Bay is relatively high, and that DTCs should be a high priority for future research on marine contamination, especially in bottom seawaters.

  17. Results of long-term experimental studies on the carcinogenicity of ethylene-bis-dithiocarbamate (Mancozeb) in rats.

    PubMed

    Belpoggi, Fiorella; Soffritti, Morando; Guarino, Marina; Lambertini, Luca; Cevolani, Daniela; Maltoni, Cesare

    2002-12-01

    Mancozeb, an ethylene-bis-dithiocarbamate (EBDC), has been one of the most commonly used fungicides in commercial use for several decades. Nevertheless, up to now, no adequate published experimental studies on the carcinogenicity of Mancozeb have been published. Because of the importance of the compound and of the number of people potentially exposed (workers engaged in the production and use of the fungicide, people living in agricultural areas where the compound is sprayed, and people consuming polluted products), a long-term experimental study of Mancozeb was begun at the Cancer Research Center of the Ramazzini Foundation. Groups of 150 male and female Sprague-Dawley rats, 8 weeks old at the start of the treatment, were administered Mancozeb at the concentration of 1000, 500, 100, 10, and 0 ppm in feed supplied ad libitum for 104 weeks. At the end of the treatment, animals were kept under controlled conditions until spontaneous death. Mancozeb caused an increase in (1) total malignant tumors, (2) malignant mammary tumors, (3) Zymbal gland and ear duct carcinomas, (4) hepatocarcinomas, (5) malignant tumors of the pancreas, (6) malignant tumors of the thyroid gland, (7) osteosarcomas of the bones of the head, and (8) hemolymphoreticular neoplasias. On the basis of these data, Mancozeb must be considered a multipotent carcinogenic agent.

  18. Molecular Aggregation in Binary Mixtures of Pyrrolidine, N-Methylpyrrolidine, Piperidine, and N-Methylpiperidine with Water: Thermodynamic, SANS and Theoretical Studies.

    PubMed

    Marczak, Wojciech; Varfolomeev, Mikhail A; Rakipov, Ilnaz T; Lodowski, Piotr; Kowalska-Szojda, Katarzyna; Łężniak, Marta; Almasy, Laszlo; Len, Adél

    2017-03-21

    Piperidine and N-methylpiperidine hydrates aggregate in liquid aqueous solutions due to hydrogen bonds between hydration water molecules. No such effects occur in the mixtures of the amines with methanol, that supports the idea of active role of water solvent in the aggregation. However, the question of contributions in thermodynamic functions due to specific interactions, van der Waals forces, and the size and shape of the molecules remains open. In the present study, limiting partial molar enthalpies of solution of pyrrolidine, N-methylpyrrolidine, piperidine and N-methylpiperidine in water and methanol and vice versa were measured and compared with those assessed from theoretically calculated molecular interaction energies using a simple "chemical reaction" model. Nearly quantitative agreement of the enthalpies was achieved for the systems studied, except the amines in water. The latter required an empirical hydrophobic hydration term to be considered. The hydrogen bonds formation and breaking which accompany the mixtures formation leads to considerable excess volumes, while the size of the solute molecules is manifested rather in the compressibility of aqueous solutions. SANS evidenced that aqueous solutions are microheterogeneous on the nanometer-order length scale. The propensity to promote phase separation increases in the order: N-methylpiperidine < N-methylpyrrolidine < piperidine < pyrrolidine.

  19. Antioxidant properties of thio-caffeine derivatives: Identification of the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine as antioxidant and highly potent cytoprotective agent.

    PubMed

    Jasiewicz, Beata; Sierakowska, Arleta; Wandyszewska, Natalia; Warżajtis, Beata; Rychlewska, Urszula; Wawrzyniak, Rafał; Mrówczyńska, Lucyna

    2016-08-15

    A series of nine thio-caffeine analogues were synthesized and characterised by NMR, FT-IR and MS spectroscopic methods. Molecular structures of four of them were determined using single crystal X-ray diffraction methods. The antioxidant properties of all compounds, at concentration ranges from 0.025 to 0.1mg/mL, were evaluated by various chemical- and cell-based antioxidant assays. Human erythrocytes were used to examine in vitro haemolytic activity of all compounds and their protective effect against oxidative haemolysis induced by AAPH, one of the commonly used free radical generator. All compounds studied showed no effect on the human erythrocytes membrane structure and permeability with the exception of 8-(phenylsulfanyl)caffeine. Among the nine caffeine thio-analogues tested, the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine possessed exceptionally high antioxidant properties. Moreover, it protects human erythrocytes against AAPH-induced oxidative damage as efficiently as the standard antioxidant Trolox. Therefore, 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine may have a significant cytoprotective potential caused by its antioxidant activity.

  20. 2-[1′-(Benz­yloxy)spiro­[indane-1,2′-pyrrolidine]-5′-yl]aceto­nitrile

    PubMed Central

    Moreno-Fuquen, Rodolfo; Soto, Diana M.; Jaramillo-Gómez, Luz M.; Ellena, Javier; Tenorio, Juan C.

    2013-01-01

    In the title compound, C21H22N2O, the planes of the two six-membered rings make a dihedral angle of 89.51 (7)°. The pyrrolidine ring has a puckering amplitude q 2 = 0.418 (3) and a pseudo-rotation phase angle ϕ2 = −166.8 (5), adopting a twist conformation (T). The other five-membered ring has a puckering amplitude q 2 = 0.247 (2) and a pseudo-rotation phase angle ϕ2 = −173.7 (5), adopting an envelope conformation with the CH2 atom adjacent to the C atom common with the pyrrolidine ring as the flap. In the crystal, mol­ecules are linked via C—H⋯N, enclosing R 2 2(20) rings, forming chains propagating along [100]. The aceto­nitrile group is disordered over two positions and was refined with a fixed occupancy ratio of 0.56:0.44. PMID:24109293

  1. Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants.

    PubMed

    Malik, Sachin; Ahuja, Priya; Sahu, Kapendra; Khan, Suroor Ahmad

    2014-09-12

    A series of 3-(benzo[d]isoxazol-3-yl)-N-substituted pyrrolidine-2, 5-dione (7a-7d, 8a-8d, 9a-9c) have been prepared and evaluated for their anticonvulsant activities. Preliminary anticonvulsant activity was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests after intraperitoneal (ip) injection into mice, which are the most widely employed models for early identification of anticonvulsant candidate. The acute neurological toxicity (NT) was determined applying rotorod test. The quantitative evaluation after oral administration in rats showed that the most active was 3-(benzo[d]isoxazol-3-yl)-1-(4-fluorophenyl) pyrrolidine-2, 5-dione (8a) with ED50 values of 14.90 mg/kg. Similarly the most potent in scPTZ was 3-(benzo[d]isoxazol-3-yl)-1-cyclohexylpyrrolidine-2, 5-dione (7d) with ED50 values of 42.30 mg/kg. These molecules were more potent and less neurotoxic than phenytoin and ethosuximide which were used as reference antiepileptic drugs.

  2. Evaluation of the influence of proline, hydroxyproline or pyrrolidine in the presence of sodium nitrite on N-nitrosamine formation when heating cured meat.

    PubMed

    Drabik-Markiewicz, G; Dejaegher, B; De Mey, E; Impens, S; Kowalska, T; Paelinck, H; Vander Heyden, Y

    2010-01-11

    N-nitrosamines are meant to be probable or possible carcinogenic components, possibly formed out of a reaction between nitrite and N-containing substances such as amino acids and secondary amines. Nitrite is often used for processing meat products because of its colouring and antimicrobial properties. During this experimental setup, the influence of proline, hydroxyproline or pyrrolidine on N-nitrosamine formation in meat samples was evaluated. The N-nitrosamines concentrations were measured with gas chromatography-thermal energy analyzer. Only the concentrations of N-nitrosodimethylamine and N-nitrosopyrrolidine were found above the limit of detection in a number of tested experimental conditions. The concentration of these two N-nitrosamines was modelled as a function of temperature and nitrite concentration for different situations (presence or absence of added natural N-containing meat components). It could be concluded that proline and pyrrolidine promoted the formation of N-nitrosopyrrolidine. It could also be confirmed that the higher the temperature of the meat processing procedure and the higher the sodium nitrite amounts added, the higher were the yields of the respective N-nitrosamines.

  3. The synthesis of N,O-ferrocenyl pyrrolidine-containing ligands and their application in the diethyl- and diphenylzinc addition to aromatic aldehydes.

    PubMed

    Ahern, Theresa; Müller-Bunz, Helge; Guiry, Patrick J

    2006-09-29

    A facile route to a series of planar chiral N,O-ferrocenyl pyrrolidine-containing ligands with varying substituents at the nitrogen and oxygen donor atoms is described. The oxygen donor atom was introduced via a diastereoselective ortho-metalation of N-methylpyrrolidinyl and N-allylpyrrolidinyl ferrocene intermediates and was quenched with various ketones. The nitrogen substituent was varied through deallylation and subsequent derivatization of a secondary pyrrolidine. The efficacy of these novel ligands was investigated in the enantioselective addition of diethylzinc and diphenylzinc to aromatic aldehydes. The ligands proved highly effective in the diethylzinc addition to benzaldehyde that resulted in high yields of up to 99% and enantioselectivities (ee's) of up to 95%. The role of planar chirality was explored and the results indicated that the planar chirality, and not the central chirality, of the ferrocenyl ligands was the dominant stereo-controlling element. Employment of a mixed ethyl-phenylzinc reagent in the phenylation of aromatic aldehydes led to a mixture of the two additional products, and the phenylated product was obtained in up to 37% ee.

  4. Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays.

    PubMed

    Noronha, Glenn; Barrett, Kathy; Boccia, Antonio; Brodhag, Tessa; Cao, Jianguo; Chow, Chun P; Dneprovskaia, Elena; Doukas, John; Fine, Richard; Gong, Xianchang; Gritzen, Colleen; Gu, Hong; Hanna, Ehab; Hood, John D; Hu, Steven; Kang, Xinshan; Key, Jann; Klebansky, Boris; Kousba, Ahmed; Li, Ge; Lohse, Dan; Mak, Chi Ching; McPherson, Andrew; Palanki, Moorthy S S; Pathak, Ved P; Renick, Joel; Shi, Feng; Soll, Richard; Splittgerber, Ute; Stoughton, Silva; Tang, Suhan; Yee, Shiyin; Zeng, Binqi; Zhao, Ningning; Zhu, Hong

    2007-02-01

    We describe the identification of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine (3), a potent, orally active Src inhibitor with desirable PK properties, demonstrated activity in human tumor cell lines and in animal models of tumor growth.

  5. The neonicotinoid pesticide imidacloprid and the dithiocarbamate fungicide mancozeb disrupt the pituitary-thyroid axis of a wildlife bird.

    PubMed

    Pandey, Surya Prakash; Mohanty, Banalata

    2015-03-01

    Thyroid is an important homeostatic regulator of metabolic activities as well as endocrine mechanisms including those of reproduction. Present investigation elucidated the thyroid disrupting potential of a neonicotinoid imidacloprid and a dithiocarbamate mancozeb in a seasonally breeding wildlife bird, Red Munia (Amandava amandava) who is vulnerable to these two pesticides through diet (seed grains and small insects). Adult male birds were exposed to 0.5% LD50 mgkg(-1)bwd(-1) of both the pesticides through food for 30days during the preparatory and breeding phases. Weight, volume and histopathology of thyroid gland were distinctly altered. Disruption of thyroid follicles reflected in nucleus-to-cytoplasm ratio (N/C) in epithelial and stromal cells, epithelial cell hypertrophy and altered colloid volume. Impairment of thyroid axis was pesticide and phase specific as evident from the plasma levels of thyroid (T4 and T3) and pituitary (TSH) hormones. In preparatory phase, plasma TSH was increased in response to decrease of T4 on mancozeb exposure showing responsiveness of the hypothalamic-pituitary-thyroid (HPT) axis to feedback regulation. On imidacloprid exposure, however, plasma levels of both T4 and TSH were decreased indicating non-functioning of negative feedback mechanism. Increased plasma T3 in response to both the pesticides exposure might be due to synthesis from non-thyroidal source(s) in a compensatory response to decrease level of T4. In breeding phase, impairment of HPT axis was more pronounced as plasma T4, T3 and TSH were significantly decreased in response to both mancozeb and imidacloprid. Thus, low dose pesticide exposure could affect the thyroid homeostasis and reproduction.

  6. Rapid preparation of (3R,4S,5R) polyhydroxylated pyrrolidine-based libraries to discover a pharmacological chaperone for treatment of Fabry disease.

    PubMed

    Cheng, Wei-Chieh; Wang, Jen-Hon; Yun, Wen-Yi; Li, Huang-Yi; Hu, Jia-Ming

    2017-01-27

    The rapid discovery of a pharmacological chaperone toward human α-Gal A for the treatment of Fabry disease is described. Two polyhydroxylated pyrrolidines with the (3R,4S,5R) configuration pattern underwent rapid substituent diversity by conjugating the primary aminomethyl moiety of each with a variety of carboxylic acids to generate two libraries (2 × 60 members). Our bioevaluation results showed one member with the (2R,3R,4S,5R) configuration pattern and bearing a 5-cyclohexylpentanoyl group as a substituent moiety possessed sufficient chaperoning capability to rescue α-Gal A activity in the lymphocyte of the N215S Fabry patient-derived cell line and other α-Gal A mutants in COS7 cells.

  7. Theoretical elucidation on the functional role of pyrrolidine-type ionic liquids in inducing stereoselectivity of the Michael addition of cyclohexanone with trans-β-nitrostyrene.

    PubMed

    Sun, Hui; Zhang, Dongju

    2011-03-01

    Density functional theory calculations have been carried out to elucidate the stereoselectivity of the Michael addition of cyclohexanone with trans-β-nitrostyrene, induced by a chiral ionic liquid (CIL) pyrrolidine-imidazolium bromide. By comparison of the C-C bond forming processes in the absence and presence of Br(-) anion, we found that intermolecular H-bonds between the imidazolium cation and the nitro group of trans-β-nitrostyrene and the steric hindrance of the imidazolium cation moiety on the Si-face of enamine dominate the stereoselectivity of the Michael addition. The presence of Br(-) anion obviously reduces the barrier by increasing the polarity of the C4=C5 bond of enamine. The theoretical results rationalize well the early experimental finding, and reveal a valuable clue for the further CIL design with high catalytic efficiency.

  8. (3RS,4SR)-Methyl 4-(2-chloro-5,8-di­methoxy­quinolin-3-yl)-1-phenyl­pyrrolidine-3-carboxyl­ate

    PubMed Central

    Benzerka, Saida; Bouraiou, Abdelmalek; Bouacida, Sofiane; Rhouati, Salah; Belfaitah, Ali

    2008-01-01

    The mol­ecule of the title compound, C23H23ClN2O4, contains a quinolyl unit linked to a functionalized pyrrolidine system with a 3,4-trans arrangement of the substituents. The unit cell contains two stereoisomers that have the absolute stereochemistry 3S,4R and 3R,4S. The pyrrolidine ring adopts a twist conformation with pseudo-rotation parameters P = 258.2 (3)° and τ(M) = 35.3 (1)°. The packing is stabilized by C—H⋯π inter­actions and offset π–π stacking (centroid-to-centroid distance = 3.849 Å, inter­planar distance = 3.293 Å and slippage = 1.994 Å) between phenyl rings, leading to a two-dimensional network. PMID:21580954

  9. A triclinic polymorph of methyl (3R,3'S)-1',1''-dimethyl-2,2''-dioxodispiro-[indoline-3,2'-pyrrolidine-3',3''-indoline]-4'-carboxyl-ate.

    PubMed

    Ganesh, G; Yuvaraj, Panneer Selvam; Divakara, Chinthalapuri; Reddy, Boreddy S R; Subbiahpandi, A

    2012-12-01

    In the title compound, C22H21N3O4, the central pyrrolidine ring adopts a C-envelope conformation with a C atom 0.6593 (13) Å displaced from the mean plane formed by the remaining ring atoms. The indoline ring systems (r.m.s. devisations of 0.0356 and 0.0547 Å) are almost perpendicular to the mean plane of the pyrrolidine ring, making dihedral angles of 89.7 (6) and 82.5 (6)°. The acetate group attached to the pyrrolidine ring assumes an extended conformation. In the crystal,N-H⋯O and C-H⋯O hydrogen bonds connect adjacent molecules, forming an infinite tape extending along [1-1-1]. The crystal packing is further consolidated by strong π-π inter-actions with a centroid-centroid distance of 3.2585 (8) Å. The title compound is a polymorph of previously reported monoclinic structure [Ganesh et al. (2012 ▶). Acta Cryst. E68, o2902-o2903].

  10. Crystal structure of 4'-(2-meth-oxy-quinolin-3-yl)-1'-methyl-dispiro-[indan-2,2'-pyrrolidine-3',3''-indoline]-1,3,2''-trione.

    PubMed

    Mathusalini, Sadasivam; Viswanathan, Vijayan; Mohan, Palathurai Subramaniam; Lin, Chia-Her; Velmurugan, Devadasan

    2015-12-01

    In the title compound, C30H23N3O4, the central 1-methyl-pyrrolidine ring adopts a twist conformation on the N-CH2 bond. The pyrrolidin-2-one ring of the indolin-2-one ring system also has a twist conformation on the C-C bond involving the spiro C atom and the carbonyl C atom. The five-membered ring of the indene-1,3-dione moiety has an envelope conformation with the spiro C atom as the flap. The quinoline ring system adopts an almost planar conformation (r.m.s. deviation = 0.04 Å). The mean planes of the indolin-2-one ring system, the indene-1,3-dione ring system and the the quinoline ring system are inclined to the mean plane of the central 1-methyl-pyrrolidine ring by 77.97 (7), 86.98 (7) and 46.58 (6)°, respectively. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming chains along the b axis. The chains are linked via a number of C-H⋯O hydrogen bonds, and C-H⋯π and π-π inter-actions [inter-centroid distance = 3.7404 (9) Å], forming a three-dimensional network.

  11. Molybdenum-containing nicotine hydroxylase genes in a nicotine degradation pathway that is a variant of the pyridine and pyrrolidine pathways.

    PubMed

    Yu, Hao; Tang, Hongzhi; Li, Yangyang; Xu, Ping

    2015-12-01

    Ochrobactrum sp. strain SJY1 utilizes nicotine as a sole source of carbon, nitrogen, and energy via a variant of the pyridine and pyrrolidine pathways (the VPP pathway). Several strains and genes involved in the VPP pathway have recently been reported; however, the first catalyzing step for enzymatic turnover of nicotine is still unclear. In this study, a nicotine hydroxylase for the initial hydroxylation step of nicotine degradation was identified and characterized. The nicotine hydroxylase (VppA), which converts nicotine to 6-hydroxynicotine in the strain SJY1, is encoded by two open reading frames (vppAS and vppAL [subunits S and L, respectively]). The vppA genes were heterologously expressed in the non-nicotine-degrading strains Escherichia coli DH5α and Pseudomonas putida KT2440; only the Pseudomonas strain acquired the ability to degrade nicotine. The small subunit of VppA contained a [2Fe-2S] cluster-binding domain, and the large subunit of VppA contained a molybdenum cofactor-binding domain; however, an FAD-binding domain was not found in VppA. Resting cells cultivated in a molybdenum-deficient medium had low nicotine transformation activity, and excess molybdenum was detected in the purified VppA by inductively coupled plasma-mass spectrometry analysis. Thus, it is demonstrated that VppA is a two-component molybdenum-containing hydroxylase.

  12. Molybdenum-Containing Nicotine Hydroxylase Genes in a Nicotine Degradation Pathway That Is a Variant of the Pyridine and Pyrrolidine Pathways

    PubMed Central

    Yu, Hao; Li, Yangyang

    2015-01-01

    Ochrobactrum sp. strain SJY1 utilizes nicotine as a sole source of carbon, nitrogen, and energy via a variant of the pyridine and pyrrolidine pathways (the VPP pathway). Several strains and genes involved in the VPP pathway have recently been reported; however, the first catalyzing step for enzymatic turnover of nicotine is still unclear. In this study, a nicotine hydroxylase for the initial hydroxylation step of nicotine degradation was identified and characterized. The nicotine hydroxylase (VppA), which converts nicotine to 6-hydroxynicotine in the strain SJY1, is encoded by two open reading frames (vppAS and vppAL [subunits S and L, respectively]). The vppA genes were heterologously expressed in the non-nicotine-degrading strains Escherichia coli DH5α and Pseudomonas putida KT2440; only the Pseudomonas strain acquired the ability to degrade nicotine. The small subunit of VppA contained a [2Fe-2S] cluster-binding domain, and the large subunit of VppA contained a molybdenum cofactor-binding domain; however, an FAD-binding domain was not found in VppA. Resting cells cultivated in a molybdenum-deficient medium had low nicotine transformation activity, and excess molybdenum was detected in the purified VppA by inductively coupled plasma-mass spectrometry analysis. Thus, it is demonstrated that VppA is a two-component molybdenum-containing hydroxylase. PMID:26407884

  13. A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities.

    PubMed

    Bharkavi, Chelliah; Vivek Kumar, Sundaravel; Ashraf Ali, Mohamed; Osman, Hasnah; Muthusubramanian, Shanmugam; Perumal, Subbu

    2016-11-15

    A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 <1.56μM) and 6l (IC50=2.87μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16μmol/L respectively.

  14. Anticonvulsant and antinociceptive activity of new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in mice.

    PubMed

    Rapacz, Anna; Obniska, Jolanta; Wiklik-Poudel, Beata; Rybka, Sabina; Sałat, Kinga; Filipek, Barbara

    2016-06-15

    The aim of the present experiments was to examine the anticonvulsant and antinociceptive activity of five new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in animal models of seizures and pain. The antiseizure activity was investigated in three acute models of seizures, namely, the maximal electroshock (MES), the subcutaneous pentylenetetrazole (scPTZ), and 6Hz psychomotor seizure tests in mice. The antinociceptive properties were estimated in the formalin model of tonic pain, and in the oxaliplatin-induced neuropathic pain model in mice. Considering drug safety evaluation, acute neurological toxicity was determined in the rotarod test. Three tested compounds (3, 4, and 7) displayed a broad spectrum of anticonvulsant activity and showed better protective indices than those obtained for MES/scPTZ/6Hz active reference drug - valproic acid. Furthermore, three compounds (3, 4, and 6) demonstrated a significant antinociceptive effect in the formalin test, as well as antiallodynic activity in the oxaliplatin-induced neuropathic pain model. Among the tested agents, compounds 3 and 4 displayed not only antiseizure properties, but also collateral prominent analgesic properties. The in vitro binding study indicated that the plausible mechanism of action of chosen compound (4) was the influence on neuronal voltage-sensitive sodium (site 2) and L-type calcium channels.

  15. C-Jun N-terminal Kinase and Apoptotic Signaling in Prostate Cancer

    DTIC Science & Technology

    2002-01-01

    hydrogen peroxide (H20 2) to induce JNK activation varied in different cell types. Pyrrolidine dithiocarbamate (PDTC), a presumed antioxidant (13,14...Down-regulation of the c-Jun N-terminal kinase (JNK) phosphatase M3/6 and activation of JNK by hydrogen peroxide and pyrrolidine dithiocarbamate...and Tan, T.-H. (2001) Down-regulation of the c-Jun N-terminal kinase (JNK) phosphatase M3/6 and activation of JNK by hydrogen peroxide and pyrrolidine

  16. Comment on "Structural and vibrational studies on 1-(5-Methyl- [1,3,4] thiadiazol-2-yl)-pyrolidin-2-ol" [Spectrochimica Acta Part A, 152 (2016) 252-261]. The importance of intramolecular OH ⋯ N hydrogen bonding in the conformational properties of thiadiazol-pyrrolidin-2-ol bearing species

    NASA Astrophysics Data System (ADS)

    Laurella, Sergio L.; Erben, Mauricio F.

    2016-07-01

    The title paper [1] reports a study on the spectroscopic and physicochemical properties of 1-(5-methyl- [1,3,4]thiadiazol-2-yl)-pyrrolidin-2-ol (MTPN) based on experimental and theoretical data. The latter ones are based on the computed molecular structure for a rather unusual conformer. Here, after a careful analysis of the conformational space of MTPN, the most stable conformation was determined for the molecule isolated in a vacuum, which results to be 21.9 kJ/mol more stable than the conformer reported previously. Our study also includes the closely related species 1-(5-trifluoromethyl- [1,3,4]thiadiazol-2-yl)-pyrrolidin-2-ol (FMTPN). An intramolecular OH ⋯ N hydrogen bond determines the conformational behavior of the [1,3,4]thiadiazol-2-yl)-pyrrolidin-2-ol group as demonstrated by Natural Bond Orbital population analysis.

  17. Comment on "Structural and vibrational studies on 1-(5-Methyl- [1,3,4] thiadiazol-2-yl)-pyrolidin-2-ol" [Spectrochimica Acta Part A, 152 (2016) 252-261]. The importance of intramolecular OH⋯N hydrogen bonding in the conformational properties of thiadiazol-pyrrolidin-2-ol bearing species.

    PubMed

    Laurella, Sergio L; Erben, Mauricio F

    2016-07-05

    The title paper [1] reports a study on the spectroscopic and physicochemical properties of 1-(5-methyl- [1,3,4]thiadiazol-2-yl)-pyrrolidin-2-ol (MTPN) based on experimental and theoretical data. The latter ones are based on the computed molecular structure for a rather unusual conformer. Here, after a careful analysis of the conformational space of MTPN, the most stable conformation was determined for the molecule isolated in a vacuum, which results to be 21.9kJ/mol more stable than the conformer reported previously. Our study also includes the closely related species 1-(5-trifluoromethyl- [1,3,4]thiadiazol-2-yl)-pyrrolidin-2-ol (FMTPN). An intramolecular OH⋯N hydrogen bond determines the conformational behavior of the [1,3,4]thiadiazol-2-yl)-pyrrolidin-2-ol group as demonstrated by Natural Bond Orbital population analysis.

  18. beta-2,2-Amino Acid N-Carboxy Anhydrides Relying on Sequential Enantioselective C(4)-Functionalization of Pyrrolidin-2,3-diones and Regioselective Baeyer-Villiger Oxidation.

    PubMed

    Palomo, Claudio; Mielgo, Antonia; Olaizola, Iurre; Vázquez, Ana; Badiola, Eider; Vera, Silvia

    2017-02-28

    A catalytic enantioselective entry to beta-2,2-amino acids enabling their direct coupling with nucleophiles is described. The approach is based upon an effective bifunctional Brønsted base catalyzed construction of a quaternary carbon stereocenter at C4 position of pyrrolidin-2,3-diones. Subsequent regioselective Baeyer-Villiger oxidation of the resultant adducts gives beta-2,2-amino acid N-carboxy anhydrides as the reactive species, which can further react with nucleophiles. Following this strategy both, 2,2-amino acid derivatives with different functionalities at the newly created stereocenter, and spirocyclic structures can be efficiently prepared.

  19. Cyclen dithiocarbamate-functionalized silver nanoparticles as a probe for colorimetric sensing of thiram and paraquat pesticides via host-guest chemistry

    NASA Astrophysics Data System (ADS)

    Rohit, Jigneshkumar V.; Kailasa, Suresh Kumar

    2014-11-01

    We have developed a simple and rapid colorimetric method for on-site analysis of thiram and paraquat using cyclen dithiocarbamate-functionalized silver nanoparticles (CN-DTC-Ag NPs) as a colorimetric probe. The synthesized CN-DTC-Ag NPs were characterized by UV-Visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy, dynamic light scattering, and transmission electron microscopic techniques. The CN-DTC molecules provide good supramolecular self assembly on the surfaces of Ag NPs to encapsulate thiram and paraquat selectively via "host-guest" chemistry, resulting in red-shift in surface plasmon resonance peak of CN-DTC-Ag NPs from 396 to 530 nm and 510 nm and color change from yellow to pink for thiram and to orange for paraquat, which can be naked-eye detected. The present method shows good linearity in the range of 10.0-20.0 µM and of 50.0-250 µM with limits of detection 2.81 × 10-6 M and 7.21 × 10-6 M for thiram and paraquat, respectively. This method was proved as a promising tool for on-site and real-time monitoring of thiram and paraquat in environmental water, potato, and wheat samples.

  20. Core-shell magnetite-silica dithiocarbamate-derivatised particles achieve the Water Framework Directive quality criteria for mercury in surface waters.

    PubMed

    Lopes, C B; Figueira, P; Tavares, D S; Lin, Z; Daniel-da-Silva, A L; Duarte, A C; Rocha, J; Trindade, T; Pereira, E

    2013-09-01

    The sorption capacity of nanoporous titanosilicate Engelhard titanosilicate number 4 (ETS-4) and silica-coated magnetite particles derivatised with dithiocarbamate groups towards Hg(II) was evaluated and compared in spiked ultra-pure and spiked surface-river water, for different batch factors. In the former, and using a batch factor of 100 m(3)/kg and an initial Hg(II) concentrations matching the maximum allowed concentration in an effluent discharge, both materials achieve Hg(II) uptake efficiencies in excess of 99 % and a residual metal concentration lower than the guideline value for drinking water quality. For the surface-river water and the same initial concentration, the Hg(II) uptake efficiency of magnetite particles is outstanding, achieving the quality criteria established by the Water Framework Directive (concerning Hg concentration in surface waters) using a batch factor of 50 m(3)/kg, while the efficiency of ETS-4 is significantly inferior. The dissimilar sorbents' Hg(II) removal efficiency is attributed to different uptake mechanisms. This study also highlights the importance of assessing the effective capacity of the sorbents under realistic conditions in order to achieve trustable results.

  1. Crystal structure of methyl 3′-benzamido-4′-(4-meth­oxy­phen­yl)-1′-methyl­spiro­[indeno­[1,2-b]quinoxaline-11,2′-pyrrolidine]-3′-carboxyl­ate

    PubMed Central

    Chandralekha, Kuppan; Sureshbabu, Adukamparai Rajukrishnan; Gavaskar, Deivasigamani; Lakshmi, Srinivasakannan

    2016-01-01

    In the title compound, C35H30N4O3, the spiro C atom connects the five-membered pyrrolidine ring and the indeno­quinoxaline ring system. The pyrrolidine ring adopts a twist conformation. An intra­molecular N—H⋯N inter­action between the amino group and the pyrazine ring is observed. In the crystal, mol­ecules are linked by a pairs of C—H⋯O hydrogen bonds, forming inversion dimers. PMID:27920911

  2. Technetium-99m and rhenium-188 complexes with one and two pendant bisphosphonate groups for imaging arterial calcification.

    PubMed

    Bordoloi, Jayanta Kumar; Berry, David; Khan, Irfan Ullah; Sunassee, Kavitha; de Rosales, Rafael Torres Martin; Shanahan, Catherine; Blower, Philip J

    2015-03-21

    The first (99m)Tc and (188)Re complexes containing two pendant bisphosphonate groups have been synthesised, based on the mononuclear M(v) nitride core with two dithiocarbamate ligands each with a pendant bisphosphonate. The structural identity of the (99)Tc and stable rhenium analogues as uncharged, mononuclear nitridobis(dithiocarbamate) complexes was determined by electrospray mass spectrometry. The (99m)Tc complex showed greater affinity for synthetic and biological hydroxyapatite, and greater stability in biological media, than the well-known but poorly-characterised and inhomogeneous bone imaging agent (99m)Tc-MDP. It gave excellent SPECT images of both bone calcification (mice and rats) and vascular calcification (rat model), but the improved stability and the availability of two pendant bisphosphonate groups conferred no dramatic advantage in imaging over the conventional (99m)Tc-MDP agent in which the bisphosphonate group is bound directly to Tc. The (188)Re complex also showed preferential uptake in bone. These tracers and the biological model of vascular calcification offer the opportunity to study the biological interpretation and clinical potential of radionuclide imaging of vascular calcification and to deliver radionuclide therapy to bone metastases.

  3. Exposure to glyphosate- and/or Mn/Zn-ethylene-bis-dithiocarbamate-containing pesticides leads to degeneration of γ-aminobutyric acid and dopamine neurons in Caenorhabditis elegans.

    PubMed

    Negga, Rekek; Stuart, J Andrew; Machen, Morgan L; Salva, Joel; Lizek, Amanda J; Richardson, S Jayne; Osborne, Amanda S; Mirallas, Oriol; McVey, Kenneth A; Fitsanakis, Vanessa A

    2012-04-01

    Previous studies demonstrate a positive correlation between pesticide usage and Parkinson's disease (PD), which preferentially targets dopaminergic (DAergic) neurons. In order to examine the potential relationship between two common pesticides and specific neurodegeneration, we chronically (24 h) or acutely (30 min) exposed two Caenorhabditis elegans (C. elegans) strains to varying concentrations (LC(25), LC(50) or LC(75)) of TouchDown(®) (TD) as percent active ingredient (glyphosate), or Mancozeb(®) (MZ) as percent active ingredient (manganese/zinc ethylene-bis-dithiocarbamate). Furthermore, to more precisely model environmental exposure, worms were also exposed to TD for 30 min, followed by 30-min incubation with varying MZ concentrations. Previous data from out lab suggested general neuronal degeneration using the worm strain NW1229 (pan-neuronal//green fluorescent protein (GFP) construct). To determine whether distinct neuronal groups were preferentially affected, we specifically used EG1285 (GABAergic neurons//GFP construct) and BZ555 (DAergic neurons//GFP construct) worms to verify GABAergic and DAergic neurodegeneration, respectively. Results indicated a statistically significant decrease, when compared to controls (CN), in number of green pixels associated with GABAergic neurons in both chronic (*P < 0.05) and acute (*P < 0.05) treatment paradigms. Analysis of the BZ555 worms indicated a statistically significant decrease (*P < 0.05) in number of green pixels associated with DAergic neurons in both treatment paradigms (chronic and acute) when compared to CN. Taken together, our data suggest that exposure to TD and/or MZ promotes neurodegeneration in both GABAergic and DAergic neurons in the model organism C. elegans.

  4. Disruption of the hypothalamic-pituitary-thyroid axis on co-exposures to dithiocarbamate and neonicotinoid pesticides: Study in a wildlife bird, Amandava amandava.

    PubMed

    Pandey, Surya Prakash; Mohanty, Banalata

    2017-02-22

    Non-target organisms, including human and wildlife, are susceptible to deleterious effects of pesticide mixtures in their environment. Present study demonstrated the disruption of the hypothalamic-pituitary-thyroid (HPT) axis in a seasonally breeding wildlife bird Amandava amandava on co-exposure to dithiocarbamate mancozeb/MCZ and neonicotinoid imidacloprid/IMI, at concentrations even lower than respective environmentally realistic exposure level of each of the pesticide. Adult male birds (n=8/group) were exposed individually to 0.25% LD50 of each of MCZ (0.14mg) and IMI (2.75μl) followed by co-exposure to their equimixture as MIX-I (0.25% LD50 of each) and MIX-II (0.5% LD50 of each) through food for 30d in preparatory phase of reproductive cycle. Disruptions of thyroid gland and pituitary-thyroid axis were evident. Altered thyroid weight and volume, follicles with inactive colloids and lesions, decrease of height and nucleus-to-cytoplasm ratio of follicular epithelial cells were noted. Plasma levels of T4 and T3 were decreased, more significant in mixture groups than in individually exposed groups. Within co-exposed groups, comparatively high plasma T4 and T3 levels in MIX-II than MIX-I indicated dose non-responsiveness of the pesticides in mixtures; a characteristic displayed by endocrine disrupters. Plasma TSH level was increased in MCZ- and IMI- but decreased in MIX-I and MIX-II suggesting the disruption of the negative feedback and impairment of the HPT axis in co-exposed groups. Effects were more prominent in co-exposed groups due to combinatorial action and cumulative toxicity of pesticides. Considering the role of thyroid hormones in reproductive development, pesticides even in low dose could affect the thyroid homeostasis and reproductive axis.

  5. Speciation of inorganic arsenic in drinking water by wavelength-dispersive X-ray fluorescence spectrometry after in situ preconcentration with miniature solid-phase extraction disks.

    PubMed

    Hagiwara, Kenta; Inui, Tetsuo; Koike, Yuya; Aizawa, Mamoru; Nakamura, Toshihiro

    2015-03-01

    A rapid and simple method using wavelength-dispersive X-ray fluorescence (WDXRF) spectrometry after in situ solid-phase extraction (SPE) was developed for the speciation and evaluation of the concentration of inorganic arsenic (As) in drinking water. The method involves the simultaneous collection of As(III) and As(V) using 13 mm ϕ SPE miniature disks. The removal of Pb(2+) from the sample water was first conducted to avoid the overlapping PbLα and AsKα spectra on the XRF spectrum. To this end, a 50 mL aqueous sample (pH 5-9) was passed through an iminodiacetate chelating disk. The filtrate was adjusted to pH 2-3 with HCl, and then ammonium pyrrolidine dithiocarbamate solution was added. The solution was passed through a hydrophilic polytetrafluoroethylene filter placed on a Zr and Ca loaded cation-exchange disk at a flow rate of 12.5 mL min(-1) to separate As(III)-pyrrolidine dithiocarbamate complex and As(V). Each SPE disk was affixed to an acrylic plate using adhesive cellophane tape, and then examined by WDXRF spectrometry. The detection limits of As(III) and As(V) were 0.8 and 0.6 μg L(-1), respectively. The proposed method was successfully applied to screening for As speciation and concentration evaluation in spring water and well water.

  6. Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (S)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor

    SciTech Connect

    Penning, Thomas D.; Zhu, Gui-Dong; Gong, Jianchun; Thomas, Sheela; Gandhi, Viraj B.; Liu, Xuesong; Shi, Yan; Klinghofer, Vered; Johnson, Eric F.; Park, Chang H.; Fry, Elizabeth H.; Donawho, Cherrie K.; Frost, David J.; Buchanan, Fritz G.; Bukofzer, Gail T.; Rodriguez, Luis E.; Bontcheva-Diaz, Velitchka; Bouska, Jennifer J.; Osterling, Donald J.; Olson, Amanda M.; Marsh, Kennan C.; Luo, Yan; Giranda, Vincent L.

    2010-06-21

    We have developed a series of phenylpyrrolidine- and phenylpiperidine-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase (PARP) inhibitors with excellent PARP enzyme potency as well as single-digit nanomolar cellular potency. These efforts led to the identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (22b, A-966492). Compound 22b displayed excellent potency against the PARP-1 enzyme with a K{sub i} of 1 nM and an EC{sub 50} of 1 nM in a whole cell assay. In addition, 22b is orally bioavailable across multiple species, crosses the blood-brain barrier, and appears to distribute into tumor tissue. It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin.

