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Sample records for hyperpolarized 13c spectroscopy

  1. In vivo13C spectroscopy in the rat brain using hyperpolarized [1- 13C]pyruvate and [2- 13C]pyruvate

    NASA Astrophysics Data System (ADS)

    Marjańska, Małgorzata; Iltis, Isabelle; Shestov, Alexander A.; Deelchand, Dinesh K.; Nelson, Christopher; Uğurbil, Kâmil; Henry, Pierre-Gilles

    2010-10-01

    The low sensitivity of 13C spectroscopy can be enhanced using dynamic nuclear polarization. Detection of hyperpolarized [1- 13C]pyruvate and its metabolic products has been reported in kidney, liver, and muscle. In this work, the feasibility of measuring 13C signals of hyperpolarized 13C metabolic products in the rat brain in vivo following the injection of hyperpolarized [1- 13C]pyruvate and [2- 13C]pyruvate is investigated. Injection of [2- 13C]pyruvate led to the detection of [2- 13C]lactate, but no other downstream metabolites such as TCA cycle intermediates were detected. Injection of [1- 13C]pyruvate enabled the detection of both [1- 13C]lactate and [ 13C]bicarbonate. A metabolic model was used to fit the hyperpolarized 13C time courses obtained during infusion of [1- 13C]pyruvate and to determine the values of VPDH and VLDH.

  2. Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy.

    PubMed

    Schroeder, Marie A; Atherton, Helen J; Ball, Daniel R; Cole, Mark A; Heather, Lisa C; Griffin, Julian L; Clarke, Kieran; Radda, George K; Tyler, Damian J

    2009-08-01

    The Krebs cycle plays a fundamental role in cardiac energy production and is often implicated in the energetic imbalance characteristic of heart disease. In this study, we measured Krebs cycle flux in real time in perfused rat hearts using hyperpolarized magnetic resonance spectroscopy (MRS). [2-(13)C]Pyruvate was hyperpolarized and infused into isolated perfused hearts in both healthy and postischemic metabolic states. We followed the enzymatic conversion of pyruvate to lactate, acetylcarnitine, citrate, and glutamate with 1 s temporal resolution. The appearance of (13)C-labeled glutamate was delayed compared with that of other metabolites, indicating that Krebs cycle flux can be measured directly. The production of (13)C-labeled citrate and glutamate was decreased postischemia, as opposed to lactate, which was significantly elevated. These results showed that the control and fluxes of the Krebs cycle in heart disease can be studied using hyperpolarized [2-(13)C]pyruvate.

  3. Detection of inflammatory cell function using 13C magnetic resonance spectroscopy of hyperpolarized [6-13C]-arginine

    PubMed Central

    Najac, Chloé; Chaumeil, Myriam M.; Kohanbash, Gary; Guglielmetti, Caroline; Gordon, Jeremy W.; Okada, Hideho; Ronen, Sabrina M.

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) are highly prevalent inflammatory cells that play a key role in tumor development and are considered therapeutic targets. MDSCs promote tumor growth by blocking T-cell-mediated anti-tumoral immune response through depletion of arginine that is essential for T-cell proliferation. To deplete arginine, MDSCs express high levels of arginase, which catalyzes the breakdown of arginine into urea and ornithine. Here, we developed a new hyperpolarized 13C probe, [6-13C]-arginine, to image arginase activity. We show that [6-13C]-arginine can be hyperpolarized, and hyperpolarized [13C]-urea production from [6-13C]-arginine is linearly correlated with arginase concentration in vitro. Furthermore we show that we can detect a statistically significant increase in hyperpolarized [13C]-urea production in MDSCs when compared to control bone marrow cells. This increase was associated with an increase in intracellular arginase concentration detected using a spectrophotometric assay. Hyperpolarized [6-13C]-arginine could therefore serve to image tumoral MDSC function and more broadly M2-like macrophages. PMID:27507680

  4. 13C magnetic resonance spectroscopy measurements with hyperpolarized [1‐13C] pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo

    PubMed Central

    Dzien, Piotr; Tee, Sui‐Seng; Kettunen, Mikko I.; Lyons, Scott K.; Larkin, Timothy J.; Timm, Kerstin N.; Hu, De‐En; Wright, Alan; Rodrigues, Tiago B.; Serrao, Eva M.; Marco‐Rius, Irene; Mannion, Elizabeth; D'Santos, Paula; Kennedy, Brett W. C.

    2015-01-01

    Purpose Dissolution dynamic nuclear polarization can increase the sensitivity of the 13C magnetic resonance spectroscopy experiment by at least four orders of magnitude and offers a novel approach to the development of MRI gene reporters based on enzymes that metabolize 13C‐labeled tracers. We describe here a gene reporter based on the enzyme pyruvate decarboxylase (EC 4.1.1.1), which catalyzes the decarboxylation of pyruvate to produce acetaldehyde and carbon dioxide. Methods Pyruvate decarboxylase from Zymomonas mobilis (zmPDC) and a mutant that lacked enzyme activity were expressed using an inducible promoter in human embryonic kidney (HEK293T) cells. Enzyme activity was measured in the cells and in xenografts derived from the cells using 13C MRS measurements of the conversion of hyperpolarized [1‐13C] pyruvate to H13 CO3–. Results Induction of zmPDC expression in the cells and in the xenografts derived from them resulted in an approximately two‐fold increase in the H13 CO3–/[1‐13C] pyruvate signal ratio following intravenous injection of hyperpolarized [1‐13C] pyruvate. Conclusion We have demonstrated the feasibility of using zmPDC as an in vivo reporter gene for use with hyperpolarized 13C MRS. Magn Reson Med 76:391–401, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:26388418

  5. Noninvasive biomarkers for acute hepatotoxicity induced by 1,3-dichloro-2-propanol: hyperpolarized 13C dynamic MR spectroscopy.

    PubMed

    Kim, Gwang-Won; Oh, Chang-Hyun; Kim, Jong-Choon; Yoon, Woong; Jeong, Yong-Yeon; Kim, Yun-Hyeon; Kim, Jae-Kyu; Park, Jin-Gyoon; Kang, Heoung-Keun; Jeong, Gwang-Woo

    2016-02-01

    The purpose of this study was to investigate the cellular metabolite change for acute hepatotoxicity induced by 1,3-dichloro-2-propanol (1,3-DCP) in rats and its correlations with the enzyme levels. In order to induce acute hepatotoxicity, a single subcutaneous injection of 1,3-DCP (80 mg/kg) was given to six male Sprague-Dawley rats. Hyperpolarized (13)C dynamic magnetic resonance spectroscopy (MRS) was performed on rat liver following injection of hyperpolarized [1-(13)C] pyruvate. The levels of serum aspartate am inotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in the 1,3-DCP treated rats were significantly increased as compared with those in normal rats. In the dynamic (13)C MR spectra, the ratios of [1-(13)C] lactate to the total carbon and [1-(13)C] alanine to the total carbon in the 1,3-DCP treated rats were significantly increased, and there were positive correlations between cellular metabolic changes and enzyme levels. The levels of [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as important biomarkers for the 1,3-DCP-induced acute hepatotoxicity.

  6. Human Hepatocellular Carcinoma Metabolism: Imaging by Hyperpolarized 13C Magnetic Resonance Spectroscopy

    PubMed Central

    Darpolor, Moses M.; Kaplan, David E.; Pedersen, Peter L.; Glickson, Jerry D.

    2013-01-01

    Purpose Most cancers exhibit high levels of aerobic glycolytic metabolism with diminished levels of mitochondrial oxidative phosphorylation even in the presence of normal or near-normal levels of oxygen (“Warburg effect”). However, technical challenges have limited the development of non-invasive in vivo imaging techniques for monitoring glycolytic metabolism of hepatocellular carcinoma (HCC) and quantitatively evaluating the impact of this effect on the growth and therapy of this disease. Thus, there is a critical need to develop non-invasive techniques for longitudinal assessment of the metabolism and treatment response of patients with unresectable HCCs. Procedures This article discusses a novel method, “Hyperpolarized 13C MRS imaging”, for achieving this objective and thus improving the prognosis of HCC patients. The primary objective has been to characterize in vivo metabolic biomarkers as determinants of HCC metabolism and treatment response of unresectable HCC tumors or viable HCC cells. Results This innovative technique capitalizes on a new technology that increases the sensitivity of MRS detection of crucial metabolites in cancer cells. Conclusion It is anticipated that this innovative approach will lead to improved methods, both for the diagnosis and staging of HCCs and for the facilitation of the development of enzyme targeted therapies and other therapeutic interventions. PMID:24224182

  7. In vivo measurement of ethanol metabolism in the rat liver using magnetic resonance spectroscopy of hyperpolarized [1-13C]pyruvate

    PubMed Central

    Spielman, Daniel M.; Mayer, Dirk; Yen, Yi-Fen; Tropp, James; Hurd, Ralph E.; Pfefferbaum, Adolf

    2009-01-01

    [1-13C]pyruvate is readily polarizable substrate that has been the subject of numerous magnetic resonance spectroscopy (MRS) studies of in vivo metabolism. In this work, 13C-MRS of hyperpolarized [1-13C]pyruvate is used to interrogate a metabolic pathway involved in neither aerobic nor anaerobic metabolism. In particular, ethanol consumption leads to altered liver metabolism, which when excessive is associated with adverse medical conditions including fatty liver disease, hepatitis, cirrhosis, and cancer. Here we present a method for noninvasively monitoring this important process in vivo. Following the bolus injection of hyperpolarized [1-13C]pyruvate, we demonstrate a significantly increased rat liver lactate production rate with the co-administration of ethanol (P = 0.0016 unpaired t-test). The affect is attributable to increased liver nicotinamide adenine dinucleotide (NADH) associated with ethanol metabolism in combination with NADH's role as a coenzyme in pyruvate to lactate conversion. Beyond studies of liver metabolism, this novel in vivo assay of changes in NADH levels makes hyperpolarized [1-13C]pyruvate a potentially viable substrate for studying the multiple in vivo metabolic pathways that use NADH (or NAD+) as a coenzyme, thus broadening the range of applications that have been discussed in the literature to date. PMID:19526498

  8. Carbonic anhydrase activity monitored in vivo by hyperpolarized 13C-magnetic resonance spectroscopy demonstrate its importance for pH regulation in tumors

    PubMed Central

    Gallagher, Ferdia A.; Sladen, Helen; Kettunen, Mikko I.; Serrao, Eva M.; Rodrigues, Tiago B.; Wright, Alan; Gill, Andrew B.; McGuire, Sarah; Booth, Thomas C.; Boren, Joan; McIntyre, Alan; Miller, Jodi L.; Lee, Shen-Han; Honess, Davina; Day, Sam E.; Hu, De-en; Howat, William J.; Harris, Adrian L.; Brindle, Kevin M.

    2015-01-01

    Carbonic anhydrase (CA) buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3−). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolarized 13C label between bicarbonate (H13CO3−) and carbon dioxide (13CO2), following injection of hyperpolarized H13CO3−, using 13C magnetic resonance spectroscopy (13C-MRS) magnetization transfer measurements. 31P-MRS measurements of the chemical shift of the pH probe, 3-aminopropylphosphonate, and 13C-MRS measurements of the H13CO3−/13CO2 peak intensity ratio showed that CAIX overexpression lowered extracellular pH in these tumors. However, the 13C measurements overestimated pH due to incomplete equilibration of the hyperpolarized 13C label between the H13CO3− and 13CO2 pools. Paradoxically, tumors overexpressing CAIX showed lower enzyme activity using magnetization transfer measurements, which can be explained by the more acidic extracellular pH in these tumors and the decreased activity of the enzyme at low pH. This explanation was confirmed by administration of bicarbonate in the drinking water, which elevates tumor extracellular pH and restored enzyme activity to control levels. These results suggest that CAIX expression is increased in hypoxia to compensate for the decrease in its activity produced by a low extracellular pH, and supports the hypothesis that a major function of CAIX is to lower the extracellular pH. PMID:26249175

  9. Carbonic Anhydrase Activity Monitored In Vivo by Hyperpolarized 13C-Magnetic Resonance Spectroscopy Demonstrates Its Importance for pH Regulation in Tumors.

    PubMed

    Gallagher, Ferdia A; Sladen, Helen; Kettunen, Mikko I; Serrao, Eva M; Rodrigues, Tiago B; Wright, Alan; Gill, Andrew B; McGuire, Sarah; Booth, Thomas C; Boren, Joan; McIntyre, Alan; Miller, Jodi L; Lee, Shen-Han; Honess, Davina; Day, Sam E; Hu, De-En; Howat, William J; Harris, Adrian L; Brindle, Kevin M

    2015-10-01

    Carbonic anhydrase buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3 (-)). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolarized (13)C label between bicarbonate (H(13)CO3(-)) and carbon dioxide ((13)CO2), following injection of hyperpolarized H(13)CO3(-), using (13)C-magnetic resonance spectroscopy ((13)C-MRS) magnetization transfer measurements. (31)P-MRS measurements of the chemical shift of the pH probe, 3-aminopropylphosphonate, and (13)C-MRS measurements of the H(13)CO3(-)/(13)CO2 peak intensity ratio showed that CAIX overexpression lowered extracellular pH in these tumors. However, the (13)C measurements overestimated pH due to incomplete equilibration of the hyperpolarized (13)C label between the H(13)CO3(-) and (13)CO2 pools. Paradoxically, tumors overexpressing CAIX showed lower enzyme activity using magnetization transfer measurements, which can be explained by the more acidic extracellular pH in these tumors and the decreased activity of the enzyme at low pH. This explanation was confirmed by administration of bicarbonate in the drinking water, which elevated tumor extracellular pH and restored enzyme activity to control levels. These results suggest that CAIX expression is increased in hypoxia to compensate for the decrease in its activity produced by a low extracellular pH and supports the hypothesis that a major function of CAIX is to lower the extracellular pH.

  10. Feasibility of Multianimal Hyperpolarized 13C MRS

    PubMed Central

    Ramirez, Marc S.; Lee, Jaehyuk; Walker, Christopher M.; Chen, Yunyun; Kingsley, Charles V.; De La Cerda, Jorge; Maldonado, Kiersten L.; Lai, Stephen Y.; Bankson, James A.

    2014-01-01

    Purpose There is great potential for real-time investigation of metabolism with MRS and hyperpolarized (HP) 13C agents. Unfortunately, HP technology has high associated costs and efficiency limitations that may constrain in vivo studies involving many animals. To improve the throughput of preclinical investigations, we evaluate the feasibility of performing HP MRS on multiple animals simultaneously. Methods Simulations helped assess the viability of a dual-coil strategy for spatially-localized multivolume MRS.A dual-mouse system was assembled and characterized based on bench- and scanner-based experiments. Enzyme phantoms mixed with HP [1-13C] pyruvate emulated real-time metabolism and offered a controlled mechanism for evaluating system performance. Finally, a normal mouse and a mouse bearing a subcutaneous xenograft of colon cancer were simultaneously scanned in vivo using an agent containing HP [1-13C] pyruvate. Results Geometric separation/rotation, active decoupling, and use of low input impedance preamplifiers permitted an encode-by-channel approach for spatially-localized MRS. A pre-calibrated shim allowed straightforward metabolite differentiation in enzyme phantom and in vivo experiments at 7 T, with performance similar to conventional acquisitions. Conclusion The initial feasibility of multi-animal HP 13C MRS was established. Throughput scales with the number of simultaneously-scanned animals, demonstrating the potential for significant improvements in study efficiency. PMID:24903532

  11. Open-Source Automated Parahydrogen Hyperpolarizer for Molecular Imaging Using (13)C Metabolic Contrast Agents.

    PubMed

    Coffey, Aaron M; Shchepin, Roman V; Truong, Milton L; Wilkens, Ken; Pham, Wellington; Chekmenev, Eduard Y

    2016-08-16

    An open-source hyperpolarizer producing (13)C hyperpolarized contrast agents using parahydrogen induced polarization (PHIP) for biomedical and other applications is presented. This PHIP hyperpolarizer utilizes an Arduino microcontroller in conjunction with a readily modified graphical user interface written in the open-source processing software environment to completely control the PHIP hyperpolarization process including remotely triggering an NMR spectrometer for efficient production of payloads of hyperpolarized contrast agent and in situ quality assurance of the produced hyperpolarization. Key advantages of this hyperpolarizer include: (i) use of open-source software and hardware seamlessly allowing for replication and further improvement as well as readily customizable integration with other NMR spectrometers or MRI scanners (i.e., this is a multiplatform design), (ii) relatively low cost and robustness, and (iii) in situ detection capability and complete automation. The device performance is demonstrated by production of a dose (∼2-3 mL) of hyperpolarized (13)C-succinate with %P13C ∼ 28% and 30 mM concentration and (13)C-phospholactate at %P13C ∼ 15% and 25 mM concentration in aqueous medium. These contrast agents are used for ultrafast molecular imaging and spectroscopy at 4.7 and 0.0475 T. In particular, the conversion of hyperpolarized (13)C-phospholactate to (13)C-lactate in vivo is used here to demonstrate the feasibility of ultrafast multislice (13)C MRI after tail vein injection of hyperpolarized (13)C-phospholactate in mice. PMID:27478927

  12. Separation of extra- and intracellular metabolites using hyperpolarized 13C diffusion weighted MR

    NASA Astrophysics Data System (ADS)

    Koelsch, Bertram L.; Sriram, Renuka; Keshari, Kayvan R.; Leon Swisher, Christine; Van Criekinge, Mark; Sukumar, Subramaniam; Vigneron, Daniel B.; Wang, Zhen J.; Larson, Peder E. Z.; Kurhanewicz, John

    2016-09-01

    This work demonstrates the separation of extra- and intracellular components of glycolytic metabolites with diffusion weighted hyperpolarized 13C magnetic resonance spectroscopy. Using b-values of up to 15,000 s mm-2, a multi-exponential signal response was measured for hyperpolarized [1-13C] pyruvate and lactate. By fitting the fast and slow asymptotes of these curves, their extra- and intracellular weighted diffusion coefficients were determined in cells perfused in a MR compatible bioreactor. In addition to measuring intracellular weighted diffusion, extra- and intracellular weighted hyperpolarized 13C metabolites pools are assessed in real-time, including their modulation with inhibition of monocarboxylate transporters. These studies demonstrate the ability to simultaneously assess membrane transport in addition to enzymatic activity with the use of diffusion weighted hyperpolarized 13C MR. This technique could be an indispensible tool to evaluate the impact of microenvironment on the presence, aggressiveness and metastatic potential of a variety of cancers.

  13. Application of Good's buffers to pH imaging using hyperpolarized (13)C MRI.

    PubMed

    Flavell, Robert R; von Morze, Cornelius; Blecha, Joseph E; Korenchan, David E; Van Criekinge, Mark; Sriram, Renuka; Gordon, Jeremy W; Chen, Hsin-Yu; Subramaniam, Sukumar; Bok, Robert A; Wang, Zhen J; Vigneron, Daniel B; Larson, Peder E; Kurhanewicz, John; Wilson, David M

    2015-09-25

    N-(2-Acetamido)-2-aminoethanesulfonic acid (ACES), one of Good's buffers, was applied to pH imaging using hyperpolarized (13)C magnetic resonance spectroscopy. Rapid NMR- and MRI-based pH measurements were obtained by exploiting the sensitive pH-dependence of its (13)C chemical shift within the physiologic range.

  14. Optical hyperpolarization of 13C nuclear spins in nanodiamond ensembles

    NASA Astrophysics Data System (ADS)

    Chen, Q.; Schwarz, I.; Jelezko, F.; Retzker, A.; Plenio, M. B.

    2015-11-01

    Dynamical nuclear polarization holds the key for orders of magnitude enhancements of nuclear magnetic resonance signals which, in turn, would enable a wide range of novel applications in biomedical sciences. However, current implementations of DNP require cryogenic temperatures and long times for achieving high polarization. Here we propose and analyze in detail protocols that can achieve rapid hyperpolarization of 13C nuclear spins in randomly oriented ensembles of nanodiamonds at room temperature. Our protocols exploit a combination of optical polarization of electron spins in nitrogen-vacancy centers and the transfer of this polarization to 13C nuclei by means of microwave control to overcome the severe challenges that are posed by the random orientation of the nanodiamonds and their nitrogen-vacancy centers. Specifically, these random orientations result in exceedingly large energy variations of the electron spin levels that render the polarization and coherent control of the nitrogen-vacancy center electron spins as well as the control of their coherent interaction with the surrounding 13C nuclear spins highly inefficient. We address these challenges by a combination of an off-resonant microwave double resonance scheme in conjunction with a realization of the integrated solid effect which, together with adiabatic rotations of external magnetic fields or rotations of nanodiamonds, leads to a protocol that achieves high levels of hyperpolarization of the entire nuclear-spin bath in a randomly oriented ensemble of nanodiamonds even at room temperature. This hyperpolarization together with the long nuclear-spin polarization lifetimes in nanodiamonds and the relatively high density of 13C nuclei has the potential to result in a major signal enhancement in 13C nuclear magnetic resonance imaging and suggests functionalized and hyperpolarized nanodiamonds as a unique probe for molecular imaging both in vitro and in vivo.

  15. Transport and imaging of brute-force (13)C hyperpolarization.

    PubMed

    Hirsch, Matthew L; Smith, Bryce A; Mattingly, Mark; Goloshevsky, Artem G; Rosay, Melanie; Kempf, James G

    2015-12-01

    We demonstrate transport of hyperpolarized frozen 1-(13)C pyruvic acid from its site of production to a nearby facility, where a time series of (13)C images was acquired from the aqueous dissolution product. Transportability is tied to the hyperpolarization (HP) method we employ, which omits radical electron species used in other approaches that would otherwise relax away the HP before reaching the imaging center. In particular, we attained (13)C HP by 'brute-force', i.e., using only low temperature and high-field (e.g., T<∼2K and B∼14T) to pre-polarize protons to a large Boltzmann value (∼0.4% (1)H polarization). After polarizing the neat, frozen sample, ejection quickly (<1s) passed it through a low field (B<100G) to establish the (1)H pre-polarization spin temperature on (13)C via the process known as low-field thermal mixing (yielding ∼0.1% (13)C polarization). By avoiding polarization agents (a.k.a. relaxation agents) that are needed to hyperpolarize by the competing method of dissolution dynamic nuclear polarization (d-DNP), the (13)C relaxation time was sufficient to transport the sample for ∼10min before finally dissolving in warm water and obtaining a (13)C image of the hyperpolarized, dilute, aqueous product (∼0.01% (13)C polarization, a >100-fold gain over thermal signals in the 1T scanner). An annealing step, prior to polarizing the sample, was also key for increasing T1∼30-fold during transport. In that time, HP was maintained using only modest cryogenics and field (T∼60K and B=1.3T), for T1((13)C) near 5min. Much greater time and distance (with much smaller losses) may be covered using more-complete annealing and only slight improvements on transport conditions (e.g., yielding T1∼5h at 30K, 2T), whereas even intercity transfer is possible (T1>20h) at reasonable conditions of 6K and 2T. Finally, it is possible to increase the overall enhancement near d-DNP levels (i.e., 10(2)-fold more) by polarizing below 100mK, where nanoparticle

  16. Transport and imaging of brute-force 13C hyperpolarization

    NASA Astrophysics Data System (ADS)

    Hirsch, Matthew L.; Smith, Bryce A.; Mattingly, Mark; Goloshevsky, Artem G.; Rosay, Melanie; Kempf, James G.