  7. Crystal structure of N-(7-di­bromo­methyl-5-methyl-1,8-naphthyridin-2-yl)benzamide–pyrrolidine-2,5-dione (1/1)

    PubMed Central

    Wang, Bang Zhong; Zhou, Jun Ping; Zhou, Yong; Luo, Jian Song; Yang, Jun Jie; Chi, Shao M.ing

    2017-01-01

    The title compound, C17H13Br2N3O·C4H5NO2, is a co-crystal of N-(7-di­bromo­methyl-5-methyl-1,8-naphthyridin-2-yl)benzamide and pyrrolidine-2,5-dione (succinimide). The benzamide mol­ecule exhibits pseudo-mirror symmetry, with an r.m.s. deviation of the non-H atoms of 0.09 Å (except for the two Br atoms). The angle between the least-squares planes of the two mol­ecules is 26.2 (2)°. In the crystal, the two mol­ecules are mutually linked by N—H⋯O and N—H⋯N hydrogen bonds. The packing is consolidated by C—H⋯(O,N) hydrogen bonds and π–π stacking inter­actions. PMID:28083121

  8. Copper(II) complexes with highly water-soluble L- and D-proline-thiosemicarbazone conjugates as potential inhibitors of Topoisomerase IIα.

    PubMed

    Bacher, Felix; Enyedy, Éva A; Nagy, Nóra V; Rockenbauer, Antal; Bognár, Gabriella M; Trondl, Robert; Novak, Maria S; Klapproth, Erik; Kiss, Tamás; Arion, Vladimir B

    2013-08-05

    Two proline-thiosemicarbazone bioconjugates with excellent aqueous solubility, namely, 3-methyl-(S)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone [L-Pro-FTSC or (S)-H2L] and 3-methyl-(R)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone [D-Pro-FTSC or (R)-H2L], have been synthesized and characterized by elemental analysis, one- and two-dimensional (1)H and (13)C NMR spectroscopy, and electrospray ionization mass spectrometry. The complexation behavior of L-Pro-FTSC with copper(II) in an aqueous solution and in a 30% (w/w) dimethyl sulfoxide/water mixture has been studied via pH potentiometry, UV-vis spectrophotometry, electron paramagnetic resonance, (1)H NMR spectroscopy, and spectrofluorimetry. By the reaction of copper(II) acetate with (S)-H2L and (R)-H2L in water, the complexes [Cu(S,R)-L] and [Cu(R,S)-L] have been synthesized and comprehensively characterized. An X-ray diffraction study of [Cu(S,R)-L] showed the formation of a square-pyramidal complex, with the bioconjugate acting as a pentadentate ligand. Both copper(II) complexes displayed antiproliferative activity in CH1 ovarian carcinoma cells and inhibited Topoisomerase IIα activity in a DNA plasmid relaxation assay.

  9. (1R*,3′S*,4′R*)-4′-(4-Chloro­phen­yl)-3′-[(4-hy­droxy-2-oxo-1,2-dihydro­quinolin-3-yl)carbon­yl]-1′-methyl­spiro­[ace­naphthyl­ene-1,2′-pyrrolidin]-2-one

    PubMed Central

    Vennila, K. N.; Sankaran, M.; Mohan, P. S.; Velmurugan, D.

    2011-01-01

    The title compound, C32H23ClN2O4, has a quinoline, a chloro­phenyl and an acenaphthalene ring system attached to a central pyrrolidine ring, which has three stereogenic centers. Nevertheless, the compound crystallizes as a racemate with two mol­ecules of identical chirality in the asymmetric unit. They differ in the conformation of the five-membered pyrrolidine ring; in one molecule it has an envelope conformation, while in the other molecule it has a twisted conformation. In each molecule there is an intra­molecular O—H⋯O hydrogen bond making an S(6) ring motif. In the crystal, pairs of N—H⋯O hydrogen bonds produce inversion dimers with R 2 2(8) motifs. There are also C—H⋯O interactions present. The crystal structure contains voids (60 Å3) within which there is no evidence of solvent mol­ecules. PMID:22199868

  10. Crystal structure of 4′-(2-meth­oxy­quinolin-3-yl)-1′-methyl­dispiro­[indan-2,2′-pyrrolidine-3′,3′′-indoline]-1,3,2′′-trione

    PubMed Central

    Mathusalini, Sadasivam; Viswanathan, Vijayan; Mohan, Palathurai Subramaniam; Lin, Chia-Her; Velmurugan, Devadasan

    2015-01-01

    In the title compound, C30H23N3O4, the central 1-methyl­pyrrolidine ring adopts a twist conformation on the N—CH2 bond. The pyrrolidin-2-one ring of the indolin-2-one ring system also has a twist conformation on the C—C bond involving the spiro C atom and the carbonyl C atom. The five-membered ring of the indene-1,3-dione moiety has an envelope conformation with the spiro C atom as the flap. The quinoline ring system adopts an almost planar conformation (r.m.s. deviation = 0.04 Å). The mean planes of the indolin-2-one ring system, the indene-1,3-dione ring system and the the quinoline ring system are inclined to the mean plane of the central 1-methyl­pyrrolidine ring by 77.97 (7), 86.98 (7) and 46.58 (6)°, respectively. In the crystal, mol­ecules are linked via N—H⋯N hydrogen bonds, forming chains along the b axis. The chains are linked via a number of C—H⋯O hydrogen bonds, and C—H⋯π and π–π inter­actions [inter-centroid distance = 3.7404 (9) Å], forming a three-dimensional network. PMID:26870486

  11. 4′-(1H-Imidazol-2-yl)-3′-[(1H-indol-3-yl)carbon­yl]-1′-methyl-2-oxo­spiro­[indoline-3,2′-pyrrolidine]-3′-carbo­nitrile 0.15-hydrate

    PubMed Central

    Inglebert, S. Antony; Arun, Yuvaraj; Sethusankar, K.; Perumal, Paramasivam T.

    2013-01-01

    In the title compound, C25H20N6O2·0.15H2O, the dihedral angles between the least-squares planes of the indole and pyrrolidine rings and between the oxindole and imidazole rings are 77.66 (7) and 45.31 (7)°, respectively. The pyrrolidine ring and the fused five-membered pyrrolidine ring of the oxindole moiety exhibit twisted conformations. The amide N atom is involved in both intra- and inter­molecular hydrogen bonding, having a bifurcated character. The mol­ecular structure is characterized by an intra­molecular N—H⋯O hydrogen bond, which generates an S(7) ring motif while an inter­molecular N—H⋯O hydrogen bond links the organic and solvent water mol­ecules. In the crystal, N—H⋯N hydrogen bonds generate a zigzag chain running parallel to c-axis direction. The H atoms of the solvent water mol­ecule were not located. PMID:24427102

  12. Formation of mono(dithiolene)-thiocarboxamido complexes in reactions of thio(dithiocarbamato)-Mo/W complexes and dimethyl acetylenedicarboxylate.

    PubMed

    Lim, Patrick J; Slizys, Damian A; Tiekink, Edward R T; Young, Charles G

    2005-01-10

    Reactions of TpMS(S(2)CNEt(2)) with dimethyl acetylenedicarboxylate in dichloromethane produce olive green/black TpM{S(2)C(2)(CO(2)Me)(2)}(SCNEt(2)-kappa(2)S,C) (M = Mo (1), W (2); Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate). The seven-coordinate complexes exhibit pseudo-octahedral (1) and distorted pentagonal bipyramidal (2) coordination spheres comprised of tridentate fac-Tp, bidentate dithiolene, and thiocarboxamido-kappa(2)S,C ligands. In the solid state, molecules of 1 exhibit pseudo-C(s)() symmetry, with the thiocarboxamide NEt(2) group in a cleft in the Tp ligand. Molecules of 2 have C(1) symmetry in the solid state; here, the thiocarboxamide unit is orientated along one of the W-S(dithiolene) bonds with its NEt(2) group projecting away from the Tp ligand. Both complexes possess effective C(s)() symmetry in solution. Reaction of TpMoI(CO)(3) with AgS(2)CNEt(2) affords olive green TpMo(S(2)CNEt(2))(CO)(2) (3), which reacts with propylene sulfide in a new synthesis for TpMoS(S(2)CNEt(2)), the starting material for 1. Complex 3 exhibits a distorted pentagonal bipyramidal structure, the axial sites being defined by a Tp nitrogen atom and a carbonyl ligand, the pentagonal plane by the remaining nitrogen and carbonyl donors and the two sulfur atoms of the bidentate dithiocarbamate ligand.

  13. Asymmetric epoxidation of unsaturated ketones catalyzed by heterobimetallic rare earth-lithium complexes bearing phenoxy-functionalized chiral diphenylprolinolate ligand.

    PubMed

    Qian, Qinqin; Tan, Yufang; Zhao, Bei; Feng, Tao; Shen, Qi; Yao, Yingming

    2014-09-05

    Four novel heterobimetallic complexes [REL2]{[(THF)3Li]2(μ-Cl)} stabilized by chiral phenoxy-functionalized prolinolate (RE = Yb (1), Y (2), Sm (3), Nd (4), H2L = (S)-2,4-di-tert-butyl-6-[[2-(hydroxydiphenylmethyl)pyrrolidin-1-yl]methyl]phenol have been synthesized and characterized. These readily available complexes are highly active in catalyzing the epoxidation of α,β-unsaturated ketones, while the enantioselectivity varies according to the ionic radii of the rare earth center. A series of chalcone derivatives were converted to chiral epoxides in 80 → 99% ee at 0 °C using TBHP as the oxidant in the presence of 10 mol % of 1.

  14. Synthesis, characterization and biocidal activities of heterobimetallic complexes having tin(IV) as a padlock

    NASA Astrophysics Data System (ADS)

    Husain, Ahmad; Nami, Shahab A. A.; Siddiqi, K. S.

    2010-04-01

    A mononuclear precursor complex, [(CH 3) 2Sn(tpdtc)] and several of its heterobimetallic derivatives of the type, [(CH 3) 2Sn(tpdtc)]MCl 2 have been synthesized by the simple addition reaction of transition metal chlorides, MCl 2· nH 2O where tpdtc = tetraethylenepentamine bis(dithiocarbamate) anion, M = Fe(II), Co(II), Ni(II), Cu(II) and Zn(II). The synthesized complexes have been systematically characterized by the physicochemical and spectroscopic techniques. A square-pyramidal geometry has been proposed for all the transition metal atoms with chloride ions occupying the axial while the three nitrogen atoms occupying the equatorial positions. A symmetrical bidentate coordination has been observed for the dithiocarbamato moiety leading to the formation of 18 member cavity. The thermal studies reveal that the mononuclear complex decomposes in three stages while its heterobimetallic analog exhibits a simple two-stage profile. The conductivity measurement data (1 mmol solution) implies a non-electrolytic behavior for all the complexes as evident by their low conductivity values obtained at room temperature. The heterobimetallic complexes have also been tested against the bacterial ( Escherichia coli and Pseudomonas aeruginosa) and antifungal strains ( Aspergillus niger and Fusarium oxysporum). All the complexes were found to be active against the test organisms and maximum activity was found for [(CH 3) 2Sn(tpdtc)]CuCl 2 complex.

  15. π donation and its effects on the excited-state lifetimes of luminescent platinum(II) terpyridine complexes in solution.

    PubMed

    Hight, Lauren M; McGuire, Meaghan C; Zhang, Yu; Bork, Matthew A; Fanwick, Phillip E; Wasserman, Adam; McMillin, David R

    2013-08-05

    Introducing electron-donating groups extends the excited-state lifetimes of platinum(II)-terpyridine complexes in fluid solution. Such systems are of interest for a variety of applications, viz., as DNA-binding agents or as components in luminescence-based devices, especially sensors. The complexes investigated here are of the form [Pt(4'-X-T)Y](+), where 4'-X-T denotes a 4'-substituted 2,2':6',2″-terpyridine ligand and Y denotes the coligand. The π-donating abilities of -X and -Y increase systematically in the orders -NHMe < -NMe2 < -(pyrrolidin-1-yl) and -CN < -Cl < -CCPh, respectively. The results presented include crystal structures of two new 4'-NHMe-T complexes of platinum, as well as absorption, emission, and excited-state lifetime data for nine complexes. Excited-state lifetimes obtained in deoxygenated dichloromethane vary by a factor of 100, ranging from 24 μs for [Pt(4'-pyrr-T)CN](+) to 0.24 μs for [Pt(4'-ma-T)Cl](+), where ma-T denotes 4'-(methylamino)-2,2':6',2″-terpyridine and pyrr-T denotes 4'-(pyrrolidin-1-yl)-2,2':6',2″-terpyridine. Analysis of experimental and computational results shows that introducing a simple amine group on the terpyridine and/or a π-donating coligand engenders the emitting state with intraligand charge-transfer (ILCT) and/or ligand-ligand charge-transfer (LLCT) character. The excited-state lifetime increases when the change in orbital parentage lowers the emission energy, suppresses quenching via d-d states, and encourages delocalization of the excitation onto the ligand(s). At some point, however, the energy is low enough that direct vibronic coupling to the ground-state surface becomes important, and the lifetime begins to decrease again.

  16. Investigation of the inhibiting action of O-, S- and N-dithiocarbamato(1,4,8,11-tetraazacyclotetradecane)cobalt(III) complexes on the corrosion of iron in HClO 4 acid

    NASA Astrophysics Data System (ADS)

    Babić-Samardžija, K.; Khaled, K. F.; Hackerman, N.

    2005-02-01

    The inhibiting properties of four macrocyclic cobalt(III) complexes of the general formula [Co III(Rdtc)cyclam](ClO 4) 2, where cyclam and Rdtc- refer to 1,4,8,11-tetraazacyclotetradecane and morpholine-, thiomorpholine-, piperazine-, N-methylpiperazine-dithiocarbamates, respectively, has been studied on the corrosion of iron in aerated 0.1 M HClO 4 solutions by potentiodynamic polarization (dc) technique and electrochemical impedance spectroscopy (ac). Inhibitor efficiency for the corrosion of iron is found to be better for cobalt complexes then for related amino-ligands. The impedance increases with inhibitor concentration. Polarization curves indicate that the inhibitors are predominantly mixed-type. Better protection by the complex inhibitors was obtained with longer immersion time. The best fit for inhibitors adsorption is obtained using the Langmuir isotherm model. Molecular modeling calculations were used to correlate structural properties of the complex species and their inhibition efficiency.

  17. Redox reactivity of mononuclear and binuclear rhenium complexes

    SciTech Connect

    Holder, G.N.

    1988-01-01

    Six different classes of monomeric and dimeric rhenium complexes containing substituted nitriles, substituted pyridines, dithiocarbamates, and substituted phosphines as ligands were synthesized. Monomers had the general formula ReCl{sub 3} (NCR) (PPh{sub 3}){sub 2}, ReCl{sub 3}-(NCCH{sub 3})(P-(aryl-R){sub 3}){sub 2}, and ReOCl{sub 3} (P-(aryl-R){sub 3}){sub 2}. Dimers had the general formula Re{sub 2}Cl{sub 4} (dppm){sub 2} (NCR) and (Re{sub 2}Cl{sub 3}(dppm){sub 2}-(NCR){sub 2}){sup +} (dppm = bis(diphenylphosphino)methane) and Re{sub 2}O{sub 3}Cl{sub 4}-(py){sub 4}, where R was an alkyl or halogenated substituent chosen to systematically vary the donor-acceptor properties of the nitrile, pyridine, or phosphine ligand. The effects of this structural change on the function of the molecule was monitored both spectrally and electrochemically. Rate constants for addition of nitriles to the metal-metal bridged dimeric complex were found to vary linearly with the identity of the substitutent. Spectroscopic data followed these trends as well. The structure-function relationships derived from this work will aid in the design of future Technetium and Rhenium-based organ selective radioimaging agents.

  18. Comparison between 3-Nitrooxyphenyl acetylsalicylate (NO-ASA) and O2-(acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA) as safe anti-inflammatory, analgesic, antipyretic, antioxidant prodrugs.

    PubMed

    Chattopadhyay, Mitali; Velazquez, Carlos A; Pruski, April; Nia, Kamran V; Abdellatif, Khaled R; Keefer, Larry K; Kashfi, Khosrow

    2010-11-01

    Chronic inflammation is an underlying etiological factor in carcinogenesis; nonsteroidal anti-inflammatory drugs (NSAIDs) and their chemically modified NO-releasing prodrugs (NO-NSAIDs) are promising chemopreventive agents. The aim of this study was to conduct a head-to-head comparison between two NO-ASAs possessing different NO donor groups, an organic nitrate [3-nitrooxyphenyl acetylsalicylate (NO-ASA; NCX-4016)] and an N-diazeniumdiolate [NONO-ASA, O(2)- (acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA; CVM-01)], as antiulcerogenic, analgesic, anti-inflammatory, and antipyretic agents. All drugs were administered orally at equimolar doses. For antiulcerogenic study, 6 h after administration, the number and size of hemorrhagic lesions in stomachs from euthanized animals were counted. Tissue samples were frozen for prostaglandin E(2) (PGE(2)), superoxide dismutase (SOD), and malondialdehyde determination. For anti-inflammatory study, 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 6 h. For antipyretic study, 1 h after dosing, fever was induced by intraperitoneal LPS, and body core temperatures measured for 5 h. For analgesic study, time-dependent analgesic effect of prodrugs was evaluated by carrageenan-induced hyperalgesia. Drugs were administered 30 min after carrageenan. NO-ASA and NONO-ASA were equipotent as analgesic and anti-inflammatory agents but were better than aspirin. Despite a drastic reduction of PGE(2) in stomach tissue, both prodrugs were devoid of gastric side effects. Lipid peroxidation induced by aspirin was higher than that observed by prodrugs. SOD activity induced by both prodrugs was similar, but approximately 2-fold higher than that induced by aspirin. CVM-01 is as effective as NCX-4016 in anti-inflammatory, analgesic, and antipyretic assays in vivo, and it showed an equivalent safety profile in the stomach. These results underscore the use of N

  19. Synthesis and biodistribution of a new 99mTc nitrido complex as a potential myocardial and cerebral imaging agent.

    PubMed

    Zhang, JunBo; Wang, XueBin; Li, ChunYun

    2002-06-01

    The bis(N-methyl, N-cyclohexyl dithiocarbamato) nitrido technetium-99m complex [99mTcN(MECHDTC)2] (MECHDTC: N-methyl, N-cyclohexyl dithiocarbamato) has been synthesized through a ligand-exchange reaction. The two-step procedure consisted of an initial reaction of 99mTcO4- with succinic dihydrazide in the presence of stannous chloride as reducing agent and propylenediamine tetraacetic acid as complexant, and successive addition of sodium salt of N-methyl, N-cyclohexyl dithiocarbamate. The radiochemical purity of the complex was over 90%, as measured by thin layer chromatography. No decomposition of the complex at room temperature was observed over a period of 6 h. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed that the complex was neutral. Biodistribution in mice showed that the complex accumulated in the heart and brain with high uptake. The heart/blood, heart/lung and brain/blood ratios were 5.55, 2.11 and 1.10, respectively, at 30 min post-injection, suggesting that this compound is a potential myocardial and cerebral imaging agent.

  20. Nicotine Dehydrogenase Complexed with 6-Hydroxypseudooxynicotine Oxidase Involved in the Hybrid Nicotine-Degrading Pathway in Agrobacterium tumefaciens S33

    PubMed Central

    Li, Huili; Xie, Kebo; Yu, Wenjun; Hu, Liejie; Huang, Haiyan; Xie, Huijun

    2016-01-01

    Nicotine, a major toxic alkaloid in tobacco wastes, is degraded by bacteria, mainly via pyridine and pyrrolidine pathways. Previously, we discovered a new hybrid of the pyridine and pyrrolidine pathways in Agrobacterium tumefaciens S33 and characterized its key enzyme 6-hydroxy-3-succinoylpyridine (HSP) hydroxylase. Here, we purified the nicotine dehydrogenase initializing the nicotine degradation from the strain and found that it forms a complex with a novel 6-hydroxypseudooxynicotine oxidase. The purified complex is composed of three different subunits encoded by ndhAB and pno, where ndhA and ndhB overlap by 4 bp and are ∼26 kb away from pno. As predicted from the gene sequences and from chemical analyses, NdhA (82.4 kDa) and NdhB (17.1 kDa) harbor a molybdopterin cofactor and two [2Fe-2S] clusters, respectively, whereas Pno (73.3 kDa) harbors an flavin mononucleotide and a [4Fe-4S] cluster. Mutants with disrupted ndhA or ndhB genes did not grow on nicotine but grew well on 6-hydroxynicotine and HSP, whereas the pno mutant did not grow on nicotine or 6-hydroxynicotine but grew well on HSP, indicating that NdhA and NdhB are responsible for initialization of nicotine oxidation. We successfully expressed pno in Escherichia coli and found that the recombinant Pno presented 2,6-dichlorophenolindophenol reduction activity when it was coupled with 6-hydroxynicotine oxidation. The determination of reaction products catalyzed by the purified enzymes or mutants indicated that NdhAB catalyzed nicotine oxidation to 6-hydroxynicotine, whereas Pno oxidized 6-hydroxypseudooxynicotine to 6-hydroxy-3-succinoylsemialdehyde pyridine. These results provide new insights into this novel hybrid pathway of nicotine degradation in A. tumefaciens S33. PMID:26729714

  1. Nicotine Dehydrogenase Complexed with 6-Hydroxypseudooxynicotine Oxidase Involved in the Hybrid Nicotine-Degrading Pathway in Agrobacterium tumefaciens S33.

    PubMed

    Li, Huili; Xie, Kebo; Yu, Wenjun; Hu, Liejie; Huang, Haiyan; Xie, Huijun; Wang, Shuning

    2016-01-04

    Nicotine, a major toxic alkaloid in tobacco wastes, is degraded by bacteria, mainly via pyridine and pyrrolidine pathways. Previously, we discovered a new hybrid of the pyridine and pyrrolidine pathways in Agrobacterium tumefaciens S33 and characterized its key enzyme 6-hydroxy-3-succinoylpyridine (HSP) hydroxylase. Here, we purified the nicotine dehydrogenase initializing the nicotine degradation from the strain and found that it forms a complex with a novel 6-hydroxypseudooxynicotine oxidase. The purified complex is composed of three different subunits encoded by ndhAB and pno, where ndhA and ndhB overlap by 4 bp and are ∼26 kb away from pno. As predicted from the gene sequences and from chemical analyses, NdhA (82.4 kDa) and NdhB (17.1 kDa) harbor a molybdopterin cofactor and two [2Fe-2S] clusters, respectively, whereas Pno (73.3 kDa) harbors an flavin mononucleotide and a [4Fe-4S] cluster. Mutants with disrupted ndhA or ndhB genes did not grow on nicotine but grew well on 6-hydroxynicotine and HSP, whereas the pno mutant did not grow on nicotine or 6-hydroxynicotine but grew well on HSP, indicating that NdhA and NdhB are responsible for initialization of nicotine oxidation. We successfully expressed pno in Escherichia coli and found that the recombinant Pno presented 2,6-dichlorophenolindophenol reduction activity when it was coupled with 6-hydroxynicotine oxidation. The determination of reaction products catalyzed by the purified enzymes or mutants indicated that NdhAB catalyzed nicotine oxidation to 6-hydroxynicotine, whereas Pno oxidized 6-hydroxypseudooxynicotine to 6-hydroxy-3-succinoylsemialdehyde pyridine. These results provide new insights into this novel hybrid pathway of nicotine degradation in A. tumefaciens S33.

  2. Synthesis, spectral, single crystal X-ray structural, CShM and BVS characterization of iron(III) cyclohexyl dithiocarbamates and their solvothermal decomposition to nano iron(II) sulphide

    NASA Astrophysics Data System (ADS)

    Ramalingam, K.; Srinivasan, S.

    2015-11-01

    [Fe(chmdtc)3] (1), [Fe(chedtc)3] (2), [Fe(achdtc)3] (3) and [Fe(chpdtc)3] (4) (where chmdtc = cyclohexylmethylcarbodithioate, chedtc = cyclohexylethylcarbodithioate, achdtc = allylcyclohexylcarbodithioate and chpdtc = cyclohexylpiperazinecarbodithioate) have been prepared and characterisized by elemental analysis, electronic, IR spectral, magnetic susceptibility, thermogravimetric analysis. The single crystal X-ray crystal structures of [Fe(chedtc)3] (2)and [Fe(chpdtc)3] (4) have been determined. Characteristic thioureide IR bands occur at 1483, 1477, 1454 and 1479 cm-1 for (1), (2), (3) and (4) respectively. Electronic spectral bands at 514,512,510 and 510 nm for (1), (2), (3) and (4) respectively are due to dxy → dx2 - y2 transition. One electron quasi reversible reductions due to Fe(III)/Fe(II) redox process are observed in CV. Magnetic susceptibility measurements exhibit a temperature dependent variation. Final residue obtained in thermal processes is FeS, which indicates the reduction of Fe(III) → Fe(II). Single crystal X-ray structures of [Fe(chedtc)3] (2)and [Fe(chpdtc)3] (4) show that the central atom is in a distorted octahedral environment. The CShM values have been calculated from the structural data as 2.5807 and 3.2329 for (2) and (4) respectively in a scale of zero to hundred. The observed values show that compound (4) is relatively more distorted than (2) in its octahedral coordination due to the steric demands of the cyclohexyl ring attached to piperazine. Both of them prefer octahedral coordination environment over trigonal prism. Bond Valence Sum (BVS) calculations confirmed the oxidation state of iron as +3. A non conventional solvothermal formation of FeS nano particles is reported with iron dithiocarbamates as single source precursors. Morphology and composition of the nano product have been characterized by PXRD and EDX analysis.

  3. Vibrational Overtone Spectroscopy of Pyrrole and Pyrrolidine

    DTIC Science & Technology

    1991-05-23

    general pattern is a strong peak accompanied by two or three weaker peaks to lower energy. For instance, the 13,305 cm-I band in pyrrole has three weaker...Orza, J.M. Anales de Quimica 1984, 80, 59. 29. Navarro, R.; Orza, J.M. Anales de Quimica 1982, 79, 557. 30. Xie, Y; Fan, K.; Boggs,J., Molec. Phys

  4. One-pot synthesis of novel (2R,4S)-N-aryl-4-hydroxy-1-(2,2,2-trifluoroacetyl) pyrrolidine-2-carboxamides via [Formula: see text]-NPs and [Formula: see text] catalysts and investigation of their biological activities.

    PubMed

    Darehkordi, Ali; Ramezani, Mahin

    2017-02-11

    A new class of (2R,4S)-N-aryl-4-hydroxy-1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carboxamide compounds was synthesized by a facile one-pot reaction of trans-4-hydroxy proline and trifluoroacetimidoyl chlorides in the presence of [Formula: see text]-nanoparticles as a catalyst and sodium bicarbonate as a base. Synthesized compounds showed cytotoxicity with [Formula: see text] values of 15.3-70.3 [Formula: see text] against K562 (Homo sapiens, human) cells. The results of the study provide a valuable method for one-pot synthesis of trans-4-hydroxy proline-based N-(2,2,2-trifluoroacetylated) compounds. Also, these compounds show significant pharmaceutical activities as antibacterial and antifungal reagents.

  5. The Fe(III) and Ga(III) coordination chemistry of 3-(1-hydroxymethylidene) and 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione: novel tetramic acid degradation products of homoserine lactone bacterial quorum sensing molecules.

    PubMed

    Romano, Ariel A; Hahn, Tobias; Davis, Nicole; Lowery, Colin A; Struss, Anjali K; Janda, Kim D; Böttger, Lars H; Matzanke, Berthold F; Carrano, Carl J

    2012-02-01

    Bacteria use small diffusible molecules to exchange information in a process called quorum sensing (QS). An important class of quorum sensing molecules used by Gram-negative bacteria is the family of N-acylhomoserine lactones (HSL). It was recently discovered that a degradation product of the QS molecule 3-oxo-C(12)-homoserine lactone, the tetramic acid 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione, is a potent antibacterial agent, thus implying roles for QS outside of simply communication. Because these tetramic acids also appear to bind iron with appreciable affinity it was suggested that metal binding might contribute to their biological activity. Here, using a variety of spectroscopic tools, we describe the coordination chemistry of both the methylidene and decylidene tetramic acid derivatives with Fe(III) and Ga(III) and discuss the potential biological significance of such metal binding.

  6. The Fe(III) and Ga(III) coordination chemistry of 3-(1-hydroxymethylidene) and 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione: Novel tetramic acid degradation products of homoserine lactone bacterial quorum sensing molecules

    PubMed Central

    Romano, Ariel A.; Hahn, Tobias; Davis, Nicole; Lowery, Colin A.; Struss, Anjali K.; Janda, Kim D.; Böttger, Lars H.; Matzanke, Berthold F.; Carrano, Carl J.

    2011-01-01

    Bacteria use small diffusible molecules to exchange information in a process called quorum sensing (QS). An important class of quorum sensing molecules used by Gram-negative bacteria is the family of N-acylhomoserine lactones (HSL). It was recently discovered that a degradation product of the QS molecule 3-oxo-C12-homoserine lactone, the tetramic acid 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione, is a potent antibacterial agent, thus implying roles for QS outside of simply communication. Because these tetramic acids also appear to bind iron with appreciable affinity it was suggested that metal binding might contribute to their biological activity. Here, using a variety of spectroscopic tools, we describe the coordination chemistry of both the methylidene and decylidene tetramic acid derivatives with Fe(III) and Ga(III) and discuss the potential biological significance of such metal binding. PMID:22178671

  7. Complexity Survey.

    ERIC Educational Resources Information Center

    Gordon, Sandra L.; Anderson, Beth C.

    To determine whether consensus existed among teachers about the complexity of common classroom materials, a survey was administered to 66 pre-service and in-service kindergarten and prekindergarten teachers. Participants were asked to rate 14 common classroom materials as simple, complex, or super-complex. Simple materials have one obvious part,…

  8. Synthesis and biodistribution of a novel [99mTcN(PNP5)(DMCHDTC)]+ complex as a potential myocardial perfusion imaging agent.

    PubMed

    Zhang, JunBo; Song, ZhiXin; Jinfeng, Chu; Wang, XueBin

    2009-09-01

    The [(99m)TcN(PNP5)(DMCHDTC)](+)(DMCHDTC: 2,3-dimethyl cyclohexyl dithiocarbamate, PNP5:bis(dimethoxypropylphosphinoethyl)ethoxyethylamine) complex was synthesized through a ligand-exchange reaction. The two-step procedure involved the initial reaction of (99m)TcO(4)(-) with succinic dihydrazide (SDH) as a donor of nitride nitrogen atom (N(3-)) in the presence of stannous chloride dihydrate as reducing agent and propylenediamine tetraacetic acid (PDTA) as complexant, followed by the addition of the PNP5 ligand and the DMCHDTC ligand. The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature was observed over a period of 6 h. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed the complex was cationic. The biodistribution results in mice indicated that [(99m)TcN(PNP5)(DMCHDTC)](+) was significantly retained into the heart. The heart uptake (ID%/g) was 14.47, 12.23 and 8.76 at 5, 30 and 60 min post-injection, respectively. The heart/liver, heart/lung and heart/blood ratios of the complex were 1.24, 3.62 and 23.05 at 60 min post-injection, suggesting it will be a potential myocardial imaging agent.

  9. Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development.

    PubMed

    Aguilar, Angelo; Lu, Jianfeng; Liu, Liu; Du, Ding; Bernard, Denzil; McEachern, Donna; Przybranowski, Sally; Li, Xiaoqin; Luo, Ruijuan; Wen, Bo; Sun, Duxin; Wang, Hengbang; Wen, Jianfeng; Wang, Guangfeng; Zhai, Yifan; Guo, Ming; Yang, Dajun; Wang, Shaomeng

    2017-04-13

    We previously reported the design of spirooxindoles with two identical substituents at the carbon-2 of the pyrrolidine core as potent MDM2 inhibitors. In this paper we describe an extensive structure-activity relationship study of this class of MDM2 inhibitors, which led to the discovery of 60 (AA-115/APG-115). Compound 60 has a very high affinity to MDM2 (Ki < 1 nM), potent cellular activity, and an excellent oral pharmacokinetic profile. Compound 60 is capable of achieving complete and long-lasting tumor regression in vivo and is currently in phase I clinical trials for cancer treatment.

  10. Complex derivatives

    NASA Astrophysics Data System (ADS)

    Battiston, Stefano; Caldarelli, Guido; Georg, Co-Pierre; May, Robert; Stiglitz, Joseph

    2013-03-01

    The intrinsic complexity of the financial derivatives market has emerged as both an incentive to engage in it, and a key source of its inherent instability. Regulators now faced with the challenge of taming this beast may find inspiration in the budding science of complex systems.

  11. Designing Complexity

    ERIC Educational Resources Information Center

    Glanville, Ranulph

    2007-01-01

    This article considers the nature of complexity and design, as well as relationships between the two, and suggests that design may have much potential as an approach to improving human performance in situations seen as complex. It is developed against two backgrounds. The first is a world view that derives from second order cybernetics and radical…

  12. Complex odontoma.

    PubMed

    Preetha, A; Balikai, Bharati S; Sujatha, D; Pai, Anuradha; Ganapathy, K S

    2010-01-01

    Odontomas are hamartomatous lesions or malformations composed of mature enamel, dentin, and pulp. They may be compound or complex, depending on the extent of morphodifferentiation or their resemblance to normal teeth. The etiology of odontoma is unknown, although several theories have been proposed. This article describes a case of a large infected complex odontoma in the residual mandibular ridge, resulting in considerable mandibular expansion.

  13. Complexation of the vulcanization accelerator tetramethylthiuram disulfide and related molecules with zinc compounds including zinc oxide clusters (Zn4O4).

    PubMed

    Steudel, Ralf; Steudel, Yana; Wong, Ming Wah

    2008-01-01

    Zinc chemicals are used as activators in the vulcanization of organic polymers with sulfur to produce elastic rubbers. In this work, the reactions of Zn(2+), ZnMe(2), Zn(OMe)(2), Zn(OOCMe)(2), and the heterocubane cluster Zn(4)O(4) with the vulcanization accelerator tetramethylthiuram disulfide (TMTD) and with the related radicals and anions Me(2)NCS(2)(*), Me(2)NCS(3)(*), Me(2)NCS(2)(-), and Me(2)NCS(3)(-) have been studied by quantum chemical methods at the MP2/6-31+G(2df,p)//B3LYP/6-31+G* level of theory. More than 35 zinc complexes have been structurally characterized and the energies of formation from their components calculated for the first time. The binding energy of TMTD as a bidendate ligand increases in the order ZnMe(2)complexes with the radicals Me(2)NCS(2)(*) and Me(2)NCS(3)(*). Dissociation of the TMTD molecule at the S-S bond on reaction with the Zn(4)O(4) cluster is predicted to be strongly exothermic, in sharp contrast to the endothermic S-S bond dissociation of the free molecule. The same holds for tetramethylthiuram trisulfide (TMTT). Surprisingly, the resulting complexes contain Zn-S as well as S-O bonds. The Zn(4)O(4) nanocluster serves here as a model for bulk zinc oxide used as an activator in rubber vulcanization by sulfur. The further uptake of sulfur atoms by the various complexes from S(8) or TMTD with formation of species derived from the radical Me(2)NCS(3)(*) or the trithiocarbamate anion Me(2)NCS(3)(-) is endothermic for mono- and dinuclear zinc dithiocarbamate (dtc) complexes such as [Zn(dtc)(2)] and [Zn(2)(dtc)(4)], but exothermic in the case of polynuclear zinc oxide species containing bridging ligands as in [Zn(4)O(4)(mu-S(2)CNMe(2))] and [Zn(4)O(4)(mu-dtc)]. Therefore, zinc oxide as a polynuclear species is predicted to promote the formation of trisulfido complexes, which are generally assumed to serve as catalysts for the transfer of

  14. Newer mixed ligand Schiff base complexes from aquo-N-(2‧-hydroxy acetophenone) glycinatocopper(II) as synthon: DFT, antimicrobial activity and molecular docking study

    NASA Astrophysics Data System (ADS)

    Pramanik, Harun A. R.; Das, Dharitri; Paul, Pradip C.; Mondal, Paritosh; Bhattacharjee, Chira R.

    2014-02-01

    Synthesis of a series of newer mixed ligand copper(II) complexes of aminoacid Schiff base of the type [CuL(X)] (L = N-(2‧-hydroxy acetophenone) glycinate, X = imidazole (im) 2, benzimidazole (benz) 3, pyridine (py) 4, hydrazine (hz) 5,8-hydroxyquinoline (8-hq) 6, pyrrolidine (pyrr) 7, piperidine (pip) 8, and nicotinamide (nic) 9) have been accomplished from the interaction of an aquated Schiff base complex, [CuL(H2O)]·H2O, 1 with some selected neutral nitrogen-donor ligands. The copper(II) Schiff base complex, [CuL(H2O)]·H2O, L = N-(2‧-hydroxy acetophenone) glycinate was synthesized from the reaction of glycine and 2‧ hydroxy acetophenone and copper(II) acetate. The compounds were characterised by elemental analysis, spectral, magnetic and thermal studies. The density functional theory calculations were performed using LANL2DZ and 6-311 G(d, p) basis sets with B3LYP correlation functional to ascertain the stable electronic structure, HOMO-LUMO energy gap, chemical hardness and dipole moment of the mixed ligand complexes. A distorted square planar geometry has been conjectured for the complexes. Antibacterial activities of the ligand and its metal complexes have been tested against selected gram-positive and gram-negative strains and correlated with computational docking scores.

  15. Amorphic complexity

    NASA Astrophysics Data System (ADS)

    Fuhrmann, G.; Gröger, M.; Jäger, T.

    2016-02-01

    We introduce amorphic complexity as a new topological invariant that measures the complexity of dynamical systems in the regime of zero entropy. Its main purpose is to detect the very onset of disorder in the asymptotic behaviour. For instance, it gives positive value to Denjoy examples on the circle and Sturmian subshifts, while being zero for all isometries and Morse-Smale systems. After discussing basic properties and examples, we show that amorphic complexity and the underlying asymptotic separation numbers can be used to distinguish almost automorphic minimal systems from equicontinuous ones. For symbolic systems, amorphic complexity equals the box dimension of the associated Besicovitch space. In this context, we concentrate on regular Toeplitz flows and give a detailed description of the relation to the scaling behaviour of the densities of the p-skeletons. Finally, we take a look at strange non-chaotic attractors appearing in so-called pinched skew product systems. Continuous-time systems, more general group actions and the application to cut and project quasicrystals will be treated in subsequent work.