    2015-12-01

    We demonstrate transport of hyperpolarized frozen 1-13C pyruvic acid from its site of production to a nearby facility, where a time series of 13C images was acquired from the aqueous dissolution product. Transportability is tied to the hyperpolarization (HP) method we employ, which omits radical electron species used in other approaches that would otherwise relax away the HP before reaching the imaging center. In particular, we attained 13C HP by 'brute-force', i.e., using only low temperature and high-field (e.g., T < ∼2 K and B ∼ 14 T) to pre-polarize protons to a large Boltzmann value (∼0.4% 1H polarization). After polarizing the neat, frozen sample, ejection quickly (<1 s) passed it through a low field (B < 100 G) to establish the 1H pre-polarization spin temperature on 13C via the process known as low-field thermal mixing (yielding ∼0.1% 13C polarization). By avoiding polarization agents (a.k.a. relaxation agents) that are needed to hyperpolarize by the competing method of dissolution dynamic nuclear polarization (d-DNP), the 13C relaxation time was sufficient to transport the sample for ∼10 min before finally dissolving in warm water and obtaining a 13C image of the hyperpolarized, dilute, aqueous product (∼0.01% 13C polarization, a >100-fold gain over thermal signals in the 1 T scanner). An annealing step, prior to polarizing the sample, was also key for increasing T1 ∼ 30-fold during transport. In that time, HP was maintained using only modest cryogenics and field (T ∼ 60 K and B = 1.3 T), for T1(13C) near 5 min. Much greater time and distance (with much smaller losses) may be covered using more-complete annealing and only slight improvements on transport conditions (e.g., yielding T1 ∼ 5 h at 30 K, 2 T), whereas even intercity transfer is possible (T1 > 20 h) at reasonable conditions of 6 K and 2 T. Finally, it is possible to increase the overall enhancement near d-DNP levels (i.e., 102-fold more) by polarizing below 100 mK, where

  17. Hyperpolarized (13)C MR imaging detects no lactate production in mutant IDH1 gliomas: Implications for diagnosis and response monitoring.

    PubMed

    Chaumeil, Myriam M; Radoul, Marina; Najac, Chloé; Eriksson, Pia; Viswanath, Pavithra; Blough, Michael D; Chesnelong, Charles; Luchman, H Artee; Cairncross, J Gregory; Ronen, Sabrina M

    2016-01-01

    Metabolic imaging of brain tumors using (13)C Magnetic Resonance Spectroscopy (MRS) of hyperpolarized [1-(13)C] pyruvate is a promising neuroimaging strategy which, after a decade of preclinical success in glioblastoma (GBM) models, is now entering clinical trials in multiple centers. Typically, the presence of GBM has been associated with elevated hyperpolarized [1-(13)C] lactate produced from [1-(13)C] pyruvate, and response to therapy has been associated with a drop in hyperpolarized [1-(13)C] lactate. However, to date, lower grade gliomas had not been investigated using this approach. The most prevalent mutation in lower grade gliomas is the isocitrate dehydrogenase 1 (IDH1) mutation, which, in addition to initiating tumor development, also induces metabolic reprogramming. In particular, mutant IDH1 gliomas are associated with low levels of lactate dehydrogenase A (LDHA) and monocarboxylate transporters 1 and 4 (MCT1, MCT4), three proteins involved in pyruvate metabolism to lactate. We therefore investigated the potential of (13)C MRS of hyperpolarized [1-(13)C] pyruvate for detection of mutant IDH1 gliomas and for monitoring of their therapeutic response. We studied patient-derived mutant IDH1 glioma cells that underexpress LDHA, MCT1 and MCT4, and wild-type IDH1 GBM cells that express high levels of these proteins. Mutant IDH1 cells and tumors produced significantly less hyperpolarized [1-(13)C] lactate compared to GBM, consistent with their metabolic reprogramming. Furthermore, hyperpolarized [1-(13)C] lactate production was not affected by chemotherapeutic treatment with temozolomide (TMZ) in mutant IDH1 tumors, in contrast to previous reports in GBM. Our results demonstrate the unusual metabolic imaging profile of mutant IDH1 gliomas, which, when combined with other clinically available imaging methods, could be used to detect the presence of the IDH1 mutation in vivo. PMID:27437179

  18. Metabolic Imaging in the Anesthetized Rat Brain Using Hyperpolarized [1-13C] Pyruvate and [1-13C] Ethyl Pyruvate

    PubMed Central

    Hurd, Ralph E.; Yen, Yi-Fen; Mayer, Dirk; Chen, Albert; Wilson, David; Kohler, Susan; Bok, Robert; Vigneron, Daniel; Kurhanewicz, John; Tropp, James; Spielman, Daniel; Pfefferbaum, Adolf

    2010-01-01

    Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1-13C]-ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and 13C spectroscopic imaging was used to compare the uptake of hyperpolarized [1-13C]-ethyl pyruvate relative to hyperpolarized [1-13C]-pyruvate into anesthetized rat brain. Hyperpolarized [1-13C]-ethyl pyruvate and [1-13C]-pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range-finding study. PMID:20432284

  19. Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-13C]butyrate and [1-13C]pyruvate

    PubMed Central

    Bastiaansen, Jessica A. M.; Merritt, Matthew E.; Comment, Arnaud

    2016-01-01

    Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) 13C magnetic resonance spectroscopy (MRS) has the unique ability to detect real-time metabolic changes in vivo due to its high sensitivity and specificity. Here a protocol using HP [1-13C]pyruvate and [1-13C]butyrate is used to measure carbohydrate versus fatty acid metabolism in vivo. Metabolic changes in fed and fasted Sprague Dawley rats (n = 36) were studied at 9.4 T after tail vein injections. Pyruvate and butyrate competed for acetyl-CoA production, as evidenced by significant changes in [13C]bicarbonate (−48%), [1-13C]acetylcarnitine (+113%), and [5-13C]glutamate (−63%), following fasting. Butyrate uptake was unaffected by fasting, as indicated by [1-13C]butyrylcarnitine. Mitochondrial pseudoketogenesis facilitated the labeling of the ketone bodies [1-13C]acetoacetate and [1-13C]β-hydroxybutyryate, without evidence of true ketogenesis. HP [1-13C]acetoacetate was increased in fasting (250%) but decreased during pyruvate co-injection (−82%). Combining HP 13C technology and co-administration of separate imaging agents enables noninvasive and simultaneous monitoring of both fatty acid and carbohydrate oxidation. This protocol illustrates a novel method for assessing metabolic flux through different enzymatic pathways simultaneously and enables mechanistic studies of the changing myocardial energetics often associated with disease. PMID:27150735

  20. Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-(13)C]butyrate and [1-(13)C]pyruvate.

    PubMed

    Bastiaansen, Jessica A M; Merritt, Matthew E; Comment, Arnaud

    2016-01-01

    Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) (13)C magnetic resonance spectroscopy (MRS) has the unique ability to detect real-time metabolic changes in vivo due to its high sensitivity and specificity. Here a protocol using HP [1-(13)C]pyruvate and [1-(13)C]butyrate is used to measure carbohydrate versus fatty acid metabolism in vivo. Metabolic changes in fed and fasted Sprague Dawley rats (n = 36) were studied at 9.4 T after tail vein injections. Pyruvate and butyrate competed for acetyl-CoA production, as evidenced by significant changes in [(13)C]bicarbonate (-48%), [1-(13)C]acetylcarnitine (+113%), and [5-(13)C]glutamate (-63%), following fasting. Butyrate uptake was unaffected by fasting, as indicated by [1-(13)C]butyrylcarnitine. Mitochondrial pseudoketogenesis facilitated the labeling of the ketone bodies [1-(13)C]acetoacetate and [1-(13)C]β-hydroxybutyryate, without evidence of true ketogenesis. HP [1-(13)C]acetoacetate was increased in fasting (250%) but decreased during pyruvate co-injection (-82%). Combining HP (13)C technology and co-administration of separate imaging agents enables noninvasive and simultaneous monitoring of both fatty acid and carbohydrate oxidation. This protocol illustrates a novel method for assessing metabolic flux through different enzymatic pathways simultaneously and enables mechanistic studies of the changing myocardial energetics often associated with disease. PMID:27150735

  1. In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-13C]glutamine

    NASA Astrophysics Data System (ADS)

    Cabella, C.; Karlsson, M.; Canapè, C.; Catanzaro, G.; Colombo Serra, S.; Miragoli, L.; Poggi, L.; Uggeri, F.; Venturi, L.; Jensen, P. R.; Lerche, M. H.; Tedoldi, F.

    2013-07-01

    Glutamine metabolism is, with its many links to oncogene expression, considered a crucial step in cancer metabolism and it is thereby a key target for alteration in cancer development. In particular, strong correlations have been reported between oncogene expression and expression and activity of the enzyme glutaminase. This mitochondrial enzyme, which is responsible for the deamidation of glutamine to form glutamate, is overexpressed in many tumour tissues. In animal models, glutaminase expression is correlated with tumour growth rate and it is readily possible to limit tumour growth by suppression of glutaminase activity. In principle, hyperpolarized 13C MR spectroscopy can provide insight to glutamine metabolism and should hence be a valuable tool to study changes in glutaminase activity as tumours progress. However, no such successful in vivo studies have been reported, even though several good biological models have been tested. This may, at least partly, be due to problems in preparing glutamine for hyperpolarization. This paper reports a new and improved preparation of hyperpolarized [5-13C]glutamine, which provides a highly sensitive 13C MR marker. With this preparation of hyperpolarized [5-13C]glutamine, glutaminase activity in vivo in a rat liver tumour was investigated. Moreover, this marker was also used to measure response to drug treatment in vitro in cancer cells. These examples of [5-13C]glutamine used in tumour models warrant the new preparation to allow metabolic studies with this conditionally essential amino acid.

  2. Hyperpolarized (13)C Magnetic Resonance and Its Use in Metabolic Assessment of Cultured Cells and Perfused Organs.

    PubMed

    Lumata, Lloyd; Yang, Chendong; Ragavan, Mukundan; Carpenter, Nicholas; DeBerardinis, Ralph J; Merritt, Matthew E

    2015-01-01

    Diseased tissue is often characterized by abnormalities in intermediary metabolism. Observing these alterations in situ may lead to an improved understanding of pathological processes and novel ways to monitor these processes noninvasively in human patients. Although (13)C is a stable isotope safe for use in animal models of disease as well as human subjects, its utility as a metabolic tracer has largely been limited to ex vivo analyses employing analytical techniques like mass spectrometry or nuclear magnetic resonance spectroscopy. Neither of these techniques is suitable for noninvasive metabolic monitoring, and the low abundance and poor gyromagnetic ratio of conventional (13)C make it a poor nucleus for imaging. However, the recent advent of hyperpolarization methods, particularly dynamic nuclear polarization (DNP), makes it possible to enhance the spin polarization state of (13)C by many orders of magnitude, resulting in a temporary amplification of the signal sufficient for monitoring kinetics of enzyme-catalyzed reactions in living tissue through magnetic resonance spectroscopy or magnetic resonance imaging. Here, we review DNP techniques to monitor metabolism in cultured cells, perfused hearts, and perfused livers, focusing on our experiences with hyperpolarized [1-(13)C]pyruvate. We present detailed approaches to optimize the DNP procedure, streamline biological sample preparation, and maximize detection of specific metabolic activities. We also discuss practical aspects in the choice of metabolic substrates for hyperpolarization studies and outline some of the current technical and conceptual challenges in the field, including efforts to use hyperpolarization to quantify metabolic rates in vivo.

  3. Multi-band frequency encoding method for metabolic imaging with hyperpolarized [1- 13C]pyruvate

    NASA Astrophysics Data System (ADS)

    von Morze, Cornelius; Reed, Galen; Shin, Peter; Larson, Peder E. Z.; Hu, Simon; Bok, Robert; Vigneron, Daniel B.

    2011-08-01

    A new method was developed for simultaneous spatial localization and spectral separation of multiple compounds based on a single echo, by designing the acquisition to place individual compounds in separate frequency encoding bands. This method was specially designed for rapid and robust metabolic imaging of hyperpolarized 13C substrates and their metabolic products, and was investigated in phantom studies and studies in normal mice and transgenic models of prostate cancer to provide rapid metabolic imaging of hyperpolarized [1- 13C]pyruvate and its metabolic products [1- 13C]lactate and [1- 13C]alanine at spatial resolutions up to 3 mm in-plane. Elevated pyruvate and lactate signals in the vicinity of prostatic tissues were observed in transgenic tumor mice. The multi-band frequency encoding technique enabled rapid metabolic imaging of hyperpolarized 13C compounds with important advantages over prior approaches, including less complicated acquisition and reconstruction methods.

  4. High-throughput hyperpolarized 13C metabolic investigations using a multi-channel acquisition system

    NASA Astrophysics Data System (ADS)

    Lee, Jaehyuk; Ramirez, Marc S.; Walker, Christopher M.; Chen, Yunyun; Yi, Stacey; Sandulache, Vlad C.; Lai, Stephen Y.; Bankson, James A.

    2015-11-01

    Magnetic resonance imaging and spectroscopy of hyperpolarized (HP) compounds such as [1-13C]-pyruvate have shown tremendous potential for offering new insight into disease and response to therapy. New applications of this technology in clinical research and care will require extensive validation in cells and animal models, a process that may be limited by the high cost and modest throughput associated with dynamic nuclear polarization. Relatively wide spectral separation between [1-13C]-pyruvate and its chemical endpoints in vivo are conducive to simultaneous multi-sample measurements, even in the presence of a suboptimal global shim. Multi-channel acquisitions could conserve costs and accelerate experiments by allowing acquisition from multiple independent samples following a single dissolution. Unfortunately, many existing preclinical MRI systems are equipped with only a single channel for broadband acquisitions. In this work, we examine the feasibility of this concept using a broadband multi-channel digital receiver extension and detector arrays that allow concurrent measurement of dynamic spectroscopic data from ex vivo enzyme phantoms, in vitro anaplastic thyroid carcinoma cells, and in vivo in tumor-bearing mice. Throughput and the cost of consumables were improved by up to a factor of four. These preliminary results demonstrate the potential for efficient multi-sample studies employing hyperpolarized agents.

  5. Kinetic modeling of hyperpolarized 13C 1-pyruvate metabolism in normal rats and TRAMP mice

    NASA Astrophysics Data System (ADS)

    Zierhut, Matthew L.; Yen, Yi-Fen; Chen, Albert P.; Bok, Robert; Albers, Mark J.; Zhang, Vickie; Tropp, Jim; Park, Ilwoo; Vigneron, Daniel B.; Kurhanewicz, John; Hurd, Ralph E.; Nelson, Sarah J.

    2010-01-01

    PurposeTo investigate metabolic exchange between 13C 1-pyruvate, 13C 1-lactate, and 13C 1-alanine in pre-clinical model systems using kinetic modeling of dynamic hyperpolarized 13C spectroscopic data and to examine the relationship between fitted parameters and dose-response. Materials and methodsDynamic 13C spectroscopy data were acquired in normal rats, wild type mice, and mice with transgenic prostate tumors (TRAMP) either within a single slice or using a one-dimensional echo-planar spectroscopic imaging (1D-EPSI) encoding technique. Rate constants were estimated by fitting a set of exponential equations to the dynamic data. Variations in fitted parameters were used to determine model robustness in 15 mm slices centered on normal rat kidneys. Parameter values were used to investigate differences in metabolism between and within TRAMP and wild type mice. ResultsThe kinetic model was shown here to be robust when fitting data from a rat given similar doses. In normal rats, Michaelis-Menten kinetics were able to describe the dose-response of the fitted exchange rate constants with a 13.65% and 16.75% scaled fitting error (SFE) for kpyr→lac and kpyr→ala, respectively. In TRAMP mice, kpyr→lac increased an average of 94% after up to 23 days of disease progression, whether the mice were untreated or treated with casodex. Parameters estimated from dynamic 13C 1D-EPSI data were able to differentiate anatomical structures within both wild type and TRAMP mice. ConclusionsThe metabolic parameters estimated using this approach may be useful for in vivo monitoring of tumor progression and treatment efficacy, as well as to distinguish between various tissues based on metabolic activity.

  6. In vivo hyperpolarized 13C MR spectroscopic imaging with 1H decoupling

    NASA Astrophysics Data System (ADS)

    Chen, Albert P.; Tropp, James; Hurd, Ralph E.; Van Criekinge, Mark; Carvajal, Lucas G.; Xu, Duan; Kurhanewicz, John; Vigneron, Daniel B.

    2009-03-01

    Application of 13C MRS in vivo on whole body MR system has been limited due to the low static field (and consequent low signal to noise ratio—SNR) of these scanners; thus there have been few reports of 1H decoupled 13C MRS in vivo using a clinical MR platform. The recent development of techniques to retain highly polarized spins in solution following DNP in a solid matrix has provided a mechanism to use endogenous pre-polarized 13C labeled substrates to study real time cellular metabolism in vivo with high SNR. In a recent in vivo hyperpolarized metabolic imaging study using 13C pyruvate, it has been demonstrated that the line shape (signal decay) of the resonances observed are greatly affected by JCH coupling in addition to inhomogeneous broadening. This study demonstrates the feasibility of improving hyperpolarized 13C metabolic imaging in vivo by incorporating 1H decoupling on a clinical whole body 3 T MR scanner. No reduction of T1 of a pre-polarized 13C substrate ([1- 13C] lactate) in solution was observed when 1H decoupling was applied with WALTZ16 sequence. Narrower linewidth for the [1- 13C] lactate resonance was observed in hyperpolarized 13C MRSI data in vivo with 1H decoupling.

  7. A method for simultaneous echo planar imaging of hyperpolarized 13C pyruvate and 13C lactate

    NASA Astrophysics Data System (ADS)

    Reed, Galen D.; Larson, Peder E. Z.; von Morze, Cornelius; Bok, Robert; Lustig, Michael; Kerr, Adam B.; Pauly, John M.; Kurhanewicz, John; Vigneron, Daniel B.

    2012-04-01

    A rapid echo planar imaging sequence for dynamic imaging of [1-13C] lactate and [1-13C] pyruvate simultaneously was developed. Frequency-based separation of these metabolites was achieved by spatial shifting in the phase-encoded direction with the appropriate choice of echo spacing. Suppression of the pyruvate-hydrate and alanine resonances is achieved through an optimized spectral-spatial RF waveform. Signal sampling efficiency as a function of pyruvate and lactate excitation angle was simulated using two site exchange models. Dynamic imaging is demonstrated in a transgenic mouse model, and phantom validations of the RF pulse frequency selectivity were performed.

  8. HYPERPOLARIZED 13C MAGNETIC RESONANCE AND ITS USE IN METABOLIC ASSESSMENT OF CULTURED CELLS AND PERFUSED ORGANS

    PubMed Central

    Lumata, Lloyd; Yang, Chendong; Ragavan, Mukundan; Carpenter, Nicholas; DeBerardinis, Ralph J.; Merritt, Matthew E.

    2016-01-01

    Diseased tissue is often characterized by abnormalities in intermediary metabolism. Observing these alterations in situ may lead to an improved understanding of pathological processes and novel ways to monitor these processes non-invasively in human patients. Although 13C is a stable isotope safe for use in animal models of disease as well as human subjects, its utility as a metabolic tracer has largely been limited to ex vivo analyses employing analytical techniques like mass spectrometry or nuclear magnetic resonance spectroscopy. Neither of these techniques is suitable for non-invasive metabolic monitoring, and the low abundance and poor gyromagnetic ratio of conventional 13C make it a poor nucleus for imaging. However, the recent advent of hyperpolarization methods, particularly dynamic nuclear polarization (DNP), make it possible to enhance the spin polarization state of 13C by many orders of magnitude, resulting in a temporary amplification of the signal sufficient for monitoring kinetics of enzyme-catalyzed reactions in living tissue through magnetic resonance spectroscopy or magnetic resonance imaging. Here we review DNP techniques to monitor metabolism in cultured cells, perfused hearts, and perfused livers, focusing on our experiences with hyperpolarized [1-13C]pyruvate. We present detailed approaches to optimize the DNP procedure, streamline biological sample preparation, and maximize detection of specific metabolic activities. We also discuss practical aspects in the choice of metabolic substrates for hyperpolarization studies, and outline some of the current technical and conceptual challenges in the field, including efforts to use hyperpolarization to quantify metabolic rates in vivo. PMID:26358902

  9. Novel Imaging Contrast Methods for Hyperpolarized 13 C Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Reed, Galen Durant

    Magnetic resonance imaging using hyperpolarized 13C-labeled small molecules has emerged as an extremely powerful tool for the in vivo monitoring of perfusion and metabolism. This work presents methods for improved imaging, parameter mapping, and image contrast generation for in vivo hyperpolarized 13C MRI. Angiography using hyperpolarized urea was greatly improved with a highly T2-weighted acquisition in combination with 15N labeling of the urea amide groups. This is due to the fact that the T2 of [13C]urea is strongly limited by the scalar coupling to the neighboring quadrupolar 14N. The long in vivo T2 values of [13C, 15N2]urea were utilized for sub-millimeter projection angiography using a contrast agent that could be safely injected in concentrations of 10-100 mM while still tolerated in patients with renal insufficiency. This study also presented the first method for in vivo T2 mapping of hyperpolarized 13C compounds. The in vivo T2 of urea was short in the blood and long within the kidneys. This persistent signal component was isolated to the renal filtrate, thus enabling for the first time direct detection of an imaging contrast agent undergoing glomerular filtration. While highly T2-weighted acquisitions select for molecules with short rotational correlation times, high diffusion weighting selects for those with the long translational correlation times. A specialized spin-echo EPI sequence was developed in order to generate highly diffusion-weighted hyperpolarized 13C images on a clinical MRI system operating within clinical peak- RF and gradient amplitude constraints. Low power adiabatic spin echo pulses were developed in order to generate a sufficiently large refocused bandwidth while maintaining low nominal power. This diffusion weighted acquisition gave enhanced tumor contrast-to-noise ratio when imaging [1-13C]lactate after infusion of [1-13C]pyruvate. Finally, the first in-man hyperpolarized 13C MRI clinical trial is discussed.

  10. The Feasibility of Assessing Branched-Chain Amino Acid Metabolism in Cellular Models of Prostate Cancer with Hyperpolarized [1-13C]-Ketoisocaproate

    PubMed Central

    Billingsley, Kelvin L.; Park, Jae Mo; Josan, Sonal; Hurd, Ralph; Mayer, Dirk; Spielman-Sun, Eleanor; Nishimura, Dwight G.; Brooks, James D.; Spielman, Daniel

    2014-01-01

    Recent advancements in the field of hyperpolarized 13C magnetic resonance spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis of metabolic pathways. These non-invasive methods have increasingly shown application in impacting disease diagnosis and have further been employed in mechanistic studies of disease onset and progression. Our goals were to investigate branched-chain aminotransferase (BCAT) activity in prostate cancer with a novel molecular probe, hyperpolarized [1-13C]-2-ketoisocaproate ([1-13C]-KIC), and explore the potential of branched-chain amino acid (BCAA) metabolism to serve as a biomarker. Using traditional spectrophotometric assays, BCAT enzymatic activities were determined in vitro for various sources of prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse and human cell lines). These preliminary studies indicated that low levels of BCAT activity were present in all models of prostate cancer but enzymatic levels are altered significantly in prostate cancer relative to healthy tissue. The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU-145) that exhibited levels of BCAA metabolism comparable to the human disease state. Hyperpolarized [1-13C]-KIC was administered to prostate cancer cell lines, and the conversion of [1-13C]-KIC to the metabolic product, [1-13C]-leucine ([1-13C]-Leu), could be monitored via hyperpolarized 13C MRS. PMID:24907854

  11. Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization

    PubMed Central

    Keshari, Kayvan R.; Wilson, David M.

    2014-01-01

    The study of transient chemical phenomena by conventional NMR has proved elusive, particularly for non-1H nuclei. For 13C, hyperpolarization using the dynamic nuclear polarization (DNP) technique has emerged as a powerful means to improve SNR. The recent development of rapid dissolution DNP methods has facilitated previously impossible in vitro and in vivo study of small molecules. This review presents the basics of the DNP technique, identification of appropriate DNP substrates, and approaches to increase hyperpolarized signal lifetimes. Also addressed are the biochemical events to which DNP-NMR has been applied, with descriptions of several probes that have met with in vivo success. PMID:24363044

  12. In Vivo Magnetic Resonance Spectroscopic Imaging of Hyperpolarized [1-13C] Pyruvate Metabolism in Rat Hepatocellular Carcinoma

    PubMed Central

    Darpolor, Moses M.; Yen, Yi-Fen; Chua, Mei-Sze; Xing, Lei; Clarke-Katzenberg, Regina H.; Shi, Wenfang; Mayer, Dirk; Josan, Sonal; Hurd, Ralph E.; Pfefferbaum, Adolf; Senadheera, Lasitha; So, Samuel; Hofmann, Lawrence V.; Glazer, Gary M.; Spielman, Daniel M.

    2010-01-01

    Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Most patients with HCC are diagnosed at an advanced stage, and no efficient marker exists for predicting prognosis and/or response(s) to therapy. We previously reported a high level of [1-13C] alanine in an orthotopic HCC using single-voxel hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy (MRS). In the present study, we implemented a 3D-magnetic resonance spectroscopic imaging (MRSI) sequence to investigate this potential hallmark of cellular metabolism in rat livers bearing HCC (N=7 buffalo rats). In addition, quantitative real-time PCR was used to determine the mRNA levels of lactate dehydrogenase A, NAD(P)H dehydrogenase quinone 1, and alanine transaminase. The enzymes levels were significantly higher in the tumor than the normal liver tissues within each rat, which is associated with the in vivo MRSI signal of [1-13C]alanine and [1-13C]lactate after a bolus intravenous injection of [1-13C]pyruvate. Histopathological analysis of these tumors confirms successful growth of HCC as a nodule in buffalo rats’ livers revealing malignancy and hyper-vascular architecture. More importantly, the results demonstrate that the metabolic fate of [1-13C]pyruvate conversion to [1-13C]alanine significantly supersedes that of [1-13C]pyruvate conversion to [1-13C]lactate potentially serving as a marker of HCC tumors. PMID:21674652

  13. In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding

    PubMed Central

    Schmidt, Rita; Laustsen, Christoffer; Dumez, Jean-Nicolas; Kettunen, Mikko I.; Serrao, Eva M.; Marco-Rius, Irene; Brindle, Kevin M.; Ardenkjaer-Larsen, Jan Henrik; Frydman, Lucio

    2016-01-01

    Hyperpolarized metabolic imaging is a growing field that has provided a tool for analyzing metabolism, particularly in cancer. Given the short life times of the hyperpolarized signal, fast and effective spectroscopic imaging methods compatible with dynamic metabolic characterizations are necessary. Several approaches have been customized for hyperpolarized 13C MRI, including CSI with a center-out k-space encoding, EPSI, and spectrally selective pulses in combination with spiral EPI acquisitions. Recent studies have described the potential of single-shot alternatives based on spatiotemporal encoding (SPEN) principles, to derive chemical-shift images within a sub-second period. By contrast to EPSI, SPEN does not require oscillating acquisition gradients to deliver chemical-shift information: its signal encodes both spatial as well as chemical shift information, at no extra cost in experimental complexity. SPEN MRI sequences with slice-selection and arbitrary excitation pulses can also be devised, endowing SPEN with the potential to deliver single-shot multi-slice chemical shift images, with a temporal resolution required for hyperpolarized dynamic metabolic imaging. The present work demonstrates this with initial in vivo results obtained from SPEN-based imaging of pyruvate and its metabolic products, after injection of hyperpolarized [1-13C]pyruvate. Multi-slice chemical-shift images of healthy rats were obtained at 4.7 T in the region of the kidney, and 4D (2D spatial, 1D spectral, 1D temporal) data sets were obtained at 7 T from a murine lymphoma tumor model. PMID:24486720

  14. In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding

    NASA Astrophysics Data System (ADS)

    Schmidt, Rita; Laustsen, Christoffer; Dumez, Jean-Nicolas; Kettunen, Mikko I.; Serrao, Eva M.; Marco-Rius, Irene; Brindle, Kevin M.; Ardenkjaer-Larsen, Jan Henrik; Frydman, Lucio

    2014-03-01

    Hyperpolarized metabolic imaging is a growing field that has provided a new tool for analyzing metabolism, particularly in cancer. Given the short life times of the hyperpolarized signal, fast and effective spectroscopic imaging methods compatible with dynamic metabolic characterizations are necessary. Several approaches have been customized for hyperpolarized 13C MRI, including CSI with a center-out k-space encoding, EPSI, and spectrally selective pulses in combination with spiral EPI acquisitions. Recent studies have described the potential of single-shot alternatives based on spatiotemporal encoding (SPEN) principles, to derive chemical-shift images within a sub-second period. By contrast to EPSI, SPEN does not require oscillating acquisition gradients to deliver chemical-shift information: its signal encodes both spatial as well as chemical shift information, at no extra cost in experimental complexity. SPEN MRI sequences with slice-selection and arbitrary excitation pulses can also be devised, endowing SPEN with the potential to deliver single-shot multi-slice chemical shift images, with a temporal resolution required for hyperpolarized dynamic metabolic imaging. The present work demonstrates this with initial in vivo results obtained from SPEN-based imaging of pyruvate and its metabolic products, after injection of hyperpolarized [1-13C]pyruvate. Multi-slice chemical-shift images of healthy rats were obtained at 4.7 T in the region of the kidney, and 4D (2D spatial, 1D spectral, 1D temporal) data sets were obtained at 7 T from a murine lymphoma tumor model.

  15. Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized (13) C MRSI.

    PubMed

    Düwel, Stephan; Durst, Markus; Gringeri, Concetta V; Kosanke, Yvonne; Gross, Claudia; Janich, Martin A; Haase, Axel; Glaser, Steffen J; Schwaiger, Markus; Schulte, Rolf F; Braren, Rickmer; Menzel, Marion I

    2016-07-01

    Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized (13) C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one-third of cancer-related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively (13) C-labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor-bearing rats before and after TAE. Two-dimensional, slice-selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three (13) C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and

  16. A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate.

    PubMed

    Daniels, Charlie J; McLean, Mary A; Schulte, Rolf F; Robb, Fraser J; Gill, Andrew B; McGlashan, Nicholas; Graves, Martin J; Schwaiger, Markus; Lomas, David J; Brindle, Kevin M; Gallagher, Ferdia A

    2016-04-01

    Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1-(13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data.

  17. Directly detected 55Mn MRI: Application to phantoms for human hyperpolarized 13C MRI development

    PubMed Central

    von Morze, Cornelius; Carvajal, Lucas; Reed, Galen D.; Swisher, Christine Leon; Tropp, James; Vigneron, Daniel B.

    2014-01-01

    In this work we demonstrate for the first time directly detected manganese-55 (55Mn) MRI using a clinical 3T MRI scanner designed for human hyperpolarized 13C clinical studies with no additional hardware modifications. Due to the similar frequency of the 55Mn and 13C resonances, the use of aqueous permanganate for large, signal-dense, and cost-effective “13C” MRI phantoms was investigated, addressing the clear need for new phantoms for these studies. Due to 100% natural abundance, higher intrinsic sensitivity, and favorable relaxation properties, 55Mn MRI of aqueous permanganate demonstrates dramatically increased sensitivity over typical 13C phantom MRI, at greatly reduced cost as compared with large 13C-enriched phantoms. A large sensitivity advantage (22-fold) was demonstrated. A cylindrical phantom (d= 8 cm) containing concentrated aqueous sodium permanganate (2.7M) was scanned rapidly by 55Mn MRI in a human head coil tuned for 13C, using a balanced SSFP acquisition. The requisite penetration of RF magnetic fields into concentrated permanganate was investigated by experiments and high frequency electromagnetic simulations, and found to be sufficient for 55Mn MRI with reasonably sized phantoms. A sub-second slice-selective acquisition yielded mean image SNR of ~60 at 0.5cm3 spatial resolution, distributed with minimum central signal ~40% of the maximum edge signal. We anticipate that permanganate phantoms will be very useful for testing HP 13C coils and methods designed for human studies. PMID:25179135

  18. Chemical Shift Separation with Controlled Aliasing for Hyperpolarized 13C Metabolic Imaging

    PubMed Central

    Shin, Peter J.; Larson, Peder E.Z.; Uecker, Martin; Reed, Galen D.; Kerr, Adam B.; Tropp, James; Ohliger, Michael A.; Nelson, Sarah J.; Pauly, John M.; Lustig, Michael; Vigneron, Daniel B.

    2014-01-01

    Purpose A chemical shift separation technique for hyperpolarized 13C metabolic imaging with high spatial and temporal resolution was developed. Specifically, a fast 3D pulse sequence and a reconstruction method were implemented to acquire signals from multiple 13C species simultaneously with subsequent separation into individual images. Methods A stack of flyback-EPI readouts and a set of multiband excitation RF pulses were designed to spatially modulate aliasing patterns of the acquired metabolite images, which translated the chemical shift separation problem into parallel imaging reconstruction problem. An eight-channel coil array was used for data acquisition and a parallel imaging method based on nonlinear inversion was developed to separate the aliased images. Results Simultaneous acquisitions of pyruvate and lactate in a phantom study and in vivo rat experiments were performed. The results demonstrated successful separation of the metabolite distributions into individual images having high spatial resolution. Conclusion This method demonstrated the ability to provide accelerated metabolite imaging in hyperpolarized 13C MR utilizing multi-channel coils, tailored readout, and specialized RF pulses. PMID:25298086

  19. Time-course metabolic changes in high-fat diet-induced obesity rats: A pilot study using hyperpolarized (13)C dynamic MRS.

    PubMed

    Kim, Gwang-Won; Ahn, Kyu-Youn; Kim, Yun-Hyeon; Jeong, Gwang-Woo

    2016-10-01

    The purpose of this study was to investigate the time-course metabolic changes based on hyperpolarized (13)C magnetic resonance spectroscopy (MRS) in high-fat diet (HFD)-induced obesity rats and the correlation between metabolic and serum enzyme levels. Sprague-Dawley rats were fed either HFD (60% fat) or normal diet (10% fat) for 6weeks. A HyperSense DNP was used to hyperpolarize [1-(13)C] pyruvic acid and the hyperpolarized (13)C MRS was examined every 2weeks in the course of 6weeks using a 3T GE MR750 scanner. The body weight of HFD-induced obese rats was significantly increased compared to normal rats at the 6th week after the onset of feeding (p=0.05). Simultaneously, the HFD-induced obese rats showed significantly increased levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and low-density lipoprotein (LDL)-cholesterol compared to normal rats (p≤0.05). In the dynamic (13)C MR spectra acquired at the 6th week, the obese rats showed significantly increased ratios of [1-(13)C] lactate/[1-(13)C] pyruvate and [1-(13)C] alanine/[1-(13)C] pyruvate (p=0.05). The (13)C spectral outcomes are positively correlated with the enzyme levels of ALT and LDH in the HFD-induced obesity. The [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as noninvasive biomarkers for the HFD-induced obesity.

  20. Development and testing of hyperpolarized 13C MR calibrationless parallel imaging

    NASA Astrophysics Data System (ADS)

    Feng, Yesu; Gordon, Jeremy W.; Shin, Peter J.; von Morze, Cornelius; Lustig, Michael; Larson, Peder E. Z.; Ohliger, Michael A.; Carvajal, Lucas; Tropp, James; Pauly, John M.; Vigneron, Daniel B.

    2016-01-01

    A calibrationless parallel imaging technique developed previously for 1H MRI was modified and tested for hyperpolarized 13C MRI for applications requiring large FOV and high spatial resolution. The technique was demonstrated with both retrospective and prospective under-sampled data acquired in phantom and in vivo rat studies. A 2-fold acceleration was achieved using a 2D symmetric EPI readout equipped with random blips on the phase encode dimension. Reconstructed images showed excellent qualitative agreement with fully sampled data. Further acceleration can be achieved using acquisition schemes that incorporate multi-dimensional under-sampling.

  1. Acute porcine renal metabolic effect of endogastric soft drink administration assessed with hyperpolarized [1‐13c]pyruvate

    PubMed Central

    Hansen, Esben Søvsø Szocska; Kjærgaard, Uffe; Bertelsen, Lotte Bonde; Ringgaard, Steffen; Stødkilde‐Jørgensen, Hans

    2015-01-01

    Purpose Our aim was to determine the quantitative reproducibility of metabolic breakdown products in the kidney following intravenous injection of hyperpolarized [1‐13C]pyruvate and secondly to investigate the metabolic effect on the pyruvate metabolism of oral sucrose load using dissolution dynamic nuclear polarization. By this technique, metabolic alterations in several different metabolic related diseases and their metabolic treatment responses can be accessed. Methods In four healthy pigs the lactate‐to‐pyruvate, alanine‐to‐pyruvate and bicarbonate‐to‐pyruvate ratio was measured following administration of regular cola and consecutive injections of hyperpolarized [1‐13C]pyruvate four times within an hour. Results The overall lactate‐to‐pyruvate metabolic profile changed significantly over one hour following an acute sucrose load leading to a significant rise in blood glucose. Conclusion The reproducibility of hyperpolarized magnetic resonance spectroscopy in the healthy pig kidney demonstrated a repeatability of more than 94% for all metabolites and, furthermore, that the pyruvate to lactate conversion and the blood glucose level is elevated following endogastric sucrose administration. Magn Reson Med 74:558–563, 2015. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. PMID:26014387

  2. Hyperpolarized 13C NMR lifetimes in the liquid-state: relating structures and T1 relaxation times

    NASA Astrophysics Data System (ADS)

    Parish, Christopher; Niedbalski, Peter; Hashami, Zohreh; Fidelino, Leila; Kovacs, Zoltan; Lumata, Lloyd

    Among the various attempts to solve the insensitivity problem in nuclear magnetic resonance (NMR), the physics-based technique dissolution dynamic nuclear polarization (DNP) is probably the most successful method of hyperpolarization or amplifying NMR signals. Using this technique, liquid-state NMR signal enhancements of several thousand-fold are expected for low-gamma nuclei such as carbon-13. The lifetimes of these hyperpolarized 13C NMR signals are directly related to their 13C spin-lattice relaxation times T1. Depending upon the 13C isotopic location, the lifetimes of hyperpolarized 13C compounds can range from a few seconds to minutes. In this study, we have investigated the hyperpolarized 13C NMR lifetimes of several 13C compounds with various chemical structures from glucose, acetate, citric acid, naphthalene to tetramethylallene and their deuterated analogs at 9.4 T and 25 deg C. Our results show that the 13C T1s of these compounds can range from a few seconds to more than 60 s at this field. Correlations between the chemical structures and T1 relaxation times will be discussed and corresponding implications of these results on 13C DNP experiments will be revealed. US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

  3. Multiband excitation pulses for hyperpolarized 13C dynamic chemical-shift imaging

    NASA Astrophysics Data System (ADS)

    Larson, Peder E. Z.; Kerr, Adam B.; Chen, Albert P.; Lustig, Michael S.; Zierhut, Matthew L.; Hu, Simon; Cunningham, Charles H.; Pauly, John M.; Kurhanewicz, John; Vigneron, Daniel B.

    2008-09-01

    Hyperpolarized 13C offers high signal-to-noise ratios for imaging metabolic activity in vivo, but care must be taken when designing pulse sequences because the magnetization cannot be recovered once it has decayed. It has a short lifetime, on the order of minutes, and gets used up by each RF excitation. In this paper, we present a new dynamic chemical-shift imaging method that uses specialized RF pulses designed to maintain most of the hyperpolarized substrate while providing adequate SNR for the metabolic products. These are multiband, variable flip angle, spectral-spatial RF pulses that use spectral selectivity to minimally excite the injected prepolarized 13C-pyruvate substrate. The metabolic products of lactate and alanine are excited with a larger flip angle to increase SNR. This excitation was followed by an RF amplitude insensitive double spin-echo and an echo-planar flyback spectral-spatial readout gradient. In vivo results in rats and mice are presented showing improvements over constant flip angle RF pulses. The metabolic products are observable for a longer window because the low pyruvate flip angle preserves magnetization, allowing for improved observation of spatially varying metabolic reactions.

  4. Transmembrane Exchange of Hyperpolarized 13C-Urea in Human Erythrocytes: Subminute Timescale Kinetic Analysis

    PubMed Central

    Pagès, Guilhem; Puckeridge, Max; Liangfeng, Guo; Tan, Yee Ling; Jacob, Chacko; Garland, Marc; Kuchel, Philip W.

    2013-01-01

    The rate of exchange of urea across the membranes of human erythrocytes (red blood cells) was quantified on the 1-s to 2-min timescale. 13C-urea was hyperpolarized and subjected to rapid dissolution and the previously reported (partial) resolution of 13C NMR resonances from the molecules inside and outside red blood cells in suspensions was observed. This enabled a stopped-flow type of experiment to measure the (initially) zero-trans transport of urea with sequential single-pulse 13C NMR spectra, every second for up to ∼2 min. Data were analyzed using Bayesian reasoning and a Markov chain Monte Carlo method with a set of simultaneous nonlinear differential equations that described nuclear magnetic relaxation combined with transmembrane exchange. Our results contribute to quantitative understanding of urea-exchange kinetics in the whole body; and the methodological approach is likely to be applicable to other cellular systems and tissues in vivo. PMID:24209840

  5. Application of Flow Sensitive Gradients for Improved Measures of Metabolism Using Hyperpolarized 13C MRI

    PubMed Central

    Gordon, Jeremy W.; Niles, David J.; Adamson, Erin B.; Johnson, Kevin M.; Fain, Sean B.

    2015-01-01

    Purpose To develop the use of bipolar gradients to suppress partial-volume and flow-related artifacts from macro-vascular, hyperpolarized spins. Methods Digital simulations were performed over a range of spatial resolutions and gradient strengths to determine the optimal bipolar gradient strength and duration to suppress flowing spins while minimizing signal loss from static tissue. In-vivo experiments were performed to determine the efficacy of this technique to suppress vascular signal in the study of hyperpolarized [1-13C]pyruvate renal metabolism. Results Digital simulations showed that in the absence of bipolar gradients, partial-volume artifacts from the vasculature were still present, causing underestimation of the apparent reaction rate of pyruvate to lactate (kP). The addition of a bipolar gradient with b = 32 s/mm2 sufficiently suppressed the vascular signal without a substantial decrease in signal from static tissue. In-vivo results corroborate digital simulations, with similar peak lactate SNR but substantially different kP in the presence of bipolar gradients. Conclusion The proposed approach suppresses signal from flowing spins while minimizing signal loss from static tissue, removing contaminating signal from the vasculature and increasing kinetic modeling accuracy without substantially sacrificing SNR or temporal resolution. PMID:25951611

  6. Hyperpolarized 13C urea relaxation mechanism reveals renal changes in diabetic nephropathy

    PubMed Central

    Stokholm Nørlinger, Thomas; Christoffer Hansen, David; Qi, Haiyun; Mose Nielsen, Per; Bonde Bertelsen, Lotte; Henrik Ardenkjaer‐Larsen, Jan; Stødkilde Jørgensen, Hans

    2015-01-01

    Purpose Our aim was to assess a novel 13C radial fast spin echo golden ratio single shot method for interrogating early renal changes in the diabetic kidney, using hyperpolarized (HP) [13C,15N2]urea as a T2 relaxation based contrast bio‐probe. Methods A novel HP 13C MR contrast experiment was conducted in a group of streptozotocin type‐1 diabetic rat model and age matched controls. Results A significantly different relaxation time (P = 0.004) was found in the diabetic kidney (0.49 ± 0.03 s) compared with the controls (0.64 ± 0.02 s) and secondly, a strong correlation between the blood oxygen saturation level and the relaxation times were observed in the healthy controls. Conclusion HP [13C,15N2]urea apparent T2 mapping may be a useful for interrogating local renal pO2 status and renal tissue alterations. Magn Reson Med, 2015. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. Magn Reson Med 75:515–518, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID:26584247

  7. Hyperpolarized [1,3-13C2 ]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer.

    PubMed

    Jensen, Pernille R; Serra, Sonia Colombo; Miragoli, Luigi; Karlsson, Magnus; Cabella, Claudia; Poggi, Luisa; Venturi, Luca; Tedoldi, Fabio; Lerche, Mathilde H

    2015-02-15

    An increased prevalence of liver diseases such as hepatitis C and nonalcoholic fatty liver results in an augmented incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC). HCC is most often found in the cirrhotic liver and it can therefore be challenging to rely on anatomical information alone when diagnosing HCC. Valuable information on specific cellular metabolism can be obtained with high sensitivity thanks to an emerging magnetic resonance (MR) technique that uses 13C labeled hyperpolarized molecules. Our interest was to explore potential new high contrast metabolic markers of HCC using hyperpolarized 13C-MR. This work led to the identification of a class of substrates, low molecular weight ethyl-esters, which showed high specificity for carboxyl esterases and proved in many cases to possess good properties for signal enhancement. In particular, hyperpolarized [1,3-13C2 ]ethyl acetoacetate (EAA) was shown to provide a metabolic fingerprint of HCC. Using this substrate a liver cancer implanted in rats was diagnosed as a consequence of an ∼4 times higher metabolic substrate-to-product ratio than in the surrounding healthy tissue, (p=0.009). Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized 13C-MR marker. This could be appreciated by the signal-to-noise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state-of-the-art hyperpolarized substrate, [1-13C]pyruvate. Also, the contrast-to-noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1-13C]pyruvate.

  8. Fast dynamic 3D MR spectroscopic imaging with compressed sensing and multiband excitation pulses for hyperpolarized 13C studies.

    PubMed

    Larson, Peder E Z; Hu, Simon; Lustig, Michael; Kerr, Adam B; Nelson, Sarah J; Kurhanewicz, John; Pauly, John M; Vigneron, Daniel B

    2011-03-01

    Hyperpolarized 13C MR spectroscopic imaging can detect not only the uptake of the pre-polarized molecule but also its metabolic products in vivo, thus providing a powerful new method to study cellular metabolism. Imaging the dynamic perfusion and conversion of these metabolites provides additional tissue information but requires methods for efficient hyperpolarization usage and rapid acquisitions. In this work, we have developed a time-resolved 3D MR spectroscopic imaging method for acquiring hyperpolarized 13C data by combining compressed sensing methods for acceleration and multiband excitation pulses to efficiently use the magnetization. This method achieved a 2 sec temporal resolution with full volumetric coverage of a mouse, and metabolites were observed for up to 60 sec following injection of hyperpolarized [1-(13)C]-pyruvate. The compressed sensing acquisition used random phase encode gradient blips to create a novel random undersampling pattern tailored to dynamic MR spectroscopic imaging with sampling incoherency in four (time, frequency, and two spatial) dimensions. The reconstruction was also tailored to dynamic MR spectroscopic imaging by applying a temporal wavelet sparsifying transform to exploit the inherent temporal sparsity. Customized multiband excitation pulses were designed with a lower flip angle for the [1-(13)C]-pyruvate substrate given its higher concentration than its metabolic products ([1-(13)C]-lactate and [1-(13)C]-alanine), thus using less hyperpolarization per excitation. This approach has enabled the monitoring of perfusion and uptake of the pyruvate, and the conversion dynamics to lactate and alanine throughout a volume with high spatial and temporal resolution. PMID:20939089

  9. Fast Dynamic 3D MRSI with Compressed Sensing and Multiband Excitation Pulses for Hyperpolarized 13C Studies

    PubMed Central

    Larson, Peder E. Z.; Hu, Simon; Lustig, Michael; Kerr, Adam B.; Nelson, Sarah J.; Kurhanewicz, John; Pauly, John M.; Vigneron, Daniel B.