  16. Complex interactions

    NASA Astrophysics Data System (ADS)

    de Régules, Sergio

    2016-04-01

    Complexity science - which describes phenomena such as collective and emergent behaviour - is the focus of a new centre where researchers are examining everything from the spread of influenza to what a healthy heartbeat looks like. Sergio de Régules reports.

  17. Complex Clouds

    Atmospheric Science Data Center

    2013-04-16

    ...     View Larger Image The complex structure and beauty of polar clouds are highlighted by these images acquired ... corner, the edge of the Antarctic coastline and some sea ice can be seen through some thin, high cirrus clouds. The right-hand panel ...

  18. Researching Complexity.

    ERIC Educational Resources Information Center

    Sumara, Dennis J.

    2000-01-01

    Discusses what Complexity Theory (presented as a rubric that collects theoretical understandings from a number of domains such as ecology, biology, neurology, and education) suggests about mind, selfhood, intelligence, and practices of reading, and the import of these reconceptualizations to reader-response researchers. Concludes that developing…

  19. Complex chemistry with complex compounds

    NASA Astrophysics Data System (ADS)

    Eichler, Robert; Asai, M.; Brand, H.; Chiera, N. M.; Di Nitto, A.; Dressler, R.; Düllmann, Ch. E.; Even, J.; Fangli, F.; Goetz, M.; Haba, H.; Hartmann, W.; Jäger, E.; Kaji, D.; Kanaya, J.; Kaneya, Y.; Khuyagbaatar, J.; Kindler, B.; Komori, Y.; Kraus, B.; Kratz, J. V.; Krier, J.; Kudou, Y.; Kurz, N.; Miyashita, S.; Morimoto, K.; Morita, K.; Murakami, M.; Nagame, Y.; Ooe, K.; Piguet, D.; Sato, N.; Sato, T. K.; Steiner, J.; Steinegger, P.; Sumita, T.; Takeyama, M.; Tanaka, K.; Tomitsuka, T.; Toyoshima, A.; Tsukada, K.; Türler, A.; Usoltsev, I.; Wakabayashi, Y.; Wang, Y.; Wiehl, N.; Wittwer, Y.; Yakushev, A.; Yamaki, S.; Yano, S.; Yamaki, S.; Qin, Z.

    2016-12-01

    In recent years gas-phase chemical studies assisted by physical pre-separation allowed for the investigation of fragile single molecular species by gas-phase chromatography. The latest success with the heaviest group 6 transactinide seaborgium is highlighted. The formation of a very volatile hexacarbonyl compound Sg(CO)6 was observed similarly to its lighter homologues molybdenum and tungsten. The interactions of these gaseous carbonyl complex compounds with quartz surfaces were investigated by thermochromatography. Second-generation experiments are under way to investigate the intramolecular bond between the central metal atom of the complexes and the ligands addressing the influence of relativistic effects in the heaviest compounds. Our contribution comprises some aspects of the ongoing challenging experiments as well as an outlook towards other interesting compounds related to volatile complex compounds in the gas phase.

  20. An unprecedented binuclear cadmium di-thio-carbamate adduct: bis-[μ2-N-(2-hydroxy-eth-yl)-N-iso-propyl-carbamodi-thio-ato-κ(3)S:S,S']bis-{[N-(2-hydroxy-eth-yl)-N-iso-propyl-carbamodi-thio-ato-κ(2)S,S'](3-{(1E)-[(E)-2-(pyridin-3-yl-methyl-idene)hydrazin-1-yl-idene]meth-yl}pyridine-κN)cadmium]} dihydrate.

    PubMed

    Arman, Hadi D; Poplaukhin, Pavel; Tiekink, Edward R T

    2016-09-01

    The asymmetric unit in the title binuclear compound, [Cd(C6H12NOS2)2(C12H10N4)]2·2H2O, comprises a Cd(II) atom, two di-thio-carbamate (dtc) anions, a monodentate 3-pyridine-aldazine ligand and a lattice water mol-ecule. The binuclear mol-ecule is constructed by the application of inversion symmetry. One dtc ligand simultaneously chelates one cadmium atom and bridges the centrosymmetric mate, while the other dtc ligand is chelating only. This leads to a centrosymmetric [Cd(dtc)2]2 core to which are appended two 3-pyridine-aldazine ligands. The resulting NS5 donor set is based on an octa-hedron. The three-dimensional mol-ecular packing is sustained by hydroxyl-O-H(hydrox-yl) and water-O-H⋯O(hydrox-yl) hydrogen bonding, leading to supra-molecular layers parallel to (101) which are connected by water-O-H⋯N(pyrid-yl) hydrogen bonding; additional C-H⋯O, S π(chelate ring) inter-actions are also evident. The retention of the central [Cd(dtc)2]2 core upon adduct formation is unprecedented in the structural chemistry of the zinc-triad di-thio-carbamates.

  1. Transition metal complexes of oxazolinylboranes and cyclopentadienyl-bis(oxazolinyl)borates: Catalysts for asymmetric olefin hydroamination and acceptorless alcohol decarbonylation

    SciTech Connect

    Manna, Kuntal

    2012-12-17

    The research presented and discussed in this dissertation involves the synthesis of transition metal complexes of oxazolinylboranes and cyclopentadienyl-bis(oxazolinyl)borates, and their application in catalytic enantioselective olefin hydroamination and acceptorless alcohol decarbonylation. Neutral oxazolinylboranes are excellent synthetic intermediates for preparing new borate ligands and also developing organometallic complexes. Achiral and optically active bis(oxazolinyl)phenylboranes are synthesized by reaction of 2-lithio-2-oxazolide and 0.50 equiv of dichlorophenylborane. These bis(oxazolinyl)phenylboranes are oligomeric species in solid state resulting from the coordination of an oxazoline to the boron center of another borane monomer. The treatment of chiral bis(oxazolinyl)phenylboranes with sodium cyclopentadienide provide optically active cyclopentadienyl-bis(oxazolinyl)borates H[PhB(C5H5)(OxR)2] [OxR = Ox4S-iPr,Me2, Ox4R-iPr,Me2, Ox4S-tBu]. These optically active proligands react with an equivalent of M(NMe2)4 (M = Ti, Zr, Hf) to afford corresponding cyclopentadienyl-bis(oxazolinyl)borato group 4 complexes {PhB(C5H4)(OxR)2}M(NMe2)2 in high yields. These group 4 compounds catalyze cyclization of aminoalkenes at room temperature or below, providing pyrrolidine, piperidine, and azepane with enantiomeric excesses up to 99%. Our mechanistic investigations suggest a non-insertive mechanism involving concerted C-N/C-H bond formation in the turnover limiting step of the catalytic cycle. Among cyclopentadienyl-bis(oxazolinyl)borato group 4 catalysts, the zirconium complex {PhB(C5H4)(Ox4S-iPr,Me2)2}Zr(NMe2)2 ({S-2}Zr(NMe2)2) displays highest activity and enantioselectivity. Interestingly, S-2

  2. Multimetallic complexes and functionalized gold nanoparticles based on a combination of d- and f-elements.

    PubMed

    Sung, Simon; Holmes, Holly; Wainwright, Luke; Toscani, Anita; Stasiuk, Graeme J; White, Andrew J P; Bell, Jimmy D; Wilton-Ely, James D E T

    2014-02-17

    The new DO3A-derived dithiocarbamate ligand, DO3A-(t)Bu-CS2K, is formed by treatment of the ammonium salt [DO3A-(t)Bu]HBr with K2CO3 and carbon disulfide. DO3A-(t)Bu-CS2K reacts with the ruthenium complexes cis-[RuCl2(dppm)2] and [Ru(CH═CHC6H4Me-4)Cl(CO)(BTD)(PPh3)2] (BTD = 2,1,3-benzothiadiazole) to yield [Ru(S2C-DO3A-(t)Bu)(dppm)2](+) and [Ru(CH═CHC6H4Me-4)(S2C-DO3A-(t)Bu)(CO)(PPh3)2], respectively. Similarly, the group 10 metal complexes [Pd(C,N-C6H4CH2NMe2)Cl]2 and [PtCl2(PPh3)2] form the dithiocarbamate compounds, [Pd(C,N-C6H4CH2NMe2)(S2C-DO3A-(t)Bu)] and [Pt(S2C-DO3A-(t)Bu)(PPh3)2](+), under the same conditions. The linear gold complexes [Au(S2C-DO3A-(t)Bu)(PR3)] are formed by reaction of [AuCl(PR3)] (R = Ph, Cy) with DO3A-(t)Bu-CS2K. However, on reaction with [AuCl(tht)] (tht = tetrahydrothiophene), the homoleptic digold complex [Au(S2C-DO3A-(t)Bu)]2 is formed. Further homoleptic examples, [M(S2C-DO3A-(t)Bu)2] (M = Ni, Cu) and [Co(S2C-DO3A-(t)Bu)3], are formed from treatment of NiCl2·6H2O, Cu(OAc)2, or Co(OAc)2, respectively, with DO3A-(t)Bu-CS2K. The molecular structure of [Ni(S2C-DO3A-(t)Bu)2] was determined crystallographically. The tert-butyl ester protecting groups of [M(S2C-DO3A-(t)Bu)2] (M = Ni, Cu) and [Co(S2C-DO3A-(t)Bu)3] are cleaved by trifluoroacetic acid to afford the carboxylic acid products, [M(S2C-DO3A)2] (M = Ni, Cu) and [Co(S2C-DO3A)3]. Complexation with Gd(III) salts yields trimetallic [M(S2C-DO3A-Gd)2] (M = Ni, Cu) and tetrametallic [Co(S2C-DO3A-Gd)3], with r(1) values of 11.5 (Co) and 11.0 (Cu) mM(-1) s(-1) per Gd center. DO3A-(t)Bu-CS2K can also be used to prepare gold nanoparticles, Au@S2C-DO3A-(t)Bu, by displacement of the surface units from citrate-stabilized nanoparticles. This material can be transformed into the carboxylic acid derivative Au@S2C-DO3A by treatment with trifluoroacetic acid. Complexation with Gd(OTf)3 or GdCl3 affords Au@S2C-DO3A-Gd with an r(1) value of 4.7 mM(-1) s(-1) per chelate and 1500 mM(-1) s(-1) per

  3. Crystal structure of ethyl (2S,2′R)-1′-benzyl-3-oxo-3H-di­spiro­[1-benzo­thio­phene-2,3′-pyrrolidine-2′,11′′-indeno[1,2-b]quinoxaline]-4′-carboxyl­ate

    PubMed Central

    Govindaraj, J.; Raja, R.; Suresh, M.; Raghunathan, R.; SubbiahPandi, A.

    2015-01-01

    In the title compound, C35H27N3O3S, the spiro-linked five-membered rings both adopt twisted conformations. The pyrrolidine ring makes dihedral angles of 80.5 (1) and 77.4 (9)° with the benzo­thio­phene ring system and the quinoxaline ring system, respectively. The S atom and C=O unit of the benzo­thio­phene ring system are disordered over two opposite orientations in a 0.768 (4):0.232 (4) ratio. The atoms of the ethyl side chain are disordered over two sets of sites in a 0.680 (16):0.320 (16) ratio. In the crystal, mol­ecules are linked by C—H⋯O, C—H⋯N and π–π inter­actions [shortest centroid–centroid distance = 3.4145 (19) Å], resulting in a three-dimensional network. PMID:25844245

  4. Conformation of the nootropic agents 1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinepropanoic acid (CI-933) and 4-hydroxymethyl-1-benzyl-pyrrolidin-2-one (WEB-1868): X-ray crystal structures, theoretical MO calculations (AM-1) and 600 MHZ 1H NMR spectra

    NASA Astrophysics Data System (ADS)

    Amato, Maria E.; Bandoli, Giuliano; Djedaïni, Florence; Dolmella, Alessandro; Grassi, Antonio; Pappalardo, Giuseppe C.

    1990-05-01

    The crystal and molecular structures of the cognition activators 1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinepropanoic acid (CI-933) ( 1) and 4-hydroxymethyl-1-benzyl-pyrrolidin-2-one (WEB-1868) ( 2) have been determined by X-ray analysis. The conformations of the isolated molecules 1 and 2 have been deduced from AM1-type theoretical calculations. Whilst in 1 there are no hydrogen bonds, in 2 stabilization of the crystal occurs through effective inter- and intramolecular ? bonds. The five-membered ring in both 1 and 2 adopts an envelope conformation in the solid with C(3) at the flap displaced from the C(1), C(2), C(4), N(5) mean plane. Bond distances and angles are normal and comparable with previously known similar structures. In the crystal, the torsion angles C(1)-N(5)-C(6)-C(7) and N(5)-C(6)-C(7)-C(8) in 1 are 43.1° and 44.8°, respectively; the same torsion angles in 2 are -101° and 42°, respectively. Results of theoretical calculations correlate well with the conformation of 1 in the solid, whilst in the case of 2 these indicate that the conformation in the crystal should not be retained by the isolated molecule. The complete analysis of the very high field (600 MHz) 1H NMR spectra of both compounds in CDCl 3, gives results well in line with the above established conformational features.

  5. Managing Complexity

    SciTech Connect

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  6. Tin(IV) complexes of pyrrolidinedithiocarbamate: synthesis, characterisation and antifungal activity.

    PubMed

    Menezes, D C; Vieira, F T; de Lima, G M; Porto, A O; Cortés, M E; Ardisson, J D; Albrecht-Schmitt, T E

    2005-12-01

    The reaction of ammonium pyrrolidinedithiocarbamate, [NH4{S2CN(CH2)4}], with SnCl2, [Sn(C6H5)2Cl2], [Sn(C6H5)3Cl], [Sn(C4H9)2Cl2] and [Sn(C6H11)3Cl] produced in good yield the compounds [Sn{S2CN(CH2)4}2Cl2] (1), [Sn{S2CN(CH2)4}2Ph2] (2), [Sn{S2CN(CH2)4}Ph3] (3), [Sn{S2CN(CH2)4}2 n-Bu2] (4) and [Sn{S2CN(CH2)4}Cy3] (5). The complexes were characterised by infrared, multinuclear NMR (1H, 13C{1H} and 119Sn{1H}) and 119Sn Mössbauer spectroscopies. In addition, the crystal structure of 4 was determined by X-ray crystallography. The in vitro antifungal activity of the tin(IV) complexes as well of the ligand was performed on human pathogenic fungi, Candida albicans, in concentrations of 0.025; 0.050; 0.100; 0.200; 0.400; 0.800; 1.600 and 3.200 mM. The microorganism presented resistance to the dithiocarbamate ligand and all tin(IV) complexes tested were actives. The highest activity was found for compounds 1 and 4.

  7. Synthesis, crystal structure and photoconductivity of the first [60]fullerene complex with metal diethyldithiocarbamate: {CuII(dedtc)2}2.C60.

    PubMed

    Konarev, Dmitri V; Kovalevsky, Andrey Y; Lopatin, Dmitri V; Umrikhin, Alexey V; Yudanova, Evgeniya I; Coppens, Philip; Lyubovskaya, Rimma N; Saito, Gunzi

    2005-05-21

    The first molecular complex of fullerene C60 with metal dithiocarbamate, namely, {CuII(dedtc)2}2.C60(dedtc: diethyldithiocarbamate) (1) was obtained as single crystals. Butterfly-shaped CuII(dedtc)2 molecules efficiently co-crystallized with spherical fullerene molecules to form a layered structure, in which closely packed hexagonal C60 layers alternate with the layers composed of CuII(dedtc)2 dimers. The formation of the complex with C60 changes geometry and the EPR spectrum of starting CuII(dedtc)2. Magnetic susceptibility of 1 follows the Curie-Weiss law in the 300-1.9 K range with the negative Weiss constant of -2.5 K showing a weak antiferromagnetic interaction between CuII centers in the dimers. The crystals of 1 have low dark conductivity of 10(-11) S cm-1, which is consistent with a neutral ground state of the complex. Illumination of the crystals by white light increases the photocurrent by 20-50 times. The photoconductivity spectrum of 1 has a maximum at 470 nm showing that both intermolecular charge transfer between neighboring C60 molecules and photoexcitation of CuII(dedtc)2 can contribute to photogeneration of free charge carriers. The effect of a weak magnetic field with Bo<0.5 T on the photoconductivity of 1 has been found.

  8. Complex Systems

    PubMed Central

    Goldberger, Ary L.

    2006-01-01

    Physiologic systems in health and disease display an extraordinary range of temporal behaviors and structural patterns that defy understanding based on linear constructs, reductionist strategies, and classical homeostasis. Application of concepts and computational tools derived from the contemporary study of complex systems, including nonlinear dynamics, fractals and “chaos theory,” is having an increasing impact on biology and medicine. This presentation provides a brief overview of an emerging area of biomedical research, including recent applications to cardiopulmonary medicine and chronic obstructive lung disease. PMID:16921107

  9. Cosmic Complexity

    NASA Technical Reports Server (NTRS)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  10. Cosmic Complexity

    NASA Technical Reports Server (NTRS)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  11. In vitro bioactivation of a selective estrogen receptor modulator (2S,3R)-(+)-3-(3-hydroxyphenyl)-2-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol (I) in liver microsomes: formation of adenine adducts.

    PubMed

    Li, Ying; Doss, George A; Li, Yan; Chen, Qing; Tang, Wei; Zhang, Zhoupeng

    2012-11-19

    As part of our efforts to develop safer selective estrogen receptor modulators (SERMs), compound I {(2S,3R)-(+)-3-(3-hydroxyphenyl)-2-[4-(2-pyrrolidin-1-ylethoxy)-phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol} was previously identified as a lead for further development. Subsequent studies showed that compound I is genotoxic in both in vitro Chinese hamster ovary (CHO) cells and in vivo mouse studies. To better understand the possible mechanisms for the observed genetoxicity effects, in vitro incubations of I with liver microsomes of human, monkey, and mouse in the presence of adenine were performed, which led to the detection of five adenine adducts. The formation of these adducts was NADPH-dependent, suggesting the involvement of oxidative bioactivation catalyzed by cytochrome P450 enzymes. The mechanism for the formation of the major adenine adduct (A1) involves the formation of a reactive ring-opened para-quinone intermediate. The formation of four other adenine adducts may involve the formation of a reactive epoxide or ortho-quinone intermediate. Furthermore, incubations of compound I with human hepatocytes showed dose-dependent DNA damages in Comet assays. All of the above suggest that some reactive metabolites of compound I, formed through bioactivation mechanisms, have a potential to interact with DNA molecules in vitro and in vivo. This may be one of the causes of the genotoxicity observed preclinically both in vitro and in vivo. This case study demonstrated an approach using in vitro DNA trapping assays for assessing the genotoxicity potential of drug candidates.

  12. (SP-4-4)-[Hydrogen N-({2-[(2S)-1-benzyl­pyrrolidine-2-carboxamido]phen­yl}(phen­yl)methyl­ene)-l-glutamato(2−)]nickel(II)

    PubMed Central

    Zhou, Jia-Dong; Cao, Fei; Ying, Han-Jie; Wei, Ping

    2009-01-01

    In the mol­ecule of the title complex, [Ni(C30H29N3O5)], the Ni atom is coordinated in a distorted square-planar geometry by three N and one O atoms. The aromatic rings are oriented at dihedral angles of 29.01 (3), 79.73 (3) and 83.37 (3)°. The remaining rings adopt envelope conformations with the C and N atoms at the flap positions. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into chains along the b axis. There is also a weak C—H⋯π inter­action. PMID:21582389

  13. (SP-4-4)-[Hydrogen N-({2-[(2S)-1-benzyl-pyrrolidine-2-carboxamido]phen-yl}(phen-yl)methyl-ene)-l-glutamato(2-)]nickel(II).

    PubMed

    Zhou, Jia-Dong; Cao, Fei; Ying, Han-Jie; Wei, Ping

    2009-03-28

    In the mol-ecule of the title complex, [Ni(C(30)H(29)N(3)O(5))], the Ni atom is coordinated in a distorted square-planar geometry by three N and one O atoms. The aromatic rings are oriented at dihedral angles of 29.01 (3), 79.73 (3) and 83.37 (3)°. The remaining rings adopt envelope conformations with the C and N atoms at the flap positions. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into chains along the b axis. There is also a weak C-H⋯π inter-action.

  14. Inorganic selenium speciation analysis in Allium and Brassica vegetables by ionic liquid assisted liquid-liquid microextraction with multivariate optimization.

    PubMed

    Castro Grijalba, Alexander; Martinis, Estefanía M; Wuilloud, Rodolfo G

    2017-03-15

    A highly sensitive vortex assisted liquid-liquid microextraction (VA-LLME) method was developed for inorganic Se [Se(IV) and Se(VI)] speciation analysis in Allium and Brassica vegetables. Trihexyl(tetradecyl)phosphonium decanoate phosphonium ionic liquid (IL) was applied for the extraction of Se(IV)-ammonium pyrrolidine dithiocarbamate (APDC) complex followed by Se determination with electrothermal atomic absorption spectrometry. A complete optimization of the graphite furnace temperature program was developed for accurate determination of Se in the IL-enriched extracts and multivariate statistical optimization was performed to define the conditions for the highest extraction efficiency. Significant factors of IL-VA-LLME method were sample volume, extraction pH, extraction time and APDC concentration. High extraction efficiency (90%), a 100-fold preconcentration factor and a detection limit of 5.0ng/L were achieved. The high sensitivity obtained with preconcentration and the non-chromatographic separation of inorganic Se species in complex matrix samples such as garlic, onion, leek, broccoli and cauliflower, are the main advantages of IL-VA-LLME.

  15. Ionic liquid-linked dual magnetic microextraction of lead(II) from environmental samples prior to its micro-sampling flame atomic absorption spectrometric determination.

    PubMed

    Yilmaz, Erkan; Soylak, Mustafa

    2013-11-15

    A novel and rapid microextraction approach termed as ionic liquid-linked dual magnetic microextraction (IL-DMME), was developed for the atomic absorption spectrometric determination of lead. The developed method based on a combination of dispersive liquid-liquid microextraction (DLLME) and dispersive micro solid-phase extraction (D-μ-SPE). In the first DLLME step, 1-butyl-3-methylimidazolium hexafluorophosphate [C4mim][PF6], was selected to extract the lead-pyrrolidine-dithiocarbamate (Pb-PDC) complex from sample solution by the assistance of vortex agitator. After the first step, fifty milligrams of Fe3O4 magnetic nanoparticles (MNPs) were added to extraction of the ionic liquid and Pb-PDC complex in aqueous solution. The effective factors in proposed IL-DMME procedure, including volume of 1-butyl-3-methylimidazolium hexafluorophosphate, amount of Fe3O4 magnetic nanoparticles, vortex time, amount of ammonium pyrrolidinedithiocarbamate, sample volume and matrix effect were optimized in details. Under the optimal conditions, the method present has low detection limit (0.57 μg L(-1)), high preconcentration factor (160) and good repeatability (<7.5%, n=10). The accuracy of the developed method was evaluated by the analysis of the certified reference materials and addition-recovery tests. The method was successfully applied to the determination of lead in water, plant and hair samples.

  16. Separation-preconcentration of nickel and lead in food samples by a combination of solid-liquid-solid dispersive extraction using SiO2 nanoparticles, ionic liquid-based dispersive liquid-liquid micro-extraction.

    PubMed

    Jalbani, Nusrat; Soylak, Mustafa

    2015-01-01

    A microextraction method for the determination of nickel and lead using solid-liquid-solid dispersive extraction followed by ionic liquid-based dispersive liquid-liquid microextraction (SLSDE-ILDLLME) was presented. It was applied to the extraction of nickel and lead from food samples. Ammonium pyrrolidine dithiocarbamate (APDC) as complexing agent, [C4MIM][PF6] as ionic liquid, SiO2 as nanoparticles and 2 mol L(-1) HNO3 as eluent were used. Several important parameters such as amount of IL, extraction time, pH and volume of the complexing agent were investigated. The quantitative recoveries were obtained at pH 7.0 for analytes. Under the optimum conditions, the limits of detection (LODs) calculated using 3(Sd)blank/m were 0.17 for Ni(II) and 0.79 µg L(-1) for Pb(II) for aqueous solutions with 125 enrichment factor (EF). The limit of detections of the analyte ions (3(Sd)blank/m) for solid samples were 0.09 µg g(-1) (Ni) and 0.40 µg g(-1) (Pb). The accuracy of the proposed method was confirmed by the analysis of standard reference material (1577c bovine liver) and spiked recovery test. The proposed method was applied to determine nickel and lead levels in chicken, fish and meat samples.

  17. Differential effects of the substrate inhibitor l-trans-pyrrolidine-2,4-dicarboxylate (PDC) and the non-substrate inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) of glutamate transporters on neuronal damage and extracellular amino acid levels in rat brain in vivo.

    PubMed

    Montiel, T; Camacho, A; Estrada-Sánchez, A M; Massieu, L

    2005-01-01

    The extracellular concentration of glutamate is highly regulated by transporter proteins, due to its neurotoxic properties. Dysfunction or reverse activation of these transporters is related to the extracellular accumulation of excitatory amino acids and neuronal damage associated with ischemia and hypoglycemia. We have investigated by microdialysis the effects of the substrate and the non-substrate inhibitors of glutamate transporters, l-trans-2,4-pyrrolidine dicarboxylate (PDC) and DL-threo-beta-benzyloxyaspartate (DL-TBOA), respectively, on the extracellular levels of amino acids in the rat hippocampus in vivo. In addition, we have studied the effect of both inhibitors on neuronal damage after direct administration into the hippocampus and striatum. Electroencephalographic activity was recorded after the intrahippocampal infusion of DL-TBOA or PDC. Microdialysis administration of 500 microM DL-TBOA into the hippocampus increased 3.4- and nine-fold the extracellular levels of aspartate and glutamate, respectively. Upon stereotaxic administration it induced neuronal damage dose-dependently in CA1 and dentate gyrus, and convulsive behavior. Electroencephalographic recording showed the appearance of limbic seizures in the hippocampus after DL-TBOA infusion. In the striatum it also induced dose-dependent neuronal damage. These effects were prevented by the i.p. administration of the glutamate receptor antagonists (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-iminemaleate and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline. In contrast to dl-TBOA, PDC (500 microM) induced a more discrete elevation of excitatory amino acids levels (2.6- and three-fold in aspartate and glutamate, respectively), no neuronal damage or behavioral changes, and no alterations in electroencephalographic activity. The differential results obtained with DL-TBOA and PDC might be attributed to their distinct effects on the extracellular concentration of amino acids. Results

  18. Towards the chiral metabolomics: Liquid chromatography-mass spectrometry based DL-amino acid analysis after labeling with a new chiral reagent, (S)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl)pyrrolidine-2-carboxylate, and the application to saliva of healthy volunteers.

    PubMed

    Mochizuki, Toshiki; Takayama, Takahiro; Todoroki, Kenichiro; Inoue, Koichi; Min, Jun Zhe; Toyo'oka, Toshimasa

    2015-05-22

    A novel triazine-type chiral derivatization reagent, i.e., (S)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl) pyrrolidine-2-carboxylate (DMT-(S)-Pro-OSu), was developed for the highly sensitive and selective detection of chiral amines and amino acids by UPLC-MS/MS analysis. The enantiomers of amino acids were easily labeled with the reagents at room temperature within 40 min in an alkaline medium containing triethylamine. The diastereomers derived from proteolytic amino acids, except serine, were well separated under isocratic elution conditions by reversed-phase chromatography using an ODS column (Rs=1.2-9.0). DL-Serine was separated by use of an ADME column which has relatively higher polar surface than the conventional ODS column. The characteristic product ions, i.e., m/z 195.3 and m/z 209.3, were detected from all the diastereomers by the collision-induced dissociation of the protonated molecule. A highly sensitive detection on the amol-fmol level was obtained from the selected reaction monitoring (SRM) chromatogram. The chiral amines (e.g., adrenaline and noradrenaline) labeled with DMT-(S)-Pro-OSu were also well separated and sensitively detected by the present procedure. The method using DMT-(S)-Pro-OSu was used for the determination of DL-amino acids in the human saliva from healthy volunteers. Various L-amino acids were identified in the saliva. Furthermore, D-alanine (D-Ala) and D-proline (D-Pro) were also detected in relatively high concentrations (>5%). The ratio was higher in male saliva than in female saliva. However, the difference in the ratio of D-Ala for one day was not very high and the effect of foods and beverage seemed to be negligible. Based on the results using L-Ala-d3, the D-Ala in saliva seemed to be produced due to the racemization with some enzymes such as racemase. The racemization reaction was reversible, i.e., D-Ala-d3 was also racemized to L-Ala-d3 in saliva. Thus, care should be taken during the analysis of DL

  19. On State Complexes and Special Cube Complexes

    ERIC Educational Resources Information Center

    Peterson, Valerie J.

    2009-01-01

    This thesis presents the first steps toward a classification of non-positively curved cube complexes called state complexes. A "state complex" is a configuration space for a "reconfigurable system," i.e., an abstract system in which local movements occur in some discrete manner. Reconfigurable systems can be used to describe, for example,…

  20. Structures of the Class D Carbapenemase OXA-24 from Acinetobacter baumannii in Complex with Doripenem

    SciTech Connect

    Schneider, Kyle D.; Ortega, Caleb J.; Renck, Nicholas A.; Bonomo, Robert A.; Powers, Rachel A.; Leonard, David A.

    2012-02-08

    The emergence of class D {beta}-lactamases with carbapenemase activity presents an enormous challenge to health practitioners, particularly with regard to the treatment of infections caused by Gram-negative pathogens such as Acinetobacter baumannii. Unfortunately, class D {beta}-lactamases with carbapenemase activity are resistant to {beta}-lactamase inhibitors. To better understand the details of the how these enzymes bind and hydrolyze carbapenems, we have determined the structures of two deacylation-deficient variants (K84D and V130D) of the class D carbapenemase OXA-24 with doripenem bound as a covalent acyl-enzyme intermediate. Doripenem adopts essentially the same configuration in both OXA-24 variant structures, but varies significantly when compared to the non-carbapenemase class D member OXA-1/doripenem complex. The alcohol of the 6a hydroxyethyl moiety is directed away from the general base carboxy-K84, with implications for activation of the deacylating water. The tunnel formed by the Y112/M223 bridge in the apo form of OXA-24 is largely unchanged by the binding of doripenem. The presence of this bridge, however, causes the distal pyrrolidine/sulfonamide group to bind in a drastically different conformation compared to doripenem bound to OXA-1. The resulting difference in the position of the side-chain bridge sulfur of doripenem is consistent with the hypothesis that the tautomeric state of the pyrroline ring contributes to the different carbapenem hydrolysis rates of OXA-1 and OXA-24. These findings represent a snapshot of a key step in the catalytic mechanism of an important class D enzyme, and might be useful for the design of novel inhibitors.

  1. STRUCTURES OF THE CLASS D CARBAPENEMASE OXA-24 FROM ACINETOBACTER BAUMANNII IN COMPLEX WITH DORIPENEM

    PubMed Central

    Schneider, Kyle D.; Ortega, Caleb J.; Renck, Nicholas A.; Bonomo, Robert A.; Powers, Rachel A.; Leonard, David A.

    2011-01-01

    The emergence of class D β-lactamases with carbapenemase activity presents an enormous challenge to health practitioners, particularly with regard to the treatment of infections caused by Gram negative pathogens such as Acinetobacter baumanii. Unfortunately, class D β-lactamases with carbapenemase activity are resistant to β-lactamase inhibitors. To better understand the details of the how these enzymes bind and hydrolyze carbapenems, we have determined the structures of two deacylation-deficient variants (K84D and V130D) of the class D carbapenemase OXA-24 with doripenem bound as a covalent acyl-enzyme intermediate. Doripenem adopts essentially the same configuration in both OXA-24 variant structures, but varies significantly when compared to the non-carbapenemase class D member OXA-1/doripenem complex. The alcohol of the 6α hydroxyethyl moiety is directed away from the general base carboxy-K84, with implications for activation of the deacylating water. The tunnel formed by the Y112/M223 bridge in the apo form of OXA-24 is largely unchanged by the binding of doripenem. The presence of this bridge, however, causes the distal pyrrolidine/sulfonamide group to bind in a drastically different conformation compared to doripenem bound to OXA-1. The resulting difference in the position of the side-chain bridge sulfur of doripenem is consistent with the hypothesis that the tautomeric state of the pyrroline ring contributes to the different carbapenem hydrolysis rates of OXA-1 and OXA-24. These findings represent a snapshot of a key step in the catalytic mechanism of an important class D enzyme, and may be useful for the design of novel inhibitors. PMID:21215758

  2. On the nature of a compound formed from dinitrosyl-iron complexes with cysteine and responsible for a long-lasting vasorelaxation.

    PubMed

    Mokh, Vladimir P; Poltorakov, Alexander P; Serezhenkov, Vladimir A; Vanin, Anatoly F

    2010-05-15

    The nature of a compound able to induce long-lasting (> or =20 min) relaxation of rat abdominal aorta rings after addition of rapidly (within several minutes) disappeared mono- and binuclear dinitrosyl iron complexes with cysteine (M- and B-DNICs, respectively) (10 micromol) to the Krebs medium has been investigated. It has been found that long-lasting vasorelaxation is not induced either by S-nitrosocysteine formed upon decomposition of DNICs or by accumulation of free nitric oxide molecules or nitrite remaining in the incubation medium. Long-term air bubbling of the Krebs medium initially containing M-DNIC is accompanied by conversion of the complex first into B-DNIC, which represents a Roussin's red salt cysteine ester and then into a more stable diamagnetic compound X, which displays an intense absorption band at 278 nm. Compound X is decomposed after treatment with the strong bivalent iron chelator bathophenanthroline disulfonate (BPDS) and N-methyl-D-glucamine dithiocarbamate (MGD). The MGD-induced decomposition of compound X is concomitant with the formation of EPR-detectable mononitrosyl iron complexes with MGD. Treatment of compound X with cysteine results in its decomposition and the appearance of optical absorption bands characteristic of M- and B-DNICs. Evidently, compound X, has an iron-nitrosyl origin similar to that of M- and B-DNICs and its formation in oxygenated DNIC solutions is determined by the lowering cysteine content in them. It is hypothesized that compound X represents a cysteine ester of nitrosyl iron complexes, namely, a black Roussin's salt cysteine ester responsible for long-lasting vasorelaxation initiated by addition of M- and B-DNICs that are rapidly decomposed to compound X to the incubation medium.

  3. Natural complexity, computational complexity and depth.

    PubMed

    Machta, J

    2011-09-01

    Depth is a complexity measure for natural systems of the kind studied in statistical physics and is defined in terms of computational complexity. Depth quantifies the length of the shortest parallel computation required to construct a typical system state or history starting from simple initial conditions. The properties of depth are discussed and it is compared with other complexity measures. Depth can only be large for systems with embedded computation.

  4. [Complexity of land ecosystem].

    PubMed

    Wu, Cifang; Chen, Meiqiu

    2002-06-01

    In recent years, complexity studies has become a new research region and been widely applied in engineering, biology, economy, management, military, police and sociology. In this paper, from the view of complex science, the main complexity characteristics of land ecosystem were described, furthermore, the application of fractal, chaos, and artificial neural network on the complexity of land ecosystem were also discussed.

  5. Speciation of very low amounts of arsenic and antimony in waters using dispersive liquid-liquid microextraction and electrothermal atomic absorption spectrometry

    NASA Astrophysics Data System (ADS)

    Rivas, Ricardo E.; López-García, Ignacio; Hernández-Córdoba, Manuel

    2009-04-01

    A new procedure for the determination of inorganic arsenic (III,V) and antimony (III,V) in water samples by dispersive liquid-liquid micro extraction separation and electrothermal atomic absorption spectrometry (ETAAS) is presented. At pH 1, As(III) and Sb(III) are complexed with ammonium pyrrolidine dithiocarbamate and extracted into the fine droplets formed when mixing carbon tetrachloride (extraction solvent), methanol (disperser solvent) and the sample solution. After extraction, the phases are separated by centrifugation, and As(III) and Sb(III) are determined in the organic phase. As(V) and Sb(V) remain in the aqueous layer. Total inorganic As and Sb are determined after the reduction of the pentavalent forms with sodium thiosulphate. As(V) and Sb(V) are calculated by difference. The detection limits are 0.01 and 0.05 µg L - 1 for As(III) and Sb(III), respectively, with an enrichment factor of 115. The relative standard deviation is in the 2.9-4.5% range. The procedure has been applied to the speciation of inorganic As and Sb in bottled, tap and sea water samples with satisfactory results.

  6. Nuclear Factor-Kappa B Activity Regulates Brain Expression of P-Glycoprotein in the Kainic Acid-Induced Seizure Rats

    PubMed Central

    Yu, Nian; Di, Qing; Liu, Hao; Hu, Yong; Jiang, Ying; Yan, Yu-kui; Zhang, Yan-fang; Zhang, Ying-dong

    2011-01-01

    This study was aimed to investigate the effect of NF-κB activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA-) induced seizure rats. Male SD rats were divided into saline control group (NS group), KA induced epilepsy group (EP group), and epilepsy group intervened with NF-κB inhibitor-pyrrolidine dithiocarbamate salt (PDTC group) or with dexamethasone (DEX group). No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-κB activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group. Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-κB activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-κB activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-κB activation, suggesting NF-κB independent pathway may also participate in regulating seizure induced P-gp over-expression. PMID:21403895

  7. Complex networks analysis of language complexity

    NASA Astrophysics Data System (ADS)

    Amancio, Diego R.; Aluisio, Sandra M.; Oliveira, Osvaldo N., Jr.; Costa, Luciano da F.

    2012-12-01

    Methods from statistical physics, such as those involving complex networks, have been increasingly used in the quantitative analysis of linguistic phenomena. In this paper, we represented pieces of text with different levels of simplification in co-occurrence networks and found that topological regularity correlated negatively with textual complexity. Furthermore, in less complex texts the distance between concepts, represented as nodes, tended to decrease. The complex networks metrics were treated with multivariate pattern recognition techniques, which allowed us to distinguish between original texts and their simplified versions. For each original text, two simplified versions were generated manually with increasing number of simplification operations. As expected, distinction was easier for the strongly simplified versions, where the most relevant metrics were node strength, shortest paths and diversity. Also, the discrimination of complex texts was improved with higher hierarchical network metrics, thus pointing to the usefulness of considering wider contexts around the concepts. Though the accuracy rate in the distinction was not as high as in methods using deep linguistic knowledge, the complex network approach is still useful for a rapid screening of texts whenever assessing complexity is essential to guarantee accessibility to readers with limited reading ability.

  8. Radioisotope trithiol complexes

    DOEpatents

    Jurisson, Silvia S.; Cutler, Cathy S.; Degraffenreid, Anthony J.