    2010-01-01

    Hyperpolarized 13C MRSI can detect not only the uptake of the pre-polarized molecule but also its metabolic products in vivo, thus providing a powerful new method to study cellular metabolism. Imaging the dynamic perfusion and conversion of these metabolites provides additional tissue information but requires methods for efficient hyperpolarization usage and rapid acquisitions. In this work, we have developed a time-resolved 3D MRSI method for acquiring hyperpolarized 13C data by combining compressed sensing methods for acceleration and multiband excitation pulses to efficiently use the magnetization. This method achieved a 2 sec temporal resolution with full volumetric coverage of a mouse, and metabolites were observed for up to 60 sec following injection of hyperpolarized [1-13C]-pyruvate. The compressed sensing acquisition used random phase encode gradient blips to create a novel random undersampling pattern tailored to dynamic MRSI with sampling incoherency in four (time, frequency and two spatial) dimensions. The reconstruction was also tailored to dynamic MRSI by applying a temporal wavelet sparsifying transform in order to exploit the inherent temporal sparsity. Customized multiband excitation pulses were designed with a lower flip angle for the [1-13C]-pyruvate substrate given its higher concentration than its metabolic products ([1-13C]-lactate and [1-13C]-alanine), thus using less hyperpolarization per excitation. This approach has enabled the monitoring of perfusion and uptake of the pyruvate, and the conversion dynamics to lactate and alanine throughout a volume with high spatial and temporal resolution. PMID:20939089

  10. Production and NMR signal optimization of hyperpolarized 13C-labeled amino acids

    NASA Astrophysics Data System (ADS)

    Parish, Christopher; Niedbalski, Peter; Ferguson, Sarah; Kiswandhi, Andhika; Lumata, Lloyd

    Amino acids are targeted nutrients for consumption by cancers to sustain their rapid growth and proliferation. 13C-enriched amino acids are important metabolic tracers for cancer diagnostics using nuclear magnetic resonance (NMR) spectroscopy. Despite this diagnostic potential, 13C NMR of amino acids however is hampered by the inherently low NMR sensitivity of the 13C nuclei. In this work, we have employed a physics technique known as dynamic nuclear polarization (DNP) to enhance the NMR signals of 13C-enriched amino acids. DNP works by transferring the high polarization of electrons to the nuclear spins via microwave irradiation at low temperature and high magnetic field. Using a fast dissolution method in which the frozen polarized samples are dissolved rapidly with superheated water, injectable solutions of 13C-amino acids with highly enhanced NMR signals (by at least 5,000-fold) were produced at room temperature. Factors that affect the NMR signal enhancement levels such as the choice of free radical polarizing agents and sample preparation will be discussed along with the thermal mixing physics model of DNP. The authors would like to acknowledge the support by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

  11. Monitoring tumor response of prostate cancer to radiation therapy by multi-parametric 1H and hyperpolarized 13C magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Vickie Yi

    Radiation therapy is one of the most common curative therapies for patients with localized prostate cancer, but despite excellent success rates, a significant number of patients suffer post- treatment cancer recurrence. The accurate characterization of early tumor response remains a major challenge for the clinical management of these patients. Multi-parametric MRI/1H MR spectroscopy imaging (MRSI) has been shown to increase the diagnostic performance in evaluating the effectiveness of radiation therapy. 1H MRSI can detect altered metabolic profiles in cancerous tissue. In this project, the concentrations of prostate metabolites from snap-frozen biopsies of recurrent cancer after failed radiation therapy were correlated with histopathological findings to identify quantitative biomarkers that predict for residual aggressive versus indolent cancer. The total choline to creatine ratio was significantly higher in recurrent aggressive versus indolent cancer, suggesting that use of a higher threshold tCho/Cr ratio in future in vivo 1H MRSI studies could improve the selection and therapeutic planning for patients after failed radiation therapy. Varying radiation doses may cause a diverse effect on prostate cancer micro-environment and metabolism, which could hold the key to improving treatment protocols for individual patients. The recent development and clinical translation of hyperpolarized 13C MRI have provided the ability to monitor both changes in the tumor micro-environment and its metabolism using a multi-probe approach, [1-13C]pyruvate and 13C urea, combined with 1H Multi-parametric MRI. In this thesis, hyperpolarized 13C MRI, 1H dynamic contrast enhancement, and diffusion weighted imaging were used to identify early radiation dose response in a transgenic prostate cancer model. Hyperpolarized pyruvate to lactate metabolism significantly decreased in a dose dependent fashion by 1 day after radiation therapy, prior to any changes observed using 1H DCE and diffusion

  12. Effects of fasting on serial measurements of hyperpolarized [1-(13) C]pyruvate metabolism in tumors.

    PubMed

    Serrao, Eva M; Rodrigues, Tiago B; Gallagher, Ferdia A; Kettunen, Mikko I; Kennedy, Brett W C; Vowler, Sarah L; Burling, Keith A; Brindle, Kevin M

    2016-08-01

    Imaging of the metabolism of hyperpolarized [1-(13) C]pyruvate has shown considerable promise in preclinical studies in oncology, particularly for the assessment of early treatment response. The repeatability of measurements of (13) C label exchange between pyruvate and lactate was determined in a murine lymphoma model in fasted and non-fasted animals. The fasted state showed lower intra-individual variability, although the [1-(13) C]lactate/[1-(13) C]pyruvate signal ratio was significantly greater in fasted than in non-fasted mice, which may be explained by the higher tumor lactate concentrations in fasted animals. These results indicate that the fasted state may be preferable for the measurement of (13) C label exchange between pyruvate and lactate, as it reduces the variability and therefore should make it easier to detect the effects of therapy. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID:27309986

  13. Effects of fasting on serial measurements of hyperpolarized [1‐13C]pyruvate metabolism in tumors

    PubMed Central

    Serrao, Eva M.; Rodrigues, Tiago B.; Gallagher, Ferdia A.; Kettunen, Mikko I.; Kennedy, Brett W. C.; Vowler, Sarah L.; Burling, Keith A.

    2016-01-01

    Imaging of the metabolism of hyperpolarized [1‐13C]pyruvate has shown considerable promise in preclinical studies in oncology, particularly for the assessment of early treatment response. The repeatability of measurements of 13C label exchange between pyruvate and lactate was determined in a murine lymphoma model in fasted and non‐fasted animals. The fasted state showed lower intra‐individual variability, although the [1‐13C]lactate/[1‐13C]pyruvate signal ratio was significantly greater in fasted than in non‐fasted mice, which may be explained by the higher tumor lactate concentrations in fasted animals. These results indicate that the fasted state may be preferable for the measurement of 13C label exchange between pyruvate and lactate, as it reduces the variability and therefore should make it easier to detect the effects of therapy. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID:27309986

  14. Fast volumetric imaging of ethanol metabolism in rat liver with hyperpolarized [1-13C]-pyruvate

    PubMed Central

    Josan, Sonal; Spielman, Daniel; Yen, Yi-Fen; Hurd, Ralph; Pfefferbaum, Adolf; Mayer, Dirk

    2012-01-01

    Rapid, volumetric imaging of hyperpolarized 13C compounds allows the real time measurement of metabolic activity and can be useful in distinguishing between normal and diseased tissues. This work extends a fast 2D under-sampled spiral magnetic resonance spectroscopic imaging (MRSI) sequence to provide volumetric coverage, acquiring a 16×16×12 matrix with a nominal 5 mm isotropic resolution in 4.5 s. The rapid acquisition enables a high temporal resolution for dynamic imaging. This dynamic 3D MRSI method was used to investigate hyperpolarized [1-13C]-pyruvate metabolism modulated by the administration of ethanol in rat liver. A significant increase in the pyruvate to lactate conversion was observed in the liver due to the greater availability of NADH from ethanol metabolism. PMID:22331837

  15. High Resolution 13C MRI With Hyperpolarized Urea: In Vivo T2 Mapping and 15N Labeling Effects

    PubMed Central

    Reed, Galen D.; von Morze, Cornelius; Bok, Robert; Koelsch, Bertram L.; Van Criekinge, Mark; Smith, Kenneth J.; Shang, Hong; Larson, Peder E. Z.; Kurhanewicz, John; Vigneron, Daniel B.

    2014-01-01

    13C steady state free precession (SSFP) magnetic resonance imaging and effective spin-spin relaxation time (T2) mapping were performed using hyperpolarized [13C] urea and [13C, 15N2] urea injected intravenously in rats. 15N labeling gave large T2 increases both in solution and in vivo due to the elimination of a strong scalar relaxation pathway. The T2 increase was pronounced in the kidney, with [13C, 15N2] urea giving T2 values of 6.3±1.3 s in the cortex and medulla, and 11±2 s in the renal pelvis. The measured T2 in the aorta was 1.3±0.3 s. [13C] urea showed shortened T2 values in the kidney of 0.23±0.03 s compared to 0.28±0.03 s measured in the aorta. The enhanced T2 of [13C, 15N2] urea was utilized to generate large signal enhancement by SSFP acquisitions with flip angles approaching the fully refocused regime. Projection images at 0.94 mm in-plane resolution were acquired with both urea isotopes, with [13C, 15N2] urea giving a greater than four-fold increase in signal-to-noise ratio [13C] over urea. PMID:24235273

  16. Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized (13) C-Labeled Molecular Probe.

    PubMed

    Nishihara, Tatsuya; Yoshihara, Hikari A I; Nonaka, Hiroshi; Takakusagi, Yoichi; Hyodo, Fuminori; Ichikawa, Kazuhiro; Can, Emine; Bastiaansen, Jessica A M; Takado, Yuhei; Comment, Arnaud; Sando, Shinsuke

    2016-08-26

    The γ-glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ-Glu-[1-(13) C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) (13) C magnetic resonance (MR). The properties of γ-Glu-[1-(13) C]Gly are suitable for in vivo HP (13) C metabolic analysis since the chemical shift between γ-Glu-[1-(13) C]Gly and its metabolic product, [1-(13) C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2 O at 9.4 T). We also demonstrate that γ-Glu-[1-(13) C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin. PMID:27483206

  17. Localized in vivo13C NMR spectroscopy of the brain

    PubMed Central

    Gruetter, Rolf; Adriany, Gregor; Choi, In-Young; Henry, Pierre-Gilles; Lei, Hongxia; Öz, Gülin

    2006-01-01

    Localized 13C NMR spectroscopy provides a new investigative tool for studying cerebral metabolism. The application of 13C NMR spectroscopy to living intact humans and animals presents the investigator with a number of unique challenges. This review provides in the first part a tutorial insight into the ingredients required for achieving a successful implementation of localized 13C NMR spectroscopy. The difficulties in establishing 13C NMR are the need for decoupling of the one-bond 13C–1H heteronuclear J coupling, the large chemical shift range, the low sensitivity and the need for localization of the signals. The methodological consequences of these technical problems are discussed, particularly with respect to (a) RF front-end considerations, (b) localization methods, (c) the low sensitivity, and (d) quantification methods. Lastly, some achievements of in vivo localized 13C NMR spectroscopy of the brain are reviewed, such as: (a) the measurement of brain glutamine synthesis and the feasibility of quantifying glutamatergic action in the brain; (b) the demonstration of significant anaplerotic fluxes in the brain; (c) the demonstration of a highly regulated malate-aspartate shuttle in brain energy metabolism and isotope flux; (d) quantification of neuronal and glial energy metabolism; and (e) brain glycogen metabolism in hypoglycemia in rats and humans. We conclude that the unique and novel insights provided by 13C NMR spectroscopy have opened many new research areas that are likely to improve the understanding of brain carbohydrate metabolism in health and disease. PMID:14679498

  18. Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-(13)C2]pyruvate in vivo.

    PubMed

    Chen, Albert P; Hurd, Ralph E; Schroeder, Marie A; Lau, Angus Z; Gu, Yi-ping; Lam, Wilfred W; Barry, Jennifer; Tropp, James; Cunningham, Charles H

    2012-02-01

    (13)C MR spectroscopy studies performed on hearts ex vivo and in vivo following perfusion of prepolarized [1-(13)C]pyruvate have shown that changes in pyruvate dehydrogenase (PDH) flux may be monitored non-invasively. However, to allow investigation of Krebs cycle metabolism, the (13)C label must be placed on the C2 position of pyruvate. Thus, the utilization of either C1 or C2 labeled prepolarized pyruvate as a tracer can only afford a partial view of cardiac pyruvate metabolism in health and disease. If the prepolarized pyruvate molecules were labeled at both C1 and C2 positions, then it would be possible to observe the downstream metabolites that were the results of both PDH flux ((13)CO(2) and H(13)CO(3)(-)) and Krebs cycle flux ([5-(13)C]glutamate) with a single dose of the agent. Cardiac pH could also be monitored in the same experiment, but adequate SNR of the (13)CO(2) resonance may be difficult to obtain in vivo. Using an interleaved selective RF pulse acquisition scheme to improve (13)CO(2) detection, the feasibility of using dual-labeled hyperpolarized [1,2-(13)C(2)]pyruvate as a substrate for dynamic cardiac metabolic MRS studies to allow simultaneous investigation of PDH flux, Krebs cycle flux and pH, was demonstrated in vivo.

  19. Increasing Pyruvate Dehydrogenase Flux as a Treatment for Diabetic Cardiomyopathy: A Combined 13C Hyperpolarized Magnetic Resonance and Echocardiography Study

    PubMed Central

    Le Page, Lydia M.; Rider, Oliver J.; Lewis, Andrew J.; Ball, Vicky; Clarke, Kieran; Johansson, Edvin; Carr, Carolyn A.; Heather, Lisa C.; Tyler, Damian J.

    2015-01-01

    Although diabetic cardiomyopathy is widely recognised, there are no specific treatments available. Altered myocardial substrate selection has emerged as a candidate mechanism behind the development of cardiac dysfunction in diabetes. As pyruvate dehydrogenase (PDH) activity appears central to the balance of substrate utilisation, we aimed to investigate the relationship between PDH flux and myocardial function in a rodent model of type-II diabetes and to explore whether or not increasing PDH flux, with dichloroacetate, would restore the balance of substrate utilisation and improve cardiac function. All animals underwent in vivo hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy and echocardiography to assess cardiac PDH flux and function respectively. Diabetic animals showed significantly higher blood glucose (10.8±0.7mM vs 8.4±0.5mM), lower PDH flux (0.005±0.001s−1 vs 0.017±0.002s−1) and significantly impaired diastolic function (E/E’ 12.2±0.8 vs 20±2) in keeping with early diabetic cardiomyopathy. Twenty-eight days treatment with dichloroacetate restored PDH flux to normal levels (0.018±0.002s−1), reversed diastolic dysfunction (E/E’ 14±1) and normalized blood glucose (7.5±0.7mM). Treatment of diabetes with dichloroacetate therefore restored the balance of myocardial substrate selection, reversed diastolic dysfunction and normalised blood glucose levels. This suggests that PDH modulation could be a novel therapy for the treatment and/or prevention of diabetic cardiomyopathy. PMID:25795215

  20. Local and bulk (13)C hyperpolarization in nitrogen-vacancy-centred diamonds at variable fields and orientations.

    PubMed

    Álvarez, Gonzalo A; Bretschneider, Christian O; Fischer, Ran; London, Paz; Kanda, Hisao; Onoda, Shinobu; Isoya, Junichi; Gershoni, David; Frydman, Lucio

    2015-01-01

    Polarizing nuclear spins is of fundamental importance in biology, chemistry and physics. Methods for hyperpolarizing (13)C nuclei from free electrons in bulk usually demand operation at cryogenic temperatures. Room temperature approaches targeting diamonds with nitrogen-vacancy centres could alleviate this need; however, hitherto proposed strategies lack generality as they demand stringent conditions on the strength and/or alignment of the magnetic field. We report here an approach for achieving efficient electron-(13)C spin-alignment transfers, compatible with a broad range of magnetic field strengths and field orientations with respect to the diamond crystal. This versatility results from combining coherent microwave- and incoherent laser-induced transitions between selected energy states of the coupled electron-nuclear spin manifold. (13)C-detected nuclear magnetic resonance experiments demonstrate that this hyperpolarization can be transferred via first-shell or via distant (13)Cs throughout the nuclear bulk ensemble. This method opens new perspectives for applications of diamond nitrogen-vacancy centres in nuclear magnetic resonance, and in quantum information processing. PMID:26404169

  1. Local and bulk 13C hyperpolarization in nitrogen-vacancy-centred diamonds at variable fields and orientations

    PubMed Central

    Álvarez, Gonzalo A.; Bretschneider, Christian O.; Fischer, Ran; London, Paz; Kanda, Hisao; Onoda, Shinobu; Isoya, Junichi; Gershoni, David; Frydman, Lucio

    2015-01-01

    Polarizing nuclear spins is of fundamental importance in biology, chemistry and physics. Methods for hyperpolarizing 13C nuclei from free electrons in bulk usually demand operation at cryogenic temperatures. Room temperature approaches targeting diamonds with nitrogen-vacancy centres could alleviate this need; however, hitherto proposed strategies lack generality as they demand stringent conditions on the strength and/or alignment of the magnetic field. We report here an approach for achieving efficient electron-13C spin-alignment transfers, compatible with a broad range of magnetic field strengths and field orientations with respect to the diamond crystal. This versatility results from combining coherent microwave- and incoherent laser-induced transitions between selected energy states of the coupled electron–nuclear spin manifold. 13C-detected nuclear magnetic resonance experiments demonstrate that this hyperpolarization can be transferred via first-shell or via distant 13Cs throughout the nuclear bulk ensemble. This method opens new perspectives for applications of diamond nitrogen-vacancy centres in nuclear magnetic resonance, and in quantum information processing. PMID:26404169

  2. Modeling non-linear kinetics of hyperpolarized [1-(13)C] pyruvate in the crystalloid-perfused rat heart.

    PubMed

    Mariotti, E; Orton, M R; Eerbeek, O; Ashruf, J F; Zuurbier, C J; Southworth, R; Eykyn, T R

    2016-04-01

    Hyperpolarized (13)C MR measurements have the potential to display non-linear kinetics. We have developed an approach to describe possible non-first-order kinetics of hyperpolarized [1-(13)C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second-order model for conversion of [1-(13)C] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second-order modeling yielded significantly improved fits of pyruvate-bicarbonate kinetics compared with the more traditionally used first-order model and suggested time-dependent decreases in pyruvate-bicarbonate flux. Second-order modeling gave time-dependent changes in forward and reverse reaction kinetics of pyruvate-lactate exchange and pyruvate-alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first-order model. The mechanism giving rise to second-order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD(+) (the cofactor for PDH), consistent with the non-linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. PMID:26777799

  3. Modeling non‐linear kinetics of hyperpolarized [1‐13C] pyruvate in the crystalloid‐perfused rat heart

    PubMed Central

    Mariotti, E.; Orton, M. R.; Eerbeek, O.; Ashruf, J. F.; Zuurbier, C. J.; Southworth, R.

    2016-01-01

    Hyperpolarized 13C MR measurements have the potential to display non‐linear kinetics. We have developed an approach to describe possible non‐first‐order kinetics of hyperpolarized [1‐13C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second‐order model for conversion of [1‐13C] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second‐order modeling yielded significantly improved fits of pyruvate–bicarbonate kinetics compared with the more traditionally used first‐order model and suggested time‐dependent decreases in pyruvate–bicarbonate flux. Second‐order modeling gave time‐dependent changes in forward and reverse reaction kinetics of pyruvate–lactate exchange and pyruvate–alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first‐order model. The mechanism giving rise to second‐order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD+ (the cofactor for PDH), consistent with the non‐linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID:26777799

  4. Low-field thermal mixing in [1-(13)C] pyruvic acid for brute-force hyperpolarization.

    PubMed

    Peat, David T; Hirsch, Matthew L; Gadian, David G; Horsewill, Anthony J; Owers-Bradley, John R; Kempf, James G

    2016-07-28

    We detail the process of low-field thermal mixing (LFTM) between (1)H and (13)C nuclei in neat [1-(13)C] pyruvic acid at cryogenic temperatures (4-15 K). Using fast-field-cycling NMR, (1)H nuclei in the molecule were polarized at modest high field (2 T) and then equilibrated with (13)C nuclei by fast cycling (∼300-400 ms) to a low field (0-300 G) that activates thermal mixing. The (13)C NMR spectrum was recorded after fast cycling back to 2 T. The (13)C signal derives from (1)H polarization via LFTM, in which the polarized ('cold') proton bath contacts the unpolarised ('hot') (13)C bath at a field so low that Zeeman and dipolar interactions are similar-sized and fluctuations in the latter drive (1)H-(13)C equilibration. By varying mixing time (tmix) and field (Bmix), we determined field-dependent rates of polarization transfer (1/τ) and decay (1/T1m) during mixing. This defines conditions for effective mixing, as utilized in 'brute-force' hyperpolarization of low-γ nuclei like (13)C using Boltzmann polarization from nearby protons. For neat pyruvic acid, near-optimum mixing occurs for tmix∼ 100-300 ms and Bmix∼ 30-60 G. Three forms of frozen neat pyruvic acid were tested: two glassy samples, (one well-deoxygenated, the other O2-exposed) and one sample pre-treated by annealing (also well-deoxygenated). Both annealing and the presence of O2 are known to dramatically alter high-field longitudinal relaxation (T1) of (1)H and (13)C (up to 10(2)-10(3)-fold effects). Here, we found smaller, but still critical factors of ∼(2-5)× on both τ and T1m. Annealed, well-deoxygenated samples exhibit the longest time constants, e.g., τ∼ 30-70 ms and T1m∼ 1-20 s, each growing vs. Bmix. Mixing 'turns off' for Bmix > ∼100 G. That T1m≫τ is consistent with earlier success with polarization transfer from (1)H to (13)C by LFTM. PMID:27362505

  5. SU-E-QI-11: Measurement of Renal Pyruvate-To-Lactate Exchange with Hyperpolarized 13C MRI

    SciTech Connect

    Adamson, E; Johnson, K; Fain, S; Gordon, J

    2014-06-15

    Purpose: Previous work [1] modeling the metabolic flux between hyperpolarized [1-13C]pyruvate and [1-13C]lactate in magnetic resonance spectroscopic imaging (MRSI) experiments failed to account for vascular signal artifacts. Here, we investigate a method to minimize the vascular signal and its impact on the fidelity of metabolic modeling. Methods: MRSI was simulated for renal metabolism in MATLAB both with and without bipolar gradients. The resulting data were fit to a two-site exchange model [1], and the effects of vascular partial volume artifacts on kinetic modeling were assessed. Bipolar gradients were then incorporated into a gradient echo sequence to validate the simulations experimentally. The degree of diffusion weighting (b = 32 s/mm{sup 2}) was determined empirically from 1H imaging of murine renal vascular signal. The method was then tested in vivo using MRSI with bipolar gradients following injection of hyperpolarized [1-{sup 13}C]pyruvate (∼80 mM at 20% polarization). Results: In simulations, vascular signal contaminated the renal metabolic signal at resolutions as high as 2 × 2 mm{sup 2} due to partial volume effects. The apparent exchange rate from pyruvate to lactate (k{sub p}) was underestimated in the presence of these artifacts due to contaminating pyruvate signal. Incorporation of bipolar gradients suppressed vascular signal and improved the accuracy of kp estimation. Experimentally, the in vivo results supported the ability of bipolar gradients to suppress vascular signal. The in vivo exchange rate increased, as predicted in simulations, from k{sub p} = 0.012 s-{sup 1} to k{sub p} = 0.020-{sup 1} after vascular signal suppression. Conclusion: We have demonstrated the limited accuracy of the two-site exchange model in the presence of vascular partial volume artifacts. The addition of bipolar gradients suppressed vascular signal and improved model accuracy in simulations. Bipolar gradients largely affected kp estimation in vivo. Currently

  6. Quantitation of a spin polarization-induced nuclear Overhauser effect (SPINOE) between a hyperpolarized 13C-labeled cell metabolite and water protons

    PubMed Central

    Marco-Rius, Irene; Bohndiek, Sarah E; Kettunen, Mikko I; Larkin, Timothy J; Basharat, Meer; Seeley, Colm; Brindle, Kevin M

    2014-01-01

    The spin polarization-induced nuclear Overhauser effect (SPINOE) describes the enhancement of spin polarization of solvent nuclei by the hyperpolarized spins of a solute. In this communication we demonstrate that SPINOEs can be observed between [1,4-13C2]fumarate, hyperpolarized using the dissolution dynamic nuclear polarization technique, and solvent water protons. We derive a theoretical expression for the expected enhancement and demonstrate that this fits well with experimental measurements. Although the magnitude of the effect is relatively small (around 2% measured here), the SPINOE increases at lower field strengths, so that at clinically relevant magnetic fields (1.5–3 T) it may be possible to track the passage through the circulation of a bolus containing a hyperpolarized 13C-labeled substrate through the increase in solvent water 1H signal. © 2014 The Authors. Contrast Media & Molecular Imaging published by John Wiley and Sons, Ltd. PMID:24523064

  7. In vivo application of sub-second spiral chemical shift imaging (CSI) to hyperpolarized 13C metabolic imaging: Comparison with phase-encoded CSI

    NASA Astrophysics Data System (ADS)

    Mayer, Dirk; Yen, Yi-Fen; Levin, Yakir S.; Tropp, James; Pfefferbaum, Adolf; Hurd, Ralph E.; Spielman, Daniel M.

    2010-06-01

    A fast spiral chemical shift imaging (CSI) has been developed to address the challenge of the limited acquisition window in hyperpolarized 13C metabolic imaging. The sequence exploits the sparsity of the spectra and prior knowledge of resonance frequencies to reduce the measurement time by undersampling the data in the spectral domain. As a consequence, multiple reconstructions are necessary for any given data set as only frequency components within a selected bandwidth are reconstructed "in-focus" while components outside that band are severely blurred ("spectral tomosynthesis"). A variable-flip-angle scheme was used for optimal use of the longitudinal magnetization. The sequence was applied to sub-second metabolic imaging of the rat in vivo after injection of hyperpolarized [1- 13C]-pyruvate on a clinical 3T MR scanner. The comparison with conventional CSI based on phase encoding showed similar signal-to-noise ratio (SNR) and spatial resolution in metabolic maps for the substrate and its metabolic products lactate, alanine, and bicarbonate, despite a 50-fold reduction in scan time for the spiral CSI acquisition. The presented results demonstrate that dramatic reductions in scan time are feasible in hyperpolarized 13C metabolic imaging without a penalty in SNR or spatial resolution.

  8. Functional groups identified by solid state 13C NMR spectroscopy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Animal manure is generally high in organic matter intensity so it is well suitable for 13C nuclear magnetic resonance (NMR) analysis. Solid-state 13C NMR techniques used in characterizing organic matter and its components include, but are not limited to, cross-polarization /magic angle spinning (CP...

  9. Hyperpolarized (13)C-lactate to (13)C-bicarbonate ratio as a biomarker for monitoring the acute response of anti-vascular endothelial growth factor (anti-VEGF) treatment.

    PubMed

    Park, Jae Mo; Spielman, Daniel M; Josan, Sonal; Jang, Taichang; Merchant, Milton; Hurd, Ralph E; Mayer, Dirk; Recht, Lawrence D

    2016-05-01

    Hyperpolarized [1-(13)C]pyruvate MRS provides a unique imaging opportunity to study the reaction kinetics and enzyme activities of in vivo metabolism because of its favorable imaging characteristics and critical position in the cellular metabolic pathway, where it can either be reduced to lactate (reflecting glycolysis) or converted to acetyl-coenzyme A and bicarbonate (reflecting oxidative phosphorylation). Cancer tissue metabolism is altered in such a way as to result in a relative preponderance of glycolysis relative to oxidative phosphorylation (i.e. Warburg effect). Although there is a strong theoretical basis for presuming that readjustment of the metabolic balance towards normal could alter tumor growth, a robust noninvasive in vivo tool with which to measure the balance between these two metabolic processes has yet to be developed. Until recently, hyperpolarized (13)C-pyruvate imaging studies had focused solely on [1-(13)C]lactate production because of its strong signal. However, without a concomitant measure of pyruvate entry into the mitochondria, the lactate signal provides no information on the balance between the glycolytic and oxidative metabolic pathways. Consistent measurement of (13)C-bicarbonate in cancer tissue, which does provide such information, has proven difficult, however. In this study, we report the reliable measurement of (13)C-bicarbonate production in both the healthy brain and a highly glycolytic experimental glioblastoma model using an optimized (13)C MRS imaging protocol. With the capacity to obtain signal in all tumors, we also confirm for the first time that the ratio of (13)C-lactate to (13)C-bicarbonate provides a more robust metric relative to (13)C-lactate for the assessment of the metabolic effects of anti-angiogenic therapy. Our data suggest a potential application of this ratio as an early biomarker to assess therapeutic effectiveness. Furthermore, although further study is needed, the results suggest that anti

  10. Spectral editing for in vivo 13C magnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Xiang, Yun; Shen, Jun

    2012-01-01

    In vivo detection of carboxylic/amide carbons is a promising technique for studying cerebral metabolism and neurotransmission due to the very low RF power required for proton decoupling. In the carboxylic/amide region, however, there is severe spectral overlap between acetate C1 and glutamate C5, complicating studies that use acetate as an astroglia-specific substrate. There are no known in vivo MRS techniques that can spectrally resolve acetate C1 and glutamate C5 singlets. In this study, we propose to spectrally separate acetate C1 and glutamate C5 by a two-step J-editing technique after introducing homonuclear 13C- 13C scalar coupling between carboxylic/amide carbons and aliphatic carbons. By infusing [1,2- 13C 2]acetate instead of [1- 13C]acetate the acetate doublet can be spectrally edited because of the large separation between acetate C2 and glutamate C4 in the aliphatic region. This technique can be applied to studying acetate transport and metabolism in brain in the carboxylic/amide region without spectral interference.

  11. Multi-channel metabolic imaging, with SENSE reconstruction, of hyperpolarized [1- 13C] pyruvate in a live rat at 3.0 tesla on a clinical MR scanner

    NASA Astrophysics Data System (ADS)

    Tropp, James; Lupo, Janine M.; Chen, Albert; Calderon, Paul; McCune, Don; Grafendorfer, Thomas; Ozturk-Isik, Esin; Larson, Peder E. Z.; Hu, Simon; Yen, Yi-Fen; Robb, Fraser; Bok, Robert; Schulte, Rolf; Xu, Duan; Hurd, Ralph; Vigneron, Daniel; Nelson, Sarah

    2011-01-01

    We report metabolic images of 13C, following injection of a bolus of hyperpolarized [1-13C] pyruvate in a live rat. The data were acquired on a clinical scanner, using custom coils for volume transmission and array reception. Proton blocking of all carbon resonators enabled proton anatomic imaging with the system body coil, to allow for registration of anatomic and metabolic images, for which good correlation was achieved, with some anatomic features (kidney and heart) clearly visible in a carbon image, without reference to the corresponding proton image. Parallel imaging with sensitivity encoding was used to increase the spatial resolution in the SI direction of the rat. The signal to noise ratio in was in some instances unexpectedly high in the parallel images; variability of the polarization among different trials, plus partial volume effects, are noted as a possible cause of this.

  12. Design of spectral-spatial outer volume suppression RF pulses for tissue specific metabolic characterization with hyperpolarized 13C pyruvate

    NASA Astrophysics Data System (ADS)

    Chen, Albert P.; Leung, Kevin; Lam, Wilfred; Hurd, Ralph E.; Vigneron, Daniel B.; Cunningham, Charles H.

    2009-10-01

    [1- 13C] pyruvate pre-polarized via DNP has been used in animal models to probe changes in metabolic enzyme activities in vivo. To more accurately assess the metabolic state and its change from disease progression or therapy in a specific region or tissue in vivo, it may be desirable to separate the downstream 13C metabolite signals resulting from the metabolic activity within the tissue of interest and those brought into the tissue by perfusion. In this study, a spectral-spatial saturation pulse that selectively saturates the signal from the metabolic products [1- 13C] lactate and [1- 13C] alanine was designed and implemented as outer volume suppression for localized MRSI acquisition. Preliminary in vivo results showed that the suppression pulse did not prevent the pre-polarized pyruvate from being delivered throughout the animal while it saturated the metabolites within the targeted saturation region.

  13. Dipolar-coupling-mediated total correlation spectroscopy in solid-state 13C NMR: Selection of individual 13C- 13C dipolar interactions

    NASA Astrophysics Data System (ADS)

    Spano, Justin; Wi, Sungsool

    2010-06-01

    Herein is described a useful approach in solid-state NMR, for selecting homonuclear 13C- 13C spin pairs in a multiple- 13C homonuclear dipolar coupled spin system. This method builds upon the zero-quantum (ZQ) dipolar recoupling method introduced by Levitt and coworkers (Marin-Montesinos et al., 2006 [30]) by extending the originally introduced one-dimensional (1D) experiment into a two-dimensional (2D) method with selective irradiation scheme, while moving the 13C- 13C mixing scheme from the transverse to the longitudinal mode, together with a dramatic improvement in the proton decoupling efficiency. Selective spin-pair recoupling experiments incorporating Gaussian and cosine-modulated Gaussian pulses for inverting specific spins were performed, demonstrating the ability to detect informative, simplified/individualized, long-range 13C- 13C homonuclear dipolar coupling interactions more accurately by removing less informative, stronger, short-range 13C- 13C interactions from 2D correlation spectra. The capability of this new approach was demonstrated experimentally on uniformly 13C-labeled Glutamine and a tripeptide sample, GAL.

  14. Hyperpolarized [1,(13)C]pyruvate in lysed human erythrocytes: effects of co-substrate supply on reaction time courses.

    PubMed

    Pagès, Guilhem; Tan, Yee Ling; Kuchel, Philip W

    2014-10-01

    Hyperpolarized [1,(13)C]pyruvate was injected rapidly into haemolysates in which hydrolysis of nicotinamide adenine dinucleotide (phosphate) (NAD(P))/NAD(P)H had been inhibited with nicotinamide. Haemolysates provide a stable glycolytic system in which membrane permeability is not a flux-controlling step, and they enable the concentration of NADH to be adjusted experimentally while keeping the rest of the sample with the same composition as that of the cytoplasm of the cell (albeit diluted twofold at the time of injection of the [1,(13)C]pyruvate). We showed that the maximum amplitude of the (13)C NMR signal from the [1,(13)C]L-lactate, produced from [1,(13)C]pyruvate, and the time at which it occurred was dependent on NADH concentration, as predicted by enzyme-kinetic analysis. The main feature of such curves was dictated by the immediacy of the supply of the co-substrate of lactate dehydrogenase (LDH, EC 1.1.1.27), and we posit that this also pertains in vivo in various tissues including neoplasms. By constructing an appropriate mathematical model and by using a Markov-chain Monte Carlo approach, we fitted experimental data to estimate LDH and NADH concentrations. Experiments carried out with only endogenous NADH present enabled the estimation of its effective concentration in human RBCs; the ability to make this estimate is a special feature of the rapid-dissolution dynamic nuclear polarization method. We found an endogenous NADH concentration in human RBCs two to four times higher than previously reported. PMID:25111006

  15. Determination of de novo synthesized amino acids in cellular proteins revisited by 13C NMR spectroscopy.

    PubMed

    Flögel, U; Willker, W; Leibfritz, D

    1997-04-01

    13C nuclear magnetic resonance spectroscopy was used to determine the absolute amounts to de novo synthesized amino acids in both the perchloric acid extracts and the hydrolyzed protein fractions of F98 glioma cells incubated for 2 h with 5 mmol/l [U-13C]glucose. 13C NMR spectra of the hydrolyzed protein fraction revealed a marked incorporation of 13C-labelled alanine, aspartate and glutamate into the proteins of F98 cells within the incubation period. Additionally, small amounts of 13C-labelled glycine, proline and serine could unambiguously be identified in the protein fraction. Astonishingly, approximately equal amounts of 13C-labelled glutamate and aspartate were incorporated into the cellular proteins, although the cytosolic steady-state concentration of aspartate was below 13C NMR detectability. Hypertonic stress decreased the incorporation of 13C-labelled amino acids into the total protein, albeit their cytosolic concentrations were increased, which reflects an inhibition of protein synthesis under these conditions. On the other hand, hypotonic stress increased the amount of 13C-labelled proline incorporated into the cellular proteins even though the cytosolic concentration of 13C-labelled proline was largely decreased. Apparently, hypoosmotic conditions stimulate the synthesis of proteins or peptides with a high proline content. The results show that already after 2 h of incubation with [U-13C]glucose there is a pronounced flux of 13C label into the cellular proteins, which is usually disregarded if cytosolic fluids are examined only. This means that calculations of metabolic fluxes based on 13C NMR spectroscopic data obtained from perchloric acid extracts of cells or tissues and also from in vivo measurements consider only the labelled 'NMR visible' cytosolic metabolites, which may have to be corrected for fast label flowing off into other compartments.

  16. Ascorbic acid prolongs the viability and stability of isolated perfused lungs: A mechanistic study using 31P and hyperpolarized 13C nuclear magnetic resonance.

    PubMed

    Shaghaghi, Hoora; Kadlecek, Stephen; Siddiqui, Sarmad; Pourfathi, Mehrdad; Hamedani, Hooman; Clapp, Justin; Profka, Harrilla; Rizi, Rahim

    2015-12-01

    Ex vivo lung perfusion (EVLP) has recently shown promise as a means of more accurately gauging the health of lung grafts and improving graft performance post-transplant. However, reperfusion of ischemic lung promotes the depletion of high-energy compounds and a progressive loss of normal mitochondrial function, and it remains unclear how and to what extent the EVLP approach contributes to this metabolic decline. Although ascorbate has been used to mitigate the effects of ischemia-reperfusion injury, the nature of its effects during EVLP are also not clear. To address these uncertainties, this study monitored the energy status of lungs during EVLP and after the administration of ascorbate using (31)P and hyperpolarized (13)C NMR (nuclear magnetic resonance). Our experiments demonstrated that the oxidative phosphorylation capacity and pyruvate dehydrogenase flux of lungs decline during ex vivo perfusion. The addition of ascorbate to the perfusate prolonged lung viability by 80% and increased the hyperpolarized (13)C bicarbonate signal by a factor of 2.7. The effect of ascorbate is apparently due not to its antioxidant quality but rather to its ability to energize cellular respiration given that it increased the lung's energy charge significantly, whereas other antioxidants (glutathione and α-lipoic acid) did not alter energy metabolism. During ascorbate administration, inhibition of mitochondrial complex I with rotenone depressed energy charge and shifted the metabolic state of the lung toward glycolysis; reenergizing the electron transport chain with TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine) recovered metabolic activity. This indicates that ascorbate slows the decline of the ex vivo perfused lung's mitochondrial activity through an independent interaction with the electron transport chain complexes.

  17. Measurement of multiple psi torsion angles in uniformly 13C,15N-labeled alpha-spectrin SH3 domain using 3D 15N-13C-13C-15N MAS dipolar-chemical shift correlation spectroscopy.

    PubMed

    Ladizhansky, Vladimir; Jaroniec, Christopher P; Diehl, Annette; Oschkinat, Hartmut; Griffin, Robert G

    2003-06-01

    We demonstrate the simultaneous measurement of several backbone torsion angles psi in the uniformly (13)C,(15)N-labeled alpha-Spectrin SH3 domain using two different 3D 15N-13C-13C-15N dipolar-chemical shift magic-angle spinning (MAS) NMR experiments. The first NCCN experiment utilizes double quantum (DQ) spectroscopy combined with the INADEQUATE type 13C-13C chemical shift correlation. The decay of the DQ coherences formed between 13C'(i) and 13C(alphai) spin pairs is determined by the "correlated" dipolar field due to 15N(i)-13C(alphai) and 13C'(i)-15N(i+1) dipolar couplings and is particularly sensitive to variations of the torsion angle in the regime |psi| > 140 degrees. However, the ability of this experiment to constrain multiple psi-torsion angles is limited by the resolution of the 13C(alpha)-(13)CO correlation spectrum. This problem is partially addressed in the second approach described here, which is an NCOCA NCCN experiment. In this case the resolution is enhanced by the superior spectral dispersion of the 15N resonances present in the 15N(i+1)-13C(alphai) part of the NCOCA chemical shift correlation spectrum. For the case of the 62-residue alpha-spectrin SH3 domain, we determined 13 psi angle constraints with the INADEQUATE NCCN experiment and 22 psi constraints were measured in the NCOCA NCCN experiment.

  18. Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy

    PubMed Central

    Bartnik-Olson, Brenda L.; Harris, Neil G.; Shijo, Katsunori; Sutton, Richard L.

    2013-01-01

    The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI) and the use of 13C labeled substrates and nuclear magnetic resonance (NMR) spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how 13C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. 13C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP) activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from 13C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle. PMID:24109452

  19. Coal structure at reactive sites by sup 1 H- sup 13 C- sup 19 F double cross polarization (DCP)/MAS sup 13 C NMR spectroscopy

    SciTech Connect

    Hagaman, E.W.; Woody, M.C. )

    1989-01-01

    The solid state NMR technique, {sup 1}H-{sup 13}C-{sup 31}P double cross polarization (DCP)/MAS {sup 13}C-NMR spectroscopy, uses the direct dipolar interaction between {sup 13}C-{sup 31}P spin pairs in organophosphorus substances to identify the subset of carbons within a spherical volume element of 0.4 nm radius centered on the {sup 31}P atom. In combination with chemical manipulation of coals designed to introduce phosphorus containing functionality into the organic matrix, the NMR experiment becomes a method to examine selectively the carbon bonding network at the reactive sites in the coal. This approach generates a statistical structure description of the coal at the reaction centers in contrast to bulk carbon characterization using conventional {sup 1}H-{sup 13}C CP/MAS {sup 13}C NMR spectroscopy. 3 refs.

  20. Voxel-by-voxel correlations of perfusion, substrate, and metabolite signals in dynamic hyperpolarized (13) C imaging.

    PubMed

    Lau, Justin Y C; Chen, Albert P; Gu, Yi-Ping; Cunningham, Charles H

    2016-08-01

    In this study, a mixture of pyruvic acid and the perfusion agent HP001 was co-polarized for simultaneous assessment of perfusion and metabolism in vivo. The pre-polarized mixture was administered to rats with subcutaneous MDA-MB-231 breast cancer xenografts and imaged using an interleaved sequence with designed spectral-spatial pulses and flyback echo-planar readouts. Voxel-by-voxel signal correlations from 10 animals (15 data sets) were analyzed for tumour, kidney, and muscle regions of interest. The relationship between perfusion and hyperpolarized signal was explored on a voxel-by-voxel basis in various metabolically active tissues, including tumour, healthy kidneys, and skeletal muscle. Positive pairwise correlations between lactate, pyruvate, and HP001 observed in all 10 tumours suggested that substrate delivery was the dominant factor limiting the conversion of pyruvate to lactate in the tumour model used in this study. On the other hand, in cases where conversion is the limiting factor, such as in healthy kidneys, both pyruvate and lactate can act as excellent perfusion markers. In intermediate cases between the two limits, such as in skeletal muscle, some perfusion information may be inferred from the (pyruvate + lactate) signal distribution. Co-administration of pyruvate with a dynamic nuclear polarization (DNP) perfusion agent is an effective approach for distinguishing between slow metabolism and poor perfusion and a practical strategy for lactate signal normalization to account for substrate delivery, especially in cases of rapid pyruvate-to-lactate conversion and in poorly perfused regions with inadequate pyruvate signal-to-noise ratio for reliable determination of the lactate-to-pyruvate ratio. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Characterization of uniformly and atom-specifically 13C-labeled heparin and heparan sulfate polysaccharide precursors using 13C NMR spectroscopy and ESI mass spectrometry

    PubMed Central

    Nguyen, Thao K. N.; Tran, Vy M.; Victor, Xylophone V.; Skalicky, Jack J.; Kuberan, Balagurunathan

    2010-01-01

    The biological actions of heparin and heparan sulfate, two structurally related glycosaminoglycans, depend on the organization of the complex heparanome. Due to the structural complexity of the heparanome, the sequence of variably sulfonated uronic acid and glucosamine residues is usually characterized by the analysis of smaller oligosaccharide and disaccharide fragments. Even characterization of smaller heparin/heparan sulfate oligosaccharide or disaccharide fragments using simple 1D 1H NMR spectroscopy is often complicated by the extensive signal overlap. 13C NMR signals, on the other hand, overlap less and therefore, 13C NMR spectroscopy can greatly facilitate the structural elucidation of the complex heparanome and provide finer insights into the structural basis for biological functions. This is the first report of the preparation of anomeric carbon-specific 13C-labeled heparin/heparan sulfate precursors from the Escherichia coli K5 strain. Uniformly 13C- and 15N-labeled precursors were also produced and characterized by 13C NMR spectroscopy. Mass spectrometric analysis of enzymatically fragmented disaccharides revealed that anomeric carbon-specific labeling efforts resulted in a minor loss/scrambling of 13C in the precursor backbone, whereas uniform labeling efforts resulted in greater than 95% 13C isotope enrichment in the precursor backbone. These labeled precursors provided high-resolution NMR signals with great sensitivity and set the stage for studying the heparanome–proteome interactions. PMID:20832774

  2. Dynamic nuclear polarization-enhanced 13C NMR spectroscopy of static biological solids

    NASA Astrophysics Data System (ADS)

    Potapov, Alexey; Yau, Wai-Ming; Tycko, Robert

    2013-06-01

    We explore the possibility of using dynamic nuclear polarization (DNP) to enhance signals in structural studies of biological solids by solid state NMR without sample spinning. Specifically, we use 2D 13C-13C exchange spectroscopy to probe the peptide backbone torsion angles (ϕ, ψ) in a series of selectively 13C-labeled 40-residue β-amyloid (Aβ1-40) samples, in both fibrillar and non-fibrillar states. Experiments are carried out at 9.39 T and 8 K, using a static double-resonance NMR probe and low-power microwave irradiation at 264 GHz. In frozen solutions of Aβ1-40 fibrils doped with DOTOPA-TEMPO, we observe DNP signal enhancement factors of 16-21. We show that the orientation- and frequency-dependent spin polarization exchange between sequential backbone carbonyl 13C labels can be simulated accurately using a simple expression for the exchange rate, after experimentally determined homogeneous 13C lineshapes are incorporated in the simulations. The experimental 2D 13C-13C exchange spectra place constraints on the ϕ and ψ angles between the two carbonyl labels. Although the data are not sufficient to determine ϕ and ψ uniquely, the data do provide non-trivial constraints that could be included in structure calculations. With DNP at low temperatures, 2D 13C-13C exchange spectra can be obtained from a 3.5 mg sample of Aβ1-40 fibrils in 4 h or less, despite the broad 13C chemical shift anisotropy line shapes that are observed in static samples.