    2016-08-30

    The present invention is directed to a series of stable radioisotope trithiol complexes that provide a simplified route for the direct complexation of radioisotopes present in low concentrations. In certain embodiments, the complex contains a linking domain configured to conjugate the radioisotope trithiol complex to a targeting vector. The invention is also directed to a novel method of linking the radioisotope to a trithiol compound to form the radioisotope trithiol complex. The inventive radioisotope trithiol complexes may be utilized for a variety of applications, including diagnostics and/or treatment in nuclear medicine.

  9. Evolution of biological complexity

    PubMed Central

    Adami, Christoph; Ofria, Charles; Collier, Travis C.

    2000-01-01

    To make a case for or against a trend in the evolution of complexity in biological evolution, complexity needs to be both rigorously defined and measurable. A recent information-theoretic (but intuitively evident) definition identifies genomic complexity with the amount of information a sequence stores about its environment. We investigate the evolution of genomic complexity in populations of digital organisms and monitor in detail the evolutionary transitions that increase complexity. We show that, because natural selection forces genomes to behave as a natural “Maxwell Demon,” within a fixed environment, genomic complexity is forced to increase. PMID:10781045

  10. Doxorubicin Lipid Complex Injection

    MedlinePlus

    Doxorubicin lipid complex is used to treat ovarian cancer that has not improved or that has worsened after treatment with other medications. Doxorubicin lipid complex is also used to treat Kaposi's sarcoma ( ...

  11. Daunorubicin Lipid Complex Injection

    MedlinePlus

    Daunorubicin lipid complex is used to treat advanced Kaposi's sarcoma (a type of cancer that causes abnormal tissue to ... body) related to acquired immunodeficiency syndrome (AIDS). Daunorubicin lipid complex is in a class of medications called ...

  12. Irinotecan Lipid Complex Injection

    MedlinePlus

    Irinotecan lipid complex is used in combination with other medications to treat pancreatic cancer that has spread to other ... worsened after treatment with other chemotherapy medications. Irinotecan lipid complex is in a class of antineoplastic medications ...

  13. Oligocyclopentadienyl transition metal complexes

    SciTech Connect

    de Azevedo, Cristina G.; Vollhardt, K. Peter C.

    2002-01-18

    Synthesis, characterization, and reactivity studies of oligocyclopentadienyl transition metal complexes, namely those of fulvalene, tercyclopentadienyl, quatercyclopentadienyl, and pentacyclopentadienyl(cyclopentadienyl) are the subject of this account. Thermal-, photo-, and redox chemistries of homo- and heteropolynuclear complexes are described.

  14. Vincristine Lipid Complex Injection

    MedlinePlus

    Vincristine lipid complex is used to treat a certain type of acute lymphoblastic leukemia (ALL; a type ... at least two different treatments with other medications. Vincristine lipid complex is in a class of medications ...

  15. Crystallization of macromolecular complexes: combinatorial complex crystallization

    NASA Astrophysics Data System (ADS)

    Stura, Enrico A.; Graille, Marc; Charbonnier, Jean-Baptiste

    2001-11-01

    The usefulness of antibody complexation, as a way of increasing the chances of crystallization needs to be re-evaluated after many antibody complexes have been crystallized and their structure determined. It is somewhat striking that among these, only a small number is a complex with a large protein antigen. The problem is that the effort of raising, cleaving and purifying an Fab is rewarded only by an extra chance of getting crystals; depending on the relative likelihood of crystallization of the complexed and uncomplexed protein. The example of the complex between HIV gp120, CD4 and an Fab fragment from a neutralizing antibody suggests that further complexation of an antigen-antibody complex with a third protein could, by increasing the number of possible combinations, improve the likelihood of crystallization. We propose the use of Ig-binding proteins as a way of extending the method from HIV gp120 to all proteins for which there are monoclonal antibodies. We discuss this technique, combinatorial complex crystallization (CCC), as part of a multi-component system for the enhancement of crystallization of macromolecular complexes. The method makes use of single Ig-binding domains from Staphylococcus aureus protein A (SpA), Peptostreptococcus magnus protein L (PpL) and the streptococcal protein G (SpG). The generality of the method depends on the ability of these domains to interact with a large repertoire of antibodies without affecting antigen binding. There is strong evidence to suggest that these Ig-binding domains bind outside the antigen-combining site of the antibody without perturbing antigen binding. It is clear from the crystal structure of the single SpG domain complexed with an Fab that the interaction involves mainly the immunoglobulin CH1 domain, a region not involved in antigen recognition. We have recently determined the structure of the complex between a human Fab and the domain D from SpA and found that steric hindrance is unlikely even for large

  16. Bonding analyses, formation energies, and vibrational properties of M-R2dtc complexes (M=Ag(I), Ni(II), Cu(II), or Zn(II)).

    PubMed

    Georgieva, I; Trendafilova, N

    2007-12-20

    Detailed theoretical studies based on density functional theory (DFT)/B3LYP calculations of dimethyl- and diethyldithiocarbamate complexes of Ni(II), Cu(II), Zn(II), and Ag(I) are performed to characterize the metal-ligand bonding type as well as the metal-ligand bonding strength depending on the metal and the dialkyl substituent. The metal-ligand interactions in the studied complexes are investigated by means of charge decomposition analysis, energy partitioning analysis (EPA), and natural bond orbital analysis. According to the EPA calculations, the electrostatic attraction is the dominant contribution to the M-S2(R2dtc) (dtc=dithiocarbamate) bonding. The electrostatic and the orbital energies follow the order of the total binding energy, and hence both contributions are responsible for the binding energy order of M(R2dtc)2 complexes. The stability of the M(R2dtc)2 complexes is estimated by means of calculated formation reaction energies in the gas phase and solution, and it decreases in the order Ni(R2dtc)2>Cu(R2dtc)2>Zn(R2dtc)2. Larger formation reaction energies are found for M(Et2dtc)2 than for M(Me2dtc)2 complexes. The calculations predict stabilization of M(II)(R2dtc)2 complexes going from the gas phase to a polar solvent and destabilization of the bidentate AgR2dtc complex in a polar solvent. Gas-phase frequency calculations of all possible bonding types, symmetrical, asymmetrical, and uni- and bidentate, predict one band due to the nu(CS) IR absorption, and therefore the number of the bands in the 1060-920 cm(-1) region could not be used to discern the metal-ligand bonding type. Periodic DFT frequency calculations for Cu(Et2dtc)2 reveal that the splitting observed in the solid-state spectra of the complexes arises from the nonplanar MS4 fragment and intermolecular contacts but not from asymmetrical bonding. The calculations suggest that the important vibrational characteristic that can be used to discern uni- and bidentate bonding is the Raman activity of

  17. Complex Correspondence Principle

    SciTech Connect

    Bender, Carl M.; Meisinger, Peter N.; Hook, Daniel W.; Wang Qinghai

    2010-02-12

    Quantum mechanics and classical mechanics are distinctly different theories, but the correspondence principle states that quantum particles behave classically in the limit of high quantum number. In recent years much research has been done on extending both quantum and classical mechanics into the complex domain. These complex extensions continue to exhibit a correspondence, and this correspondence becomes more pronounced in the complex domain. The association between complex quantum mechanics and complex classical mechanics is subtle and demonstrating this relationship requires the use of asymptotics beyond all orders.

  18. Complex virial theorem and complex scaling

    SciTech Connect

    Junker, B.R.

    1983-06-01

    We present the simple generalization to complex energies of the normal global real scaling used for bound-state calculations to produce a variational energy which satisfies the virial theorem. We show that in two limiting cases, one or the other of which is almost always p satisfied in all calculations, the virially stabilized complex energy is sensitive to only the real part or the imaginary part of the complex virial expression. We then compute the virial expression for a number of wave functions for the 1s2s/sup 2/ /sup 2/S He/sup -/, 1s2s2p /sup 2/P/sup o/ He/sup -/, and 1s/sup 2/2s/sup 2/kp /sup 2/P/sup o/ Be/sup -/ resonances and the corresponding virially stabilized resonance energies. In all calculations one of the limiting cases was applicable.

  19. Assessing physiological complexity.

    PubMed

    Burggren, W W; Monticino, M G

    2005-09-01

    Physiologists both admire and fear complexity, but we have made relatively few attempts to understand it. Inherently complex systems are more difficult to study and less predictable. However, a deeper understanding of physiological systems can be achieved by modifying experimental design and analysis to account for complexity. We begin this essay with a tour of some mathematical views of complexity. After briefly exploring chaotic systems, information theory and emergent behavior, we reluctantly conclude that, while a mathematical view of complexity provides useful perspectives and some narrowly focused tools, there are too few generally practical take-home messages for physiologists studying complex systems. Consequently, we attempt to provide guidelines as to how complex systems might be best approached by physiologists. After describing complexity based on the sum of a physiological system's structures and processes, we highlight increasingly refined approaches based on the pattern of interactions between structures and processes. We then provide a series of examples illustrating how appreciating physiological complexity can improve physiological research, including choosing experimental models, guiding data collection, improving data interpretations and constructing more rigorous system models. Finally, we conclude with an invitation for physiologists, applied mathematicians and physicists to collaborate on describing, studying and learning from studies of physiological complexity.

  20. Complexation of Optoelectronic Systems

    NASA Astrophysics Data System (ADS)

    Boreisho, A. S.; Il‧in, M. Yu.; Konyaev, M. A.; Mikhailenko, A. S.; Morozov, A. V.; Strakhov, S. Yu.

    2016-05-01

    Problems of increasing the efficiency and the functionality of complex optoelectronic systems for monitoring real atmospheric conditions and of their use are discussed. It is shown by the example of a meteorological complex comprising an infrared wind-sensing lidar and an X-range Doppler radar that the complexation of probing systems working in different electromagnetic-radiation ranges opens up new opportunities for determining the meteorological parameters of a turbulent atmosphere and investigating the interaction of radiation with it.

  1. Complexity and schizophrenia.

    PubMed

    Fernández, Alberto; Gómez, Carlos; Hornero, Roberto; López-Ibor, Juan José

    2013-08-01

    Complexity estimators have been broadly utilized in schizophrenia investigation. Early studies reported increased complexity in schizophrenia patients, associated with a higher variability or "irregularity" of their brain signals. However, further investigations showed reduced complexities, thus introducing a clear divergence. Nowadays, both increased and reduced complexity values are reported. The explanation of such divergence is a critical issue to understand the role of complexity measures in schizophrenia research. Considering previous arguments a complementary hypothesis is advanced: if the increased irregularity of schizophrenia patients' neurophysiological activity is assumed, a "natural" tendency to increased complexity in EEG and MEG scans should be expected, probably reflecting an abnormal neuronal firing pattern in some critical regions such as the frontal lobes. This "natural" tendency to increased complexity might be modulated by the interaction of three main factors: medication effects, symptomatology, and age effects. Therefore, young, medication-naïve, and highly symptomatic (positive symptoms) patients are expected to exhibit increased complexities. More importantly, the investigation of these interacting factors by means of complexity estimators might help to elucidate some of the neuropathological processes involved in schizophrenia.

  2. Visual complexity: a review.

    PubMed

    Donderi, Don C

    2006-01-01

    The idea of visual complexity, the history of its measurement, and its implications for behavior are reviewed, starting with structuralism and Gestalt psychology at the beginning of the 20th century and ending with visual complexity theory, perceptual learning theory, and neural circuit theory at the beginning of the 21st. Evidence is drawn from research on single forms, form and texture arrays and visual displays. Form complexity and form probability are shown to be linked through their reciprocal relationship in complexity theory, which is in turn shown to be consistent with recent developments in perceptual learning and neural circuit theory. Directions for further research are suggested.

  3. DNA damage in Wistar rats exposed to dithiocarbamate pesticide mancozeb.

    PubMed

    Goldoni, A; Klauck, C R; Da Silva, S T; Da Silva, M D; Ardenghi, P G; Da Silva, L B

    2014-01-01

    Pesticides are used in large amounts in agriculture and the evaluation of their toxic effects is of major concern to public and environmental health. The aim of the present study was to investigate the genotoxic potential of a commercial formulation of the fungicide mancozeb by the micronucleus test in bone marrow and the comet assay in total blood of Wistar rats. Adult male Wistar rats were treated with a solution of mancozeb at a concentration of 40 mg/kg/day, administered intraperitoneally for 18 consecutive days, and compared to a control group. The results indicate that mancozeb induced significantly higher DNA damage as detected by the comet assay and increased the frequency of micronuclei. The results show that mancozeb is genotoxic and may adversely affect the DNA integrity of exposed organisms.

  4. Adaptive Leadership: Fighting Complexity with Complexity

    DTIC Science & Technology

    2014-06-01

    It appears that, as Jorge Luis Borges put it, “Everything touches everything.”39 Army ants and the World Wide Web are exemplars of complex systems...Star Trek: USS Enterprise: Haynes Manual (San Jose , CA: Simon and Schuster, 2010). 66 Spillane, Distributed Leadership. 24... Jose , CA: Simon and Schuster, 2010. Smythe, Elizabeth, and Andrew Norton. “Thinking as Leadership/Leadership As Thinking.” Leadership 3, no. 1 (2007

  5. U1A Complex

    SciTech Connect

    2014-10-28

    Some of the most sophisticated experiments in the stockpile stewardship program are conducted in an environmentally safe manner, nearly 1000 feet below the ground at the site. The U1a complex a sprawling underground laboratory and tunnel complex is home to a number of unique capabilities.

  6. U1A Complex

    ScienceCinema

    None

    2016-07-12

    Some of the most sophisticated experiments in the stockpile stewardship program are conducted in an environmentally safe manner, nearly 1000 feet below the ground at the site. The U1a complex a sprawling underground laboratory and tunnel complex is home to a number of unique capabilities.

  7. Bacterial formate hydrogenlyase complex

    PubMed Central

    McDowall, Jennifer S.; Murphy, Bonnie J.; Haumann, Michael; Palmer, Tracy; Armstrong, Fraser A.; Sargent, Frank

    2014-01-01

    Under anaerobic conditions, Escherichia coli can carry out a mixed-acid fermentation that ultimately produces molecular hydrogen. The enzyme directly responsible for hydrogen production is the membrane-bound formate hydrogenlyase (FHL) complex, which links formate oxidation to proton reduction and has evolutionary links to Complex I, the NADH:quinone oxidoreductase. Although the genetics, maturation, and some biochemistry of FHL are understood, the protein complex has never been isolated in an intact form to allow biochemical analysis. In this work, genetic tools are reported that allow the facile isolation of FHL in a single chromatographic step. The core complex is shown to comprise HycE (a [NiFe] hydrogenase component termed Hyd-3), FdhF (the molybdenum-dependent formate dehydrogenase-H), and three iron-sulfur proteins: HycB, HycF, and HycG. A proportion of this core complex remains associated with HycC and HycD, which are polytopic integral membrane proteins believed to anchor the core complex to the cytoplasmic side of the membrane. As isolated, the FHL complex retains formate hydrogenlyase activity in vitro. Protein film electrochemistry experiments on Hyd-3 demonstrate that it has a unique ability among [NiFe] hydrogenases to catalyze production of H2 even at high partial pressures of H2. Understanding and harnessing the activity of the FHL complex is critical to advancing future biohydrogen research efforts. PMID:25157147

  8. Complexity and Relations

    ERIC Educational Resources Information Center

    Lancaster, Jeanette Elizabeth

    2013-01-01

    A central feature of complexity is that it is based on non-linear, recursive relations. However, in most current accounts of complexity such relations, while non-linear, are based on the reductive relations of a Newtonian onto-epistemological framework. This means that the systems that are emergent from the workings of such relations are a…

  9. The Tom Core Complex

    PubMed Central

    Ahting, Uwe; Thun, Clemens; Hegerl, Reiner; Typke, Dieter; Nargang, Frank E.; Neupert, Walter; Nussberger, Stephan

    1999-01-01

    Translocation of nuclear-encoded preproteins across the outer membrane of mitochondria is mediated by the multicomponent transmembrane TOM complex. We have isolated the TOM core complex of Neurospora crassa by removing the receptors Tom70 and Tom20 from the isolated TOM holo complex by treatment with the detergent dodecyl maltoside. It consists of Tom40, Tom22, and the small Tom components, Tom6 and Tom7. This core complex was also purified directly from mitochondria after solubilization with dodecyl maltoside. The TOM core complex has the characteristics of the general insertion pore; it contains high-conductance channels and binds preprotein in a targeting sequence-dependent manner. It forms a double ring structure that, in contrast to the holo complex, lacks the third density seen in the latter particles. Three-dimensional reconstruction by electron tomography exhibits two open pores traversing the complex with a diameter of ∼2.1 nm and a height of ∼7 nm. Tom40 is the key structural element of the TOM core complex. PMID:10579717

  10. COMPLEXITY IN ECOLOGICAL SYSTEMS

    EPA Science Inventory

    The enormous complexity of ecosystems is generally obvious under even the most cursory examination. In the modern world, this complexity is further augmented by the linkage of ecosystems to economic and social systems through the human use of the environment for technological pu...

  11. Complexity and emergent phenomena.

    PubMed

    Suki, Béla; Bates, Jason H T; Frey, Urs

    2011-04-01

    Complex biological systems operate under non-equilibrium conditions and exhibit emergent properties associated with correlated spatial and temporal structures. These properties may be individually unpredictable, but tend to be governed by power-law probability distributions and/or correlation. This article reviews the concepts that are invoked in the treatment of complex systems through a wide range of respiratory-related examples. Following a brief historical overview, some of the tools to characterize structural variabilities and temporal fluctuations associated with complex systems are introduced. By invoking the concept of percolation, the notion of multiscale behavior and related modeling issues are discussed. Spatial complexity is then examined in the airway and parenchymal structures with implications for gas exchange followed by a short glimpse of complexity at the cellular and subcellular network levels. Variability and complexity in the time domain are then reviewed in relation to temporal fluctuations in airway function. Next, an attempt is given to link spatial and temporal complexities through examples of airway opening and lung tissue viscoelasticity. Specific examples of possible and more direct clinical implications are also offered through examples of optimal future treatment of fibrosis, exacerbation risk prediction in asthma, and a novel method in mechanical ventilation. Finally, the potential role of the science of complexity in the future of physiology, biology, and medicine is discussed.

  12. Performance Improvement Assuming Complexity

    ERIC Educational Resources Information Center

    Rowland, Gordon

    2007-01-01

    Individual performers, work teams, and organizations may be considered complex adaptive systems, while most current human performance technologies appear to assume simple determinism. This article explores the apparent mismatch and speculates on future efforts to enhance performance if complexity rather than simplicity is assumed. Included are…

  13. Visual Complexity: A Review

    ERIC Educational Resources Information Center

    Donderi, Don C.

    2006-01-01

    The idea of visual complexity, the history of its measurement, and its implications for behavior are reviewed, starting with structuralism and Gestalt psychology at the beginning of the 20th century and ending with visual complexity theory, perceptual learning theory, and neural circuit theory at the beginning of the 21st. Evidence is drawn from…

  14. Complexity and behavioral economics.

    PubMed

    Rosser, J Barkley; Rosser, Marina V

    2015-04-01

    This paper will consider the relationship between complexity economics and behavioral economics. A crucial key to this is to understand that Herbert Simon was both the founder of explicitly modern behavioral economics as well as one of the early developers of complexity theory. Bounded rationality was essentially derived from Simon's view of the impossibility of full rationality on the part of economic agents. Modern complexity theory through such approaches as agent-based modeling offers an approach to understanding behavioral economics by allowing for specific behavioral responses to be assigned to agents who interact within this context, even without full rationality. Other parts of modern complexity theory are considered in terms of their relationships with behavioral economics. Fundamentally, complexity provides an ultimate foundation for bounded rationality and hence the need to use behavioral economics in a broader array of contexts than most economists have thought appropriate.

  15. Complexity: against systems.

    PubMed

    Chu, Dominique

    2011-09-01

    This article assumes a specific intuitive notion of complexity as a difficulty to generate and/or assess the plausibility of models. Based on this intuitive understanding of complexity, it identifies two main causes of complexity, namely, radical openness and contextuality. The former is the idea that there are no natural systems. The modeler always needs to draw artificial boundaries around phenomena to generate feasible models. Contextuality is intimately connected to the requirement to simplify models and to leave out most aspects. Complexity occurs when contextuality and radical openness cannot be contained that is when it is not clear where the boundaries of the system are and which abstractions are the correct ones. This concept of complexity is illustrated using a number of example from evolution.

  16. Selenophene transition metal complexes

    SciTech Connect

    White, Carter James

    1994-07-27

    This research shows that selenophene transition metal complexes have a chemistry that is similar to their thiophene analogs. Selenophene coordination has been demonstrated and confirmed by molecular structure in both the η5- and the η1(Se)-coordination modes. The reaction chemistry of selenophene complexes closely resembles that of the analogous thiophene complexes. One major difference, however, is that selenophene is a better donor ligand than thiophene making the selenophene complexes more stable than the corresponding thiophene complexes. The 77Se NMR chemical shift values for selenophene complexes fall within distinct regions primarily depending on the coordination mode of the selenophene ligand. In the final paper, the C-H bond activation of η1(S)-bound thiophenes, η1(S)-benzothiophene and η1(Se)-bound selenophenes has been demonstrated. The deprotonation and rearrangement of the η1(E)-bound ligand to the carbon bound L-yl complex readily occurs in the presence of base. Reprotonation with a strong acid gives a carbene complex that is unreactive towards nucleophilic attack at the carbene carbon and is stable towards exposure to air. The molecular structure of [Cp(NO)(PPh3)Re(2-benzothioenylcarbene)]O3SCF3 was determined and contains a Re-C bond with substantial double bond character. Methyl substitution for the thienylcarbene or selenylcarbene gives a carbene that rearranges thermally to give back the η1(E)-bound complex. Based on these model reactions, a new mechanism for the H/D exchange of thiophene over the hydrodesulfurization catalyst has been proposed.

  17. Afterglow Complex Plasma

    SciTech Connect

    Samarian, A. A.; Boufendi, L.; Mikikian, M.

    2008-09-07

    The review of the first detailed experimental and theoretical studies of complex plasma in RF discharge afterglow is presented. The studies have been done in a frame of FAST collaborative research project between Complex Plasma Laboratory of the University of Sydney and the GREMI laboratory of Universite d'Orleans. We examined the existing models of plasma decay, presents experimental observations of dust dynamics under different afterglow complex plasma conditions, presents the experimental data obtained (in particular the presence of positively charged particles in discharge afterglow), discusses the use of dust particles as a probe to study the diffusion losses in afterglow plasmas.

  18. Complexity and robustness

    PubMed Central

    Carlson, J. M.; Doyle, John

    2002-01-01

    Highly optimized tolerance (HOT) was recently introduced as a conceptual framework to study fundamental aspects of complexity. HOT is motivated primarily by systems from biology and engineering and emphasizes, (i) highly structured, nongeneric, self-dissimilar internal configurations, and (ii) robust yet fragile external behavior. HOT claims these are the most important features of complexity and not accidents of evolution or artifices of engineering design but are inevitably intertwined and mutually reinforcing. In the spirit of this collection, our paper contrasts HOT with alternative perspectives on complexity, drawing on real-world examples and also model systems, particularly those from self-organized criticality. PMID:11875207

  19. Complexity and forensic pathology.

    PubMed

    Jones, Richard Martin

    2015-12-01

    It has become increasingly apparent that nonlinearity and complexity are the norm in human physiological systems, the relevance of which is informing an enhanced understanding of basic pathological processes such as inflammation, the host response to severe trauma, and critical illness. This article will explore how an understanding of nonlinear systems and complexity might inform the study of the pathophysiology of deaths of medicolegal interest, and how 'complexity thinking' might usefully be incorporated into modern forensic medicine and forensic pathology research, education and practice.

  20. A Novel Ternary Ligand System Useful for Preparation of Cationic 99mTc-Diazenido Complexes and 99mTc-Labeling of Small Biomolecules

    PubMed Central

    Kim, Young-Seung; He, Zhengjie; Hsieh, Wen-Yuan; Liu, Shuang

    2008-01-01

    This report describes a novel ternary ligand system composed of a phenylhydrazine, a crown ether-containing dithiocarbamate (DTC) and a PNP-type bisphosphine (PNP). The combination of three different ligands with 99mTc results in cationic 99mTc-diazenido complexes,[99mTc(NNAr)(DTC)(PNP)]+, with potential radiopharmaceuticals for heart imaging. Synthesis of cationic 99mTc-diazenido complexes can be accomplished in two steps with high yield. For example, the reaction of phenylhydrazine with 99mTcO4− at 100 °C in the presence of excess stannous chloride and 1,2-diaminopropane-N,N,N’,N’-tetraacetic acid (PDTA) results in the [99mTc(NNPh)(PDTA)n] intermediate, which then reacts with sodium N-(dithiocarbamato)-2-aminimethyl-15-Crown-5 (L4) and N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]ethoxy-ethylamine (PNP6) at 100 °C for 15 min to give the complex, [99mTc(NNPh)(L4)(PNP6)]+ in high yield (> 90%). Cationic complexes [99mTc(NNPh)(DTC)(PNP)]+ are stable for ≥6 h. Their composition was determined to be 1:1:1:1 for Tc:NNPh:DTC:PNP using the mixed-ligand experiments on the tracer (99mTc) level, and was further confirmed by the ESI-MS spectral data of a model compound [Re(NNPh)(L4)(L6)]+. It was found that both DTCs and bisphosphines have a significant impact on the lipophilicity of their cationic 99mTc-diazenido complexes. Results from a 99mTc-labeling efficiency experiment showed that 4-hydrazinobenzoic acid (HYBA) might be useful as a bifunctional coupling agent for 99mTc-labeling of small biomolecules. However, the 99mTc-labeling efficiency of HYBA is much lower than that of 6-hydrazinonicotinic acid (HYNIC) with tricine and trisodium triphenylphosphine-3,3’,3”-trisulfonate (TPPTS) as coligands. PMID:16536480

  1. A complex legacy

    NASA Astrophysics Data System (ADS)

    Moore, Cristopher

    2011-11-01

    In his tragically short life, Alan Turing helped define what computing machines are capable of, and where they reach inherent limits. His legacy is still felt every day, in areas ranging from computational complexity theory to cryptography and quantum computing.

  2. Indicators: Physical Habitat Complexity

    EPA Pesticide Factsheets

    Physical habitat complexity measures the amount and variety of all types of cove at the water’s edge in lakes. In general, dense and varied shoreline habitat is able to support more diverse communities of aquatic life.

  3. Complex Regional Pain Syndrome

    MedlinePlus

    Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. ... in skin temperature, color, or texture Intense burning pain Extreme skin sensitivity Swelling and stiffness in affected ...

  4. Reconstruction Using Witness Complexes

    PubMed Central

    Oudot, Steve Y.

    2010-01-01

    We present a novel reconstruction algorithm that, given an input point set sampled from an object S, builds a one-parameter family of complexes that approximate S at different scales. At a high level, our method is very similar in spirit to Chew’s surface meshing algorithm, with one notable difference though: the restricted Delaunay triangulation is replaced by the witness complex, which makes our algorithm applicable in any metric space. To prove its correctness on curves and surfaces, we highlight the relationship between the witness complex and the restricted Delaunay triangulation in 2d and in 3d. Specifically, we prove that both complexes are equal in 2d and closely related in 3d, under some mild sampling assumptions. PMID:21643440

  5. Complex Flow Workshop Report

    SciTech Connect

    none,

    2012-05-01

    This report documents findings from a workshop on the impacts of complex wind flows in and out of wind turbine environments, the research needs, and the challenges of meteorological and engineering modeling at regional, wind plant, and wind turbine scales.

  6. Complex and unpredictable Cardano

    NASA Astrophysics Data System (ADS)

    Ekert, Artur

    2008-08-01

    This purely recreational paper is about one of the most colorful characters of the Italian Renaissance, Girolamo Cardano, and the discovery of two basic ingredients of quantum theory, probability and complex numbers.

  7. Determination of traces of silver in waters by anion exchange and atomic absorption spectrophotometry

    USGS Publications Warehouse

    Chao, T.T.; Fishman, M. J.; Ball, J.W.

    1969-01-01

    A method has been developed for the accurate determination of 0.1-1 ??g of silver per liter of water. The method permits stabilization of silver in water without loss to container walls. Optimum conditions have been established for the complete recovery of silver from water with an anion-exchange column, for quantitative elution of silver from the resin, and for measurement of silver by atomic absorption spectrophotometry after chelation with ammonium pyrrolidine dithiocarbamate and extraction of the chelate with MIBK. Silver in the 1-10 ??g 1 range can be determined by extraction without pre-concentration on an ion-exchange resin. ?? 1969.

  8. Inside the complexity labyrinth

    NASA Astrophysics Data System (ADS)

    Fraser, Gordon

    2010-02-01

    Although the world we live in is complex, complexity as a science does not have a long history. For generations, most physicists tried to understand everything in terms of interactions between pairs of idealized "test particles". Then, about a 100 years ago, Henri Poincaré pointed out that a fully interacting three-body system was not just the sum of its three component pairs. The famous "three-body problem" was born.

  9. Electrospun complexes - functionalised nanofibres

    NASA Astrophysics Data System (ADS)

    Meyer, T.; Wolf, M.; Dreyer, B.; Unruh, D.; Krüger, C.; Menze, M.; Sindelar, R.; Klingelhöfer, G.; Renz, F.

    2016-12-01

    Here we present a new approach of using iron-complexes in electro-spun fibres. We modify poly(methyl methacrylate) (PMMA) by replacing the methoxy group with Diaminopropane or Ethylenediamine. The complex is bound covalently via an imine-bridge or an amide. The resulting polymer can be used in the electrospinning process without any further modifications in method either as pure reagent or mixed with small amounts of not functionalised polymer resulting in fibres of different qualities (Fig. 1).

  10. An erupted complex odontoma.

    PubMed

    Tozoglu, Sinan; Yildirim, Umran; Buyukkurt, M Cemil

    2010-01-01

    Odontomas are benign tumors of odontogenic origin. The cause of the odontoma is unknown, but it is believed to be hereditary or due to a disturbance in tooth development triggered by trauma or infection. Odontomas may be either compound or complex. Although these tumors are seen frequently, erupted odontomas are rare. The purpose of this study is to present a rare case of complex odontoma that erupted into the oral cavity.

  11. Pulling complexes out of complex diseases

    PubMed Central

    Mohan, Ryan D; Abmayr, Susan M; Workman, Jerry L

    2014-01-01

    Spinocerebellar ataxia 7 (SCA7) is an incurable disease caused by expansion of CAG trinucleotide sequences within the Ataxin-7 gene. This elongated CAG tract results in an Ataxin-7 protein bearing an expanded polyglutamine (PolyQ) repeat. SCA7 disease is characterized by progressive neural and retinal degeneration leading to ataxia and blindness. Evidence gathered from investigating SCA7 and other PolyQ diseases strongly suggest that misregulation of gene expression contributes to neurodegeneration. In fact, Ataxin-7 is a subunit of the essential Spt-Ada-Gcn5-Acetltransferase (SAGA) chromatin modifying complex that regulates expression of a large number of genes. Here we discuss recent insights into Ataxin-7 function and, considering these findings, propose a model for how polyglutamine expansion of Ataxin-7 may affect Ataxin-7 function to alter chromatin modifications and gene expression. PMID:25054097

  12. Cell complexes through time

    NASA Astrophysics Data System (ADS)

    Klette, Reinhard

    2000-10-01

    The history of cell complexes is closely related to the birth and development of topology in general. Johann Benedict Listing (1802 - 1882) introduced the term 'topology' into mathematics in a paper published in 1847, and he also defined cell complexes for the first time in a paper published in 1862. Carl Friedrich Gauss (1777 - 1855) is often cited as the one who initiated these ideas, but he did not publish either on topology or on cell complexes. The pioneering work of Leonhard Euler (1707 - 1783) on graphs is also often cited as the birth of topology, and Euler's work was cited by Listing in 1862 as a stimulus for his research on cell complexes. There are different branches in topology which have little in common: point set topology, algebraic topology, differential topology etc. Confusion may arise if just 'topology' is specified, without clarifying the used concept. Topological subjects in mathematics are often related to continuous models, and therefore quite irrelevant to computer based solutions in image analysis. Compared to this, only a minority of topology publications in mathematics addresses discrete spaces which are appropriate for computer-based image analysis. In these cases, often the notion of a cell complex plays a crucial role. This paper briefly reports on a few of these publications. This paper is not intended to cover the very lively progress in cell complex studies within the context of image analysis during the last two decades. Basically it stops its historic review at the time when this subject in image analysis research gained speed in 1980 - 1990. As a general point of view, the paper indicates that image analysis contributes to a fusion of topological concepts, the geometric and the abstract cell structure approach and point set topology, which may lead towards new problems for the study of topologies defined on geometric or abstract cell complexes.

  13. Hydridomethyl iridium complex

    DOEpatents

    Bergman, Robert G.; Buchanan, J. Michael; Stryker, Jeffrey M.; Wax, Michael J.

    1989-01-01

    A process for functionalizing methane comprising: (a) reacting methane with a hydridoalkyl metal complex of the formula: CpIr[P(R.sub.1).sub.3 ]H(R.sub.2) wherein Cp represents a cyclopentadienyl or alkylcyclopentadienyl radical having from 1 to 5 carbon atoms; Ir represents an iridium atom; P represents a phosphorus atom; R.sub.1 represents an alkyl group; R.sub.2 represents an alkyl group having at least two carbon atoms; and H represents a hydrogen atom, in the presence of a liquid alkane R.sub.3 H having at least three carbon atoms to form a hydridomethyl complex of the formula: CpIr[P(R.sub.1).sub.3 ]HMe where Me represents a methyl radical. (b) reacting said hydridomethyl complex with an organic halogenating agent such as a tetrahalomethane or a haloform of the formulas: CX'X"X'"X"" or CHX'X"X'"; wherein X', X", X"', and X"" represent halogens selected from bromine, iodine and chlorine, to halomethyl complex of step (a) having the formula: CpIr[P(R.sub.1).sub.3 ]MeX: (c) reacting said halomethyl complex with a mercuric halide of the formula HgX.sub.2 to form a methyl mercuric halide of the formula HgMeX; and (d) reacting said methyl mercuric halide with a molecular halogen of the formula X.sub.2 to form methyl halide.

  14. Quantum Complexity in Graphene

    NASA Astrophysics Data System (ADS)

    Baskaran, G.

    Carbon has a unique position among elements in the periodic table. It produces an allotrope, graphene, a mechanically robust two dimensional semimetal. The multifarious properties that graphene exhibits has few parallels among elemental metals. From simplicity, namely carbon atoms connected by pure sp2 bonds, a wealth of novel quantum properties emerge. In classical complex systems such as a spin glass or a finance market, several competing agents or elements are responsible for unanticipated and difficult to predict emergent properties. The complex (sic) structure of quantum mechanics is responsbile for an unanticipated set of emergent properties in graphene. We call this quantum complexity. In fact, most quantum systems, phenomena and modern quantum field theory could be viewed as examples of quantum complexity. After giving a brief introduction to the quantum complexity we focus on our own work, which indicates the breadth in the type of quantum phenomena that graphene could support. We review our theoretical suggestions of, (i) spin-1 collective mode in netural graphene, (ii) relativistic type of phenomena in crossed electric and magnetic fields, (iii) room temperature superconductivity in doped graphene and (iv) composite Fermi sea in neutral graphene in uniform magnetic field and (v) two-channel Kondo effect. Except for the relativistic type of phenomena, the rest depend in a fundamental way on a weak electron correlation that exists in the broad two-dimensional band of graphene.

  15. Quantum Complexity in Graphene

    NASA Astrophysics Data System (ADS)

    Baskaran, G.

    Carbon has a unique position among elements in the periodic table. It produces an allotrope, graphene, a mechanically robust two dimensional semimetal. The multifarious properties that graphene exhibits has few parallels among elemental metals. From simplicity, namely carbon atoms connected by pure sp2 bonds, a wealth of novel quantum properties emerge. In classical complex systems such as a spin glass or a finance market, several competing agents or elements are responsible for unanticipated and difficult to predict emergent properties. The complex (sic) structure of quantum mechanics is responsbile for an unanticipated set of emergent properties in graphene. We call this quantum complexity. Infact, most quantum systems, phenomena and modern quantum field theory could be viewed as examples of quantum complexity. After giving a brief introduction to the quantum complexity we focus on our own work, which indicates the breadth in the type of quantum phenomena that graphene could support. We review our theoretical suggestions of, (i) spin-1 collective mode in netural graphene, (ii) relativistic type of phenomena in crossed electric and magnetic fields, (iii) room temperature superconductivity in doped graphene and (iv) composite Fermi sea in neutral graphene in uniform magnetic field and (v) 2-channel Kondo effect. Except for the relativistic type of phenomena and Kondo effect, the rest depend in a fundamental way on a weak electron correlations that exist in graphene.

  16. Alanine water complexes.

    PubMed

    Vaquero, Vanesa; Sanz, M Eugenia; Peña, Isabel; Mata, Santiago; Cabezas, Carlos; López, Juan C; Alonso, José L

    2014-04-10

    Two complexes of alanine with water, alanine-(H2O)n (n = 1,2), have been generated by laser ablation of the amino acid in a supersonic jet containing water vapor and characterized using Fourier transform microwave spectroscopy. In the observed complexes, water molecules bind to the carboxylic group of alanine acting as both proton donors and acceptors. In alanine-H2O, the water molecule establishes two intermolecular hydrogen bonds forming a six-membered cycle, while in alanine-(H2O)2 the two water molecules establish three hydrogen bonds forming an eight-membered ring. In both complexes, the amino acid moiety is in its neutral form and shows the conformation observed to be the most stable for the bare molecule. The microsolvation study of alanine-(H2O)n (n = 1,2) can be taken as a first step toward understanding bulk properties at a microscopic level.

  17. The complex pendulum

    NASA Astrophysics Data System (ADS)

    Bender, Carl M.

    1998-12-01

    In this talk we propose to broaden the conventional notion of quantum mechanics. In conventional quantum mechanics one imposes the condition H†=H, where † represents complex conjugation and matrix transpose, to ensure that the Hamiltonian has a real spectrum. Replacing this mathematical condition by the weaker and more physical requirement H‡=H, where ‡=PT represents combined parity reflection and time reversal, one obtains new infinite classes of complex Hamiltonians whose spectra are also real and positive. These PT-symmetric theories may be viewed as analytic continuations of conventional theories from real to complex phase space. This talk describes the unusual classical and quantum properties of PT-symmetric quantum mechanical and quantum field theoretic models.

  18. The complex pendulum

    NASA Astrophysics Data System (ADS)

    Bender, Carl M.

    1999-07-01

    This talk proposes a generalization of conventional quantum mechanics. In conventional quantum mechanics one imposes the condition H †=H , where † represents complex conjugation and matrix transpose, to ensure that the Hamiltonian has a real spectrum. By replacing this mathematical condition with the weaker and more physical requirement H ‡=H , where ‡= PT represents combined parity reflection and time reversal, one obtains new infinite classes of complex Hamiltonians whose spectra are also real and positive. These PT-symmetric theories may be viewed as analytic continuations of conventional theories from real to complex-phase space. This talk describes the unusual classical and quantum properties of PT-symmetric quantum-mechanical and quantum-field-theoretic models.

  19. Nonergodic complexity management

    NASA Astrophysics Data System (ADS)

    Piccinini, Nicola; Lambert, David; West, Bruce J.; Bologna, Mauro; Grigolini, Paolo

    2016-06-01

    Linear response theory, the backbone of nonequilibrium statistical physics, has recently been extended to explain how and why nonergodic renewal processes are insensitive to simple perturbations, such as in habituation. It was established that a permanent correlation results between an external stimulus and the response of a complex system generating nonergodic renewal processes, when the stimulus is a similar nonergodic process. This is the principle of complexity management, whose proof relies on ensemble distribution functions. Herein we extend the proof to the nonergodic case using time averages and a single time series, hence making it usable in real life situations where ensemble averages cannot be performed because of the very nature of the complex systems being studied.

  20. Synchronization in complex networks

    SciTech Connect

    Arenas, A.; Diaz-Guilera, A.; Moreno, Y.; Zhou, C.; Kurths, J.

    2007-12-12

    Synchronization processes in populations of locally interacting elements are in the focus of intense research in physical, biological, chemical, technological and social systems. The many efforts devoted to understand synchronization phenomena in natural systems take now advantage of the recent theory of complex networks. In this review, we report the advances in the comprehension of synchronization phenomena when oscillating elements are constrained to interact in a complex network topology. We also overview the new emergent features coming out from the interplay between the structure and the function of the underlying pattern of connections. Extensive numerical work as well as analytical approaches to the problem are presented. Finally, we review several applications of synchronization in complex networks to different disciplines: biological systems and neuroscience, engineering and computer science, and economy and social sciences.

  1. Engineering complex tissues.

    PubMed

    Atala, Anthony; Kasper, F Kurtis; Mikos, Antonios G

    2012-11-14

    Tissue engineering has emerged at the intersection of numerous disciplines to meet a global clinical need for technologies to promote the regeneration of functional living tissues and organs. The complexity of many tissues and organs, coupled with confounding factors that may be associated with the injury or disease underlying the need for repair, is a challenge to traditional engineering approaches. Biomaterials, cells, and other factors are needed to design these constructs, but not all tissues are created equal. Flat tissues (skin); tubular structures (urethra); hollow, nontubular, viscus organs (vagina); and complex solid organs (liver) all present unique challenges in tissue engineering. This review highlights advances in tissue engineering technologies to enable regeneration of complex tissues and organs and to discuss how such innovative, engineered tissues can affect the clinic.

  2. Viral quasispecies complexity measures.

    PubMed

    Gregori, Josep; Perales, Celia; Rodriguez-Frias, Francisco; Esteban, Juan I; Quer, Josep; Domingo, Esteban

    2016-06-01

    Mutant spectrum dynamics (changes in the related mutants that compose viral populations) has a decisive impact on virus behavior. The several platforms of next generation sequencing (NGS) to study viral quasispecies offer a magnifying glass to study viral quasispecies complexity. Several parameters are available to quantify the complexity of mutant spectra, but they have limitations. Here we critically evaluate the information provided by several population diversity indices, and we propose the introduction of some new ones used in ecology. In particular we make a distinction between incidence, abundance and function measures of viral quasispecies composition. We suggest a multidimensional approach (complementary information contributed by adequately chosen indices), propose some guidelines, and illustrate the use of indices with a simple example. We apply the indices to three clinical samples of hepatitis C virus that display different population heterogeneity. Areas of virus biology in which population complexity plays a role are discussed.

  3. Planning Complex Projects Automatically

    NASA Technical Reports Server (NTRS)

    Henke, Andrea L.; Stottler, Richard H.; Maher, Timothy P.

    1995-01-01

    Automated Manifest Planner (AMP) computer program applies combination of artificial-intelligence techniques to assist both expert and novice planners, reducing planning time by orders of magnitude. Gives planners flexibility to modify plans and constraints easily, without need for programming expertise. Developed specifically for planning space shuttle missions 5 to 10 years ahead, with modifications, applicable in general to planning other complex projects requiring scheduling of activities depending on other activities and/or timely allocation of resources. Adaptable to variety of complex scheduling problems in manufacturing, transportation, business, architecture, and construction.

  4. Complexity and Animal Models

    DTIC Science & Technology

    2015-01-01

    SEP 2015 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Complexity and animal models 5a. CONTRACT NUMBER 5b. GRANT NUMBER...decrease W/Wmax, thereby maintaining the relationship between variability and W/Wmax. doi:10.1016/j.jcrc.2010.05.012 Complexity and animal models...may not be possible during mass casualty and natural disaster situations or may need to be postponed during combat to avoid danger to the medic’s life

  5. Universality classes of complexity

    NASA Astrophysics Data System (ADS)

    Saakian, David B.

    We give several criteria of complexity and define different universality classes. According to our classification, at the lowest class of complexity are random graph, Markov Models and Hidden Markov Models. At the next level is Sherrington-Kirkpatrick spin glass, connected with neuron-network models. On a higher level are critical theories, spin glass phase of Random Energy Model, percolation, self organized criticality (SOC). The top level class involves HOT design, error threshold in optimal coding, language, and, maybe, financial market. Alive systems are also related with the last class.

  6. The ESCRT Complexes

    PubMed Central

    Hurley, James H.

    2010-01-01

    The ESCRT machinery consists of the peripheral membrane protein complexes, ESCRT-0, -I, -II, -III, and Vps4-Vta1, and the ALIX homodimer. The ESCRT system is required for degradation of unneeded or dangerous plasma membrane proteins; biogenesis of the lysosome and the yeast vacuole; the budding of most membrane enveloped viruses; the membrane abscission step in cytokinesis; macroautophagy; and several other processes. From their initial discovery in 2001-2002, the literature on ESCRTs has grown exponentially. This review will describe the structure and function of the six complexes noted above and summarizes current knowledge of their mechanistic roles in cellular pathways and in disease. PMID:20653365

  7. Luminescent macrocyclic lanthanide complexes

    DOEpatents

    Raymond, Kenneth N [Berkeley, CA; Corneillie, Todd M [Campbell, CA; Xu, Jide [Berkeley, CA

    2012-05-08

    The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds incorporate hydroxy-isophthalamide moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability. These characteristics distinguish them from known, open-structured ligands.

  8. The Corona Australis Complex.

    NASA Astrophysics Data System (ADS)

    Vaile, Roberta Anne

    What began as a HI study of the CrA star formation region has grown to incorporate the following: (1) a detailed investigation of the HI content of the CrA dark cloud; (2) an extensive molecular survey of the CrA dark cloud, from which the CrA molecular abundances were determined and compared to those of other Galactic environments; (3) an extensive HI survey of the CrA complex, which was compared to the established Galactic distributions in and near the region; (4) an examination of the extent and nature of the CrA IVCs, components of gas at intermediate, anomalous velocities; (5) an investigation of the correlations which may exist between the features of the CrA region; and (6) an evaluation of where the CrA complex fits within the framework of our understanding of the Galaxy. A review of our perceptions of the Galactic structure is contained in Chapter I. The established state of knowledge of the CrA dark cloud region--chiefly, that of a region of young and on-going star formation--is given in Chapter II. The observational studies of the CrA dark cloud region specifically are presented in Chapter III. The HI survey of the CrA complex is presented in Chapter IV, with the CrA IVCs results presented in Chapter V. A comparison of the CrA HI structure with nearby Galactic features suggests that the CrA complex--exemplified by the T_ {rm A} morphology given as a frontispiece and in Figure 4.1--is a coherently -moving HI structure falling subject to the Rayleigh-Taylor, Kelvin-Helmholtz, flute and Parker hydrodynamic and magnetohydrodynamic instabilities under the Galactic gravitational and differential rotation forces. As the distance to the CrA IVCs still remains speculative, no definitive identity for the CrA IVCs was established. Considering the whole, the CrA complex was interpreted as a feature triggered by the Sco-Cen association, possibly a late-comer to the Lindblad Ring and possibly a result of the Tau-Gem events. The similarities with the Oph northern

  9. Complexity and Fly Swarms

    NASA Astrophysics Data System (ADS)

    Cates, Grant; Murray, Joelle

    Complexity is the study of phenomena that emerge from a collection of interacting objects and arises in many systems throughout physics, biology, finance, economics and more. Certain kinds of complex systems can be described by self-organized criticality (SOC). An SOC system is one that is internally driven towards some critical state. Recent experimental work suggests scaling behavior of fly swarms-one of the hallmarks of an SOC system. Our goal is to look for SOC behavior in computational models of fly swarms.

  10. Luminescent macrocyclic lanthanide complexes

    DOEpatents

    Raymond, Kenneth N; Corneillie, Todd M; Xu, Jide

    2014-05-20

    The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds incorporate hydroxy-isophthalamide moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability. These characteristics distinguish them from known, open-structured ligands.

  11. Salen complexes with dianionic counterions

    DOEpatents

    Job, Gabriel E.; Farmer, Jay J.; Cherian, Anna E.

    2016-08-02

    The present invention describes metal salen complexes having dianionic counterions. Such complexes can be readily precipitated and provide an economical method for the purification and isolation of the complexes, and are useful to prepare novel polymer compositions.

  12. Graphical Representation of Complex Functions.

    ERIC Educational Resources Information Center

    Renka, Robert J.

    1988-01-01

    Describes methods and software for graphing representation of a complex function of a complex variable. Includes an application of a graphical interpretation of the complex zeros of the cubic and their properties. (PK)

  13. Surface complexation modeling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adsorption-desorption reactions are important processes that affect the transport of contaminants in the environment. Surface complexation models are chemical models that can account for the effects of variable chemical conditions, such as pH, on adsorption reactions. These models define specific ...

  14. Complexity in Cultural Identity

    ERIC Educational Resources Information Center

    Holliday, Adrian

    2010-01-01

    Despite their diverse national backgrounds, 28 interviewees speak similarly about the complexity of the cultural realities with which they live, and refuse to be pinned down to specific cultural types. While nation is of great importance, unless personally inspiring, it tends to be an external force which is in conflict with a wide variety of…

  15. Coordination Complexes of Cobalt.

    ERIC Educational Resources Information Center

    Williams, Gregory M.; And Others

    1989-01-01

    Described is an experiment involving the synthesis and spectral studies of cobalt complexes that not only give general chemistry students an introduction to inorganic synthesis but allows them to conduct a systematic study on the effect of different ligands on absorption spectra. Background information, procedures, and experimental results are…

  16. Complex Digital Visual Systems

    ERIC Educational Resources Information Center

    Sweeny, Robert W.

    2013-01-01

    This article identifies possibilities for data visualization as art educational research practice. The author presents an analysis of the relationship between works of art and digital visual culture, employing aspects of network analysis drawn from the work of Barabási, Newman, and Watts (2006) and Castells (1994). Describing complex network…

  17. Hydridomethyl iridium complex

    SciTech Connect

    Bergman, R.G; Buchanan, J.M.; Stryker, J.M.; Wax, M.J.

    1989-07-18

    This patent describes a hydridomethyl complex of the formula: CpIr(P(R{sub 1}){sub 3})HMe. Cp represents a cyclopentadienyl or alkyl cyclopentadienyl radical; Ir represents an iridium atom; P represents a phosphorus atom; R{sub 1} represents an alkyl group; and Me represents a methyl group.

  18. Complexity, Systems, and Software

    DTIC Science & Technology

    2014-08-14

    2014 Carnegie Mellon University Complexity, Systems, and Software Software Engineering Institute Carnegie Mellon University Pittsburgh, PA...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Software Engineering Institute Carnegie Mellon University Pittsburgh, PA 15213 8...for the operation of the Software Engineering Institute, a federally funded research and development center sponsored by the United States

  19. Subelliptic Estimates for Complexes

    PubMed Central

    Guillemin, Victor; Sternberg, Shlomo

    1970-01-01

    New results are announced linking properties of the symbol module and characteristic variety of a differential complex with test estimates near the characteristic variety of the type considered by Hörmander (½-estimate). The first result is the invariance of the test estimates under pseudo-differential change of coordinates, and this leads to the introduction of a normal form for the complex in the neighborhood of a Cohen-MacCauley point of the symbol module. If the characteristic variety V is a manifold near the Cohen-MacCauley point (x0,ζ0) with parametrizing functions p1,...,pq, where q is the codimension of the characteristic variety in the complexified contangent bundle, the matrix [Formula: see text] of Poisson brackets defines invariantly a Hermitian form Q on the normal space to V at (x0,ζ0) when the dpζ(x0,ζ0) are used as basis, and the test estimates are satisfied at the ith stage of the complex if sig. Q (signature of Q) is ≥ n - i + 1 (n the dimension of the base manifold) or rank Q - sig. Q ≥ i + 1. Finally, conditions are given in order that, on a manifold with smooth boundary, the associated boundary complexes satisfy the ½-estimate. PMID:16591855

  20. Restricting Grammatical Complexity

    ERIC Educational Resources Information Center

    Frank, Robert

    2004-01-01

    Theories of natural language syntax often characterize grammatical knowledge as a form of abstract computation. This paper argues that such a characterization is correct, and that fundamental properties of grammar can and should be understood in terms of restrictions on the complexity of possible grammatical computation, when defined in terms of…

  1. Complex Planar Splines.

    DTIC Science & Technology

    1981-05-01

    try todefine a complex planar spline by holomorphic elements like polynomials, then by the well known identity theorem (e.g. Diederich- Remmert [9, p...R. Remmert : Funktionentheorie I, Springer, Berlin, Heidelberg, New York, 1972, 246 p. 10 0. Lehto - K.I. Virtanen: Quasikonforme AbbildunQen, Springer

  2. Managing Complex Dynamical Systems

    ERIC Educational Resources Information Center

    Cox, John C.; Webster, Robert L.; Curry, Jeanie A.; Hammond, Kevin L.

    2011-01-01

    Management commonly engages in a variety of research designed to provide insight into the motivation and relationships of individuals, departments, organizations, etc. This paper demonstrates how the application of concepts associated with the analysis of complex systems applied to such data sets can yield enhanced insights for managerial action.

  3. The Complexity of Care

    ERIC Educational Resources Information Center

    Collins, Steve; Ting, Hermia

    2014-01-01

    The profession of teaching is unique because of the extent to which a teacher becomes involved in the lives of their "clients". The level of care required to support students well can be intense, confusing, and overwhelming. Relationships co-evolve within an ever-changing process and care is considered an essential aspect of complex relationships…

  4. Launching Complex Tasks

    ERIC Educational Resources Information Center

    Jackson, Kara J.; Shahan, Emily C.; Gibbons, Lynsey K.; Cobb, Paul A.

    2012-01-01

    Mathematics lessons can take a variety of formats. In this article, the authors discuss lessons organized around complex mathematical tasks. These lessons usually unfold in three phases. First, the task is introduced to students. Second, students work on solving the task. Third, the teacher "orchestrates" a concluding whole-class discussion in…

  5. Cytarabine Lipid Complex Injection

    MedlinePlus

    ... used to treat lymphomatous meningitis (a type of cancer in the covering of the spinal cord and brain). Cytarabine lipid complex is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in your body.

  6. Complex WS 2 nanostructures

    NASA Astrophysics Data System (ADS)

    Whitby, R. L. D.; Hsu, W. K.; Lee, T. H.; Boothroyd, C. B.; Kroto, H. W.; Walton, D. R. M.

    2002-06-01

    A range of elegant tubular and conical nanostructures has been created by template growth of (WS 2) n layers on the surfaces of single-walled carbon nanotube bundles. The structures exhibit remarkably perfect straight segments together with interesting complexities at the intersections, which are discussed here in detail in order to enhance understanding of the structural features governing tube growth.

  7. Complex Characters Made Simple

    ERIC Educational Resources Information Center

    Kettle, Sidney F. A.

    2009-01-01

    The physical significance of complex characters is explored with particular reference to the C[subscript 4] point group. While a diagrammatic representation of these characters in this group is possible, the extension to higher groups C[subscript n], n greater than 4 is left as a problem for discussion. (Contains 3 tables, 8 figures, and 1 note.)

  8. Complex Event Recognition Architecture

    NASA Technical Reports Server (NTRS)

    Fitzgerald, William A.; Firby, R. James

    2009-01-01

    Complex Event Recognition Architecture (CERA) is the name of a computational architecture, and software that implements the architecture, for recognizing complex event patterns that may be spread across multiple streams of input data. One of the main components of CERA is an intuitive event pattern language that simplifies what would otherwise be the complex, difficult tasks of creating logical descriptions of combinations of temporal events and defining rules for combining information from different sources over time. In this language, recognition patterns are defined in simple, declarative statements that combine point events from given input streams with those from other streams, using conjunction, disjunction, and negation. Patterns can be built on one another recursively to describe very rich, temporally extended combinations of events. Thereafter, a run-time matching algorithm in CERA efficiently matches these patterns against input data and signals when patterns are recognized. CERA can be used to monitor complex systems and to signal operators or initiate corrective actions when anomalous conditions are recognized. CERA can be run as a stand-alone monitoring system, or it can be integrated into a larger system to automatically trigger responses to changing environments or problematic situations.

  9. Crystal structure and photoluminescence properties of a new Cd(II) coordination polymer catena-poly[bis[4-bromo-2-({[2-(pyrrolidin-1-yl)ethyl]imino}methyl)phenolato-κ(3)N,N',O]di-μ3-chlorido-di-μ2-chlorido-bis(methanol-κO)tricadmium(II)].

    PubMed

    Yahsi, Yasemin; Ozbek, Hatice; Aygun, Muhittin; Kara, Hulya

    2016-05-01

    Schiff base-metal complexes have been used widely as catalysts for many organic reactions, such as ring-opening polymerization and oxidation. In view of the importance of Cd(II) coordination polymers and in an effort to enlarge the library of such complexes, the title novel polymeric Cd(II) tridentate Schiff base complex, [Cd3(C13H16BrN2O)2Cl4(CH4O)2]n, has been synthesized and characterized by elemental analyses, UV and IR spectroscopies, and single-crystal X-ray diffraction. The complex crystallizes in the triclinic P-1 space group with two symmetry-independent Cd(II) atoms, one of which lies on an inversion centre, and analysis of the crystal structure shows that both Cd(II) atoms are six-coordinated; the environment around one Cd(II) atom can be described as distorted octahedral, while that around the second Cd(II) atom is octahedral. The Cd(II) atoms are linked by chloride ligands to form a one-dimensional coordination polymer. The nonbonding intermolecular Cd...Cd distances are 3.7009 (4) and 4.3563 (5) Å. Furthermore, the photoluminescence properties of the complex have been investigated and it displays a strong red emission in the solid state at room temperature.

  10. Minimization of mass interferences in quadrupole inductively coupled plasma mass spectrometric (ICP-MS) determination of palladium using a flow injection on-line displacement solid-phase extraction protocol

    NASA Astrophysics Data System (ADS)

    Fang, Jing; Liu, Li-Wen; Yan, Xiu-Ping

    2006-07-01

    A flow injection on-line displacement solid-phase extraction protocol was employed to minimize mass interferences with determination of palladium by inductively coupled plasma mass spectrometry (ICP-MS). The developed method involved in on-line complexing of Ag + with pyrrolidine dithiocarbamate (PDC), presorption of the resultant Ag-PDC onto a microcolumn packed with the cigarette filter, displacement sorption of Pd 2+ through loading the sample solution onto the microcolumn due to on-line displacement reaction between Pd 2+ and the presorbed Ag-PDC, elution of the retained Pd 2+ with 50 μL of ethanol for on-line ICP-MS detection. Interferences from co-existing heavy metal ions with lower stability of their PDC complexes relative to Ag-PDC were minimized/eliminated. No interferences from 5 mg L - 1 Zn and 3 mg L - 1 Pb for 104Pd, 0.4 mg L - 1 Cu for 105Pd, 6 mg L - 1 Zn and 2 mg L - 1 Cd for 106Pd, 6 mg L - 1 Zn and 3 mg L - 1 Cd for 108Pd, and 2 mg L - 1 Cd for 110Pd were observed for the determination of 100 ng L - 1 Pd. The enhancement factors of 71-75, sample throughput of 23 samples h - 1 and detection limits of 2.8-3.5 ng L - 1 were achieved with the consumption of 3.0 mL of sample solution. The precision (RSD) for eleven replicate determinations of Pd at the 100 ng L - 1 level was 1.8-2.7%. The developed method was applied to the determination of palladium in rock samples.

  11. Classification of Software Projects' Complexity

    NASA Astrophysics Data System (ADS)

    Fitsilis, P.; Kameas, A.; Anthopoulos, L.

    Software project complexity is a subject that has not received detailed attention. The purpose of this chapter is to present a systematic way for studying and modeling software project complexity. The proposed model is based on the widely known and accepted Project Management Body of Knowledge and it uses a typology for modeling complexity based on complexity of faith, fact, and interaction.

  12. Statistical Factors in Complexation Reactions.

    ERIC Educational Resources Information Center

    Chung, Chung-Sun

    1985-01-01

    Four cases which illustrate statistical factors in complexation reactions (where two of the reactants are monodentate ligands) are presented. Included are tables showing statistical factors for the reactions of: (1) square-planar complexes; (2) tetrahedral complexes; and (3) octahedral complexes. (JN)

  13. Complexity Leadership: A Theoretical Perspective

    ERIC Educational Resources Information Center

    Baltaci, Ali; Balci, Ali

    2017-01-01

    Complex systems are social networks composed of interactive employees interconnected through collaborative, dynamic ties such as shared goals, perspectives and needs. Complex systems are largely based on "the complex system theory". The complex system theory focuses mainly on finding out and developing strategies and behaviours that…

  14. Debating complexity in modeling

    USGS Publications Warehouse

    Hunt, Randall J.; Zheng, Chunmiao

    1999-01-01

    As scientists trying to understand the natural world, how should our effort be apportioned? We know that the natural world is characterized by complex and interrelated processes. Yet do we need to explicitly incorporate these intricacies to perform the tasks we are charged with? In this era of expanding computer power and development of sophisticated preprocessors and postprocessors, are bigger machines making better models? Put another way, do we understand the natural world better now with all these advancements in our simulation ability? Today the public's patience for long-term projects producing indeterminate results is wearing thin. This increases pressure on the investigator to use the appropriate technology efficiently. On the other hand, bringing scientific results into the legal arena opens up a new dimension to the issue: to the layperson, a tool that includes more of the complexity known to exist in the real world is expected to provide the more scientifically valid answer.

  15. Reducing GWAS Complexity

    PubMed Central

    Hazelett, Dennis J.; Conti, David V.; Han, Ying; Al Olama, Ali Amin; Easton, Doug; Eeles, Rosalind A.; Kote-Jarai, Zsofia; Haiman, Christopher A.; Coetzee, Gerhard A.

    2016-01-01

    ABSTRACT Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 20151,2 from our groups. PMID:26771711

  16. Compressively sensed complex networks.

    SciTech Connect

    Dunlavy, Daniel M.; Ray, Jaideep; Pinar, Ali

    2010-07-01

    The aim of this project is to develop low dimension parametric (deterministic) models of complex networks, to use compressive sensing (CS) and multiscale analysis to do so and to exploit the structure of complex networks (some are self-similar under coarsening). CS provides a new way of sampling and reconstructing networks. The approach is based on multiresolution decomposition of the adjacency matrix and its efficient sampling. It requires preprocessing of the adjacency matrix to make it 'blocky' which is the biggest (combinatorial) algorithm challenge. Current CS reconstruction algorithm makes no use of the structure of a graph, its very general (and so not very efficient/customized). Other model-based CS techniques exist, but not yet adapted to networks. Obvious starting point for future work is to increase the efficiency of reconstruction.

  17. Carney Complex: an update

    PubMed Central

    Correa, Ricardo; Salpea, Paraskevi; Stratakis, Constantine

    2015-01-01

    Carney Complex (CNC) is a rare autosomal dominant syndrome, characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous and other myxomas, and multiple endocrine tumors. The disease is caused by inactivating mutations or large deletions of the PRKAR1A gene located at 17q22–24 coding for the regulatory subunit type I alpha of protein kinase A (PKA) gene. Most recently, components of the complex have been associated with defects of other PKA subunits, such as the catalytic subunits PRKACA (adrenal hyperplasia) and PRKACB (pigmented spots, myxomas, pituitary adenomas). In this report, we review CNC, its clinical features, diagnosis, treatment, and molecular etiology including PRKAR1A mutations and the newest on PRKACA and PRKACB defects especially as they pertain to adrenal tumors and Cushing’s syndrome. PMID:26130139

  18. Oscillations of complex networks

    NASA Astrophysics Data System (ADS)

    Wang, Xingang; Lai, Ying-Cheng; Lai, Choy Heng

    2006-12-01

    A complex network processing information or physical flows is usually characterized by a number of macroscopic quantities such as the diameter and the betweenness centrality. An issue of significant theoretical and practical interest is how such quantities respond to sudden changes caused by attacks or disturbances in recoverable networks, i.e., functions of the affected nodes are only temporarily disabled or partially limited. By introducing a model to address this issue, we find that, for a finite-capacity network, perturbations can cause the network to oscillate persistently in the sense that the characterizing quantities vary periodically or randomly with time. We provide a theoretical estimate of the critical capacity-parameter value for the onset of the network oscillation. The finding is expected to have broad implications as it suggests that complex networks may be structurally highly dynamic.

  19. Complex Flows by Nanohydrodynamics

    SciTech Connect

    Alley, E; Covello, P; Alder, B

    2004-03-01

    The study of complex flows by particle simulations is speeded up over molecular dynamics (MD) by more than two orders of magnitude by employing a stochastic collision dynamics method (DSMC) extended to high density (CBA). As a consequence, a picture generated on a single processor shows the typical features of the Rayleigh-Taylor instability and is in quantitative agreement with the experimentally found long time behavior.

  20. The Complex Information Process

    NASA Astrophysics Data System (ADS)

    Taborsky, Edwina

    2000-09-01

    This paper examines the semiosic development of energy to information within a dyadic reality that operates within the contradictions of both classical and quantum physics. These two realities are examined within the three Peircean modal categories of Firstness, Secondness and Thirdness. The paper concludes that our world cannot operate within either of the two physical realities but instead filiates the two to permit a semiosis or information-generation of complex systems.

  1. Operational Shock Complexity Theory

    DTIC Science & Technology

    2005-05-26

    but lies essentially at the door of the Westerner’s perceived need for order, theory and lack of belief in the concept of fate.25 Finally, complexity...elsewhere and the entire system exhibits properties and behaviors different from the parts.61 The two main types of system are open and closed systems...62 Open systems take on board excess energy to replace that which is lost in order to continue operating and remain alive. Closed systems seek

  2. Complex spatiotemporal convection patterns

    NASA Astrophysics Data System (ADS)

    Pesch, W.

    1996-09-01

    This paper reviews recent efforts to describe complex patterns in isotropic fluids (Rayleigh-Bénard convection) as well as in anisotropic liquid crystals (electro-hydrodynamic convection) when driven away from equilibrium. A numerical scheme for solving the full hydrodynamic equations is presented that allows surprisingly well for a detailed comparison with experiments. The approach can also be useful for a systematic construction of models (order parameter equations).

  3. Engineering Complex Tissues

    PubMed Central

    MIKOS, ANTONIOS G.; HERRING, SUSAN W.; OCHAREON, PANNEE; ELISSEEFF, JENNIFER; LU, HELEN H.; KANDEL, RITA; SCHOEN, FREDERICK J.; TONER, MEHMET; MOONEY, DAVID; ATALA, ANTHONY; VAN DYKE, MARK E.; KAPLAN, DAVID; VUNJAK-NOVAKOVIC, GORDANA

    2010-01-01

    This article summarizes the views expressed at the third session of the workshop “Tissue Engineering—The Next Generation,” which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a “guided interplay” between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from “adult biology” of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician’s perspective for functional tissue

  4. [Complex vascular access].

    PubMed

    Mangiarotti, G; Cesano, G; Thea, A; Hamido, D; Pacitti, A; Segoloni, G P

    1998-03-01

    Availability of a proper vascular access is a basic condition for a proper extracorporeal replacement in end-stage chronic renal failure. However, biological factors, management and other problems, may variously condition their middle-long term survival. Therefore, personal experience of over 25 years has been critically reviewed in order to obtain useful information. In particular "hard" situations necessitating complex procedures have been examined but, if possible, preserving the peripherical vascular features.

  5. Sporadic meteoroid complex: Modeling

    NASA Astrophysics Data System (ADS)

    Andreev, V.

    2014-07-01

    The distribution of the sporadic meteoroids flux density over the celestial sphere is the common form of representation of the meteoroids distribution in the vicinity of the Earth's orbit. The determination of the flux density of sporadic meteor bodies is Q(V,e,f) = Q_0 P_e(V) P(e,f) where V is the meteoroid velocity, e,f are the radiant coordinates, Q_0 is the meteoroid flux over whole celestial sphere, P_e(V) is the conditional velocity distributions and P(e,f) is the radiant distribution over the celestial sphere. The sporadic meteoroid complex model is analytical and based on heliocentric velocities and radiant distributions. The multi-mode character of the heliocentric velocity and radiant distributions follows from the analysis of meteor observational data. This fact points to a complicated structure of the sporadic meteoroid complex. It is the consequence of the plurality of the parent bodies and the origin mechanisms of the meteoroids. The meteoroid complex was divided into four groups for that reason and with a goal of more accurate modelling of velocities and radiant distributions. As the classifying parameter to determine the meteoroid membership in any group, we adopt the Tisserand invariant relative to Jupiter T_J = 1/a + 2 A_J^{-3/2} √{a (1 - e^2)} cos i and the meteoroid orbit inclination i. Two meteoroid groups relate to long-period and short-period comets. One meteoroid group is related to asteroids. The relationship to the last, fourth group is a problematic one. Then, we construct models of radiant and velocity distributions for each group. The analytical model for the whole sporadic meteoroid complex is the sum of the ones for each group.

  6. Keynes, Hayek and Complexity

    NASA Astrophysics Data System (ADS)

    Ormerod, Paul

    In the spirit of the overall topic of the conference, in this paper I consider the extent to which economic theory includes elements of the complex systems approach. I am setting to one side here the developments over the past decade in applying complex systems analysis to economic problems. This is not because this recent work is not important. It most certainly is. But I want to argue that there is a very distinct tradition of what we would now describe as a complex systems approach in the works of two of the greatest economists of the 20th century. There is of course a dominant intellectual paradigm within economics, that known as `neo-classical'economics. This paradigm is by no means an empty box, and is undoubtedly useful in helping to understand how some aspects of the social and economic worlds work. But even in its heyday, neo-classical economics never succeeded by its empirical success in driving out completely other theoretical approaches, for its success was simply not sufficient to do so. Much more importantly, economics over the past twenty or thirty years has become in an increasing state of flux.

  7. Emergent Complex Network Geometry

    PubMed Central

    Wu, Zhihao; Menichetti, Giulia; Rahmede, Christoph; Bianconi, Ginestra

    2015-01-01

    Networks are mathematical structures that are universally used to describe a large variety of complex systems such as the brain or the Internet. Characterizing the geometrical properties of these networks has become increasingly relevant for routing problems, inference and data mining. In real growing networks, topological, structural and geometrical properties emerge spontaneously from their dynamical rules. Nevertheless we still miss a model in which networks develop an emergent complex geometry. Here we show that a single two parameter network model, the growing geometrical network, can generate complex network geometries with non-trivial distribution of curvatures, combining exponential growth and small-world properties with finite spectral dimensionality. In one limit, the non-equilibrium dynamical rules of these networks can generate scale-free networks with clustering and communities, in another limit planar random geometries with non-trivial modularity. Finally we find that these properties of the geometrical growing networks are present in a large set of real networks describing biological, social and technological systems. PMID:25985280

  8. Coherence, Complexity and Creativity

    NASA Astrophysics Data System (ADS)

    Arecchi, Fortunato Tito

    We review the ideas and experiments that established the onset of laser coherence beyond a suitable threshold. That threshold is the first of a chain of bifurcations in a non linear dynamics, leading eventually to deterministic chaos in lasers. In particular, the so called HC behavior has striking analogies with the electrical activity of neurons. Based on these considerations, we develop a dynamical model of neuron synchronization leading to coherent global perceptions. Synchronization implies a transitory control of neuron chaos. Depending on the time duration of this control, a cognitive agent has different amounts of awareness. Combining this with a stream of external inputs, one can point at an optimal use of internal resources, that is called cognitive creativity. While coherence is associated with long range correlations, complexity arises whenever an array of coupled dynamical systems displays multiple paths of coherence. What is the relation among the three concepts in the title? While coherence is associated with long range correlations, complexity arises whenever an array of coupled dynamical systems displays multiple paths of coherence. Creativity corresponds to a free selection of a coherence path within a complex nest. As sketched above, it seems dynamically related to chaos control.

  9. The Emparassment of Complexity

    NASA Astrophysics Data System (ADS)

    Nowotny, Helga

    My vision of complexity sciences targets their potential to extend the range, precision, and depth in making predictions. While this has always been the ambition and yardstick for the physicalmathematical sciences, complexity sciences now allow to include society and social behavior - to some extent. There is agreement that society is a complex adaptive system, CAS, with a few peculiarities. Ignoring, downplaying, or naturalizing them, i.e. to take them as essential and given, carries the risk to end up with abstractions which are cutoff from the dynamics of societal contexts. One of the peculiarities of society as a CAS is that the models with which we try to make sense of the world are invented and constructed by us. It is humans who make observations and provide the assumptions on which models are based. Humans leave traces that are collected and processed to be transformed into data. Humans decide to which purpose they will be put and how they will be repurposed. Humans are object of research and subject. Coping with these peculiarities requires an inbuilt reflexivity. Practioners must perform a double act and do so repeatedly. They must engage in a focused way with their scientific work and equally distance themselves by critically reflecting their often tacit assumptions. A friend of mine, Yehuda Elkana, called this twotier thinking...

  10. Manufacturing complexity analysis

    NASA Technical Reports Server (NTRS)

    Delionback, L. M.

    1977-01-01

    The analysis of the complexity of a typical system is presented. Starting with the subsystems of an example system, the step-by-step procedure for analysis of the complexity of an overall system is given. The learning curves for the various subsystems are determined as well as the concurrent numbers of relevant design parameters. Then trend curves are plotted for the learning curve slopes versus the various design-oriented parameters, e.g. number of parts versus slope of learning curve, or number of fasteners versus slope of learning curve, etc. Representative cuts are taken from each trend curve, and a figure-of-merit analysis is made for each of the subsystems. Based on these values, a characteristic curve is plotted which is indicative of the complexity of the particular subsystem. Each such characteristic curve is based on a universe of trend curve data taken from data points observed for the subsystem in question. Thus, a characteristic curve is developed for each of the subsystems in the overall system.

  11. Predictive Surface Complexation Modeling

    SciTech Connect

    Sverjensky, Dimitri A.

    2016-11-29

    Surface complexation plays an important role in the equilibria and kinetics of processes controlling the compositions of soilwaters and groundwaters, the fate of contaminants in groundwaters, and the subsurface storage of CO2 and nuclear waste. Over the last several decades, many dozens of individual experimental studies have addressed aspects of surface complexation that have contributed to an increased understanding of its role in natural systems. However, there has been no previous attempt to develop a model of surface complexation that can be used to link all the experimental studies in order to place them on a predictive basis. Overall, my research has successfully integrated the results of the work of many experimentalists published over several decades. For the first time in studies of the geochemistry of the mineral-water interface, a practical predictive capability for modeling has become available. The predictive correlations developed in my research now enable extrapolations of experimental studies to provide estimates of surface chemistry for systems not yet studied experimentally and for natural and anthropogenically perturbed systems.

  12. The use of a cis-dioxomolybdenum(VI) dinuclear complex with quadradentate 1,4-benzenediylbis(benzyldithiocarbamate)(2-) as model compound for the active site of oxo transfer molybdoenzymes: reactivity, kinetics, and catalysis.

    PubMed

    Moradi-Shoeili, Zeinab; Boghaei, Davar M

    2012-03-01

    Dinuclear cis-dioxomolybdenum(VI) complex [{MoO(2)(Bz(2)Benzenediyldtc)}(2)] coordinated by a quadradentate dithiocarbamate (Bz(2)Benzenediyldtc(2-)=1,4-benzenediylbis(benzyldithiocarbamate)(2-)) has been prepared and characterized by elemental analysis, (13)C NMR, IR and UV-vis spectroscopy. The kinetics of the oxygen atom transfer between [{MoO(2)(Bz(2)Benzenediyldtc)}(2)] and PPh(3) was studied spectrophotometrically in CH(2)Cl(2) medium at 520 nm and four different temperatures, 288, 293, 298 and 303 K, respectively. The reaction follows second order kinetics with the rate constant k=0.163(2)M(-1)S(-1) and its increasingly strong absorption at 520 nm clearly indicate the formation of a μ-oxo molybdenum(V) species as a product. Despite the steric restrictions imposed by the ligand structure to prevent the formation of Mo(V) species, experimental evidence confirms its interference during the process. The product can then be formulated as [MoO(2)(Bz(2)Benzenediyldtc)(2)Mo(2)O(3)(Bz(2)Benzenediyldtc)(2)MoO(2)] which has one μ-oxomolybdenum(V) moiety. An Eyring plot allows the activation parameters ΔH(‡)=64.2(1) kJ mol(-1) and ΔS(‡)=-45.1(6) J K(-1) mol(-1) to be determined from the temperature dependence of the rate constant, suggesting an associative transition state for the oxo transfer reaction. Catalytic oxygen atom transfer reaction from DMSO to PPh(3) was also followed by monitoring the chemical shift changes in (31)P NMR spectroscopy. The substrate oxidation process follows a well-defined catalytic cycle capable of 100% conversion for the reaction of PPh(3) and DMSO without intervention of Mo(V) formation during about 36 h.