  3. Dynamic nuclear polarization-enhanced 13C NMR spectroscopy of static biological solids

    PubMed Central

    Potapov, Alexey; Yau, Wai-Ming; Tycko, Robert

    2013-01-01

    We explore the possibility of using dynamic nuclear polarization (DNP) to enhance signals in structural studies of biological solids by solid state NMR without sample spinning. Specifically, we use 2D 13C-13C exchange spectroscopy to probe the peptide backbone torsion angles (ϕ,ψ) in a series of selectively 13C-labeled 40-residue β-amyloid (Aβ1–40) samples, in both fibrillar and non-fibrillar states. Experiments are carried out at 9.39 T and 8 K, using a static double-resonance NMR probe and low-power microwave irradiation at 264 GHz. In frozen solutions of Aβ1–40 fibrils doped with DOTOPA-TEMPO, we observe DNP signal enhancement factors of 16–21. We show that the orientation- and frequency-dependent spin polarization exchange between sequential backbone carbonyl 13C labels can be simulated accurately using a simple expression for the exchange rate, after experimentally determined homogeneous 13C lineshapes are incorporated in the simulations. The experimental 2D 13C-13C exchange spectra place constraints on the ϕ and ψ angles between the two carbonyl labels. Although the data are not sufficient to determine ϕ and ψ uniquely, the data do provide non-trivial constraints that could be included in structure calculations. With DNP at low temperatures, 2D 13C-13C exchange spectra can be obtained from a 3.5 mg sample of Aβ1–40 fibrils in 4 hr or less, despite the broad 13C chemical shift anisotropy line shapes that are observed in static samples. PMID:23562665

  4. Simultaneous hyperpolarized (13)C-pyruvate MRI and (18)F-FDG-PET in cancer (hyperPET): feasibility of a new imaging concept using a clinical PET/MRI scanner.

    PubMed

    Gutte, Henrik; Hansen, Adam E; Henriksen, Sarah T; Johannesen, Helle H; Ardenkjaer-Larsen, Jan; Vignaud, Alexandre; Hansen, Anders E; Børresen, Betina; Klausen, Thomas L; Wittekind, Anne-Mette N; Gillings, Nic; Kristensen, Annemarie T; Clemmensen, Andreas; Højgaard, Liselotte; Kjær, Andreas

    2015-01-01

    In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and (18)F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have named this concept hyper PET. Intravenous injection of the hyperpolarized (13)C-pyruvate results in an increase of (13)C-lactate, (13)C-alanine and (13)C-CO2 ((13)C-HCO3) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use of (13)C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of (13)C-pyruvate to (13)C-lactate. In this study, we combined it with (18)F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence of a liposarcoma on the right forepaw was imaged using a combined PET/MR clinical scanner. PET was performed as a single-bed, 10 min acquisition, 107 min post injection of 310 MBq (18)F-FDG. (13)C-chemical shift imaging (CSI) was performed just after FDG-PET and 30 s post injection of 23 mL hyperpolarized (13)C-pyruvate. Peak heights of (13)C-pyruvate and (13)C-lactate were quantified using a general linear model. Anatomic (1)H-MRI included axial and coronal T1 vibe, coronal T2-tse and axial T1-tse with fat saturation following gadolinium injection. In the tumor we found clearly increased (13)C-lactate production, which also corresponded to high (18)F-FDG uptake on PET. This is in agreement with the fact that glycolysis and production of lactate are increased in tumor cells compared to normal cells. Yet, most interestingly, also in the muscle of the forepaw of the dog high (18)F-FDG uptake was observed. This was due to activity in these muscles prior to anesthesia, which was not accompanied by a similarly high (13)C-lactate production. Accordingly, this clearly

  5. Accurate measurements of {sup 13}C-{sup 13}C distances in uniformly {sup 13}C-labeled proteins using multi-dimensional four-oscillating field solid-state NMR spectroscopy

    SciTech Connect

    Straasø, Lasse Arnt; Nielsen, Jakob Toudahl; Bjerring, Morten; Nielsen, Niels Chr.; Khaneja, Navin

    2014-09-21

    Application of sets of {sup 13}C-{sup 13}C internuclear distance restraints constitutes a typical key element in determining the structure of peptides and proteins by magic-angle-spinning solid-state NMR spectroscopy. Accurate measurements of the structurally highly important {sup 13}C-{sup 13}C distances in uniformly {sup 13}C-labeled peptides and proteins, however, pose a big challenge due to the problem of dipolar truncation. Here, we present novel two-dimensional (2D) solid-state NMR experiments capable of extracting distances between carbonyl ({sup 13}C′) and aliphatic ({sup 13}C{sub aliphatic}) spins with high accuracy. The method is based on an improved version of the four-oscillating field (FOLD) technique [L. A. Straasø, M. Bjerring, N. Khaneja, and N. C. Nielsen, J. Chem. Phys. 130, 225103 (2009)] which circumvents the problem of dipolar truncation, thereby offering a base for accurate extraction of internuclear distances in many-spin systems. The ability to extract reliable accurate distances is demonstrated using one- and two-dimensional variants of the FOLD experiment on uniformly {sup 13}C,{sup 15}N-labeled-L-isoleucine. In a more challenging biological application, FOLD 2D experiments are used to determine a large number of {sup 13}C′-{sup 13}C{sub aliphatic} distances in amyloid fibrils formed by the SNNFGAILSS fibrillating core of the human islet amyloid polypeptide with uniform {sup 13}C,{sup 15}N-labeling on the FGAIL fragment.

  6. Compartmentalized Cerebral Metabolism of [1,6-13C]Glucose Determined by in vivo 13C NMR Spectroscopy at 14.1 T

    PubMed Central

    Duarte, João M. N.; Lanz, Bernard; Gruetter, Rolf

    2011-01-01

    Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by 13C nuclear magnetic resonance (NMR) spectroscopy upon infusion of 13C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-13C]glucose and 13C enrichment in the brain metabolites was measured by 13C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining 13C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (VTCA) and neurotransmission rate (VNT) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial VTCA was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (VPC) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism. PMID:21713114

  7. Protonation of carbon single-walled nanotubes studied using 13C and 1H-13C cross polarization nuclear magnetic resonance and Raman spectroscopies.

    PubMed

    Engtrakul, Chaiwat; Davis, Mark F; Gennett, Thomas; Dillon, Anne C; Jones, Kim M; Heben, Michael J

    2005-12-14

    The reversible protonation of carbon single-walled nanotubes (SWNTs) in sulfuric acid and Nafion was investigated using solid-state nuclear magnetic resonance (NMR) and Raman spectroscopies. Magic-angle spinning (MAS) was used to obtain high-resolution 13C and 1H-13C cross polarization (CP) NMR spectra. The 13C NMR chemical shifts are reported for bulk SWNTs, H2SO4-treated SWNTs, SWNT-Nafion polymer composites, SWNT-AQ55 polymer composites, and SWNTs in contact with water. Protonation occurs without irreversible oxidation of the nanotube substrate via a charge-transfer process. This is the first report of a chemically induced change in a SWNT 13C resonance brought about by a reversible interaction with an acidic proton, providing additional evidence that carbon nanotubes behave as weak bases. Cross polarization was found to be a powerful technique for providing an additional contrast mechanism for studying nanotubes in contact with other chemical species. The CP studies confirmed polarization transfer from nearby protons to nanotube carbon atoms. The CP technique was also applied to investigate water adsorbed on carbon nanotube surfaces. Finally, the degree of bundling of the SWNTs in Nafion films was probed with the 1H-13C CP-MAS technique. PMID:16332107

  8. Quantitative identification of metastable magnesium carbonate minerals by solid-state 13C NMR spectroscopy.

    PubMed

    Moore, Jeremy K; Surface, J Andrew; Brenner, Allison; Wang, Louis S; Skemer, Philip; Conradi, Mark S; Hayes, Sophia E

    2015-01-01

    In the conversion of CO2 to mineral carbonates for the permanent geosequestration of CO2, there are multiple magnesium carbonate phases that are potential reaction products. Solid-state (13)C NMR is demonstrated as an effective tool for distinguishing magnesium carbonate phases and quantitatively characterizing magnesium carbonate mixtures. Several of these mineral phases include magnesite, hydromagnesite, dypingite, and nesquehonite, which differ in composition by the number of waters of hydration or the number of crystallographic hydroxyl groups. These carbonates often form in mixtures with nearly overlapping (13)C NMR resonances which makes their identification and analysis difficult. In this study, these phases have been investigated with solid-state (13)C NMR spectroscopy, including both static and magic-angle spinning (MAS) experiments. Static spectra yield chemical shift anisotropy (CSA) lineshapes that are indicative of the site-symmetry variations of the carbon environments. MAS spectra yield isotropic chemical shifts for each crystallographically inequivalent carbon and spin-lattice relaxation times, T1, yield characteristic information that assist in species discrimination. These detailed parameters, and the combination of static and MAS analyses, can aid investigations of mixed carbonates by (13)C NMR.

  9. Methylation patterns of aquatic humic substances determined by 13C NMR spectroscopy

    USGS Publications Warehouse

    Thorn, K.A.; Steelink, C.; Wershaw, R. L.

    1987-01-01

    13C NMR spectroscopy is used to examine the hydroxyl group functionality of a series of humic and fulvic acids from different aquatic environments. Samples first are methylated with 13C-labeled diazomethane. The NMR spectra of the diazomethylated samples allow one to distinguish between methyl esters of carboxylic acids, methyl ethers of phenolic hydroxyls, and methyl ethers of phenolic hydroxyls adjacent to two substituents. Samples are then permethylated with 13C-labeled methyl iodide/NaH. 13C NMR spectra of permethylated samples show that a significant fraction of the hydroxyl groups is not methylated with diazomethane alone. In these spectra methyl ethers of carbohydrate and aliphatic hydroxyls overlap with methyl ethers of phenolic hydroxyls. Side reactions of the methyltion procedure including carbon methylation in the CH3I/NaH procedure, are also examined. Humic and fulvic acids from bog, swamp, groundwater, and lake waters showssome differences in their distribution of hydroxyl groups, mainly in the concentrations of phenolic hydroxyls, which may be attributed to their different biogeochemical origins. ?? 1987.

  10. [Characterization of biochar by X-ray photoelectron spectroscopy and 13C nuclear magnetic resonance].

    PubMed

    Xu, Dong-yu; Jin, Jie; Yan, Yu; Han, Lan-fang; Kang, Ming-jie; Wang, Zi-ying; Zhao, Ye; Sun, Ke

    2014-12-01

    The wood (willow branch) and grass (rice straw) materials were pyrolyzed at different temperatures (300, 450 and 600 °C) to obtain the biochars used in the present study. The biochars were characterized using elementary analysis, X-ray photoelectron spectroscopy (XPS) and solid state 13C cross-polarization and magic angle spinning nuclear magnetic resonance spectroscopy (13C NMR) to illuminate the structure and composition of the biochars which were derived from the different thermal temperatures and biomass. The results showed that the H/C, O/C and (O+N)/C ratios of the biochars decreased with the increase in the pyrolysis temperatures. The surface polarity and ash content of the grass-derived biochars were higher than those of the wood-derived biochars. The minerals of the wood-derived biochars were mainly covered by the organic matter; in contrast, parts of the mineral surfaces of the grass-derived biochars were not covered by organic matter? The 13C NMR of the low temperature-derived biochars revealed a large contribution of aromatic carbon, aliphatic carbon, carboxyl and carbonyl carbon, while the high temperature-derived biochars contained a large amount of aromatic carbon. Moreover, the wood-derived biochars produced at low heat treatment temperatures contained more lignin residues than grass-derived ones, probably due to the existence of high lignin content in the feedstock soures of wood-derived biochars. The results of the study would be useful for environmental application of biochars.

  11. Direct measurement of brain glucose concentrations in humans by sup 13 C NMR spectroscopy

    SciTech Connect

    Gruetter, R.; Novotny, E.J.; Boulware, S.D.; Rothman, D.L.; Mason, G.F.; Shulman, G.I.; Shulan, R.G.; Tamborlane, W.V. )

    1992-02-01

    Glucose is the main fuel for energy metabolism in the normal human brain. It is generally assumed that glucose transport into the brain is not rate-limiting for metabolism. Since brain glucose concentrations cannot be determined directly by radiotracer techniques, the authors used {sup 13}C NMR spectroscopy after infusing enriched D-(1-{sup 13}C)glucose to measure brain glucose concentrations at euglycemia and at hyperglycemia in six healthy children. Brain glucose concentrations averaged 1.0 {plus minus} 0.1 {mu}mol/ml at euglycemia and 1.8-2.7 {mu}mol/ml at hyperglycemia. Michaelis-Menten parameters of transport were calculated from the relationship between plasma and brain glucose concentrations. The brain glucose concentrations and transport constants are consistent with transport not being rate-limiting for resting brain metabolism at plasma levels >3 mM.

  12. [Characterization of biochar by X-ray photoelectron spectroscopy and 13C nuclear magnetic resonance].

    PubMed

    Xu, Dong-yu; Jin, Jie; Yan, Yu; Han, Lan-fang; Kang, Ming-jie; Wang, Zi-ying; Zhao, Ye; Sun, Ke

    2014-12-01

    The wood (willow branch) and grass (rice straw) materials were pyrolyzed at different temperatures (300, 450 and 600 °C) to obtain the biochars used in the present study. The biochars were characterized using elementary analysis, X-ray photoelectron spectroscopy (XPS) and solid state 13C cross-polarization and magic angle spinning nuclear magnetic resonance spectroscopy (13C NMR) to illuminate the structure and composition of the biochars which were derived from the different thermal temperatures and biomass. The results showed that the H/C, O/C and (O+N)/C ratios of the biochars decreased with the increase in the pyrolysis temperatures. The surface polarity and ash content of the grass-derived biochars were higher than those of the wood-derived biochars. The minerals of the wood-derived biochars were mainly covered by the organic matter; in contrast, parts of the mineral surfaces of the grass-derived biochars were not covered by organic matter? The 13C NMR of the low temperature-derived biochars revealed a large contribution of aromatic carbon, aliphatic carbon, carboxyl and carbonyl carbon, while the high temperature-derived biochars contained a large amount of aromatic carbon. Moreover, the wood-derived biochars produced at low heat treatment temperatures contained more lignin residues than grass-derived ones, probably due to the existence of high lignin content in the feedstock soures of wood-derived biochars. The results of the study would be useful for environmental application of biochars. PMID:25881450

  13. 13C editing of glutamate in human brain using J-refocused coherence transfer spectroscopy at 4.1 T.

    PubMed

    Pan, J W; Mason, G F; Vaughan, J T; Chu, W J; Zhang, Y; Hetherington, H P

    1997-03-01

    The method of single quantum 13C editing is analyzed and implemented with water suppressed J-refocused coherence transfer spectroscopy. Analysis of the 13C inversion pulse demonstrates that it is optimally placed into the second echo of the J-refocused sequence. We have used this method to acquire 13C-edited spectra of glutamate from phantoms and in vivo. The turnover of 13C4-labeled glutamate in human brain in vivo was observed in parasagittal gray matter using a volume head coil at 4.1 T with a time resolution of 5.3 min.

  14. Heteronuclear Cross-Relaxation Effects in the NMR Spectroscopy of Hyperpolarized Targets

    PubMed Central

    Donovan, Kevin J.; Lupulescu, Adonis; Frydman, Lucio

    2016-01-01

    Dissolution DNP enables high-sensitivity solution phase NMR experiments on long-lived nuclear spin species such as 15N and 13C. This report explores certain features arising in solution-state 1H NMR, upon polarizing low-γ nuclear species. Following solid state hyperpolarization of both 13C and 1H, solution-phase 1H NMR experiments on dissolved samples revealed transient effects whereby peaks arising from protons bonded to the naturally-occurring 13C nuclei, appeared larger than the typically dominant 12C-bonded 1H resonances. This enhancement of the satellite-peaks was examined in detail, with respect to a variety of mechanisms that could potentially originate it. Both two- and three-spin phenomena active in the solid state could lead to this kind of effect; still, experimental observations revealed that the enhancement originates from 13C→1H polarization transfer processes active in the liquid state. Kinetic equations based on modified heteronuclear cross-relaxation models were examined, and found to describe well the distinct patterns of growth and decay shown by the 13C-bound 1H NMR satellite resonances. The dynamics of these novel cross-relaxation phenomena were determined, and their potential usefulness as tools for investigating hyperpolarized ensembles and for obtaining enhanced-sensitivity 1H NMR traces, is explored. PMID:24403222

  15. Simultaneous steady-state and dynamic 13C NMR can differentiate alternative routes of pyruvate metabolism in living cancer cells.

    PubMed

    Yang, Chendong; Harrison, Crystal; Jin, Eunsook S; Chuang, David T; Sherry, A Dean; Malloy, Craig R; Merritt, Matthew E; DeBerardinis, Ralph J

    2014-02-28

    Metabolic reprogramming facilitates cancer cell growth, so quantitative metabolic flux measurements could produce useful biomarkers. However, current methods to analyze flux in vivo provide either a steady-state overview of relative activities (infusion of (13)C and analysis of extracted metabolites) or a dynamic view of a few reactions (hyperpolarized (13)C spectroscopy). Moreover, although hyperpolarization has successfully quantified pyruvate-lactate exchanges, its ability to assess mitochondrial pyruvate metabolism is unproven in cancer. Here, we combined (13)C hyperpolarization and isotopomer analysis to quantify multiple fates of pyruvate simultaneously. Two cancer cell lines with divergent pyruvate metabolism were incubated with thermally polarized [3-(13)C]pyruvate for several hours, then briefly exposed to hyperpolarized [1-(13)C]pyruvate during acquisition of NMR spectra using selective excitation to maximize detection of H[(13)C]O3(-) and [1-(13)C]lactate. Metabolites were then extracted and subjected to isotopomer analysis to determine relative rates of pathways involving [3-(13)C]pyruvate. Quantitation of hyperpolarized H[(13)C]O3(-) provided a single definitive metabolic rate, which was then used to convert relative rates derived from isotopomer analysis into quantitative fluxes. This revealed that H[(13)C]O3(-) appearance reflects activity of pyruvate dehydrogenase rather than pyruvate carboxylation followed by subsequent decarboxylation reactions. Glucose substantially altered [1-(13)C]pyruvate metabolism, enhancing exchanges with [1-(13)C]lactate and suppressing H[(13)C]O3(-) formation. Furthermore, inhibiting Akt, an oncogenic kinase that stimulates glycolysis, reversed these effects, indicating that metabolism of pyruvate by both LDH and pyruvate dehydrogenase is subject to the acute effects of oncogenic signaling on glycolysis. The data suggest that combining (13)C isotopomer analyses and dynamic hyperpolarized (13)C spectroscopy may enable

  16. Simultaneous Steady-state and Dynamic 13C NMR Can Differentiate Alternative Routes of Pyruvate Metabolism in Living Cancer Cells*

    PubMed Central

    Yang, Chendong; Harrison, Crystal; Jin, Eunsook S.; Chuang, David T.; Sherry, A. Dean; Malloy, Craig R.; Merritt, Matthew E.; DeBerardinis, Ralph J.

    2014-01-01

    Metabolic reprogramming facilitates cancer cell growth, so quantitative metabolic flux measurements could produce useful biomarkers. However, current methods to analyze flux in vivo provide either a steady-state overview of relative activities (infusion of 13C and analysis of extracted metabolites) or a dynamic view of a few reactions (hyperpolarized 13C spectroscopy). Moreover, although hyperpolarization has successfully quantified pyruvate-lactate exchanges, its ability to assess mitochondrial pyruvate metabolism is unproven in cancer. Here, we combined 13C hyperpolarization and isotopomer analysis to quantify multiple fates of pyruvate simultaneously. Two cancer cell lines with divergent pyruvate metabolism were incubated with thermally polarized [3-13C]pyruvate for several hours, then briefly exposed to hyperpolarized [1-13C]pyruvate during acquisition of NMR spectra using selective excitation to maximize detection of H[13C]O3− and [1-13C]lactate. Metabolites were then extracted and subjected to isotopomer analysis to determine relative rates of pathways involving [3-13C]pyruvate. Quantitation of hyperpolarized H[13C]O3− provided a single definitive metabolic rate, which was then used to convert relative rates derived from isotopomer analysis into quantitative fluxes. This revealed that H[13C]O3− appearance reflects activity of pyruvate dehydrogenase rather than pyruvate carboxylation followed by subsequent decarboxylation reactions. Glucose substantially altered [1-13C]pyruvate metabolism, enhancing exchanges with [1-13C]lactate and suppressing H[13C]O3− formation. Furthermore, inhibiting Akt, an oncogenic kinase that stimulates glycolysis, reversed these effects, indicating that metabolism of pyruvate by both LDH and pyruvate dehydrogenase is subject to the acute effects of oncogenic signaling on glycolysis. The data suggest that combining 13C isotopomer analyses and dynamic hyperpolarized 13C spectroscopy may enable quantitative flux measurements in

  17. Optimized [1-13C]glucose infusion protocol for 13C magnetic resonance spectroscopy at 3 Tesla of human brain glucose metabolism under euglycemic and hypoglycemic conditions

    PubMed Central

    van de Ven, Kim C.C.; van der Graaf, Marinette; Tack, Cees J.J.; Klomp, Dennis W.J.; Heerschap, Arend; de Galan, Bastiaan E.

    2009-01-01

    The effect of insulin-induced hypoglycemia on cerebral glucose metabolism is largely unknown. 13C MRS is a unique tool to study cerebral glucose metabolism, but the concurrent requirement for [1-13C]glucose administration limits its use under hypoglycemic conditions. To facilitate 13C MRS data analysis we designed separate [1-13C]glucose infusion protocols for hyperinsulinemic euglycemic and hypoglycemic clamps in such a way that plasma isotopic enrichment of glucose was stable and comparable under both glycemic conditions. 13C MR spectra were acquired with optimized 13C MRS measurement techniques to obtain high quality 13C MR spectra with these protocols. PMID:19913052

  18. High-resolution (13)C nuclear magnetic resonance spectroscopy pattern recognition of fish oil capsules.

    PubMed

    Aursand, Marit; Standal, Inger B; Axelson, David E

    2007-01-10

    13C NMR (nuclear magnetic resonance) spectroscopy, in conjunction with multivariate analysis of commercial fish oil-related health food products, have been used to provide discrimination concerning the nature, composition, refinement, and/or adulteration or authentication of the products. Supervised (probabilistic neural networks, PNN) and unsupervised (principal component analysis, PCA; Kohonen neural networks; generative topographic mapping, GTM) pattern recognition techniques were used to visualize and classify samples. Simple PCA score plots demonstrated excellent, but not totally unambiguous, class distinctions, whereas Kohonen and GTM visualization provided better results. Quantitative class predictions with accuracies >95% were achieved with PNN analysis. Trout, salmon, and cod oils were completely and correctly classified. Samples reported to be salmon oils and cod liver oils did not cluster with true salmon and cod liver oil samples, indicating mislabeling or adulteration.

  19. Identification and quantitative determination of lignans in Cedrus atlantica resins using 13C NMR spectroscopy.

    PubMed

    Nam, Anne-Marie; Paoli, Mathieu; Castola, Vincent; Casanova, Joseph; Bighelli, Ange

    2011-03-01

    Identification and quantitative determination of individual components of resin collected on the trunk of 28 Cedrus atlantica trees, grown in Corsica, has been carried out using 13C NMR spectroscopy. Eight resin acids bearing either the pimarane or abietane skeleton, two monoterpene hydrocarbons and four oxygenated neutral diterpenes have been identified, as well as three lignans, scarcely found in resins. Three groups could be distinguished within the 28 resin samples. The nine samples of Group I had their composition dominated by diterpene acids (33.7-45.8%), with abietic acid (6.2-18.7%) and isopimaric acid (5.1-12.6%) being the major components. The four samples of Group II contained resin acids (main components) and lignans in moderate amounts (up to 10.3%). Conversely, lignans (38.8-63.8%) were by far the major components of the 15 samples of Group III. Depending on the sample, the major component was pinoresinol (18.1-38.9%), lariciresinol (17.2-33.7%) or lariciresinol 9'-acetate (16.9-29.1%). Finally, due to the high biological interest in lignans, a rapid procedure, based on 1H NMR spectroscopy, was developed for quantification of lignans in resins of C. atlantica.