  13. Development of catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium complexes.

    PubMed

    Tsubogo, Tetsu; Saito, Susumu; Seki, Kazutaka; Yamashita, Yasuhiro; Kobayashi, Shu

    2008-10-08

    Catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3 + 2] cycloaddition occurred in the reactions with crotonate derivatives, affording substituted pyrrolidine derivatives in high yields with high enantioselectivities. On the basis of this finding, we investigated asymmetric [3 + 2] cycloadditions, and it was revealed that several kinds of optically active substituted pyrrolidine derivatives containing contiguous stereogenic tertiary and quaternary carbon centers were obtained with high diastereo- and enantioselectivities. In addition, optically active pyrrolidine cores of hepatitis C virus RNA-dependent polymerase inhibitors and potential effective antiviral agents have been synthesized using this [3 + 2] cycloaddition reaction. NMR spectroscopic analysis and observation of nonamplification of enantioselectivity in nonlinear effect experiments suggested that a monomeric calcium species with an anionic ligand was formed as an active catalyst. A stepwise mechanism of the [3 + 2] cycloaddition, consisting of 1,4-addition and successive intramolecular Mannich-type reaction was suggested. Furthermore, modification of the Schiff base structure resulted in a modification of the reaction course from a [3 + 2] cycloaddition to a 1,4-addition, affording 3-substituted glutamic acid derivatives with high diasterero- and enantioselectivities.

  14. The Stigma Complex

    PubMed Central

    Pescosolido, Bernice A.; Martin, Jack K.

    2016-01-01

    Since the beginning of the twenty-first century, research on stigma has continued. Building on conceptual and empirical work, the recent period clarifies new types of stigmas, expansion of measures, identification of new directions, and increasingly complex levels. Standard beliefs have been challenged, the relationship between stigma research and public debates reconsidered, and new scientific foundations for policy and programs suggested. We begin with a summary of the most recent Annual Review articles on stigma, which reminded sociologists of conceptual tools, informed them of developments from academic neighbors, and claimed findings from the early period of “resurgence.” Continued (even accelerated) progress has also revealed a central problem. Terms and measures are often used interchangeably, leading to confusion and decreasing accumulated knowledge. Drawing from this work but focusing on the past 14 years of stigma research (including mental illness, sexual orientation, HIV/AIDS, and race/ethnicity), we provide a theoretical architecture of concepts (e.g., prejudice, experienced/received discrimination), drawn together through a stigma process (i.e., stigmatization), based on four theoretical premises. Many characteristics of the mark (e.g., discredited, concealable) and variants (i.e., stigma types and targets) become the focus of increasingly specific and multidimensional definitions. Drawing from complex and systems science, we propose a stigma complex, a system of interrelated, heterogeneous parts bringing together insights across disciplines to provide a more realistic and complicated sense of the challenge facing research and change efforts. The Framework Integrating Normative Influences on Stigma (FINIS) offers a multilevel approach that can be tailored to stigmatized statuses. Finally, we outline challenges for the next phase of stigma research, with the goal of continuing scientific activity that enhances our understanding of stigma and builds

  15. Complex-Valued Autoencoders

    PubMed Central

    Baldi, Pierre; Lu, Zhiqin

    2012-01-01

    Autoencoders are unsupervised machine learning circuits, with typically one hidden layer, whose learning goal is to minimize an average distortion measure between inputs and outputs. Linear autoencoders correspond to the special case where only linear transformations between visible and hidden variables are used. While linear autoencoders can be defined over any field, only real-valued linear autoencoders have been studied so far. Here we study complex-valued linear autoencoders where the components of the training vectors and adjustable matrices are defined over the complex field with the L2 norm. We provide simpler and more general proofs that unify the real-valued and complex-valued cases, showing that in both cases the landscape of the error function is invariant under certain groups of transformations. The landscape has no local minima, a family of global minima associated with Principal Component Analysis, and many families of saddle points associated with orthogonal projections onto sub-space spanned by sub-optimal subsets of eigenvectors of the covariance matrix. The theory yields several iterative, convergent, learning algorithms, a clear understanding of the generalization properties of the trained autoencoders, and can equally be applied to the hetero-associative case when external targets are provided. Partial results on deep architecture as well as the differential geometry of autoencoders are also presented. The general framework described here is useful to classify autoencoders and identify general properties that ought to be investigated for each class, illuminating some of the connections between autoencoders, unsupervised learning, clustering, Hebbian learning, and information theory. PMID:22622264

  16. Proteins : paradigms of complexity /

    SciTech Connect

    Frauenfelder, Hans,

    2001-01-01

    Proteins are the working machines of living systems. Directed by the DNA, of the order of a few hundred building blocks, selected from twenty different amino acids, are covalently linked into a linear polypeptide chain. In the proper environment, the chain folds into the working protein, often a globule of linear dimensions of a few nanometers. The biologist considers proteins units from which living systems are built. Many physical scientists look at them as systems in which the laws of complexity can be studied better than anywhere else. Some of the results of such studies will be sketched.

  17. Chalcogenide centred gold complexes.

    PubMed

    Gimeno, M Concepción; Laguna, Antonio

    2008-09-01

    Chalcogenide-centred gold complexes are an important class of compounds in which a central chalcogen is surrounded by several gold atoms or gold and other metals. They have special characteristics such as unusual geometries, electron deficiency and properties such as luminescence or non-linear optical properties. The best known species are the trinuclear [E(AuPR3)3]+, 'oxonium' type species, that have high synthetic applicability, not only in other chalcogen-centred species, but in many other organometallic derivatives. The aurophilic interactions play an important role in the stability, preference for a particular geometry and luminescence properties in this type of derivatives (critical review, 117 references).

  18. Organization of complex networks

    NASA Astrophysics Data System (ADS)

    Kitsak, Maksim

    Many large complex systems can be successfully analyzed using the language of graphs and networks. Interactions between the objects in a network are treated as links connecting nodes. This approach to understanding the structure of networks is an important step toward understanding the way corresponding complex systems function. Using the tools of statistical physics, we analyze the structure of networks as they are found in complex systems such as the Internet, the World Wide Web, and numerous industrial and social networks. In the first chapter we apply the concept of self-similarity to the study of transport properties in complex networks. Self-similar or fractal networks, unlike non-fractal networks, exhibit similarity on a range of scales. We find that these fractal networks have transport properties that differ from those of non-fractal networks. In non-fractal networks, transport flows primarily through the hubs. In fractal networks, the self-similar structure requires any transport to also flow through nodes that have only a few connections. We also study, in models and in real networks, the crossover from fractal to non-fractal networks that occurs when a small number of random interactions are added by means of scaling techniques. In the second chapter we use k-core techniques to study dynamic processes in networks. The k-core of a network is the network's largest component that, within itself, exhibits all nodes with at least k connections. We use this k-core analysis to estimate the relative leadership positions of firms in the Life Science (LS) and Information and Communication Technology (ICT) sectors of industry. We study the differences in the k-core structure between the LS and the ICT sectors. We find that the lead segment (highest k-core) of the LS sector, unlike that of the ICT sector, is remarkably stable over time: once a particular firm enters the lead segment, it is likely to remain there for many years. In the third chapter we study how

  19. Complex regional pain syndrome

    PubMed Central

    Sebastin, Sandeep J

    2011-01-01

    Complex regional pain syndrome (CRPS) previously known as reflex sympathetic dystrophy is a chronic neurological disorder involving the limbs characterized by disabling pain, swelling, vasomotor instability, sudomotor abnormality, and impairment of motor function. CRPS is not uncommon after hand surgery and may complicate post-operative care. There is no specific diagnostic test for CRPS and the diagnosis is based on history, clinical examination, and supportive laboratory findings. Recent modifications to diagnostic criteria have enabled clinicians to diagnose this disease more consistently. This review gives a synopsis of CRPS and discusses the diagnosis, pathophysiology, and treatment options based on the limited evidence in the literature. PMID:22022040

  20. Complexity, contingency, and criticality.

    PubMed Central

    Bak, P; Paczuski, M

    1995-01-01

    Complexity originates from the tendency of large dynamical systems to organize themselves into a critical state, with avalanches or "punctuations" of all sizes. In the critical state, events which would otherwise be uncoupled become correlated. The apparent, historical contingency in many sciences, including geology, biology, and economics, finds a natural interpretation as a self-organized critical phenomenon. These ideas are discussed in the context of simple mathematical models of sandpiles and biological evolution. Insights are gained not only from numerical simulations but also from rigorous mathematical analysis. Images Fig. 3 Fig. 4 PMID:11607561

  1. Macroevolution of complex retroviruses.

    PubMed

    Katzourakis, Aris; Gifford, Robert J; Tristem, Michael; Gilbert, M Thomas P; Pybus, Oliver G

    2009-09-18

    Retroviruses can leave a "fossil record" in their hosts' genomes in the form of endogenous retroviruses. Foamy viruses, complex retroviruses that infect mammals, have been notably absent from this record. We have found an endogenous foamy virus within the genomes of sloths and show that foamy viruses were infecting mammals more than 100 million years ago and codiverged with their hosts across an entire geological era. Our analysis highlights the role of evolutionary constraint in maintaining viral genome structure and indicates that accessory genes and mammalian mechanisms of innate immunity are the products of macroevolutionary conflict played out over a geological time scale.

  2. Linking social complexity and vocal complexity: a parid perspective

    PubMed Central

    Krams, Indrikis; Krama, Tatjana; Freeberg, Todd M.; Kullberg, Cecilia; Lucas, Jeffrey R.

    2012-01-01

    The Paridae family (chickadees, tits and titmice) is an interesting avian group in that species vary in important aspects of their social structure and many species have large and complex vocal repertoires. For this reason, parids represent an important set of species for testing the social complexity hypothesis for vocal communication—the notion that as groups increase in social complexity, there is a need for increased vocal complexity. Here, we describe the hypothesis and some of the early evidence that supported the hypothesis. Next, we review literature on social complexity and on vocal complexity in parids, and describe some of the studies that have made explicit tests of the social complexity hypothesis in one parid—Carolina chickadees, Poecile carolinensis. We conclude with a discussion, primarily from a parid perspective, of the benefits and costs of grouping and of physiological factors that might mediate the relationship between social complexity and changes in signalling behaviour. PMID:22641826

  3. Polyhydride complexes for hydrogen storage

    SciTech Connect

    Jensen, C.M.

    1995-09-01

    Polyhydride metal complexes are being developed for application in hydrogen storage. Efforts have focused on developing complexes with improved available hydrogen weight percentages. We have explored the possibility that complexes containing aromatic hydrocarbon ligands could store hydrogen at both the metal center and in the ligands. We have synthesized novel indenyl hydride complexes and explored their reactivity with hydrogen. The reversible hydrogenation of [IrH{sub 3}(PPh{sub 3})({eta}{sup 5}-C{sub 10}H{sub 7})]{sup +} has been achieved. While attempting to prepare {eta}{sup 6}-tetrahydronaphthalene complexes, we discovered that certain polyhydride complexes catalyze both the hydrogenation and dehydrogenation of tetrahydronaphthalene.

  4. Method for preparing radiopharmaceutical complexes

    DOEpatents

    Jones, Alun G.; Davison, Alan; Abrams, Michael J.

    1989-05-02

    A method for preparing radiopharmaceutical complexes that are substantially free of the reaction materials used to produce the radiopharmaceutical complex is disclosed. The method involves admixing in a suitable first solvent in a container a target seeking ligand or salt or metal adduct thereof, a radionuclide label, and a reducing agent for said radionuclide, thereby forming said radiopharmaceutical complex; coating the interior walls of the container with said pharmaceutical complex; discarding the solvent containing by-products and unreacted starting reaction materials; and removing the radiopharmaceutical complex from said walls by dissolving it in a second solvent, thereby obtaining said radiopharmaceutical complex substantially free of by-products and unreacted starting materials.

  5. Complex Semantic Networks

    NASA Astrophysics Data System (ADS)

    Teixeira, G. M.; Aguiar, M. S. F.; Carvalho, C. F.; Dantas, D. R.; Cunha, M. V.; Morais, J. H. M.; Pereira, H. B. B.; Miranda, J. G. V.

    Verbal language is a dynamic mental process. Ideas emerge by means of the selection of words from subjective and individual characteristics throughout the oral discourse. The goal of this work is to characterize the complex network of word associations that emerge from an oral discourse from a discourse topic. Because of that, concepts of associative incidence and fidelity have been elaborated and represented the probability of occurrence of pairs of words in the same sentence in the whole oral discourse. Semantic network of words associations were constructed, where the words are represented as nodes and the edges are created when the incidence-fidelity index between pairs of words exceeds a numerical limit (0.001). Twelve oral discourses were studied. The networks generated from these oral discourses present a typical behavior of complex networks and their indices were calculated and their topologies characterized. The indices of these networks obtained from each incidence-fidelity limit exhibit a critical value in which the semantic network has maximum conceptual information and minimum residual associations. Semantic networks generated by this incidence-fidelity limit depict a pattern of hierarchical classes that represent the different contexts used in the oral discourse.

  6. The authority of complexity.

    PubMed

    Stehr, N; Grundmann, R

    2001-06-01

    The assertion about the unique 'complexity' or the peculiarly intricate character of social phenomena has, at least within sociology, a long, venerable and virtually uncontested tradition. At the turn of the last century, classical social theorists, for example, Georg Simmel and Emile Durkheim, made prominent and repeated reference to this attribute of the subject matter of sociology and the degree to which it complicates, even inhibits the develop and application of social scientific knowledge. Our paper explores the origins, the basis and the consequences of this assertion and asks in particular whether the classic complexity assertion still deserves to be invoked in analyses that ask about the production and the utilization of social scientific knowledge in modern society. We present John Maynard Keynes' economic theory and its practical applications as an illustration. We conclude that the practical value of social scientific knowledge is not dependent on a faithful, in the sense of complete, representation of social reality. Instead, social scientific knowledge that wants to optimize its practicality has to attend and attach itself to elements of social situations that can be altered or are actionable.

  7. Tuberous sclerosis complex.

    PubMed

    Islam, Monica P; Roach, E Steve

    2015-01-01

    Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can affect the brain, skin, eyes, kidneys, heart, and lungs. TSC alters cellular proliferation and differentiation, resulting in hamartomas of various organs, tumor formation, and altered neuronal migration. The phenotype is highly variable. Most individuals have seizures, commonly including infantile spasms, and there is variable intellectual disability and autism. Neonates can present with cardiac failure due to intracardiac rhabdomyomas. The likelihood of renal angiomyolipomas increases with age, and renal disease is the most common cause of death in adults with TSC. Pulmonary involvement occurs predominantly in women and carries a high morbidity and mortality. TSC is inherited as an autosomal dominant trait, but spontaneous mutations are common. A mutation of either TSC1 on chromosome 9 or TSC2 on chromosome 16 leads to dysfunction of hamartin or tuberin, respectively. These two proteins form a functional complex that modulates the mammalian target of rapamycin (mTOR) pathway. Medications that inhibit mTOR are being used to treat TSC-related tumors, and current studies are investigating whether these agents could alleviate other TSC complications. Consensus statements guide identification and optimal management of many of the TSC-related complications at diagnosis and throughout the lifespan. A multidisciplinary approach is necessary for optimal management of individuals with TSC.

  8. Complexity in language acquisition.

    PubMed

    Clark, Alexander; Lappin, Shalom

    2013-01-01

    Learning theory has frequently been applied to language acquisition, but discussion has largely focused on information theoretic problems-in particular on the absence of direct negative evidence. Such arguments typically neglect the probabilistic nature of cognition and learning in general. We argue first that these arguments, and analyses based on them, suffer from a major flaw: they systematically conflate the hypothesis class and the learnable concept class. As a result, they do not allow one to draw significant conclusions about the learner. Second, we claim that the real problem for language learning is the computational complexity of constructing a hypothesis from input data. Studying this problem allows for a more direct approach to the object of study--the language acquisition device-rather than the learnable class of languages, which is epiphenomenal and possibly hard to characterize. The learnability results informed by complexity studies are much more insightful. They strongly suggest that target grammars need to be objective, in the sense that the primitive elements of these grammars are based on objectively definable properties of the language itself. These considerations support the view that language acquisition proceeds primarily through data-driven learning of some form.

  9. Growth of Complex Organizations

    NASA Astrophysics Data System (ADS)

    Nunes Amaral, Luis A.

    2000-03-01

    We analyze a database comprising all publicly-traded US firms within the years 1974--93(M.H.R. Stanley et al.), Nature 379, 804 (1996); L.A.N. Amaral et al., J. Phys. (France) I 7, 621 (1997). We find (i) that the distribution of the annual growth rates ---for companies with approximately the same size S--- decays as an exponential, and (ii) that the standard deviation σ of these distributions scales as σ ~ S^-β. We introduce a dynamical model in which we assume that each firm has a complex internal structure comprising many subunits(L.A.N. Amaral et al.), Phys. Rev. Lett. 80, 1385 (1998). We study the case in which (i) each subunit grows in a multiplicative manner, and (ii) the interactions between the firms are mean field. We find agreement between our predictions and the empirical results for firms. We then analyze the fluctuations in the gross domestic product of 152 countries for the period 1950--92 and find a surprising agreement with the results for firm growth (Y. Lee et al.), Phys. Rev. Lett. 81, 3275 (1998). Finally, we analyze the fluctuations in the research output and research input of US universities and find sinilar scaling laws(V. Plerou et al.), Nature 400, 433 (1999). Our empirical results and model suggest that the growth of organizations with complex structure are governed by similar mechanisms.

  10. Tuberous sclerosis complex.

    PubMed

    Henske, Elizabeth P; Jóźwiak, Sergiusz; Kingswood, J Christopher; Sampson, Julian R; Thiele, Elizabeth A

    2016-05-26

    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects multiple organ systems and is caused by loss-of-function mutations in one of two genes: TSC1 or TSC2. The disorder can affect both adults and children. First described in depth by Bourneville in 1880, it is now estimated that nearly 2 million people are affected by the disease worldwide. The clinical features of TSC are distinctive and can vary widely between individuals, even within one family. Major features of the disease include tumours of the brain, skin, heart, lungs and kidneys, seizures and TSC-associated neuropsychiatric disorders, which can include autism spectrum disorder and cognitive disability. TSC1 (also known as hamartin) and TSC2 (also known as tuberin) form the TSC protein complex that acts as an inhibitor of the mechanistic target of rapamycin (mTOR) signalling pathway, which in turn plays a pivotal part in regulating cell growth, proliferation, autophagy and protein and lipid synthesis. Remarkable progress in basic and translational research, in addition to several randomized controlled trials worldwide, has led to regulatory approval of the use of mTOR inhibitors for the treatment of renal angiomyolipomas, brain subependymal giant cell astrocytomas and pulmonary lymphangioleiomyomatosis, but further research is needed to establish full indications of therapeutic treatment. In this Primer, we review the state-of-the-art knowledge in the TSC field, including the molecular and cellular basis of the disease, medical management, major knowledge gaps and ongoing research towards a cure.

  11. Complex master slave interferometry.

    PubMed

    Rivet, Sylvain; Maria, Michael; Bradu, Adrian; Feuchter, Thomas; Leick, Lasse; Podoleanu, Adrian

    2016-02-08

    A general theoretical model is developed to improve the novel Spectral Domain Interferometry method denoted as Master/Slave (MS) Interferometry. In this model, two functions, g and h are introduced to describe the modulation chirp of the channeled spectrum signal due to nonlinearities in the decoding process from wavenumber to time and due to dispersion in the interferometer. The utilization of these two functions brings two major improvements to previous implementations of the MS method. A first improvement consists in reducing the number of channeled spectra necessary to be collected at Master stage. In previous MSI implementation, the number of channeled spectra at the Master stage equated the number of depths where information was selected from at the Slave stage. The paper demonstrates that two experimental channeled spectra only acquired at Master stage suffice to produce A-scans from any number of resolved depths at the Slave stage. A second improvement is the utilization of complex signal processing. Previous MSI implementations discarded the phase. Complex processing of the electrical signal determined by the channeled spectrum allows phase processing that opens several novel avenues. A first consequence of such signal processing is reduction in the random component of the phase without affecting the axial resolution. In previous MSI implementations, phase instabilities were reduced by an average over the wavenumber that led to reduction in the axial resolution.

  12. Syntactic Complexity as an Aspect of Text Complexity

    ERIC Educational Resources Information Center

    Frantz, Roger S.; Starr, Laura E.; Bailey, Alison L.

    2015-01-01

    Students' ability to read complex texts is emphasized in the Common Core State Standards (CCSS) for English Language Arts and Literacy. The standards propose a three-part model for measuring text complexity. Although the model presents a robust means for determining text complexity based on a variety of features inherent to a text as well as…

  13. Not so Complex: Iteration in the Complex Plane

    ERIC Educational Resources Information Center

    O'Dell, Robin S.

    2014-01-01

    The simple process of iteration can produce complex and beautiful figures. In this article, Robin O'Dell presents a set of tasks requiring students to use the geometric interpretation of complex number multiplication to construct linear iteration rules. When the outputs are plotted in the complex plane, the graphs trace pleasing designs…

  14. Nuclear Weapons Complex reconfiguration study

    SciTech Connect

    Not Available

    1991-01-01

    Shortly after assuming duties as Secretary of Energy, I reviewed the Nuclear Weapons Complex Modernization Report'' submitted to the Congress in January 1989 as required by the National Defense Authorization Act of 1988 and 1989. My review showed that several of the report's assumptions needed to be re-evaluated. During this eighteen-month review, dramatic world changes forced further reassessments of the future Nuclear Weapons Complex. These changes are reflected in the new report. The new report presents a plan to achieve a reconfigured complex, called Complex-21. Complex-21 would be smaller, less diverse, and less expensive to operated than the Complex of today. Complex-21 would be able to safely and reliability support nuclear deterrent stockpile objectives set forth by the President and funded by the Congress. It would be consistent with realities of the emerging international security environment and flexible enough to accommodate the likely range of deterrent contingencies. In addition, Complex-21 would be constructed and operated to comply with all applicable federal, state, and local laws, regulations, and orders. Achieving Complex-21 will require significant resources. This report provides and organized approach toward selecting the most appropriate configuration for Complex-21, satisfying environmental requirements, and minimizing costs. The alternative -- to continue to use piecemeal fixes to run an antiquated complex -- will be more expensive and provide a less reliable Nuclear Weapons Complex. As a consequence, implementation of the Complex-21 plan is considered necessary to ensure continued viability of our nuclear deterrent.

  15. Proepithelin stimulates growth plate chondrogenesis via nuclear factor-kappaB-p65-dependent mechanisms.

    PubMed

    Wu, Shufang; Zang, Weijin; Li, Xu; Sun, Hongzhi

    2011-07-08

    Proepithelin, a previously unrecognized growth factor in cartilage, has recently emerged as an important regulator for cartilage formation and function. In the present study, we provide several lines of evidences in proepithelin-mediated induction of cell proliferation, differentiation, and apoptosis in the metatarsal growth plate. Proepithelin-mediated stimulation of metatarsal growth and growth plate chondrogenesis was neutralized by pyrrolidine dithiocarbamate, a known NF-κB inhibitor. In rat growth plate chondrocytes, proepithelin induced NF-κB-p65 nuclear translocation, and nuclear NF-κB-p65 initiated its target gene cyclin D1 to regulate chondrocyte functions. The inhibition of NF-κB-p65 expression and activity (by p65 short interfering RNA (siRNA) and pyrrolidine dithiocarbamate, respectively) in chondrocytes reversed the proepithelin-mediated induction of cell proliferation and differentiation and the proepithelin-mediated prevention of cell apoptosis. Moreover, the inhibition of the phosphatidylinositol 3-kinase and Akt abolished the effects of proepithelin on NF-κB activation. Finally, using siRNA and antisense strategies, we demonstrated that endogenously produced proepithelin by chondrocytes is important for chondrocyte growth in serum-deprived conditions. These results support the hypothesis that the induction of NF-κB activity of in growth plate chondrocytes is critical in proepithelin-mediated growth plate chondrogenesis and longitudinal bone growth.

  16. Amphotericin B Lipid Complex Injection

    MedlinePlus

    Amphotericin B lipid complex injection is used to treat serious, possibly life-threatening fungal infections in people who did ... respond or are unable to tolerate conventional amphotericin B therapy. Amphotericin B lipid complex injection is in ...

  17. Complexity in scalable computing.

    SciTech Connect

    Rouson, Damian W. I.

    2008-12-01

    The rich history of scalable computing research owes much to a rapid rise in computing platform scale in terms of size and speed. As platforms evolve, so must algorithms and the software expressions of those algorithms. Unbridled growth in scale inevitably leads to complexity. This special issue grapples with two facets of this complexity: scalable execution and scalable development. The former results from efficient programming of novel hardware with increasing numbers of processing units (e.g., cores, processors, threads or processes). The latter results from efficient development of robust, flexible software with increasing numbers of programming units (e.g., procedures, classes, components or developers). The progression in the above two parenthetical lists goes from the lowest levels of abstraction (hardware) to the highest (people). This issue's theme encompasses this entire spectrum. The lead author of each article resides in the Scalable Computing Research and Development Department at Sandia National Laboratories in Livermore, CA. Their co-authors hail from other parts of Sandia, other national laboratories and academia. Their research sponsors include several programs within the Department of Energy's Office of Advanced Scientific Computing Research and its National Nuclear Security Administration, along with Sandia's Laboratory Directed Research and Development program and the Office of Naval Research. The breadth of interests of these authors and their customers reflects in the breadth of applications this issue covers. This article demonstrates how to obtain scalable execution on the increasingly dominant high-performance computing platform: a Linux cluster with multicore chips. The authors describe how deep memory hierarchies necessitate reducing communication overhead by using threads to exploit shared register and cache memory. On a matrix-matrix multiplication problem, they achieve up to 96% parallel efficiency with a three-part strategy: intra

  18. Development of a sequential injection dispersive liquid-liquid microextraction system for electrothermal atomic absorption spectrometry by using a hydrophobic sorbent material: determination of lead and cadmium in natural waters.

    PubMed

    Anthemidis, Aristidis N; Ioannou, Kallirroy-Ioanna G

    2010-05-23

    A novel on-line sequential injection (SI) dispersive liquid-liquid microextraction (DLLME) system coupled to electrothermal atomic absorption spectrometry (ETAAS) was developed for metal preconcentration in micro-scale, eliminating the laborious and time consuming procedure of phase separation with centrifugation. The potentials of the system were demonstrated for trace lead and cadmium determination in water samples. An appropriate disperser solution which contains the extraction solvent (xylene) and the chelating agent (ammonium pyrrolidine dithiocarbamate) in methanol is mixed on-line with the sample solution (aqueous phase), resulting thus, a cloudy solution, which is consisted of fine droplets of xylene, dispersed throughout the aqueous phase. Three procedures are taking place simultaneously: cloudy solution creation, analyte complex formation and extraction from aqueous phase into the fine droplets of xylene. Subsequently the droplets were retained on the hydrophobic surface of PTFE-turnings into the column. A part of 30 microL of the eluent (methyl isobutyl ketone) was injected into furnace graphite for analyte atomization and quantification. The sampling frequency was 10 h(-1), and the obtained enrichment factor was 80 for lead and 34 for cadmium. The detection limit was 10 ng L(-1) and 2 ng L(-1), while the precision expressed as relative standard deviation (RSD) was 3.8% (at 0.5 microg L(-1)) and 4.1% (at 0.03 microg L(-1)) for lead and cadmium respectively. The proposed method was evaluated by analyzing certified reference materials and was applied to the analysis of natural waters.

  19. NF-κB activation mediates crystal translocation and interstitial inflammation in adenine overload nephropathy.

    PubMed

    Okabe, Cristiene; Borges, Raquel Lerner; de Almeida, Danilo Candido; Fanelli, Camilla; Barlette, Grasiela Pedreira; Machado, Flavia Gomes; Arias, Simone Costa Alarcon; Malheiros, Denise Maria Avancini Costa; Camara, Niels Olsen Saraiva; Zatz, Roberto; Fujihara, Clarice Kazue

    2013-07-15

    Adenine overload promotes intratubular crystal precipitation and interstitial nephritis. We showed recently that these abnormalities are strongly attenuated in mice knockout for Toll-like receptors-2, -4, MyD88, ASC, or caspase-1. We now investigated whether NF-κB activation also plays a pathogenic role in this model. Adult male Munich-Wistar rats were distributed among three groups: C (n = 17), receiving standard chow; ADE (n = 17), given adenine in the chow at 0.7% for 1 wk and 0.5% for 2 wk; and ADE + pyrrolidine dithiocarbamate (PDTC; n = 14), receiving adenine as above and the NF-κB inhibitor PDTC (120 mg·kg⁻¹·day⁻¹ in the drinking water). After 3 wk, widespread crystal deposition was seen in tubular lumina and in the renal interstitium, along with granuloma formation, collagen accumulation, intense tubulointerstitial proliferation, and increased interstitial expression of inflammatory mediators. Part of the crystals were segregated from tubular lumina by a newly formed cell layer and, at more advanced stages, appeared to be extruded to the interstitium. p65 nuclear translocation and IKK-α increased abundance indicated activation of the NF-κB system. PDTC treatment prevented p65 migration and normalized IKK-α, limited crystal shift to the interstitium, and strongly attenuated interstitial fibrosis/inflammation. These findings indicate that the complex inflammatory phenomena associated with this model depend, at least in part, on NF-κB activation, and suggest that the NF-κB system may become a therapeutic target in the treatment of chronic kidney disease.

  20. Speciation and determination of ultra trace amounts of inorganic tellurium in environmental water samples by dispersive liquid-liquid microextraction and electrothermal atomic absorption spectrometry.

    PubMed

    Najafi, Nahid Mashkouri; Tavakoli, Hamed; Alizadeh, Reza; Seidi, Shahram

    2010-06-18

    A simple and powerful method has been developed for the rapid and selective determination of Te(IV) and Te(VI), employing dispersive liquid-liquid microextraction combined with electrothermal atomic absorption spectrometry using palladium as permanent modifier. Under acidic conditions pH 1, only Te(IV) can form a complex with ammonium pyrrolidine dithiocarbamate (APDC) and therefore be extracted into fine droplets of carbon tetrachloride (extraction solvent) which are dispersed with ethanol into the water sample solution. After centrifugation, Te(IV) was determined in the sedimented organic phase while Te(VI) remained in the aqueous phase. Total inorganic tellurium was determined after the reduction of the Te(VI) to Te(IV). Te(VI) was calculated as the difference between the measured total inorganic tellurium and Te(IV) content. The effective parameters for improving the efficiency of microextraction process were investigated by using experimental and central composite designs. Under optimal conditions the enrichment factor was 125 and the calibration graph was linear in the range of 0.015-1 ng mL(-1) with detection limit and characteristic mass of 0.004 ng mL(-1) and 0.033 pg, respectively. The relative standard deviation for 0.5 ng mL(-1) of tellurium measurement was 3.6% (n=6) at ash and atomization temperature, 900 and 2600 degrees C, respectively. The recoveries of spiked Te(IV) and Te(VI) to the environmental water samples were 89.6-101.3% and 96.6-99.1%, respectively. The accuracy is also evaluated by applying the proposed method to certified reference material (NIST SRM 1643e), for which the result was in a good agreement with the certified values reported for this CRM (95% confidence level).

  1. Response surface methodology based on central composite design as a chemometric tool for optimization of dispersive-solidification liquid-liquid microextraction for speciation of inorganic arsenic in environmental water samples.

    PubMed

    Asadollahzadeh, Mehdi; Tavakoli, Hamed; Torab-Mostaedi, Meisam; Hosseini, Ghaffar; Hemmati, Alireza

    2014-06-01

    Dispersive-solidification liquid-liquid microextraction (DSLLME) coupled with electrothermal atomic absorption spectrometry (ETAAS) was developed for preconcentration and determination of inorganic arsenic (III, V) in water samples. At pH=1, As(III) formed complex with ammonium pyrrolidine dithiocarbamate (APDC) and extracted into the fine droplets of 1-dodecanol (extraction solvent) which were dispersed with ethanol (disperser solvent) into the water sample solution. After extraction, the organic phase was separated by centrifugation, and was solidified by transferring into an ice bath. The solidified solvent was transferred to a conical vial and melted quickly at room temperature. As(III) was determined in the melted organic phase while As(V) remained in the aqueous layer. Total inorganic As was determined after the reduction of the pentavalent forms of arsenic with sodium thiosulphate and potassium iodide. As(V) was calculated by difference between the concentration of total inorganic As and As(III). The variable of interest in the DSLLME method, such as the volume of extraction solvent and disperser solvent, pH, concentration of APDC (chelating agent), extraction time and salt effect, was optimized with the aid of chemometric approaches. First, in screening experiments, fractional factorial design (FFD) was used for selecting the variables which significantly affected the extraction procedure. Afterwards, the significant variables were optimized using response surface methodology (RSM) based on central composite design (CCD). In the optimum conditions, the proposed method has been successfully applied to the determination of inorganic arsenic in different environmental water samples and certified reference material (NIST RSM 1643e).

  2. Complex Dark Matter

    ScienceCinema

    Lincoln, Don

    2016-07-12

    After a century of study, scientists have come to the realization that the ordinary matter made of atoms is a minority in the universe. In order to explain observations, it appears that there exists a new and undiscovered kind of matter, called dark matter, that is five times more prevalent than ordinary matter. The evidence for this new matter’s existence is very strong, but scientists know only a little about its nature. In today’s video, Fermilab’s Dr. Don Lincoln talks about an exciting and unconventional idea, specifically that dark matter might have a very complex set of structures and interactions. While this idea is entirely speculative, it is an interesting hypothesis and one that scientists are investigating.

  3. Complex Dark Matter

    SciTech Connect

    Lincoln, Don

    2015-04-16

    After a century of study, scientists have come to the realization that the ordinary matter made of atoms is a minority in the universe. In order to explain observations, it appears that there exists a new and undiscovered kind of matter, called dark matter, that is five times more prevalent than ordinary matter. The evidence for this new matter’s existence is very strong, but scientists know only a little about its nature. In today’s video, Fermilab’s Dr. Don Lincoln talks about an exciting and unconventional idea, specifically that dark matter might have a very complex set of structures and interactions. While this idea is entirely speculative, it is an interesting hypothesis and one that scientists are investigating.

  4. Complex pendulum biomass sensor

    DOEpatents

    Hoskinson, Reed L.; Kenney, Kevin L.; Perrenoud, Ben C.

    2007-12-25

    A complex pendulum system biomass sensor having a plurality of pendulums. The plurality of pendulums allow the system to detect a biomass height and density. Each pendulum has an angular deflection sensor and a deflector at a unique height. The pendulums are passed through the biomass and readings from the angular deflection sensors are fed into a control system. The control system determines whether adjustment of machine settings is appropriate and either displays an output to the operator, or adjusts automatically adjusts the machine settings, such as the speed, at which the pendulums are passed through the biomass. In an alternate embodiment, an entanglement sensor is also passed through the biomass to determine the amount of biomass entanglement. This measure of entanglement is also fed into the control system.

  5. Complexity, Metastability and Nonextensivity

    NASA Astrophysics Data System (ADS)

    Beck, C.; Benedek, G.; Rapisarda, A.; Tsallis, C.

    Work and heat fluctuations in systems with deterministic and stochastic forces / E. G. D. Cohen and R. Van Zon -- Is the entropy S[symbol] extensive or nonextensive? / C. Tsallis -- Superstatistics: recent developments and applications / C. Beck -- Two stories outside Boltzmann-Gibbs statistics: Mori's Q-phase transitions and glassy dynamics at the onset of chaos / A. Robledo, F. Baldovin and E. Mayoral -- Time-averages and the heat theorem / A. Carati -- Fundamental formulae and numerical evidences for the central limit theorem in Tsallis statistics / H. Suyari -- Generalizing the Planck distribution / A. M. C. Soma and C. Tsallis -- The physical roots of complexity: renewal or modulation? / P. Grigolini -- Nonequivalent ensembles and metastability / H. Touchette and R. S. Ellis -- Statistical physics for cosmic structures / L. Pietronero and F. Sylos Labini -- Metastability and anomalous behavior in the HMF model: connections to nonextensive thermodynamics and glassy dynamics / A. Pluchino, A. Rapisarda and V. Latora -- Vlasov analysis of relaxation and meta-equilibrium / C. Anteneodo and R. O. Vallejos -- Weak chaos in large conservative systems - infinite-range coupled standard maps / L. G. Moyano, A. P. Majtey and C. Tsallis -- Deterministc aging / E. Barkai -- Edge of chaos of the classical kicked top map: sensitivity to initial conditions / S. M. Duarte Queirós and C. Tsallis -- What entropy at the edge of chaos? / M. Lissia, M. Coraddu and R. Tonelli -- Fractal growth of carbon schwarzites / G. Benedek ... [et al.] -- Clustering and interface propagation in interacting particle dynamics / A. Provata and V. K. Noussiou -- Resonant activation and noise enhanced stability in Josephson junctions / A. L. Pankratov and B. Spagnolo -- Symmetry breaking induced directed motions / C.-H. Chang and T. Y. Tsong -- General theory of Galilean-invariant entropic lattic Boltzmann models / B. M. Boghosian -- Unifying approach to the jamming transition in granular media and

  6. The tuberous sclerosis complex

    PubMed Central

    Orlova, Ksenia A.; Crino, Peter B.

    2010-01-01

    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes and is associated with hamartoma formation in multiple organ systems. The neurological manifestations of TSC are particularly challenging and include infantile spasms, intractable epilepsy, cognitive disabilities, and autism. Progress over the past 15 years has demonstrated that the TSC1 or TSC2 encoded proteins modulate cell function via the mTOR signaling cascade and serve as keystones in regulating cell growth and proliferation. The mTOR pathway provides an intersection for an intricate network of protein cascades that respond to cellular nutrition, energy levels, and growth-factor stimulation. In the brain, TSC1 and TSC2 have been implicated in cell body size, dendritic arborization, axonal outgrowth and targeting, neuronal migration, cortical lamination, and spine formation. Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients. PMID:20146692

  7. Recognizing complex patterns.

    PubMed

    Sinha, Pawan

    2002-11-01

    How the brain recognizes complex patterns in the environment is a central, but little understood question in neuroscience. The problem is of great significance for a host of applications such as biometric-based access control, autonomous robots and content-based information management. Although some headway in these directions has been made, the current artificial systems do not match the robustness and versatility of their biological counterparts. Here I examine recognition tasks drawn from two different sensory modalities--face recognition and speaker/speech recognition. The goal is to characterize the present state of artificial recognition technologies for these tasks, the influence of neuroscience on the design of these systems and the key challenges they face.