  20. J-refocused 1H PRESS DEPT for localized 13C MR spectroscopy.

    PubMed

    Chen, X; Boesiger, P; Henning, A

    2013-09-01

    Proton point-resolved spectroscopy (PRESS) localization has been combined with distortionless enhanced polarization transfer (DEPT) in multinuclear MRS to overcome the signal contamination problem in image-selected in vivo spectroscopy (ISIS)-combined DEPT, especially for lipid detection. However, homonuclear proton scalar couplings reduce the DEPT enhancement by modifying the spin coherence distribution under J modulation during proton PRESS localization. Herein, a J-refocused proton PRESS-localized DEPT sequence is presented to obtain simultaneously enhanced and localized signals from a large number of metabolites by in vivo (13) C MRS. The suppression of J modulation during PRESS and the substantial recovery of signal enhancement by J-refocused PRESS-localized DEPT were demonstrated theoretically by product operator formalism, numerically by the spin density matrix simulations for different scalar coupling conditions, and experimentally with a glutamate phantom at various TEs, as well as a colza oil phantom. The application of the sequence for localized detection of saturated and unsaturated fatty acids in the calf bone marrow and skeletal muscle of healthy subjects yielded high signal enhancements simultaneously obtained for all components. PMID:23440698

  1. Characterization of Acetate and Pyruvate Metabolism in Suspension Cultures of Zea mays by 13C NMR Spectroscopy

    PubMed Central

    Ashworth, Dennis J.; Lee, Rino Y.; Adams, Douglas O.

    1987-01-01

    Carbon-13 nuclear magnetic resonance (NMR) spectroscopy has been applied to the direct observation of acetate and pyruvate metabolism in suspension cultures of Zea mays (var Black Mexican Sweet). Growth of the corn cells in the presence of 2 millimolar [2-13C]acetate resulted in a rapid uptake of the substrate from the medium and initial labeling (0-4 hours) of primarily the intracellular glutamate and malate pools. Further metabolism of these intermediates resulted in labeling of glutamine, aspartate, and alanine. With [1-13C]acetate as the substrate very little incorporation into intermediary metabolites was observed in the 13C NMR spectra due to loss of the label as 13CO2. Uptake of [3-13C]pyruvate by the cells was considerably slower than with [2-13C]acetate; however, the labelling patterns were similar with the exception of increased [3-13C] alanine generation with pyruvate as the substrate. Growth of the cells for up to 96 hours with 2 millimolar [3-13C]pyruvate ultimately resulted in labeling of valine, leucine, isoleucine, threonine, and the polyamine putrescine. PMID:16665721

  2. Thz Spectroscopy of Acetaldehyde and Search of 13C Species in Orion

    NASA Astrophysics Data System (ADS)

    Margulès, L.; Motiyenko, R. A.; Ilyushin, V. V.; Tercero, B.; Cernicharo, J.; Guillemin, J.-C.

    2012-06-01

    Acetaldehyde (CH_3CHO) is one of the high priority complex organic molecules for the astrophysical community. There is a lack of data concerning the 13C species since the measurements are limited to 40 GHz up to date. This molecule displays a large amplitude motion: the hindered rotation of the methyl group with respect to the rest of the molecule. The analysis is performed with RAM36 code which used the Rho Axis Method. Last year we presented the analysis of the millimeterwave spectra of the 13CH_3CHO species. We extended the analysis to the THz range of the vibrational ground state for both species. We are also analyzing the first torsional state (≈140 cm-1) for two reasons: first, this permits to remove correlation between parameters. Second, this state contribute to the partition function even at ISM temperature (100--150 K) since there is an influence on the column density determined in case of detection. The searches of these isotopomers are in progress in ORION. This work was supported by the CNES and the Action sur Projets de l'INSU, PCMI. This work was also done under the ANR-08-BLAN-0054. Kilb, R.W.; Lin, C.C.; and Wilson, E.B. J. Chem. Phys. 26, (1957) 1695 Ilyushin, V.V. et al J. Mol. Spectrosc. 259, (2010) 26 Margules, L. et al. FA07, 66th International Symposium on Molecular Spectroscopy (2011)

  3. Stable isotope-enhanced two- and three-dimensional diffusion ordered 13C-NMR spectroscopy (SIE-DOSY 13C-NMR)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stable Isotope-Enhanced Diffusion Ordered (SIE-DOSY) 13C-NMR has been applied to 13C-enriched carbohydrates and has been used to determine diffusion coefficients for pentose and hexose monosaccharides, a disaccharide and a trisaccharide. These 2D spectra were obtained with as little as 8 min of acq...

  4. Detection of intracellular lactate with localized diffusion { 1H- 13C}-spectroscopy in rat glioma in vivo

    NASA Astrophysics Data System (ADS)

    Pfeuffer, Josef; Lin, Joseph C.; DelaBarre, Lance; Ugurbil, Kamil; Garwood, Michael

    2005-11-01

    The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of 13C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). 13C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, { 1H- 13C}-lactate and { 1H- 13C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into { 1H- 13C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/μm 2). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, 1H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([ 13C] lactate) originates from an intracellular compartment.

  5. Ethanol reassimilation and ethanol tolerance in Pitchia stipitis CBS 6054 as studied by [sup 13]C nuclear magnetic resonance spectroscopy

    SciTech Connect

    Skoog, K.; Hahn-Haegerdal, B. ); Degn, H.; Jacobsen, H.S.; Jacobsen, J.P. )

    1992-08-01

    Ethanol reassimilation in Pichia stipitis CBS 6054 was studied by using continuous cultures, and the oxidation of [1-[sup 13]C] ethanol was monitored by in vivo and in vitro [sup 13]C nuclear magnetic resonance spectroscopy. Acetate was formed when ethanol was reassimilated. The ATP/ADP ratio and the carbon dioxide production decreased, whereas the malate dehydrogenase activity increased, in ethanol-reassimilating cells. The results are discussed in terms of the low ethanol tolerance in P. stipitis compared with that in Saccharomyces cerevisiae.

  6. Sucrose octabenzoate: assignment of 13C and 1H resonances of the sucrose moiety and the 13C resonances of the carbonyl carbons. Use of 13C-n.m.r. spectroscopy for the study of selective deacylation.

    PubMed

    Colquhoun, I J; Haines, A H; Konowicz, P A; Jones, H F

    1990-09-19

    Assignment of the 1H and 13C signals arising from the carbohydrate portion of sucrose octabenzoate has been achieved using homonuclear shift correlation experiments (COSY) and one-bond 1H-13C heteronuclear shift correlation measurements, respectively. The 13C resonances of the carbonyl carbon atoms of the eight benzoyl groups are readily distinguished for solutions in benzene-d6-pyridine-d5 (1:1), and have been assigned by means of three-bond 1H-13C shift correlation studies coupled with measurement of the 13C-n.m.r. spectrum of a sucrose octabenzoate specifically labelled with 13C in some of the carbonyl groups. With this assignment, products of partial deacylation of the octabenzoate may readily be identified by treatment with excess of benzoyl-carbonyl-13C chloride followed by measurement of the 13C-n.m.r. spectrum of the labelled sucrose octabenzoate, so prepared, in the carbonyl region. PMID:2276151

  7. (13)C NMR assignments of regenerated cellulose from solid-state 2D NMR spectroscopy.

    PubMed

    Idström, Alexander; Schantz, Staffan; Sundberg, Johan; Chmelka, Bradley F; Gatenholm, Paul; Nordstierna, Lars

    2016-10-20

    From the assignment of the solid-state (13)C NMR signals in the C4 region, distinct types of crystalline cellulose, cellulose at crystalline surfaces, and disordered cellulose can be identified and quantified. For regenerated cellulose, complete (13)C assignments of the other carbon regions have not previously been attainable, due to signal overlap. In this study, two-dimensional (2D) NMR correlation methods were used to resolve and assign (13)C signals for all carbon atoms in regenerated cellulose. (13)C-enriched bacterial nanocellulose was biosynthesized, dissolved, and coagulated as highly crystalline cellulose II. Specifically, four distinct (13)C signals were observed corresponding to conformationally different anhydroglucose units: two signals assigned to crystalline moieties and two signals assigned to non-crystalline species. The C1, C4 and C6 regions for cellulose II were fully examined by global spectral deconvolution, which yielded qualitative trends of the relative populations of the different cellulose moieties, as a function of wetting and drying treatments. PMID:27474592

  8. Metabolic pathways for ketone body production. /sup 13/C NMR spectroscopy of rat liver in vivo using /sup 13/C-multilabeled fatty acids

    SciTech Connect

    Pahl-Wostl, C.; Seelig, J.

    1986-11-04

    The hormonal regulation of ketogenesis in the liver of living rat has been studied noninvasively with /sup 13/C nuclear magnetic resonance. The spatial selection for the liver was better than 90%, with extrahepatic adipose tissue contribution only a very small amount of signal. The metabolic activities of the liver were investigated by infusion of /sup 13/C-labeled butyrate in the jugular vein of the anesthetized rat. The rate of butyrate infusion was chosen to be close to the maximum oxidative capacity of the rat liver, and the /sup 13/C signal intensities were enhanced by using doubly labeled (1,3-/sup 13/C)butyrate as a substrate. Different /sup 13/C NMR spectra and hence different metabolites were observed depending on the hormonal state of the animal. The /sup 13/C NMR studies demonstrate that even when rate of acetyl-CoA production are high, the disposal of this compound is not identical in fasted and diabetic animals. This supports previous suggestions that the redox state of the mitochondrion represents the most important factor in regulation. For a given metabolic state of the animal, different signal intensities were obtained depending on whether butyrate was labeled at C-1, C-3, or C-1,3. From the ratios of incorporation of /sup 13/C label into the carbons of 3-hydroxybutyrate, it could be estimated that a large fraction of butyrate evaded ..beta..-oxidation to acetyl-CoA but was converted directly to acetoacetyl-CoA. /sup 13/C-labeled glucose could be detected in vivo in the liver of diabetic rats.

  9. Quantitative Analysis of Metabolic Mixtures by 2D 13C-Constant-Time TOCSY NMR Spectroscopy

    PubMed Central

    Bingol, Kerem; Zhang, Fengli; Bruschweiler-Li, Lei; Brüschweiler, Rafael

    2013-01-01

    An increasing number of organisms can be fully 13C-labeled, which has the advantage that their metabolomes can be studied by high-resolution 2D NMR 13C–13C constant-time (CT) TOCSY experiments. Individual metabolites can be identified via database searching or, in the case of novel compounds, through the reconstruction of their backbone-carbon topology. Determination of quantitative metabolite concentrations is another key task. Because significant peak overlaps in 1D NMR spectra prevents straightforward quantification through 1D peak integrals, we demonstrate here the direct use of 13C–13C CT-TOCSY spectra for metabolite quantification. This is accomplished through the quantum-mechanical treatment of the TOCSY magnetization transfer at short and long mixing times or by the use of analytical approximations, which are solely based on the knowledge of the carbon-backbone topologies. The methods are demonstrated for carbohydrate and amino-acid mixtures. PMID:23773204

  10. 13C NMR spectroscopy of the insoluble carbon of carbonaceous chondrites.

    PubMed

    Cronin, J R; Pizzarello, S; Frye, J S

    1987-01-01

    13C NMR spectra have been obtained of the insoluble carbon residues resulting from HF-digestion of three carbonaceous chondrites, Orgueil (C1), Murchison (CM2), and Allende (CV3). Spectra obtained using the cross polarization magic-angle spinning technique show two major features attributable respectively to carbon in aliphatic/olefinic structures. The spectrum obtained from the Allende sample was weak, presumably as a consequence of its low hydrogen content. Single pulse excitation spectra, which do not depend on 1H-13C polarization transfer for signal enhancement were also obtained. These spectra, which may be more representative of the total carbon in the meteorite samples, indicate a greater content of carbon in aromatic/olefinic structures. These results suggest that extensive polycyclic aromatic sheets are important structural features of the insoluble carbon of all three meteorites. The Orgueil and Murchison materials contain additional hydrogenated aromatic/olefinic and aliphatic groups.

  11. 13C NMR spectroscopy of the insoluble carbon of carbonaceous chondrites

    NASA Technical Reports Server (NTRS)

    Cronin, J. R.; Pizzarello, S.; Frye, J. S.

    1987-01-01

    13C NMR spectra have been obtained of the insoluble carbon residues resulting from HF-digestion of three carbonaceous chondrites, Orgueil (C1), Murchison (CM2), and Allende (CV3). Spectra obtained using the cross polarization magic-angle spinning technique show two major features attributable respectively to carbon in aliphatic/olefinic structures. The spectrum obtained from the Allende sample was weak, presumably as a consequence of its low hydrogen content. Single pulse excitation spectra, which do not depend on 1H-13C polarization transfer for signal enhancement were also obtained. These spectra, which may be more representative of the total carbon in the meteorite samples, indicate a greater content of carbon in aromatic/olefinic structures. These results suggest that extensive polycyclic aromatic sheets are important structural features of the insoluble carbon of all three meteorites. The Orgueil and Murchison materials contain additional hydrogenated aromatic/olefinic and aliphatic groups.

  12. High resolution 13C-detected solid-state NMR spectroscopy of a deuterated protein

    PubMed Central

    Tang, Ming; Comellas, Gemma; Mueller, Leonard J.

    2011-01-01

    High resolution 13C-detected solid-state NMR spectra of the deuterated beta-1 immunoglobulin binding domain of the protein G (GB1) have been collected to show that all 15N, 13C′, 13Cα and 13Cβ sites are resolved in 13C–13C and 15N–13C spectra, with significant improvement in T2 relaxation times and resolution at high magnetic field (750 MHz). The comparison of echo T2 values between deuterated and protonated GB1 at various spinning rates and under different decoupling schemes indicates that 13Cα T2′ times increase by almost a factor of two upon deuteration at all spinning rates and under moderate decoupling strength, and thus the deuteration enables application of scalar-based correlation experiments that are challenging from the standpoint of transverse relaxation, with moderate proton decoupling. Additionally, deuteration in large proteins is a useful strategy to selectively detect polar residues that are often important for protein function and protein–protein interactions. PMID:20803233

  13. Landmarks in the application of 13C-magnetic resonance spectroscopy to studies of neuronal/glial relationships.

    PubMed

    Bachelard, H

    1998-01-01

    The development of the use of carbon isotopes as metabolic tracers is briefly described. 13C-labelled precursors (13CO2, 13CH4) first became available in 1940 and were studied in microorganisms, but their use was limited by very low enrichments and lack of suitable analytical equipment. More success was achieved with 11C and especially 14C, as these radioactive tracers did not need to be highly enriched. Although the stable 13C isotope can be used at a low percentage enrichment in mass spectrometry, its application to magnetic resonance spectroscopy (MRS) requires very highly enriched precursors, due to its low natural abundance and low sensitivity. Despite such limitations, however, the great advantage of 13C-MRS lies in its exquisite chemical specificity, in that labelling of different carbon atoms can be distinguished within the same molecule. Effective exploitation became feasible in the early 1970s with the advent of stable instruments, Fourier transform 13C-MRS, and the availability of highly enriched precursors. Reports of its use in brain research began to appear in the mid-1980s. The applications of 13C isotopomer analysis to research on neuronal/glial relationships are reviewed. The presence of neighbouring 13C-labelled atoms affects the appearance of the resonances (splitting due to C-C coupling), and so allows for unique quantification of rates through different and possibly competing pathways. Isotopomer patterns in resonances labelled from a combination of [1-13C]glucose and [1, 2-13C2]acetate have revealed aspects of neuronal/glial metabolic trafficking on depolarization and under hypoxic conditions in vitro. This approach has now been applied to in vivo studies on inhibition of glial metabolism using fluoroacetate. The results confirm the glial specificity of the toxin and demonstrate that it does not affect entry of acetate. When the glial TCA cycle is inhibited, the ability of the glia to participate in the glutamate/glutamine cycle remains

  14. Differentiation of histidine tautomeric states using 15N selectively filtered 13C solid-state NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Miao, Yimin; Cross, Timothy A.; Fu, Riqiang

    2014-08-01

    The histidine imidazole ring in proteins usually contains a mixture of three possible tautomeric states (two neutral - τ and π states and a charged state) at physiological pHs. Differentiating the tautomeric states is critical for understanding how the histidine residue participates in many structurally and functionally important proteins. In this work, one dimensional 15N selectively filtered 13C solid-state NMR spectroscopy is proposed to differentiate histidine tautomeric states and to identify all 13C resonances of the individual imidazole rings in a mixture of tautomeric states. When 15N selective 180° pulses are applied to the protonated or non-protonated nitrogen region, the 13C sites that are bonded to the non-protonated or protonated nitrogen sites can be identified, respectively. A sample of 13C, 15N labeled histidine powder lyophilized from a solution at pH 6.3 has been used to illustrate the usefulness of this scheme by uniquely assigning resonances of the neutral τ and charged states from the mixture.

  15. The Influence of Plant Litter on Soil Water Repellency: Insight from 13C NMR Spectroscopy.

    PubMed

    Cesarano, Gaspare; Incerti, Guido; Bonanomi, Giuliano

    2016-01-01

    Soil water repellency (SWR, i.e. reduced affinity for water owing to the presence of organic hydrophobic coatings on soil particles) has relevant hydrological implications because low rates of infiltration enhance water runoff, and untargeted diffusion of fertilizers and pesticides. Previous studies investigated the occurrence of SWR in ecosystems with different vegetation cover but did not clarify its relationships with litter biochemical quality. Here, we investigated the capability of different plant litter types to induce SWR by using fresh and decomposed leaf materials from 12 species, to amend a model sandy soil over a year-long microcosm experiment. Water repellency, measured by the Molarity of an Ethanol Droplet (MED) test, was tested for the effects of litter species and age, and compared with litter quality assessed by 13C-CPMAS NMR in solid state and elemental chemical parameters. All litter types were highly water repellent, with MED values of 18% or higher. In contrast, when litter was incorporated into the soil, only undecomposed materials induced SWR, but with a large variability of onset and peak dynamics among litter types. Surprisingly, SWR induced by litter addition was unrelated to the aliphatic fraction of litter. In contrast, lignin-poor but labile C-rich litter, as defined by O-alkyl C and N-alkyl and methoxyl C of 13C-CPMAS NMR spectral regions, respectively, induced a stronger SWR. This study suggests that biochemical quality of plant litter is a major controlling factor of SWR and, by defining litter quality with 13C-CPMAS NMR, our results provide a significant novel contribution towards a full understanding of the relationships between plant litter biochemistry and SWR. PMID:27022916

  16. The Influence of Plant Litter on Soil Water Repellency: Insight from 13C NMR Spectroscopy.

    PubMed

    Cesarano, Gaspare; Incerti, Guido; Bonanomi, Giuliano

    2016-01-01

    Soil water repellency (SWR, i.e. reduced affinity for water owing to the presence of organic hydrophobic coatings on soil particles) has relevant hydrological implications because low rates of infiltration enhance water runoff, and untargeted diffusion of fertilizers and pesticides. Previous studies investigated the occurrence of SWR in ecosystems with different vegetation cover but did not clarify its relationships with litter biochemical quality. Here, we investigated the capability of different plant litter types to induce SWR by using fresh and decomposed leaf materials from 12 species, to amend a model sandy soil over a year-long microcosm experiment. Water repellency, measured by the Molarity of an Ethanol Droplet (MED) test, was tested for the effects of litter species and age, and compared with litter quality assessed by 13C-CPMAS NMR in solid state and elemental chemical parameters. All litter types were highly water repellent, with MED values of 18% or higher. In contrast, when litter was incorporated into the soil, only undecomposed materials induced SWR, but with a large variability of onset and peak dynamics among litter types. Surprisingly, SWR induced by litter addition was unrelated to the aliphatic fraction of litter. In contrast, lignin-poor but labile C-rich litter, as defined by O-alkyl C and N-alkyl and methoxyl C of 13C-CPMAS NMR spectral regions, respectively, induced a stronger SWR. This study suggests that biochemical quality of plant litter is a major controlling factor of SWR and, by defining litter quality with 13C-CPMAS NMR, our results provide a significant novel contribution towards a full understanding of the relationships between plant litter biochemistry and SWR.

  17. The Influence of Plant Litter on Soil Water Repellency: Insight from 13C NMR Spectroscopy

    PubMed Central

    Cesarano, Gaspare; Incerti, Guido; Bonanomi, Giuliano

    2016-01-01

    Soil water repellency (SWR, i.e. reduced affinity for water owing to the presence of organic hydrophobic coatings on soil particles) has relevant hydrological implications because low rates of infiltration enhance water runoff, and untargeted diffusion of fertilizers and pesticides. Previous studies investigated the occurrence of SWR in ecosystems with different vegetation cover but did not clarify its relationships with litter biochemical quality. Here, we investigated the capability of different plant litter types to induce SWR by using fresh and decomposed leaf materials from 12 species, to amend a model sandy soil over a year-long microcosm experiment. Water repellency, measured by the Molarity of an Ethanol Droplet (MED) test, was tested for the effects of litter species and age, and compared with litter quality assessed by 13C-CPMAS NMR in solid state and elemental chemical parameters. All litter types were highly water repellent, with MED values of 18% or higher. In contrast, when litter was incorporated into the soil, only undecomposed materials induced SWR, but with a large variability of onset and peak dynamics among litter types. Surprisingly, SWR induced by litter addition was unrelated to the aliphatic fraction of litter. In contrast, lignin-poor but labile C-rich litter, as defined by O-alkyl C and N-alkyl and methoxyl C of 13C-CPMAS NMR spectral regions, respectively, induced a stronger SWR. This study suggests that biochemical quality of plant litter is a major controlling factor of SWR and, by defining litter quality with 13C-CPMAS NMR, our results provide a significant novel contribution towards a full understanding of the relationships between plant litter biochemistry and SWR. PMID:27022916

  18. Complete (1)H and (13)C signal assignment of prenol-10 with 3D NMR spectroscopy.

    PubMed

    Misiak, Maria; Koźmiński, Wiktor; Kwasiborska, Maria; Wójcik, Jacek; Ciepichal, Ewa; Swiezewska, Ewa

    2009-10-01

    The complete assignment of (1)H and (13)C chemical shifts of natural abundance prenol-10 is reported for the first time. It was achieved using 3D NMR experiments, which were based on random sampling of the evolution time space followed by multidimensional Fourier transform. This approach makes it possible to acquire 3D NMR spectra in a reasonable time and preserves high resolution in indirectly detected dimensions. It is shown that the interpretation of 3D COSY-HMBC and 3D TOCSY-HSQC spectra is crucial in the structural analysis of prenol-10.

  19. Thz Spectroscopy of 13C Isotopic Species of a "weed": Acetaldehyde

    NASA Astrophysics Data System (ADS)

    Margulès, L.; Motiyenko, R. A.; Guillemin, J.-C.