  8. Understanding complex chiral plasmonics.

    PubMed

    Duan, Xiaoyang; Yue, Song; Liu, Na

    2015-11-07

    Chiral nanoplasmonics exhibits great potential for novel nanooptical devices due to the generation of a strong chiroptical response within nanoscale metallic structures. Recently, a number of different approaches have been utilized to create chiral nanoplasmonic structures. However, particularly for tailoring nanooptical chiral sensing devices, the understanding of the resulting chiroptical response when coupling chiral and achiral structures together is crucial and has not been completely understood to date. Here, we present a thorough and step-by-step experimental study to understand the intriguing chiral-achiral coupling scheme. We set up a hybrid plasmonic system, which bears resemblance to the 'host-guest' system in supramolecular chemistry to analyze and explain the complex chiral response both at the chiral and achiral plasmonic resonances. We also provide an elegant and simple analytical model, which can describe, predict, and comprehend the chiroptical spectra in detail. Our study will shed light on designing well-controlled chiral-achiral coupling platforms for reliable chiral sensing.

  9. Complex regional pain syndrome

    PubMed Central

    Carr, Emily S.; De La Cerda, Ashley

    2016-01-01

    Complex regional pain syndrome (CRPS) is a neurologic disorder that often results in debilitating chronic pain, but the diagnosis may elude providers as it is one of exclusion. A history of trauma may be elucidated. We report a case of CRPS and review the clinical findings, appropriate workup, and treatment options for the patient. The patient we describe went through an extensive workup before receiving the correct diagnosis. Delay in diagnosis leads to prolonged suffering for the patient and, at times, unnecessary invasive debridement procedures. Raising awareness of this entity may help physicians make the correct diagnosis early, as well as initiate a collaborative effort between neurology, anesthesiology, and dermatology to provide the patient the most favorable outcome. PMID:27365892

  10. Complex Tectonism on Ganymede

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Complex tectonism is evident in these images of Ganymede's surface. The solid state imaging camera on NASA's Galileo spacecraft imaged this region as it passed Ganymede during its second orbit through the Jovian system. The 80 kilometer (50 mile) wide lens-shaped feature in the center of the image is located at 32 degrees latitude and 188 degrees longitude along the border of a region of ancient dark terrain known as Marius Regio, and is near an area of younger bright terrain named Nippur Sulcus. The tectonism that created the structures in the bright terrain nearby has strongly affected the local dark terrain to form unusual structures such as the one shown here. The lens-like appearance of this feature is probably due to shearing of the surface, where areas have slid past each other and also rotated slightly. Note that in several places in these images, especially around the border of the lens-shaped feature, bright ridges appear to turn into dark grooves. Analysis of the geologic structures in areas like this are helping scientists to understand the complex tectonic history of Ganymede.

    North is to the top-left of the image, and the sun illuminates the surface from the southeast. The image covers an area about 63 kilometers (39 miles) by 120 kilometers (75 miles) across at a resolution of 188 meters (627 feet) per picture element. The images were taken on September 6, 1996 at a range of 18,522 kilometers (11,576 miles) by the solid state imaging (CCD) system on NASA's Galileo spacecraft.

    The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov.

  11. Managing complexity of aerospace systems

    NASA Astrophysics Data System (ADS)

    Tamaskar, Shashank

    Growing complexity of modern aerospace systems has exposed the limits of conventional systems engineering tools and challenged our ability to design them in a timely and cost effective manner. According to the US Government Accountability Office (GAO), in 2009 nearly half of the defense acquisition programs are expecting 25% or more increase in unit acquisition cost. Increase in technical complexity has been identified as one of the primary drivers behind cost-schedule overruns. Thus to assure the affordability of future aerospace systems, it is increasingly important to develop tools and capabilities for managing their complexity. We propose an approach for managing the complexity of aerospace systems to address this pertinent problem. To this end, we develop a measure that improves upon the state-of-the-art metrics and incorporates key aspects of system complexity. We address the problem of system decomposition by presenting an algorithm for module identification that generates modules to minimize integration complexity. We demonstrate the framework on diverse spacecraft and show the impact of design decisions on integration cost. The measure and the algorithm together help the designer track and manage complexity in different phases of system design. We next investigate how complexity can be used as a decision metric in the model-based design (MBD) paradigm. We propose a framework for complexity enabled design space exploration that introduces the idea of using complexity as a non-traditional design objective. We also incorporate complexity with the component based design paradigm (a sub-field of MBD) and demonstrate it on several case studies. The approach for managing complexity is a small but significant contribution to the vast field of complexity management. We envision our approach being used in concert with a suite of complexity metrics to provide an ability to measure and track complexity through different stages of design and development. This will not

  12. Grammatical complexity of strange sets

    NASA Astrophysics Data System (ADS)

    Auerbach, Ditza; Procaccia, Itamar

    1990-06-01

    Chaotic dynamical systems can be organized around an underlying strange set, which is comprised of all the unstable periodic orbits. In this paper, we quantify the complexity of such an organization; this complexity addresses the difficulty of predicting the structure of the strange set from low-order data and is independent of the entropy and the algorithmic complexity. We refer to the new measure as the grammatical complexity. The notion is introduced, discussed, and illustrated in the context of simple dynamical systems. In addition, the grammatical complexity is generalized to include metric properties arising due to the nonuniform distribution of the invariant measure on the strange set.

  13. Complexity and Diversity of Digraphs

    NASA Astrophysics Data System (ADS)

    Bertz, Steven H.; Pereira, Gil Z.; Zamfirescu, Christina M. D.

    There has been a great deal of ferment in `Complexity Science' in recent years, as chronicled in the proceedings of the New England Complex Systems Institute's International Conference on Complex Systems [Minai & Bar-Yam 2006, 2008] and those of the Santa Fe Institute [Nadel & Stein 1995, Cowan 1994]. We have been primarily focused on developing metrics of complexity relevant to chemistry, especially synthetic chemistry [Bertz 2003a-c]. Our approach involves abstracting a molecule or a plan for its synthesis as a graph and then using the tools of graph theory to characterize its complexity and diversity.

  14. Complexity of formation in holography

    NASA Astrophysics Data System (ADS)

    Chapman, Shira; Marrochio, Hugo; Myers, Robert C.

    2017-01-01

    It was recently conjectured that the quantum complexity of a holographic boundary state can be computed by evaluating the gravitational action on a bulk region known as the Wheeler-DeWitt patch. We apply this complexity=action duality to evaluate the `complexity of formation' [1, 2], i.e. the additional complexity arising in preparing the entangled thermofield double state with two copies of the boundary CFT compared to preparing the individual vacuum states of the two copies. We find that for boundary dimensions d > 2, the difference in the complexities grows linearly with the thermal entropy at high temperatures. For the special case d = 2, the complexity of formation is a fixed constant, independent of the temperature. We compare these results to those found using the complexity=volume duality.

  15. Understanding complex chiral plasmonics

    NASA Astrophysics Data System (ADS)

    Duan, Xiaoyang; Yue, Song; Liu, Na

    2015-10-01

    Chiral nanoplasmonics exhibits great potential for novel nanooptical devices due to the generation of a strong chiroptical response within nanoscale metallic structures. Recently, a number of different approaches have been utilized to create chiral nanoplasmonic structures. However, particularly for tailoring nanooptical chiral sensing devices, the understanding of the resulting chiroptical response when coupling chiral and achiral structures together is crucial and has not been completely understood to date. Here, we present a thorough and step-by-step experimental study to understand the intriguing chiral-achiral coupling scheme. We set up a hybrid plasmonic system, which bears resemblance to the `host-guest' system in supramolecular chemistry to analyze and explain the complex chiral response both at the chiral and achiral plasmonic resonances. We also provide an elegant and simple analytical model, which can describe, predict, and comprehend the chiroptical spectra in detail. Our study will shed light on designing well-controlled chiral-achiral coupling platforms for reliable chiral sensing.Chiral nanoplasmonics exhibits great potential for novel nanooptical devices due to the generation of a strong chiroptical response within nanoscale metallic structures. Recently, a number of different approaches have been utilized to create chiral nanoplasmonic structures. However, particularly for tailoring nanooptical chiral sensing devices, the understanding of the resulting chiroptical response when coupling chiral and achiral structures together is crucial and has not been completely understood to date. Here, we present a thorough and step-by-step experimental study to understand the intriguing chiral-achiral coupling scheme. We set up a hybrid plasmonic system, which bears resemblance to the `host-guest' system in supramolecular chemistry to analyze and explain the complex chiral response both at the chiral and achiral plasmonic resonances. We also provide an elegant

  16. The Mycobacterium avium complex.

    PubMed Central

    Inderlied, C B; Kemper, C A; Bermudez, L E

    1993-01-01

    Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing

  17. Complexity of vesicle microcirculation

    NASA Astrophysics Data System (ADS)

    Kaoui, B.; Tahiri, N.; Biben, T.; Ez-Zahraouy, H.; Benyoussef, A.; Biros, G.; Misbah, C.

    2011-10-01

    This study focuses numerically on dynamics in two dimensions of vesicles in microcirculation. The method used is based on boundary integral formulation. This study is inspired by the behavior of red blood cells (RBCs) in the microvasculature. Red RBCs carry oxygen from the lungs and deliver it through the microvasculature. The shape adopted by RBCs can affect blood flow and influence oxygen delivery. Our simulation using vesicles (a simple model for RBC) reveals unexpected complexity as compared to the case where a purely unbounded Poiseuille flow is considered [Kaoui, Biros, and Misbah, Phys. Rev. Lett.10.1103/PhysRevLett.103.188101 103, 188101 (2009)]. In sufficiently large channels (in the range of 100μm; the vesicle size and its reduced volume are taken in the range of those of a human RBC), such as arterioles, a slipperlike (asymmetric) shape prevails. A parachutelike (symmetric) shape is adopted in smaller channels (in the range of 20μm, as in venules), but this shape loses stability and again changes to a pronounced slipperlike morphology in channels having a size typical of capillaries (5-10 μm). Stiff membranes, mimicking malaria infection, for example, adopt a centered or off-centered snakelike locomotion instead (the denomination snaking is used for this regime). A general scenario of how and why vesicles adopt their morphologies and dynamics among several distinct possibilities is provided. This finding potentially points to nontrivial RBCs dynamics in the microvasculature.

  18. [Toxic complex from parrotfish].

    PubMed

    Chungue, E; Bagnis, R; Fusetani, N; Yasumoto, T

    1977-01-01

    Clinical and epidemiological observations suggested that a complex toxic molecule is involved in the parrotfish flesh (Scarus gibbus) poisoning from Gambier Islands. The fat soluble extract obtained from the muscles upon ciguatoxin preparation showed two toxic substances after fractionation by DEAE cellulose column chromatography. The major toxin is different from ciguatoxin judging by its chromatographic behaviour. The other is closely similar to (or identical with) ciguatoxin from the moray eel Gymnothorax javanicus. They were named SG1 for the new toxin and SG2 for the ciguatoxin like compound. Successive filtrations on Sephadex LH-20 of SG1 and SG2 gave respectively a lethality to mice of 0.03 microgram/g and 0.06 microgram/g. SG1, specifically occurs in the muscles of the parrotfish family (scaritoxin) while it is absent from other ciguateric fishes. According to that specificity and the lack of SG1 in S. gibbus liver and gut contents, the origin of scaritoxin is briefly discussed.

  19. Sociality influences cultural complexity

    PubMed Central

    Muthukrishna, Michael; Shulman, Ben W.; Vasilescu, Vlad; Henrich, Joseph

    2014-01-01

    Archaeological and ethnohistorical evidence suggests a link between a population's size and structure, and the diversity or sophistication of its toolkits or technologies. Addressing these patterns, several evolutionary models predict that both the size and social interconnectedness of populations can contribute to the complexity of its cultural repertoire. Some models also predict that a sudden loss of sociality or of population will result in subsequent losses of useful skills/technologies. Here, we test these predictions with two experiments that permit learners to access either one or five models (teachers). Experiment 1 demonstrates that naive participants who could observe five models, integrate this information and generate increasingly effective skills (using an image editing tool) over 10 laboratory generations, whereas those with access to only one model show no improvement. Experiment 2, which began with a generation of trained experts, shows how learners with access to only one model lose skills (in knot-tying) more rapidly than those with access to five models. In the final generation of both experiments, all participants with access to five models demonstrate superior skills to those with access to only one model. These results support theoretical predictions linking sociality to cumulative cultural evolution. PMID:24225461

  20. Fact Sheet: Range Complex

    NASA Technical Reports Server (NTRS)

    Cornelson, C.; Fretter, E.

    2004-01-01

    NASA Ames has a long tradition in leadership with the use of ballistic ranges and shock tubes for the purpose of studying the physics and phenomena associated with hypervelocity flight. Cutting-edge areas of research run the gamut from aerodynamics, to impact physics, to flow-field structure and chemistry. This legacy of testing began in the NACA era of the 1940's with the Supersonic Free Flight Tunnel, and evolved dramatically up through the late 1950s with the pioneering work in the Ames Hypersonic Ballistic Range. The tradition continued in the mid-60s with the commissioning of the three newest facilities: the Ames Vertical Gun Range (AVGR) in 1964, the Hypervelocity Free Flight Facility (HFFF) in 1965 and the Electric Arc Shock Tube (EAST) in 1966. Today the Range Complex continues to provide unique and critical testing in support of the Nation's programs for planetary geology and geophysics; exobiology; solar system origins; earth atmospheric entry, planetary entry, and aerobraking vehicles; and various configurations for supersonic and hypersonic aircraft.

  1. A new approach for the photosynthetic antenna-reaction center complex with a model organized around an s-triazine linker.

    PubMed

    Kuhri, Susanne; Charalambidis, Georgios; Angaridis, Panagiotis A; Lazarides, Theodore; Pagona, Georgia; Tagmatarchis, Nikos; Coutsolelos, Athanassios G; Guldi, Dirk M

    2014-02-10

    Two new artificial mimics of the photosynthetic antenna-reaction center complex have been designed and synthesized (BDP-H2 P-C60 and BDP-ZnP-C60). The resulting electron-donor/acceptor conjugates contain a porphyrin (either in its free-base form (H2P) or as Zn-metalated complex (ZnP)), a boron dipyrrin (BDP), and a fulleropyrrolidine possessing, as substituent of the pyrrolidine nitrogen, an ethylene glycol chain terminating in an amino group C60-X-NH2 (X=spacer). In both cases, the three different components were connected by s-triazine through stepwise substitution reactions of cyanuric chloride. In addition to the facile synthesis, the star-type arrangement of the three photo- and redox-active components around the central s-triazine unit permits direct interaction between one another, in contrast to reported examples in which the three components are arranged in a linear fashion. The energy- and electron-transfer properties of the resulting electron-donor/acceptor conjugates were investigated by using UV/Vis absorption and emission spectroscopy, cyclic voltammetry, and femtosecond transient absorption spectroscopy. Comparison of the absorption spectra and cyclic voltammograms of BDP-H2P-C60 and BDP-ZnP-C60 with those of BDP-H2P, BDP-ZnP and BDP-C60, which were used as references, showed that the spectroscopic and electrochemical properties of the individual constituents are basically retained, although some appreciable shifts in terms of absorption indicate some interactions in the ground state. Fluorescence lifetime measurements and transient absorption experiments helped to elucidate the antenna function of BDP, which upon selective excitation undergoes a rapid and efficient energy transfer from BDP to H2P or ZnP. This is then followed by an electron transfer to C60, yielding the formation of the singlet charge-separated states, namely BDP-H2(·+) -C60(·-) and BDP-ZnP(·+)-C60(·-). As such, the sequence of energy transfer and electron transfer in the

  2. Complexity measurement based on information theory and kolmogorov complexity.

    PubMed

    Lui, Leong Ting; Terrazas, Germán; Zenil, Hector; Alexander, Cameron; Krasnogor, Natalio

    2015-01-01

    In the past decades many definitions of complexity have been proposed. Most of these definitions are based either on Shannon's information theory or on Kolmogorov complexity; these two are often compared, but very few studies integrate the two ideas. In this article we introduce a new measure of complexity that builds on both of these theories. As a demonstration of the concept, the technique is applied to elementary cellular automata and simulations of the self-organization of porphyrin molecules.

  3. Physical Complexity and Cognitive Evolution

    NASA Astrophysics Data System (ADS)

    Jedlicka, Peter

    Our intuition tells us that there is a general trend in the evolution of nature, a trend towards greater complexity. However, there are several definitions of complexity and hence it is difficult to argue for or against the validity of this intuition. Christoph Adami has recently introduced a novel measure called physical complexity that assigns low complexity to both ordered and random systems and high complexity to those in between. Physical complexity measures the amount of information that an organism stores in its genome about the environment in which it evolves. The theory of physical complexity predicts that evolution increases the amount of `knowledge' an organism accumulates about its niche. It might be fruitful to generalize Adami's concept of complexity to the entire evolution (including the evolution of man). Physical complexity fits nicely into the philosophical framework of cognitive biology which considers biological evolution as a progressing process of accumulation of knowledge (as a gradual increase of epistemic complexity). According to this paradigm, evolution is a cognitive `ratchet' that pushes the organisms unidirectionally towards higher complexity. Dynamic environment continually creates problems to be solved. To survive in the environment means to solve the problem, and the solution is an embodied knowledge. Cognitive biology (as well as the theory of physical complexity) uses the concepts of information and entropy and views the evolution from both the information-theoretical and thermodynamical perspective. Concerning humans as conscious beings, it seems necessary to postulate an emergence of a new kind of knowledge - a self-aware and self-referential knowledge. Appearence of selfreflection in evolution indicates that the human brain reached a new qualitative level in the epistemic complexity.

  4. Titan's chemical complexity

    NASA Astrophysics Data System (ADS)

    Vuitton, Veronique

    2012-04-01

    We review here our current knowledge of Titan's gas phase chemistry. We base our discussion on photochemical models as well as on laboratory experiments. We identify the lower mass positive [1,2] and negative [3] ions detected in the upper atmosphere and we show that their formation is a direct consequence of the presence of heavy neutrals. We demonstrate that the observed densities of CO, CO2 and H2O can be explained by a combination of exogenous O, and OH/H2O input [4]. We argue that benzene [5] and ammonia [6] are created in the upper atmosphere through complex chemical processes involving both neutral and ion chemistry. These species diffuse downward where they are at the origin of heavier aromatics and amines, respectively. Finally, we discuss the impact on hydrocarbon densities of recent theoretical calculations of the rate constants of association reactions [7]. [1] V. Vuitton, R. V. Yelle and V. G. Anicich, Astrophys. J., 647, L175 (2006). [2] V. Vuitton, R. V. Yelle and M. J. McEwan, Icarus, 191, 722 (2007). [3] V. Vuitton, P. Lavvas, R. V. Yelle, M. Galand, A. Wellbrock, G. R. Lewis, A. J. Coates and J.-E. Wahlund, Planet. Space Sci., 57, 1558 (2009). [4] S. M. Hörst, V. Vuitton, and R. V. Yelle, J. Geophys. Res., 113, E10006 (2008). [5] V. Vuitton, R. V. Yelle and J. Cui, J. Geophys. Res., 113, E05007 (2008). [6] R. V. Yelle, V. Vuitton, P. Lavvas, S. J. Klippenstein, M. A. Smith, S. M. Hörst and J. Cui, Faraday Discuss., 147, 31 (2010). [7] V. Vuitton, R. V. Yelle, S. J. Klippenstein and P. Lavvas, Astrophys. J., in press.

  5. Complex oxides: Intricate disorder

    SciTech Connect

    Uberuaga, Blas Pedro

    2016-02-29

    In this study, complex oxides such as pyrochlores have a myriad of potential technological applications, including as fast ion conductors and radiation-tolerant nuclear waste forms. They are also of interest for their catalytic and spin ice properties. Many of these functional properties are enabled by the atomic structure of the cation sublattices. Pyrochlores (A2B2O7) contain two different cations (A and B), typically a 3+ rare earth and a 4+ transition metal such as Hf, Zr, or Ti. The large variety of chemistries that can form pyrochlores leads to a rich space in which to search for exotic new materials. Furthermore, how cations order or disorder on their respective sublattices for a given chemical composition influences the functional properties of the oxide. For example, oxygen ionic conductivity is directly correlated with the level of cation disorder — the swapping of A and B cations1. Further, the resistance of these materials against amorphization has also been connected with the ability of the cations to disorder2, 3. These correlations between cation structure and functionality have spurred great interest in the structure of the cation sublattice under irradiation, with significant focus on the disordering mechanisms and disordered structure. Previous studies have found that, upon irradiation, pyrochlores often undergo an order-to-disorder transformation, in which the resulting structure is, from a diffraction point of view, indistinguishable from fluorite (AO2) (ref. 3). Shamblin et al. now reveal that the structure of disordered pyrochlore is more complicated than previously thought4.

  6. Carney complex (CNC)

    PubMed Central

    Bertherat, Jérôme

    2006-01-01

    The Carney complex (CNC) is a dominantly inherited syndrome characterized by spotty skin pigmentation, endocrine overactivity and myxomas. Skin pigmentation anomalies include lentigines and blue naevi. The most common endocrine gland manifestations are acromegaly, thyroid and testicular tumors, and adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD, a rare cause of Cushing's syndrome, is due to primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations or familial history of the disease. Myxomas can be observed in the heart, skin and breast. Cardiac myxomas can develop in any cardiac chamber and may be multiple. One of the putative CNC genes located on 17q22-24, (PRKAR1A), has been identified to encode the regulatory subunit (R1A) of protein kinase A. Heterozygous inactivating mutations of PRKAR1A were reported initially in 45 to 65 % of CNC index cases, and may be present in about 80 % of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cAMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Genetic analysis should be proposed to all CNC index cases. Patients with CNC or with a genetic predisposition to CNC should have regular screening for manifestations of the disease. Clinical work-up for all the manifestations of CNC should be performed at least once a year in all patients and should start in infancy. Cardiac myxomas require surgical removal. Treatment of the other manifestations of CNC should be discussed and may include follow-up, surgery, or medical treatment depending on the location of the tumor, its size, the existence of clinical signs of tumor mass or hormonal excess, and the suspicion of malignancy. Bilateral adrenalectomy is the most common treatment for Cushing's syndrome due to PPNAD

  7. Complex oxides: Intricate disorder

    DOE PAGES

    Uberuaga, Blas Pedro

    2016-02-29

    In this study, complex oxides such as pyrochlores have a myriad of potential technological applications, including as fast ion conductors and radiation-tolerant nuclear waste forms. They are also of interest for their catalytic and spin ice properties. Many of these functional properties are enabled by the atomic structure of the cation sublattices. Pyrochlores (A2B2O7) contain two different cations (A and B), typically a 3+ rare earth and a 4+ transition metal such as Hf, Zr, or Ti. The large variety of chemistries that can form pyrochlores leads to a rich space in which to search for exotic new materials. Furthermore,more » how cations order or disorder on their respective sublattices for a given chemical composition influences the functional properties of the oxide. For example, oxygen ionic conductivity is directly correlated with the level of cation disorder — the swapping of A and B cations1. Further, the resistance of these materials against amorphization has also been connected with the ability of the cations to disorder2, 3. These correlations between cation structure and functionality have spurred great interest in the structure of the cation sublattice under irradiation, with significant focus on the disordering mechanisms and disordered structure. Previous studies have found that, upon irradiation, pyrochlores often undergo an order-to-disorder transformation, in which the resulting structure is, from a diffraction point of view, indistinguishable from fluorite (AO2) (ref. 3). Shamblin et al. now reveal that the structure of disordered pyrochlore is more complicated than previously thought4.« less

  8. Phonological Complexity and Language Learnability

    PubMed Central

    Gierut, Judith A.

    2008-01-01

    Purpose To extend formal models of language learnability to applications in clinical treatment of children with functional phonological delays. Method The focus of the narrative review is on phonological complexity. This follows from learnability theory, whereby complexity in the linguistic input to children has been shown to trigger language learning. Drawing from the literature, phonological complexity is defined from epistemic, ontological, and functional perspectives, with specific emphasis on the application of language universals in the selection of target sounds for treatment. Results The cascading effects of phonological complexity on children’s generalization learning are illustrated, and frequently asked questions about complexity in treatment are addressed. Conclusion The role of complexity in cognitive development is introduced to demonstrate the apparent robustness of effects. PMID:17329671

  9. Increasing complexity with quantum physics.

    PubMed

    Anders, Janet; Wiesner, Karoline

    2011-09-01

    We argue that complex systems science and the rules of quantum physics are intricately related. We discuss a range of quantum phenomena, such as cryptography, computation and quantum phases, and the rules responsible for their complexity. We identify correlations as a central concept connecting quantum information and complex systems science. We present two examples for the power of correlations: using quantum resources to simulate the correlations of a stochastic process and to implement a classically impossible computational task.

  10. Complex higher order derivative theories

    SciTech Connect

    Margalli, Carlos A.; Vergara, J. David

    2012-08-24

    In this work is considered a complex scalar field theory with higher order derivative terms and interactions. A procedure is developed to quantize consistently this system avoiding the presence of negative norm states. In order to achieve this goal the original real scalar high order field theory is extended to a complex space attaching a complex total derivative to the theory. Next, by imposing reality conditions the complex theory is mapped to a pair of interacting real scalar field theories without the presence of higher derivative terms.

  11. New types of lanthanide complexes

    SciTech Connect

    Kahwa, I.A.K.

    1986-01-01

    Three new types of lanthanide (Ln) complexes, namely, the first examples of homodinuclear macrocyclic lanthanide complexes, novel binary and ternary gaseous polyatomic lanthanide oxides and new lanthanide oxalato complexes are described in chapters one, two and three respectively. The homodinuclear complexes are 2:2 condensation products of 2,6-diformyl-p-cresol and triethylenetetramine templated by Ln(NO/sub 3/)/sub 3/ and Ln(ClO/sub 4/)/sub 3/. The complexes are dimorphic, and are off-white (the more stable form) when they are obtained from dilute solutions and orange if they arise from more concentrated reactants. The complexes were characterized by elemental analysis, fast atom bombardment mass spectrometry (FAB MS), electronic absorption and IR spectroscopy, thermogravimetry along with preliminary spectroscopic studies using electron paramagnetic resonance, magnetic susceptibility and luminescence. The orange complexes exhibit more antiferromagnetic exchange interactions, low Ln/sup 3 +/magnetic moments and multi-exponential luminescence decay kinetics, whereas the off-white complexes show single exponential luminescence decay and free ion magnetic moments. At low temperatures and in presence of excess triethylenetetramine, solvated light lanthanide mononuclear complexes of a 1:1 acyclic Schiff base acetal were isolated and the structure of one of these was confirmed by single crystal x-ray diffraction crystallography.

  12. Societal Complexity and Familial Complexity: Evidence for the Curvilinear Hypothesis

    ERIC Educational Resources Information Center

    Blumberg, Rae Lesser; Winch, Robert F.

    1972-01-01

    The hypothesis is supported that the most extended, complex familial systems should be found among societies in an intermediate range of societal complexity, particularly among settled agricultural peoples. Among the simple hunting-gathering groups and in modern industrial states is found the nuclear family system: small, independent, nonextended…

  13. Sustainability, Complexity and Learning: Insights from Complex Systems Approaches

    ERIC Educational Resources Information Center

    Espinosa, A.; Porter, T.

    2011-01-01

    Purpose: The purpose of this research is to explore core contributions from two different approaches to complexity management in organisations aiming to improve their sustainability,: the Viable Systems Model (VSM), and the Complex Adaptive Systems (CAS). It is proposed to perform this by summarising the main insights each approach offers to…

  14. Complex Constructivism: A Theoretical Model of Complexity and Cognition

    ERIC Educational Resources Information Center

    Doolittle, Peter E.

    2014-01-01

    Education has long been driven by its metaphors for teaching and learning. These metaphors have influenced both educational research and educational practice. Complexity and constructivism are two theories that provide functional and robust metaphors. Complexity provides a metaphor for the structure of myriad phenomena, while constructivism…

  15. Competing Complexity Metrics and Adults' Production of Complex Sentences.

    ERIC Educational Resources Information Center

    Cheung, Hintat; Kemper, Susan

    1992-01-01

    Evaluation of the adequacy of 11 metrics for measuring linguistic complexity of language samples obtained from 60 to 90 year olds indicated that, although most of the metrics adequately accounted for age-group and individual differences in complexity, the amount and type of embedding proved to predict how easily sentences are understood and how…

  16. Waves in complex systems

    NASA Astrophysics Data System (ADS)

    Xie, Hang

    The theme of this thesis is the study of wave phenomena in complex systems. In particular, the following three topics constitute the foci of my research. The first topic involves the generalization of an electronic transport mechanism commonly observed in disordered media, fluctuation induced tunneling conduction, by considering tunneling through not just insulating potential barriers, but also narrow conducting channels. Here the wave nature of the electron implies that a narrow conduction channel can act as an electronic waveguide, with a cutoff transverse dimension that is half the Fermi wavelength. My research involves the study of electronic transport through finite-length conducting channels with transverse dimensions below the cutoff. Such narrow conduction channel may be physically realized by chains of single conducting atoms, for example. At small voltage bias across the conduction channel, only tunneling transport is possible at zero temperature. But at finite temperatures some of the electrons with energies above the Fermi level can ballistically transport across the channel. By considering both tunneling and thermal activation mechanisms, with thermally-generated (random) voltage bias across the narrow channel, we obtained a temperature-dependent conductivity behavior that is in good agreement with the measured two-lead conductance of RuO2 and IrO2 nanowires. Furthermore, by considering high applied voltage across the nano conduction channels, our model predicts interesting electronic Fabry-Perot behavior whose experimental verification is presently underway. The second topic involves the study of the Hall effect in mesoscopic samples. In particular, we are interested in the possibility of enhancing the Hall effect by nano-patterning samples of 2D electron gas. Through numerical solution of the Schrodinger equation in the presence of a magnetic field, mesoscopic transport behavior is obtained for samples with given geometric patterns of the

  17. Forecasting in Complex Systems

    NASA Astrophysics Data System (ADS)

    Rundle, J. B.; Holliday, J. R.; Graves, W. R.; Turcotte, D. L.; Donnellan, A.

    2014-12-01

    Complex nonlinear systems are typically characterized by many degrees of freedom, as well as interactions between the elements. Interesting examples can be found in the areas of earthquakes and finance. In these two systems, fat tails play an important role in the statistical dynamics. For earthquake systems, the Gutenberg-Richter magnitude-frequency is applicable, whereas for daily returns for the securities in the financial markets are known to be characterized by leptokurtotic statistics in which the tails are power law. Very large fluctuations are present in both systems. In earthquake systems, one has the example of great earthquakes such as the M9.1, March 11, 2011 Tohoku event. In financial systems, one has the example of the market crash of October 19, 1987. Both were largely unexpected events that severely impacted the earth and financial systems systemically. Other examples include the M9.3 Andaman earthquake of December 26, 2004, and the Great Recession which began with the fall of Lehman Brothers investment bank on September 12, 2013. Forecasting the occurrence of these damaging events has great societal importance. In recent years, national funding agencies in a variety of countries have emphasized the importance of societal relevance in research, and in particular, the goal of improved forecasting technology. Previous work has shown that both earthquakes and financial crashes can be described by a common Landau-Ginzburg-type free energy model. These metastable systems are characterized by fat tail statistics near the classical spinodal. Correlations in these systems can grow and recede, but do not imply causation, a common source of misunderstanding. In both systems, a common set of techniques can be used to compute the probabilities of future earthquakes or crashes. In this talk, we describe the basic phenomenology of these systems and emphasize their similarities and differences. We also consider the problem of forecast validation and verification

  18. Understanding and Teaching Complex Texts

    ERIC Educational Resources Information Center

    Fisher, Douglas; Frey, Nancy

    2014-01-01

    Teachers in today's classrooms struggle every day to design instructional interventions that would build students' reading skills and strategies in order to ensure their comprehension of complex texts. Text complexity can be determined in both qualitative and quantitative ways. In this article, the authors describe various innovative…

  19. Too Dumb for Complex Texts?

    ERIC Educational Resources Information Center

    Bauerlein, Mark

    2011-01-01

    High school students' lack of experience and practice with reading complex texts is a primary cause of their difficulties with college-level reading. Filling the syllabus with digital texts does little to address this deficiency. Complex texts demand three dispositions from readers: a willingness to probe works characterized by dense meanings, the…

  20. Complexity and Education: Vital Simultaneities

    ERIC Educational Resources Information Center

    Davis, Brent

    2008-01-01

    This article explores the place of complexity science within education and educational research. The discussion begins with the suggestion that educational research has a history of adopting interpretive frames from other domains with little adaptation. Complexity science is argued to compel a different sort of positioning, one that requires…

  1. Complex Variables in Secondary Schools

    ERIC Educational Resources Information Center

    Dwyer, Jerry; Moskal, Barbara; Duke, Billy; Wilhelm, Jennifer

    2007-01-01

    This article describes the work of outreach mathematicians introducing the topic of complex variables to eighth and ninth grade students (13- to 15-year-olds) in the US. Complex variables is an area of mathematics that is not typically studied at secondary level. The authors developed seven lessons designed to stimulate students' interest in…

  2. Improve Reading with Complex Texts

    ERIC Educational Resources Information Center

    Fisher, Douglas; Frey, Nancy

    2015-01-01

    The Common Core State Standards have cast a renewed light on reading instruction, presenting teachers with the new requirements to teach close reading of complex texts. Teachers and administrators should consider a number of essential features of close reading: They are short, complex texts; rich discussions based on worthy questions; revisiting…

  3. A Simple Explanation of Complexation

    ERIC Educational Resources Information Center

    Elliott, J. Richard

    2010-01-01

    The topics of solution thermodynamics, activity coefficients, and complex formation are introduced through computational exercises and sample applications. The presentation is designed to be accessible to freshmen in a chemical engineering computations course. The MOSCED model is simplified to explain complex formation in terms of hydrogen…

  4. Teacher Knowledge: A Complex Tapestry

    ERIC Educational Resources Information Center

    Adoniou, Misty

    2015-01-01

    Teachers need to know a great deal, in many areas and in multiple ways. Teacher knowledge is a complex tapestry, and teachers must successfully weave the multiple threads. In this article, I present a conceptualisation of teacher knowledge that provides a framework for describing the complexity of teacher knowledge. The framework describes three…

  5. The Algebra of Complex Numbers.

    ERIC Educational Resources Information Center

    LePage, Wilbur R.

    This programed text is an introduction to the algebra of complex numbers for engineering students, particularly because of its relevance to important problems of applications in electrical engineering. It is designed for a person who is well experienced with the algebra of real numbers and calculus, but who has no experience with complex number…

  6. The Complexity of Language Learning

    ERIC Educational Resources Information Center

    Nelson, Charles

    2011-01-01

    This paper takes a complexity theory approach to looking at language learning, an approach that investigates how language learners adapt to and interact with people and their environment. Based on interviews with four graduate students, it shows how complexity theory can help us understand both the situatedness of language learning and also…

  7. Complex Training: A Brief Review

    PubMed Central

    Ebben, William P.

    2002-01-01

    The effectiveness of plyometric training is well supported by research. Complex training has gained popularity as a training strategy combining weight training and plyometric training. Anecdotal reports recommend training in this fashion in order to improve muscular power and athletic performance. Recently, several studies have examined complex training. Despite the fact that questions remain about the potential effectiveness and implementation of this type of training, results of recent studies are useful in guiding practitioners in the development and implementation of complex training programs. In some cases, research suggests that complex training has an acute ergogenic effect on upper body power and the results of acute and chronic complex training include improved jumping performance. Improved performance may require three to four minutes rest between the weight training and plyometrics sets and the use of heavy weight training loads. PMID:24688269

  8. Ternary complexes in analytical chemistry.

    PubMed

    Babko, A K

    1968-08-01

    Reactions between a complex AB and a third component C do not always proceed by a displacement mechanism governed by the energy difference of the chemical bonds A-B and A-C. The third component often becomes part of the complex, forming a mixed co-ordination sphere or ternary complex. The properties of this ternary complex ABC are not additive functions of the properties of AB and AC. Such reactions are important in many methods in analytical chemistry, particularly in photometric analysis, extractive separation, masking, etc. The general properties of the four basic types of ternary complex are reviewed and examples given. The four types comprise the systems (a) metal ion, electronegative ligand, organic base, (b) one metal ion, two different electronegative ligands, (c) ternary heteropoly acids, and (d) two different metal ions, one ligand.

  9. Complex systems in metabolic engineering.

    PubMed

    Winkler, James D; Erickson, Keesha; Choudhury, Alaksh; Halweg-Edwards, Andrea L; Gill, Ryan T

    2015-12-01

    Metabolic engineers manipulate intricate biological networks to build efficient biological machines. The inherent complexity of this task, derived from the extensive and often unknown interconnectivity between and within these networks, often prevents researchers from achieving desired performance. Other fields have developed methods to tackle the issue of complexity for their unique subset of engineering problems, but to date, there has not been extensive and comprehensive examination of how metabolic engineers use existing tools to ameliorate this effect on their own research projects. In this review, we examine how complexity affects engineering at the protein, pathway, and genome levels within an organism, and the tools for handling these issues to achieve high-performing strain designs. Quantitative complexity metrics and their applications to metabolic engineering versus traditional engineering fields are also discussed. We conclude by predicting how metabolic engineering practices may advance in light of an explicit consideration of design complexity.

  10. [Health: an adaptive complex system].

    PubMed

    Toro-Palacio, Luis Fernando; Ochoa-Jaramillo, Francisco Luis

    2012-02-01

    This article points out the enormous gap that exists between complex thinking of an intellectual nature currently present in our environment, and complex experimental thinking that has facilitated the scientific and technological advances that have radically changed the world. The article suggests that life, human beings, global society, and all that constitutes health be considered as adaptive complex systems. This idea, in turn, prioritizes the adoption of a different approach that seeks to expand understanding. When this rationale is recognized, the principal characteristics and emerging properties of health as an adaptive complex system are sustained, following a care and services delivery model. Finally, some pertinent questions from this perspective are put forward in terms of research, and a series of appraisals are expressed that will hopefully serve to help us understand all that we have become as individuals and as a species. The article proposes that the delivery of health care services be regarded as an adaptive complex system.

  11. The evolution of complex life.

    PubMed

    Billingham, J

    1989-01-01

    In considering the probabilities that intelligent life might exist elsewhere in the Universe, it is important to ask questions about the factors governing the emergence of complex living organisms in the context of evolutionary biology, planetary environments and events in space. Two important problems arise. First, what can be learned about the general laws governing the evolution of complex life anywhere in space by studying its history on the Earth? Second, how is the evolution of complex life affected by events in space? To address these problems, a series of Science Workshops on the Evolution of Complex Life was held at the Ames Research Center. Included in this paper are highlights of those workshops, with particular emphasis on the first question, namely the evolution of complex extraterrestrial life.

  12. Diastereo- and enantioselective conjugate addition of alpha-ketoesters to nitroalkenes catalyzed by a chiral Ni(OAc)(2) complex under mild conditions.

    PubMed

    Nakamura, Ayako; Lectard, Sylvain; Hashizume, Daisuke; Hamashima, Yoshitaka; Sodeoka, Mikiko

    2010-03-31

    A highly efficient, catalytic, diastereo- and enantioselective conjugate addition of alpha-ketoesters to nitroalkenes has been devised. The reaction was applicable to various substrates. Notably, the combination of endogenous and exogenous bases was effective, allowing a small amount of the catalyst (0.1-1 mol % Ni) to promote the reaction efficiently. The synthetic utility of this reaction was demonstrated in the synthesis of substituted pyrrolidine derivatives, whose stereochemistry is closely related to biologically important natural products such as kainic acid.

  13. A catalytic-enantioselective entry to planar chiral pi-complexes: enantioselective methoxycarbonylation of 1,2-dichlorobenzene-Cr(CO)(3).

    PubMed

    Gotov, B; Schmalz, H G

    2001-05-31

    The palladium-catalyzed mono-methoxycarbonylation of 1,2-dichlorobenzene tricarbonylchromium(0) has been achieved with up to 95% ee in the presence of the chiral ferrocene ligand (R,S)-PPF-pyrrolidine. It was found that the enantioselectivity strongly depends on the reaction time (conversion). Obviously, the initial enantioselectivity is enhanced by a subsequent kinetic resolution connected to the formation of the bis-methoxycarbonylated byproduct.

  14. Kinetics of actinide complexation reactions

    SciTech Connect

    Nash, K.L.; Sullivan, J.C.

    1997-09-01

    Though the literature records extensive compilations of the thermodynamics of actinide complexation reactions, the kinetics of complex formation and dissociation reactions of actinide ions in aqueous solutions have not been extensively investigated. In light of the central role played by such reactions in actinide process and environmental chemistry, this situation is somewhat surprising. The authors report herein a summary of what is known about actinide complexation kinetics. The systems include actinide ions in the four principal oxidation states (III, IV, V, and VI) and complex formation and dissociation rates with both simple and complex ligands. Most of the work reported was conducted in acidic media, but a few address reactions in neutral and alkaline solutions. Complex formation reactions tend in general to be rapid, accessible only to rapid-scan and equilibrium perturbation techniques. Complex dissociation reactions exhibit a wider range of rates and are generally more accessible using standard analytical methods. Literature results are described and correlated with the known properties of the individual ions.

  15. The energetics of genome complexity.

    PubMed

    Lane, Nick; Martin, William

    2010-10-21

    All complex life is composed of eukaryotic (nucleated) cells. The eukaryotic cell arose from prokaryotes just once in four billion years, and otherwise prokaryotes show no tendency to evolve greater complexity. Why not? Prokaryotic genome size is constrained by bioenergetics. The endosymbiosis that gave rise to mitochondria restructured the distribution of DNA in relation to bioenergetic membranes, permitting a remarkable 200,000-fold expansion in the number of genes expressed. This vast leap in genomic capacity was strictly dependent on mitochondrial power, and prerequisite to eukaryote complexity: the key innovation en route to multicellular life.

  16. Quantum Tunneling and Complex Trajectories

    NASA Astrophysics Data System (ADS)

    Meynig, Max; Haggard, Hal

    2017-01-01

    In general, the semiclassical approximation of quantum mechanical tunneling fails to treat tunneling through barriers if real initial conditions and trajectories are used. By analytically continuing classical dynamics to the complex plane the problems encountered in the approximation can be resolved. While, the complex methods discussed here have been previously explored, no one has exhibited an analytically solvable case. The essential features of the complex method will be discussed in the context of a novel, analytically solvable problem. These methods could be useful in quantum gravity, with applications to the tunneling of spacetime geometries.

  17. [Carney's Complex: familial cardiac myxoma].

    PubMed

    Guerra, Miguel S; Santos, Nelson; Neves, Fátima; Carlos Mota, João; Miranda, José António; Vouga, Luis

    2006-01-01

    The Carney Complex is a very rare autosomal dominant disease including multiple neoplasia syndrome. This syndrome was initially described in 1985 under the rubric "...the complex of myxomas, spotty pigmentation, and endocrine overactivity". We present a case report of an old woman with Carney Complex who had the characteristic features of facial hirsutism and acromegalic facies, a large pigmented swelling over the face and a cardiac myxoma arising from the left atrium. We emphasize the need for periodic echocardiographic screening of patients and family members.

  18. The future of complexity engineering

    NASA Astrophysics Data System (ADS)

    Frei, Regina; Di Marzo Serugendo, Giovanna

    2012-06-01

    Complexity Engineering encompasses a set of approaches to engineering systems which are typically composed of various interacting entities often exhibiting self-* behaviours and emergence. The engineer or designer uses methods that benefit from the findings of complexity science and often considerably differ from the classical engineering approach of "divide and conquer". This article provides an overview on some very interdisciplinary and innovative research areas and projects in the field of Complexity Engineering, including synthetic biology, chemistry, artificial life, self-healing materials and others. It then classifies the presented work according to five types of nature-inspired technology, namely: (1) using technology to understand nature, (2) nature-inspiration for technology, (3) using technology on natural systems, (4) using biotechnology methods in software engineering, and (5) using technology to model nature. Finally, future trends in Complexity Engineering are indicated and related risks are discussed.

  19. Mathematicians, Attributional Complexity, and Gender

    NASA Astrophysics Data System (ADS)

    Stalder, Daniel R.

    Given indirect indications in sex role and soda! psychology research that mathematical-deductive reasoning may negatively relate to social acuity, Study 1 investigated whether mathematicians were less attributionally complex than nonmathematicians. Study 1 administered the Attributional Complexity Scale, a measure of social acuity, to female and male faculty members and graduate students in four Midwestern schools. Atlrihutional complexity (AC) is the ability and motivation to give complex explanations for behavior. Study 1 found a significant interaction between field and gender. Only among women did mathematicians score lower on AC. In addition, an established gender difference in AC (that women score higher than men) was present only among nonmathematicians. Studies 2 and 3 offered some preliminary support for the possibility that it is generally female students who score tow on AC who aspire to he mathematicians and for the underlying view that female students' perceived similarity to mathematicians can influence their vocational choices.

  20. Complex bile duct injuries: management

    PubMed Central

    Ardiles, V.; Pekolj, J.

    2008-01-01

    Background. Laparoscopic cholecystectomy is the present treatment of choice for patients with gallbladder stones, despite its being associated with a higher incidence of biliary injuries compared with the open procedure. Injuries occurring during the laparoscopic approach seem to be more complex. A complex biliary injury is a disease that is difficult to diagnose and treat. We considered complex injuries: 1) injuries that involve the confluence; 2) injuries in which repair attempts have failed; 3) any bile duct injury associated with a vascular injury; 4) or any biliary injury in association with portal hypertension or secondary biliary cirrhosis. The present review is an evaluation of our experience in the treatment of these complex biliary injuries and an analysis of the international literature on the management of patients. PMID:18695753

  1. Complex Topographic Feature Ontology Patterns

    USGS Publications Warehouse

    Varanka, Dalia E.; Jerris, Thomas J.

    2015-01-01

    Semantic ontologies are examined as effective data models for the representation of complex topographic feature types. Complex feature types are viewed as integrated relations between basic features for a basic purpose. In the context of topographic science, such component assemblages are supported by resource systems and found on the local landscape. Ontologies are organized within six thematic modules of a domain ontology called Topography that includes within its sphere basic feature types, resource systems, and landscape types. Context is constructed not only as a spatial and temporal setting, but a setting also based on environmental processes. Types of spatial relations that exist between components include location, generative processes, and description. An example is offered in a complex feature type ‘mine.’ The identification and extraction of complex feature types are an area for future research.

  2. Making the Tent Function Complex

    ERIC Educational Resources Information Center

    Sprows, David J.

    2010-01-01

    This note can be used to illustrate to the student such concepts as periodicity in the complex plane. The basic construction makes use of the Tent function which requires only that the student have some working knowledge of binary arithmetic.

  3. Complex Hydrides for Hydrogen Storage

    SciTech Connect

    Slattery, Darlene; Hampton, Michael

    2003-03-10

    This report describes research into the use of complex hydrides for hydrogen storage. The synthesis of a number of alanates, (AIH4) compounds, was investigated. Both wet chemical and mechano-chemical methods were studied.

  4. SDO: Complex Mass of Plasma

    NASA Video Gallery

    A small, but complex mass of solar material gyrated and spun about over the course of 40 hours above the surface of the sun on Sept. 1-3, 2015. It was stretched and pulled back and forth by powerfu...

  5. Unitarity and Complex Mass Fields

    NASA Astrophysics Data System (ADS)

    Bollini, C. G.; Oxman, L. E.

    We consider a field obeying a simple higher order equation with a real mass and two complex conjugate mass parameters. The evaluation of vacuum expectation values leads to the propagators, which are (resp.) a Feynman causal function and two complex conjugate Wheeler-Green functions (half retarded plus half advanced). By means of the computation of convolutions, we are able to show that the total self-energy has an absorptive part which is only due to the real mass. In this way it is shown that this diagram is compatible with unitarity and the elimination of free complex-mass asymptotic states from the set of external legs of the S-matrix. It is also shown that the complex masses act as regulators of ultraviolet divergences.

  6. Auditory Perception of Complex Sounds.

    DTIC Science & Technology

    1987-10-30

    processes that underlie several aspects of complex pattern recog- nition -- whether of speech, of music , or of environmental sounds. These patterns differ...quality or timbre can play similar grouping roles in auditory steams. Most of the experimental work has concerned timing of successive sounds in sequences...auditory perceptual processes that underlie several aspects of complex pattern recognition - whether of speech, of music , or of environmental sounds

  7. Septin pairs, a complex choreography.

    PubMed

    Ewers, Helge

    2011-06-13

    Septins form a filamentous collar at the mother-bud neck in budding yeast. In cytokinesis, this collar splits into two rings and the septin complexes undergo a dramatic reorientation. Using fluorescence polarization microscopy, DeMay et al. (2011. J. Cell Biol. doi:10.1083/jcb.201012143) now demonstrate that septin complexes assemble as paired filaments in vivo and reveal new insights into septin organization during cytokinesis.

  8. Mixed real/complex factorization

    SciTech Connect

    Lima, L.T.G. . Dept. of Electrical Engineering); Martines, N.; Pinto, H.J.C.P. . Centro de Pesquisas de Energia Electrica)

    1993-02-01

    This paper describes a mixed real/complex sparse matrix factorization and solution scheme applied to a large matrix problem. Large system eigenanalysis and frequency domain methods will directly benefit from the proposed scheme, which can reduce both memory and CPU time requirements when compared to conventional complex-only solutions. The application in hand is the small signal electromechanical stability analysis of large power systems. The savings obtained are significant considering the CPU intensive nature of these matrix problems.

  9. Complexity, action, and black holes

    DOE PAGES

    Brown, Adam R.; Roberts, Daniel A.; Susskind, Leonard; ...

    2016-04-18

    In an earlier paper "Complexity Equals Action" we conjectured that the quantum computational complexity of a holographic state is given by the classical action of a region in the bulk (the `Wheeler-DeWitt' patch). We provide calculations for the results quoted in that paper, explain how it fits into a broader (tensor) network of ideas, and elaborate on the hypothesis that black holes are the fastest computers in nature.

  10. Complexity, action, and black holes

    NASA Astrophysics Data System (ADS)

    Brown, Adam R.; Roberts, Daniel A.; Susskind, Leonard; Swingle, Brian; Zhao, Ying

    2016-04-01

    Our earlier paper "Complexity Equals Action" conjectured that the quantum computational complexity of a holographic state is given by the classical action of a region in the bulk (the "Wheeler-DeWitt" patch). We provide calculations for the results quoted in that paper, explain how it fits into a broader (tensor) network of ideas, and elaborate on the hypothesis that black holes are the fastest computers in nature.

  11. Symbolic Dynamics and Grammatical Complexity

    NASA Astrophysics Data System (ADS)

    Hao, Bai-Lin; Zheng, Wei-Mou

    The following sections are included: * Formal Languages and Their Complexity * Formal Language * Chomsky Hierarchy of Grammatical Complexity * The L-System * Regular Language and Finite Automaton * Finite Automaton * Regular Language * Stefan Matrix as Transfer Function for Automaton * Beyond Regular Languages * Feigenbaum and Generalized Feigenbaum Limiting Sets * Even and Odd Fibonacci Sequences * Odd Maximal Primitive Prefixes and Kneading Map * Even Maximal Primitive Prefixes and Distinct Excluded Blocks * Summary of Results

  12. Complex Hybrid Inflation and Baryogenesis

    SciTech Connect

    Delepine, David; Martinez, Carlos; Urena-Lopez, L. Arturo

    2007-04-20

    We propose a hybrid inflation model with a complex waterfall field which contains an interaction term that breaks the U(1) global symmetry associated with the waterfall field charge. We show that the asymmetric evolution of the real and imaginary parts of the complex field during the phase transition at the end of inflation translates into a charge asymmetry. The latter strongly depends on the vacuum expectation value of the waterfall field, which is well constrained by diverse cosmological observations.

  13. Quantum complexity and negative curvature

    NASA Astrophysics Data System (ADS)

    Brown, Adam R.; Susskind, Leonard; Zhao, Ying

    2017-02-01

    As time passes, once simple quantum states tend to become more complex. For strongly coupled k -local Hamiltonians, this growth of computational complexity has been conjectured to follow a distinctive and universal pattern. In this paper we show that the same pattern is exhibited by a much simpler system—classical geodesics on a compact two-dimensional geometry of uniform negative curvature. This striking parallel persists whether the system is allowed to evolve naturally or is perturbed from the outside.

  14. Goldstone Deep Space Communication Complex

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Three 34m (110 ft.) diameter Beam Waveguide antennas located at the Goldstone Deep Space Communications Complex, situated in the Mojave Desert in California. This is one of three complexes which comprise NASA's Deep Space Network (DSN). The DSN provides radio communications for all of NASA's interplanetary spacecraft and is also utilized for radio astronomy and radar observations of the solar system and the universe.

  15. Complex numbers in quantum theory

    NASA Astrophysics Data System (ADS)

    Maynard, Glenn

    In 1927, Nobel prize winning physicist, E. Schrodinger, in correspondence with Ehrenfest, wrote the following about the new theory: "What is unpleasant here, and indeed directly to be objected to, is the use of complex numbers. Psi is surely fundamentally a real function." This seemingly simple issue remains unexplained almost ninety years later. In this dissertation I elucidate the physical and theoretical origins of the complex requirement. (Abstract shortened by ProQuest.).

  16. Thermochemical Radii of Complex Ions

    NASA Astrophysics Data System (ADS)

    Roobottom, Helen K.; Jenkins, H. Donald B.; Passmore, Jack; Glasser, Leslie

    1999-11-01

    Using rectilinear correlations of lattice energy with the inverse cubic root of the volume per molecule of complex salts of type MX (1:1), M2X (2:1), and MX2 (1:2) we have generated a comprehensive self-consistent tabulation of more than 400 thermochemical radii for complex ions. These radii can be used in the Kapustinskii equation to generate lattice energies and also as ion size parameters.

  17. Conforming Morse-Smale Complexes

    SciTech Connect

    Gyulassy, Attila; Gunther, David; Levine, Joshua A.; Tierny, Julien; Pascucci, Valerio

    2014-08-11

    Morse-Smale (MS) complexes have been gaining popularity as a tool for feature-driven data analysis and visualization. However, the quality of their geometric embedding and the sole dependence on the input scalar field data can limit their applicability when expressing application-dependent features. In this paper we introduce a new combinatorial technique to compute an MS complex that conforms to both an input scalar field and an additional, prior segmentation of the domain. The segmentation constrains the MS complex computation guaranteeing that boundaries in the segmentation are captured as separatrices of the MS complex. We demonstrate the utility and versatility of our approach with two applications. First, we use streamline integration to determine numerically computed basins/mountains and use the resulting segmentation as an input to our algorithm. This strategy enables the incorporation of prior flow path knowledge, effectively resulting in an MS complex that is as geometrically accurate as the employed numerical integration. Our second use case is motivated by the observation that often the data itself does not explicitly contain features known to be present by a domain expert. We introduce edit operations for MS complexes so that a user can directly modify their features while maintaining all the advantages of a robust topology-based representation.

  18. Formulation of Complex Action Theory

    NASA Astrophysics Data System (ADS)

    Nagao, K.; Nielsen, H. B.

    2011-12-01

    We formulate a complex action theory which includes operators of coordinate and momentum hat{q} and hat{p} being replaced with non-hermitian operators hat{q}_{new} and hat{p}_{new}, and their eigenstates | q >_{new} and | p >_{new} with complex eigenvalues q and p. Introducing a philosophy of keeping the analyticity in path integration variables, we define a modified set of complex conjugate, real and imaginary parts, hermitian conjugates and bras, and explicitly construct hat{q}_{new}, hat{p}_{new}, |q >_{new} and |p >_{new} by formally squeezing coherent states. We also pose a theorem on the relation between functions on the phase space and the corresponding operators. Only in our formalism can we describe a complex action theory or a real action theory with complex saddle points in the tunneling effect etc. in terms of bras and kets in the functional integral. Furthermore, in a system with a non-hermitian diagonalizable bounded Hamiltonian, we show that the mechanism to obtain a hermitian Hamiltonian after a long time development proposed in our paper [Prog. Theor. Phys. 125 (2011), 633] works also in the complex coordinate formalism. If the hermitian Hamiltonian is given in a local form, a conserved probability current density can be constructed with two kinds of wave functions.

  19. The Ndc80 complex bridges two Dam1 complex rings

    PubMed Central

    Kim, Jae ook; Zelter, Alex; Umbreit, Neil T; Bollozos, Athena; Riffle, Michael; Johnson, Richard; MacCoss, Michael J; Asbury, Charles L; Davis, Trisha N

    2017-01-01

    Strong kinetochore-microtubule attachments are essential for faithful segregation of sister chromatids during mitosis. The Dam1 and Ndc80 complexes are the main microtubule binding components of the Saccharomyces cerevisiae kinetochore. Cooperation between these two complexes enhances kinetochore-microtubule coupling and is regulated by Aurora B kinase. We show that the Ndc80 complex can simultaneously bind and bridge across two Dam1 complex rings through a tripartite interaction, each component of which is regulated by Aurora B kinase. Mutations in any one of the Ndc80p interaction regions abrogates the Ndc80 complex’s ability to bind two Dam1 rings in vitro, and results in kinetochore biorientation and microtubule attachment defects in vivo. We also show that an extra-long Ndc80 complex, engineered to space the two Dam1 rings further apart, does not support growth. Taken together, our work suggests that each kinetochore in vivo contains two Dam1 rings and that proper spacing between the rings is vital. DOI: http://dx.doi.org/10.7554/eLife.21069.001 PMID:28191870

  20. "Computational Modeling of Actinide Complexes"

    SciTech Connect

    Balasubramanian, K

    2007-03-07

    We will present our recent studies on computational actinide chemistry of complexes which are not only interesting from the standpoint of actinide coordination chemistry but also of relevance to environmental management of high-level nuclear wastes. We will be discussing our recent collaborative efforts with Professor Heino Nitsche of LBNL whose research group has been actively carrying out experimental studies on these species. Computations of actinide complexes are also quintessential to our understanding of the complexes found in geochemical, biochemical environments and actinide chemistry relevant to advanced nuclear systems. In particular we have been studying uranyl, plutonyl, and Cm(III) complexes are in aqueous solution. These studies are made with a variety of relativistic methods such as coupled cluster methods, DFT, and complete active space multi-configuration self-consistent-field (CASSCF) followed by large-scale CI computations and relativistic CI (RCI) computations up to 60 million configurations. Our computational studies on actinide complexes were motivated by ongoing EXAFS studies of speciated complexes in geo and biochemical environments carried out by Prof Heino Nitsche's group at Berkeley, Dr. David Clark at Los Alamos and Dr. Gibson's work on small actinide molecules at ORNL. The hydrolysis reactions of urnayl, neputyl and plutonyl complexes have received considerable attention due to their geochemical and biochemical importance but the results of free energies in solution and the mechanism of deprotonation have been topic of considerable uncertainty. We have computed deprotonating and migration of one water molecule from the first solvation shell to the second shell in UO{sub 2}(H{sub 2}O){sub 5}{sup 2+}, UO{sub 2}(H{sub 2}O){sub 5}{sup 2+}NpO{sub 2}(H{sub 2}O){sub 6}{sup +}, and PuO{sub 2}(H{sub 2}O){sub 5}{sup 2+} complexes. Our computed Gibbs free energy(7.27 kcal/m) in solution for the first time agrees with the experiment (7.1 kcal

  1. Restricted Complexity Framework for Nonlinear Adaptive Control in Complex Systems

    NASA Astrophysics Data System (ADS)

    Williams, Rube B.

    2004-02-01

    Control law adaptation that includes implicit or explicit adaptive state estimation, can be a fundamental underpinning for the success of intelligent control in complex systems, particularly during subsystem failures, where vital system states and parameters can be impractical or impossible to measure directly. A practical algorithm is proposed for adaptive state filtering and control in nonlinear dynamic systems when the state equations are unknown or are too complex to model analytically. The state equations and inverse plant model are approximated by using neural networks. A framework for a neural network based nonlinear dynamic inversion control law is proposed, as an extrapolation of prior developed restricted complexity methodology used to formulate the adaptive state filter. Examples of adaptive filter performance are presented for an SSME simulation with high pressure turbine failure to support extrapolations to adaptive control problems.

  2. Restricted Complexity Framework for Nonlinear Adaptive Control in Complex Systems

    SciTech Connect

    Williams, Rube B.

    2004-02-04

    Control law adaptation that includes implicit or explicit adaptive state estimation, can be a fundamental underpinning for the success of intelligent control in complex systems, particularly during subsystem failures, where vital system states and parameters can be impractical or impossible to measure directly. A practical algorithm is proposed for adaptive state filtering and control in nonlinear dynamic systems when the state equations are unknown or are too complex to model analytically. The state equations and inverse plant model are approximated by using neural networks. A framework for a neural network based nonlinear dynamic inversion control law is proposed, as an extrapolation of prior developed restricted complexity methodology used to formulate the adaptive state filter. Examples of adaptive filter performance are presented for an SSME simulation with high pressure turbine failure to support extrapolations to adaptive control problems.

  3. Complexity analysis of angiogenesis vasculature

    NASA Astrophysics Data System (ADS)

    Mahadevan, Vijay; Tyrell, James A.; Tong, Ricky T.; Brown, Edward B.; Jain, Rakesh K.; Roysam, Badrinath

    2005-04-01

    Tumor vasculature has a high degree of irregularity as compared to normal vasculature. The quantification of the morphometric complexity in tumor images can be useful in diagnosis. Also, it is desirable in several other medical applications to have an automated complexity analysis to aid in diagnosis and prognosis under treatment. e.g. in diabetic retinopathy and in arteriosclerosis. In addition, prior efforts at segmentation of the tumor vasculature using matched filtering, template matching and splines have been hampered by the irregularity of these vessels. We try to solve both problems by introducing a novel technique for vessel detection, followed by a tracing-independent complexity analysis based on a combination of ideas. First, the vessel cross-sectional profile is modeled using a continuous and everywhere differentiable family of super-Gaussian curves. This family generates rectangular profiles that can accurately localize the vessel boundaries in microvasculature images. Second, a robust non-linear regression algorithm based on M-estimators is used to estimate the parameters that optimally characterize the vessel"s shape. A framework for the quantitative analysis of the complexity of the vasculature based on the vessel detection is presented. A set of measures that quantify the complexity are proposed viz. Squared Error, Entropy-based and Minimum Description Length-based Shape Complexities. They are completely automatic and can deal with complexities of the entire vessel unlike existing tortuousity measures which deal only with vessel centerlines. The results are validated using carefully constructed phantom and real image data with ground truth information from an expert observer.

  4. Complex systems: physics beyond physics

    NASA Astrophysics Data System (ADS)

    Holovatch, Yurij; Kenna, Ralph; Thurner, Stefan

    2017-03-01

    Complex systems are characterised by specific time-dependent interactions among their many constituents. As a consequence they often manifest rich, non-trivial and unexpected behaviour. Examples arise both in the physical and non-physical worlds. The study of complex systems forms a new interdisciplinary research area that cuts across physics, biology, ecology, economics, sociology, and the humanities. In this paper we review the essence of complex systems from a physicists' point of view, and try to clarify what makes them conceptually different from systems that are traditionally studied in physics. Our goal is to demonstrate how the dynamics of such systems may be conceptualised in quantitative and predictive terms by extending notions from statistical physics and how they can often be captured in a framework of co-evolving multiplex network structures. We mention three areas of complex-systems science that are currently studied extensively, the science of cities, dynamics of societies, and the representation of texts as evolutionary objects. We discuss why these areas form complex systems in the above sense. We argue that there exists plenty of new ground for physicists to explore and that methodical and conceptual progress is needed most.

  5. Cortical complexity in cetacean brains.

    PubMed

    Hof, Patrick R; Chanis, Rebecca; Marino, Lori

    2005-11-01

    Cetaceans (dolphins, whales, and porpoises) have a long, dramatically divergent evolutionary history compared with terrestrial mammals. Throughout their 55-60 million years of evolution, cetaceans acquired a compelling set of characteristics that include echolocation ability (in odontocetes), complex auditory and communicative capacities, and complex social organization. Moreover, although cetaceans have not shared a common ancestor with primates for over 90 million years, they possess a set of cognitive attributes that are strikingly convergent with those of many primates, including great apes and humans. In contrast, cetaceans have evolved a highly unusual combination of neurobiological features different from that of primates. As such, cetacean brains offer a critical opportunity to address questions about how complex behavior can be based on very different neuroanatomical and neurobiological evolutionary products. Cetacean brains and primate brains are arguably most meaningfully conceived as alternative evolutionary routes to neurobiological and cognitive complexity. In this article, we summarize data on brain size and hemisphere surface configuration in several cetacean species and present an overview of the cytoarchitectural complexity of the cerebral cortex of the bottlenose dolphin.

  6. Control principles of complex systems

    NASA Astrophysics Data System (ADS)

    Liu, Yang-Yu; Barabási, Albert-László

    2016-07-01

    A reflection of our ultimate understanding of a complex system is our ability to control its behavior. Typically, control has multiple prerequisites: it requires an accurate map of the network that governs the interactions between the system's components, a quantitative description of the dynamical laws that govern the temporal behavior of each component, and an ability to influence the state and temporal behavior of a selected subset of the components. With deep roots in dynamical systems and control theory, notions of control and controllability have taken a new life recently in the study of complex networks, inspiring several fundamental questions: What are the control principles of complex systems? How do networks organize themselves to balance control with functionality? To address these questions here recent advances on the controllability and the control of complex networks are reviewed, exploring the intricate interplay between the network topology and dynamical laws. The pertinent mathematical results are matched with empirical findings and applications. Uncovering the control principles of complex systems can help us explore and ultimately understand the fundamental laws that govern their behavior.

  7. Articulation points in complex networks

    PubMed Central

    Tian, Liang; Bashan, Amir; Shi, Da-Ning; Liu, Yang-Yu

    2017-01-01

    An articulation point in a network is a node whose removal disconnects the network. Those nodes play key roles in ensuring connectivity of many real-world networks, from infrastructure networks to protein interaction networks and terrorist communication networks. Despite their fundamental importance, a general framework of studying articulation points in complex networks is lacking. Here we develop analytical tools to study key issues pertinent to articulation points, such as the expected number of them and the network vulnerability against their removal, in an arbitrary complex network. We find that a greedy articulation point removal process provides us a different perspective on the organizational principles of complex networks. Moreover, this process results in a rich phase diagram with two fundamentally different types of percolation transitions. Our results shed light on the design of more resilient infrastructure networks and the effective destruction of terrorist communication networks. PMID:28139697

  8. Graph distance for complex networks

    NASA Astrophysics Data System (ADS)

    Shimada, Yutaka; Hirata, Yoshito; Ikeguchi, Tohru; Aihara, Kazuyuki

    2016-10-01

    Networks are widely used as a tool for describing diverse real complex systems and have been successfully applied to many fields. The distance between networks is one of the most fundamental concepts for properly classifying real networks, detecting temporal changes in network structures, and effectively predicting their temporal evolution. However, this distance has rarely been discussed in the theory of complex networks. Here, we propose a graph distance between networks based on a Laplacian matrix that reflects the structural and dynamical properties of networked dynamical systems. Our results indicate that the Laplacian-based graph distance effectively quantifies the structural difference between complex networks. We further show that our approach successfully elucidates the temporal properties underlying temporal networks observed in the context of face-to-face human interactions.

  9. Multi-stage complex contagions

    NASA Astrophysics Data System (ADS)

    Melnik, Sergey; Ward, Jonathan A.; Gleeson, James P.; Porter, Mason A.

    2013-03-01

    The spread of ideas across a social network can be studied using complex contagion models, in which agents are activated by contact with multiple activated neighbors. The investigation of complex contagions can provide crucial insights into social influence and behavior-adoption cascades on networks. In this paper, we introduce a model of a multi-stage complex contagion on networks. Agents at different stages—which could, for example, represent differing levels of support for a social movement or differing levels of commitment to a certain product or idea—exert different amounts of influence on their neighbors. We demonstrate that the presence of even one additional stage introduces novel dynamical behavior, including interplay between multiple cascades, which cannot occur in single-stage contagion models. We find that cascades—and hence collective action—can be driven not only by high-stage influencers but also by low-stage influencers.

  10. Multi-stage complex contagions.

    PubMed

    Melnik, Sergey; Ward, Jonathan A; Gleeson, James P; Porter, Mason A

    2013-03-01

    The spread of ideas across a social network can be studied using complex contagion models, in which agents are activated by contact with multiple activated neighbors. The investigation of complex contagions can provide crucial insights into social influence and behavior-adoption cascades on networks. In this paper, we introduce a model of a multi-stage complex contagion on networks. Agents at different stages-which could, for example, represent differing levels of support for a social movement or differing levels of commitment to a certain product or idea-exert different amounts of influence on their neighbors. We demonstrate that the presence of even one additional stage introduces novel dynamical behavior, including interplay between multiple cascades, which cannot occur in single-stage contagion models. We find that cascades-and hence collective action-can be driven not only by high-stage influencers but also by low-stage influencers.

  11. Articulation points in complex networks

    NASA Astrophysics Data System (ADS)

    Tian, Liang; Bashan, Amir; Shi, Da-Ning; Liu, Yang-Yu

    2017-01-01

    An articulation point in a network is a node whose removal disconnects the network. Those nodes play key roles in ensuring connectivity of many real-world networks, from infrastructure networks to protein interaction networks and terrorist communication networks. Despite their fundamental importance, a general framework of studying articulation points in complex networks is lacking. Here we develop analytical tools to study key issues pertinent to articulation points, such as the expected number of them and the network vulnerability against their removal, in an arbitrary complex network. We find that a greedy articulation point removal process provides us a different perspective on the organizational principles of complex networks. Moreover, this process results in a rich phase diagram with two fundamentally different types of percolation transitions. Our results shed light on the design of more resilient infrastructure networks and the effective destruction of terrorist communication networks.

  12. Complexity matching in dyadic conversation.

    PubMed

    Abney, Drew H; Paxton, Alexandra; Dale, Rick; Kello, Christopher T

    2014-12-01

    Recent studies of dyadic interaction have examined phenomena of synchronization, entrainment, alignment, and convergence. All these forms of behavioral matching have been hypothesized to play a supportive role in establishing coordination and common ground between interlocutors. In the present study, evidence is found for a new kind of coordination termed complexity matching. Temporal dynamics in conversational speech signals were analyzed through time series of acoustic onset events. Timing in periods of acoustic energy was found to exhibit behavioral matching that reflects complementary timing in turn-taking. In addition, acoustic onset times were found to exhibit power law clustering across a range of timescales, and these power law functions were found to exhibit complexity matching that is distinct from behavioral matching. Complexity matching is discussed in terms of interactive alignment and other theoretical principles that lead to new hypotheses about information exchange in dyadic conversation and interaction in general.

  13. Phosphoroorganic Metal Complexes in Therapeutics.

    PubMed

    Demkowicz, Sebastian; Kozak, Witold; Daśko, Mateusz; Rachon, Janusz

    2016-01-01

    The present mini-review highlights recent developments on antitumor activity of metal-based therapeutics which have been a subject of researches for the last few decades. In 1965, Rosenberg found that during an electrolysis on platinum electrodes a complex of Pt is generated which inhibited to a great extent a binary fission in Escherichia coli bacteria. This discovery started a new chapter in medicinal chemistry and the interesting properties of cisplatin were soon applied in cancer therapy especially in curing genitourinary tumors. However, various side effects limited its use in medical treatment. Since then a great number of other metal-organic complexes based on platinum, palladium, ruthenium, gold, copper, silver, rhodium, osmium, rhenium, iridium and others have been synthesized. Among them, NAMI-A and KP1019 have recently undergone clinical trials. In this review paper we report a detailed account of metal complexes with phosphorus-based ligands which are of particular interest in therapeutics.

  14. Exact controllability of complex networks

    PubMed Central

    Yuan, Zhengzhong; Zhao, Chen; Di, Zengru; Wang, Wen-Xu; Lai, Ying-Cheng

    2013-01-01

    Controlling complex networks is of paramount importance in science and engineering. Despite the recent development of structural controllability theory, we continue to lack a framework to control undirected complex networks, especially given link weights. Here we introduce an exact controllability paradigm based on the maximum multiplicity to identify the minimum set of driver nodes required to achieve full control of networks with arbitrary structures and link-weight distributions. The framework reproduces the structural controllability of directed networks characterized by structural matrices. We explore the controllability of a large number of real and model networks, finding that dense networks with identical weights are difficult to be controlled. An efficient and accurate tool is offered to assess the controllability of large sparse and dense networks. The exact controllability framework enables a comprehensive understanding of the impact of network properties on controllability, a fundamental problem towards our ultimate control of complex systems. PMID:24025746

  15. Graph distance for complex networks

    PubMed Central

    Shimada, Yutaka; Hirata, Yoshito; Ikeguchi, Tohru; Aihara, Kazuyuki

    2016-01-01

    Networks are widely used as a tool for describing diverse real complex systems and have been successfully applied to many fields. The distance between networks is one of the most fundamental concepts for properly classifying real networks, detecting temporal changes in network structures, and effectively predicting their temporal evolution. However, this distance has rarely been discussed in the theory of complex networks. Here, we propose a graph distance between networks based on a Laplacian matrix that reflects the structural and dynamical properties of networked dynamical systems. Our results indicate that the Laplacian-based graph distance effectively quantifies the structural difference between complex networks. We further show that our approach successfully elucidates the temporal properties underlying temporal networks observed in the context of face-to-face human interactions. PMID:27725690

  16. Complex Fluids and Hydraulic Fracturing.

    PubMed

    Barbati, Alexander C; Desroches, Jean; Robisson, Agathe; McKinley, Gareth H

    2016-06-07

    Nearly 70 years old, hydraulic fracturing is a core technique for stimulating hydrocarbon production in a majority of oil and gas reservoirs. Complex fluids are implemented in nearly every step of the fracturing process, most significantly to generate and sustain fractures and transport and distribute proppant particles during and following fluid injection. An extremely wide range of complex fluids are used: naturally occurring polysaccharide and synthetic polymer solutions, aqueous physical and chemical gels, organic gels, micellar surfactant solutions, emulsions, and foams. These fluids are loaded over a wide range of concentrations with particles of varying sizes and aspect ratios and are subjected to extreme mechanical and environmental conditions. We describe the settings of hydraulic fracturing (framed by geology), fracturing mechanics and physics, and the critical role that non-Newtonian fluid dynamics and complex fluids play in the hydraulic fracturing process.

  17. Emergence: complexity pedagogy in action.

    PubMed

    Jonas-Simpson, Christine; Mitchell, Gail; Cross, Nadine

    2015-01-01

    Many educators are looking for new ways to engage students and each other in order to enrich curriculum and the teaching-learning process. We describe an example of how we enacted teaching-learning approaches through the insights of complexity thinking, an approach that supports the emergence of new possibilities for teaching-learning in the classroom and online. Our story begins with an occasion to meet with 10 nursing colleagues in a three-hour workshop using four activities that engaged learning about complexity thinking and pedagogy. Guiding concepts for the collaborative workshop were nonlinearity, distributed decision-making, divergent thinking, self-organization, emergence, and creative exploration. The workshop approach considered critical questions to spark our collective inquiry. We asked, "What is emergent learning?" and "How do we, as educators and learners, engage a community so that new learning surfaces?" We integrated the arts, creative play, and perturbations within a complexity approach.

  18. Manipulating Complex Light with Metamaterials

    PubMed Central

    Zeng, Jinwei; Wang, Xi; Sun, Jingbo; Pandey, Apra; Cartwright, Alexander N.; Litchinitser, Natalia M.

    2013-01-01

    Recent developments in the field of metamaterials have revealed unparalleled opportunities for “engineering” space for light propagation; opening a new paradigm in spin- and quantum-related phenomena in optical physics. Here we show that unique optical properties of metamaterials (MMs) open unlimited prospects to “engineer” light itself. We propose and demonstrate for the first time a novel way of complex light manipulation in few-mode optical fibers using optical MMs. Most importantly, these studies highlight how unique properties of MMs, namely the ability to manipulate both electric and magnetic field components of electromagnetic (EM) waves, open new degrees of freedom in engineering complex polarization states of light at will, while preserving its orbital angular momentum (OAM) state. These results lay the first steps in manipulating complex light in optical fibers, likely providing new opportunities for high capacity communication systems, quantum information, and on-chip signal processing. PMID:24084836

  19. Hilbert complexes of nonlinear elasticity

    NASA Astrophysics Data System (ADS)

    Angoshtari, Arzhang; Yavari, Arash

    2016-12-01

    We introduce some Hilbert complexes involving second-order tensors on flat compact manifolds with boundary that describe the kinematics and the kinetics of motion in nonlinear elasticity. We then use the general framework of Hilbert complexes to write Hodge-type and Helmholtz-type orthogonal decompositions for second-order tensors. As some applications of these decompositions in nonlinear elasticity, we study the strain compatibility equations of linear and nonlinear elasticity in the presence of Dirichlet boundary conditions and the existence of stress functions on non-contractible bodies. As an application of these Hilbert complexes in computational mechanics, we briefly discuss the derivation of a new class of mixed finite element methods for nonlinear elasticity.

  20. Complex Educational Design: A Course Design Model Based on Complexity

    ERIC Educational Resources Information Center

    Freire, Maximina Maria

    2013-01-01

    Purpose: This article aims at presenting a conceptual framework which, theoretically grounded on complexity, provides the basis to conceive of online language courses that intend to respond to the needs of students and society. Design/methodology/approach: This paper is introduced by reflections on distance education and on the paradigmatic view…