    2011-06-01

    Our studies of the isotopic species of 13C and D isotopologues of methyl formate (HCOOCH_3), have allowed the detection of more than 600 lines in Orion. This confirms that many observed U-lines are coming from isotopic species of one of the most abundant molecules in space. Since its first detection in 1976 in SgrB2 and in Orion A, acetaldehyde (CH_3CHO) was detected in many other numerous objects. If its deuterated species (CD_3CHO and CH_3CDO) have been previously studied in the millimeterwave range, the data concerning the 13C species are limited to few lines measured in 1957 up to 40 GHz. In this context we decided to study the 13C species of acetaldehyde. Acetaldehyde molecule displays a large amplitude motion: the hindered rotation of the methyl group with respect to the rest of the molecule. The analysis is performed with the Rho Axis Method. Recent versions of the codes include high orders term in order to reproduce the observed frequencies for large quantum numbers values as J-values as high as 70a,b,. Measurements and analysis of the rotational spectra of 13C isotopic species are in progress in Lille with a solid-state submillimetre-wave spectrometer (50-950 GHz), the first results will be presented. This work is supported by the contract ANR-08-BLAN-0054 and by the Programme National de Physico-Chimie du Milieu Interstellaire (PCMI-CNRS). Carvajal, M.; Margulès, L.; Tercero, B.; et al.A&A 500, (2009) 1109 Margulès, L.; Huet, T. R.; Demaison J.; et al.,ApJ 714, (2010) 1120. Ikeda, M.; Ohishi, M.; Nummelin, A.; et al., ApJ, 560, (2001) 792 Kleiner, I.; Lopez, J.-C.; Blanco, S.; et al.J. Mol. Spectrosc. 197, (1999) 275 Elkeurti M.; Coudert, L. H.; Medvedev, I. R.; et al.J. Mol. Spectrosc. 263, (2010) 145 Kilb, R.W.; Lin, C.C.; and Wilson, E.B.J. Chem. Phys. 26, (1957) 1695 Kleiner, I. J. Mol. Spectrosc. 260, (2010) 1 Ilyushin, V.V.; Kryvda, A; and Alekseev, E;J. Mol. Spectrosc. 255, (2009) 32

  20. Enantiomeric differentiation of acyclic terpenes by 13C NMR spectroscopy using a chiral lanthanide shift reagent.

    PubMed

    Blanc, Marie-Cécile; Bradesi, Pascale; Casanova, Joseph

    2005-02-01

    The 13C NMR behaviour of ten acyclic terpene alcohols was examined in the presence of a chiral lanthanide shift reagent (CLSR). For each alcohol, we measured the lanthanide-induced shift (LIS) on the signals of the carbons and the splitting of some signals, which allowed the enantiomeric differentiation. As expected, the LIS decreased with the number of bonds between the binding function and the considered carbon. The enantiomeric splitting is observed for several signals in the spectrum of each compound. The influence of the hindrance of the binding function (primary, secondary or tertiary alcohol) and that of the stereochemistry of the double bonds is discussed.

  1. Spectroscopic characterization of the 1-substituted 3,3-diphenyl-4-(2'-hydroxyphenyl)azetidin-2-ones: Application of 13C NMR, 1H- 13C COSY NMR and mass spectroscopy

    NASA Astrophysics Data System (ADS)

    Singh, Girija S.; Pheko, Tshepo

    2008-08-01

    The article deals with spectroscopic characterization of azetidin-2-ones. The presence of substituents like hydroxyl, fluoro, methoxy and benzhydryl, etc., on the azetidin-2-one ring significantly affects the IR absorption and 13C NMR frequencies of the carbonyl group present in these compounds. The presence of an ester carbonyl group or too many methine protons in the molecule has been observed to limit the scope of IR and 1H NMR spectroscopy in unambiguous assignment of the structure. The application of 13C NMR, 2D NMR ( 1H- 13C COSY) and mass spectroscopy in characterization of complex azetidin-2-ones is discussed. An application of the latter two techniques is described in deciding unequivocally between an azetidin-2-one ring and chroman-2-one ring structure for the product obtained by treatment of the 1-substituted 3,3-diphenyl-4-[2'-( O-diphenylacyl)hydroxyphenyl]-2-azetidinones with ethanolic sodium hydroxide at room temperature.

  2. Biosynthesis of pyrroloquinoline quinone. 1. Identification of biosynthetic precursors using /sup 13/C labeling and NMR spectroscopy

    SciTech Connect

    Houck, D.R.; Hanners, J.L.; Unkefer, C.J.

    1988-09-28

    The biosynthesis of pyrroloquinoline quinone (PQQ) in the methylotropic bacterium methylobacterium AM1 has been investigated using /sup 13/C-labelling of the products and NMR spectroscopy. The data indicated that the quinoline portion of PQQ is formed by a novel condensation of N-1, C-2, -3, and -4 of glutamate with a symmetrical six-carbon ring derived from the shikimate pathway. It is postulated that tyrosine is the shikimate-derived percursor, since pyrrole could be formed by the internal cyclization of the amino acid backbone. 18 references, 2 figures, 2 tables.

  3. Characterization of aging in organic materials on atomic-, meso- and macro-length scales by {sup 13}C NMR spectroscopy

    SciTech Connect

    Assink, R.A.; Jamison, G.M.; Alam, T.M.; Gillen, K.T.

    1997-10-01

    A fundamental understanding of aging in an organic material requires that one understand how aging affects the chemical structure of a material, and how these chemical changes are related to the material`s macroscopic properties. This level of understanding is usually achieved by examining the material on a variety of length scales ranging from atomic to meso-scale to macroscopic. The authors are developing and applying several {sup 13}C nuclear magnetic resonance (NMR) spectroscopy experiments to characterize the aging process of organic materials over a broad range of length scales. Examples of studies which range from atomic to macroscopic will be presented.

  4. Triterpenes in the hexane extract of leaves of Olea europaea L.: analysis using 13C-NMR spectroscopy.

    PubMed

    Duquesnoy, Emilie; Castola, Vincent; Casanova, Joseph

    2007-01-01

    Two neutral triterpenes and a triterpene acid were identified and quantified directly, in the absence of any purification steps, in a precipitate obtained during the industrial extraction of the leaves of Olea europaea L. using 13C-NMR spectroscopy (spectrometer operating at 4.7 T equipped with a 10 mm probe). The method was optimised in order to reduce the duration of analysis with a routine NMR spectrometer. Together with long-chain linear compounds, erythrodiol, uvaol and oleanolic acid accounted for 27.3, 18.3 and 12.5% of the precipitate, respectively.

  5. Identification and quantitative determination of carbohydrates in ethanolic extracts of two conifers using 13C NMR spectroscopy.

    PubMed

    Duquesnoy, Emilie; Castola, Vincent; Casanova, Joseph

    2008-04-01

    We developed a method for the direct identification and quantification of carbohydrates in raw vegetable extracts using (13)C NMR spectroscopy without any preliminary step of precipitation or reduction of the components. This method has been validated (accuracy, precision and response linearity) using pure compounds and artificial mixtures before being applied to authentic ethanolic extracts of pine needles, pine wood and pine cones and fir twigs. We determined that carbohydrates represented from 15% to 35% of the crude extracts in which pinitol was the principal constituent accompanied by arabinitol, mannitol, glucose and fructose.

  6. Glutamatergic and GABAergic energy metabolism measured in the rat brain by (13) C NMR spectroscopy at 14.1 T.

    PubMed

    Duarte, João M N; Gruetter, Rolf

    2013-09-01

    Energy metabolism supports both inhibitory and excitatory neurotransmission processes. This study investigated the specific contribution of astrocytic metabolism to γ-aminobutyric acid (GABA) synthesis and inhibitory GABAergic neurotransmission that remained to be ilucidated in vivo. Therefore, we measured (13)C incorporation into brain metabolites by dynamic (13)C nuclear magnetic resonance spectroscopy at 14.1 T in rats under α-chloralose anaesthesia during infusion of [1,6-(13)C]glucose. The enhanced sensitivity at 14.1 T allowed to quantify incorporation of (13) C into the three aliphatic carbons of GABA non-invasively. Metabolic fluxes were determined with a mathematical model of brain metabolism comprising glial, glutamatergic and GABAergic compartments. GABA synthesis rate was 0.11 ± 0.01 μmol/g/min. GABA-glutamine cycle was 0.053 ± 0.003 μmol/g/min and accounted for 22 ± 1% of total neurotransmitter cycling between neurons and glia. Cerebral glucose oxidation was 0.47 ± 0.02 μmol/g/min, of which 35 ± 1% and 7 ± 1% was diverted to the glutamatergic and GABAergic tricarboxylic acid cycles, respectively. The remaining fraction of glucose oxidation was in glia, where 12 ± 1% of the TCA cycle flux was dedicated to oxidation of GABA. 16 ± 2% of glutamine synthesis was provided to GABAergic neurons. We conclude that substantial metabolic activity occurs in GABAergic neurons and that glial metabolism supports both glutamatergic and GABAergic neurons in the living rat brain. PMID:23745684

  7. Compositional differences among Chinese soy sauce types studied by (13)C NMR spectroscopy coupled with multivariate statistical analysis.

    PubMed

    Kamal, Ghulam Mustafa; Wang, Xiaohua; Bin Yuan; Wang, Jie; Sun, Peng; Zhang, Xu; Liu, Maili

    2016-09-01

    Soy sauce a well known seasoning all over the world, especially in Asia, is available in global market in a wide range of types based on its purpose and the processing methods. Its composition varies with respect to the fermentation processes and addition of additives, preservatives and flavor enhancers. A comprehensive (1)H NMR based study regarding the metabonomic variations of soy sauce to differentiate among different types of soy sauce available on the global market has been limited due to the complexity of the mixture. In present study, (13)C NMR spectroscopy coupled with multivariate statistical data analysis like principle component analysis (PCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) was applied to investigate metabonomic variations among different types of soy sauce, namely super light, super dark, red cooking and mushroom soy sauce. The main additives in soy sauce like glutamate, sucrose and glucose were easily distinguished and quantified using (13)C NMR spectroscopy which were otherwise difficult to be assigned and quantified due to serious signal overlaps in (1)H NMR spectra. The significantly higher concentration of sucrose in dark, red cooking and mushroom flavored soy sauce can directly be linked to the addition of caramel in soy sauce. Similarly, significantly higher level of glutamate in super light as compared to super dark and mushroom flavored soy sauce may come from the addition of monosodium glutamate. The study highlights the potentiality of (13)C NMR based metabonomics coupled with multivariate statistical data analysis in differentiating between the types of soy sauce on the basis of level of additives, raw materials and fermentation procedures. PMID:27343582

  8. Dynamic UltraFast 2D EXchange SpectroscopY (UF-EXSY) of hyperpolarized substrates

    PubMed Central

    Swisher, Christine Leon; Koelsch, Bertram; Sukumar, Subramianam; Sriram, Renuka; Santos, Romelyn Delos; Wang, Zhen Jane; Kurhanewicz, John; Vigneron, Daniel; Larson, Peder

    2015-01-01

    In this work, we present a new ultrafast method for acquiring dynamic 2D EXchange SpectroscopY (EXSY) within a single acquisition. This technique reconstructs two-dimensional EXSY spectra from one-dimensional spectra based on the phase accrual during echo times. The Ultrafast-EXSY acquisition overcomes long acquisition times typically needed to acquire 2D NMR data by utilizing sparsity and phase dependence to dramatically undersample in the indirect time dimension. This allows for the acquisition of the 2D spectrum within a single shot. We have validated this method in simulations and hyperpolarized enzyme assay experiments separating the dehydration of pyruvate and lactate-to-pyruvate conversion. In a renal cell carcinoma cell (RCC) line, bidirectional exchange was observed. This new technique revealed decreased conversion of lactate-to-pyruvate with high expression of monocarboxylate transporter 4 (MCT4), known to correlate with aggressive cancer phenotypes. We also showed feasibility of this technique in vivo in a RCC model where bidirectional exchange was observed for pyruvate–lactate, pyruvate–alanine, and pyruvate–hydrate and were resolved in time. Broadly, the technique is well suited to investigate the dynamics of multiple exchange pathways and applicable to hyperpolarized substrates where chemical exchange has shown great promise across a range of disciplines. PMID:26117655

  9. Dynamic UltraFast 2D EXchange SpectroscopY (UF-EXSY) of hyperpolarized substrates

    NASA Astrophysics Data System (ADS)

    Leon Swisher, Christine; Koelsch, Bertram; Sukumar, Subramianam; Sriram, Renuka; Santos, Romelyn Delos; Wang, Zhen Jane; Kurhanewicz, John; Vigneron, Daniel; Larson, Peder

    2015-08-01

    In this work, we present a new ultrafast method for acquiring dynamic 2D EXchange SpectroscopY (EXSY) within a single acquisition. This technique reconstructs two-dimensional EXSY spectra from one-dimensional spectra based on the phase accrual during echo times. The Ultrafast-EXSY acquisition overcomes long acquisition times typically needed to acquire 2D NMR data by utilizing sparsity and phase dependence to dramatically undersample in the indirect time dimension. This allows for the acquisition of the 2D spectrum within a single shot. We have validated this method in simulations and hyperpolarized enzyme assay experiments separating the dehydration of pyruvate and lactate-to-pyruvate conversion. In a renal cell carcinoma cell (RCC) line, bidirectional exchange was observed. This new technique revealed decreased conversion of lactate-to-pyruvate with high expression of monocarboxylate transporter 4 (MCT4), known to correlate with aggressive cancer phenotypes. We also showed feasibility of this technique in vivo in a RCC model where bidirectional exchange was observed for pyruvate-lactate, pyruvate-alanine, and pyruvate-hydrate and were resolved in time. Broadly, the technique is well suited to investigate the dynamics of multiple exchange pathways and applicable to hyperpolarized substrates where chemical exchange has shown great promise across a range of disciplines.

  10. Continuous Flow - Cavity RingDown Spectroscopy Using a Novel Universal Interface for High-Precision Bulk 13C Analysis

    NASA Astrophysics Data System (ADS)

    Saad, Nabil; Richman, Bruce

    2010-05-01

    We have developed the world's first optical spectroscopy-based system for bulk stable isotope analysis of 13C. The system is based on a novel universal interface, named LIAISON, capable of coupling to almost any CO2-generating sample preparation front-end ranging from an elemental analyzer to any dissolved carbon analysis module, which are of significant use in geochemical, ecological and food authentication studies. In one specific application, we have coupled LIAISON to an elemental analyzer (EA) and to a cavity ring-down spectrometer (CRDS) for 13C isotopic analysis of adulterated honey samples. Another application was developed to analyze dissolved inorganic carbon in water samples. LIAISON is suited for handling a high-throughput sample analysis process by running three different gas handling operations in parallel: Admitting combustion gas from the EA into a first gas bellows, analyzing the previous sample collected into a second gas bellows with CRDS, and flushing and purging a third gas bellows in preparation for the upcoming sample collection operation. The sample-to-sample analysis time is 10 minutes and the operation is completely automated for the whole front-end auto-sampler tray capacity, requiring no operator intervention. The CRDS data are collected, tabulated and saved into an output text file. The memory effect between the USGS L-Glutamic acid standard at natural abundance and the moderately enriched USGS L-Glutamic acid standard is excluded by the selection of the adequate number and duration of flush and purge cycles of the gas sample bags. The system's proven accuracy was cross-checked with EA-IRMS and its achieved precision was typically less than 0.2 permil, including the 13C-enriched tested samples. The LIAISON-CRDS system presented here provides a fully automated solution for 13C bulk stable isotope analysis with unprecedented ease-of-use and possible field portability and application with the availability of a compact front-end. In

  11. Recent applications of /sup 13/C NMR spectroscopy to biological systems

    SciTech Connect

    Matwiyoff, N.A.

    1981-01-01

    Carbon-13 nuclear magnetic resonance (NMR) spectroscopy, in conjunction with carbon-13 labelling, is a powerful new analytical technique for the study of metabolic pathways and structural components in intact organelles, cells, and tissues. The technique can provide, rapidly and non-destructively, unique information about: the architecture and dynamics of structural components; the nature of the intracellular environment; and metabolic pathways and relative fluxes of individual carbon atoms. With the aid of results recently obtained by us and those reported by a number of other laboratories, the problems and potentialities of the technique will be reviewed with emphasis on: the viscosities of intracellular fluids; the structure and dynamics of the components of membranes; and the primary and secondary metabolic pathways of carbon in microorganisms, plants, and mammalian cells in culture.

  12. Bonded Cumomer Analysis of Human Melanoma Metabolism Monitored by 13C NMR Spectroscopy of Perfused Tumor Cells.

    PubMed

    Shestov, Alexander A; Mancuso, Anthony; Lee, Seung-Cheol; Guo, Lili; Nelson, David S; Roman, Jeffrey C; Henry, Pierre-Gilles; Leeper, Dennis B; Blair, Ian A; Glickson, Jerry D

    2016-03-01

    A network model for the determination of tumor metabolic fluxes from (13)C NMR kinetic isotopomer data has been developed and validated with perfused human DB-1 melanoma cells carrying the BRAF V600E mutation, which promotes oxidative metabolism. The model generated in the bonded cumomer formalism describes key pathways of tumor intermediary metabolism and yields dynamic curves for positional isotopic enrichment and spin-spin multiplets. Cells attached to microcarrier beads were perfused with 26 mm [1,6-(13)C2]glucose under normoxic conditions at 37 °C and monitored by (13)C NMR spectroscopy. Excellent agreement between model-predicted and experimentally measured values of the rates of oxygen and glucose consumption, lactate production, and glutamate pool size validated the model. ATP production by glycolytic and oxidative metabolism were compared under hyperglycemic normoxic conditions; 51% of the energy came from oxidative phosphorylation and 49% came from glycolysis. Even though the rate of glutamine uptake was ∼ 50% of the tricarboxylic acid cycle flux, the rate of ATP production from glutamine was essentially zero (no glutaminolysis). De novo fatty acid production was ∼ 6% of the tricarboxylic acid cycle flux. The oxidative pentose phosphate pathway flux was 3.6% of glycolysis, and three non-oxidative pentose phosphate pathway exchange fluxes were calculated. Mass spectrometry was then used to compare fluxes through various pathways under hyperglycemic (26 mm) and euglycemic (5 mm) conditions. Under euglycemic conditions glutamine uptake doubled, but ATP production from glutamine did not significantly change. A new parameter measuring the Warburg effect (the ratio of lactate production flux to pyruvate influx through the mitochondrial pyruvate carrier) was calculated to be 21, close to upper limit of oxidative metabolism. PMID:26703469

  13. The Contribution of Blood Lactate to Brain Energy Metabolism in Humans Measured by Dynamic 13C Nuclear Magnetic Resonance Spectroscopy

    PubMed Central

    BOUMEZBEUR, Fawzi; PETERSEN, Kitt F.; CLINE, Gary W.; MASON, Graeme F.; BEHAR, Kevin L; SHULMAN, Gerald I.; ROTHMAN, Douglas L.

    2010-01-01

    To determine whether plasma lactate can be a significant fuel for human brain energy metabolism infusions of [3-13C]lactate and 1H-13C polarization transfer spectroscopy were used to detect the entry and utilization of lactate. During the 2-hour infusion study, 13C incorporation in the amino acid pools of glutamate and glutamine were measured with a 5 minutes time-resolution. With a plasma concentration ([Lac]P) being in the 0.8–2.8 mmol/L range, the tissue lactate concentration ([Lac]B) was assessed as well as the fractional contribution of lactate to brain energy metabolism (CMRlac). From the measured relationship between unidirectional lactate influx (Vin) and plasma and brain lactate concentrations lactate transport constants were calculated using a reversible Michaelis-Menten model. The results show (i) that in the physiological range plasma lactate unidirectional transport (Vin) and concentration in tissue increases close to linearly with the lactate concentration in plasma, (ii) the maximum potential contribution of plasma lactate to brain metabolism is 10% under basal plasma lactate conditions of ~ 1.0 mmol/L and as much as 60% at supra-physiological plasma lactate concentrations when the transporters are saturated, (iii) the half-saturation constant KT is 5.1±2.7 mmol/L and VMAX is 0.40±0.13 μmol/g/min (68% confidence interval), (iv) the majority of plasma lactate is metabolized in neurons similar to glucose. PMID:20962220

  14. 13C-13C and 15N-13C correlation spectroscopy of membrane-associated and uniformly labeled human immunodeficiency virus and influenza fusion peptides: Amino acid-type assignments and evidence for multiple conformations

    NASA Astrophysics Data System (ADS)

    Bodner, Michele L.; Gabrys, Charles M.; Struppe, Jochem O.; Weliky, David P.

    2008-02-01

    Many viruses which cause disease including human immunodeficiency virus (HIV) and influenza are "enveloped" by a membrane and infection of a host cell begins with joining or "fusion" of the viral and target cell membranes. Fusion is catalyzed by viral proteins in the viral membrane. For HIV and for the influenza virus, these fusion proteins contain an ˜20-residue apolar "fusion peptide" that binds to target cell membranes and plays a critical role in fusion. For this study, the HIV fusion peptide (HFP) and influenza virus fusion peptide (IFP) were chemically synthesized with uniform C13, N15 labeling over large contiguous regions of amino acids. Two-dimensional C13-C13 and N15-C13 spectra were obtained for the membrane-bound fusion peptides and an amino acid-type C13 assignment was obtained for the labeled residues in HFP and IFP. The membrane used for the HFP sample had a lipid headgroup and cholesterol composition comparable to that of host cells of the virus, and the C13 chemical shifts were more consistent with β strand conformation than with helical conformation. The membrane used for the IFP sample did not contain cholesterol, and the chemical shifts of the dominant peaks were more consistent with helical conformation than with β strand conformation. There were additional peaks in the IFP spectrum whose shifts were not consistent with helical conformation. An unambiguous C13 and N15 assignment was obtained in an HFP sample with more selective labeling, and two shifts were identified for the Leu-9 CO, Gly-10 N, and Gly-10 Cα nuclei. These sets of two shifts may indicate two β strand registries such as parallel and antiparallel. Although most spectra were obtained on a 9.4T instrument, one C13-C13 correlation spectrum was obtained on a 16.4T instrument and was better resolved than the comparable 9.4T spectrum. More selective labeling and higher field may, therefore, be approaches to obtaining unambiguous assignments for membrane-associated fusion peptides.

  15. Characterization of alkyl carbon in forest soils by CPMAS 13C NMR spectroscopy and dipolar dephasing

    USGS Publications Warehouse

    Kogel-Knabner, I.; Hatcher, P.G.

    1989-01-01

    Samples obtained from forest soils at different stages of decomposition were treated sequentially with chloroform/methanol (extraction of lipids), sulfuric acid (hydrolysis), and sodium chlorite (delignification) to enrich them in refractory alkyl carbon. As revealed by NMR spectroscopy, this treatment yielded residues with high contents of alkyl carbon. In the NMR spectra of residues obtained from litter samples, resonances for carbohydrates are also present, indicating that these carbohydrates are tightly bound to the alkyl carbon structures. During decomposition in the soils this resistant carbohydrate fraction is lost almost completely. In the litter samples the alkyl carbon shows a dipolar dephasing behavior indicative of two structural components, a rigid and a more mobile component. As depth and decomposition increase, only the rigid component is observed. This fact could be due to selective degradation of the mobile component or to changes in molecular mobility during decomposition, e.g., because of an increase in cross linking or contact with the mineral matter of the soil.

  16. Evolution of organic matter during composting of different organic wastes assessed by CPMAS {sup 13}C NMR spectroscopy

    SciTech Connect

    Caricasole, P.; Provenzano, M.R.; Senesi, N.

    2011-03-15

    In this paper, the evolution of organic matter (OM) during composting of different mixtures of various organic wastes was assessed by means of chemical analyses and CPMAS {sup 13}C NMR spectroscopy measured during composting. The trends of temperatures and C/N ratios supported the correct evolution of the processes. The CPMAS {sup 13}C NMR spectra of all composting substrates indicated a reduction in carbohydrates and an increase in aromatic, phenolic, carboxylic and carbonylic C which suggested a preference by microorganisms for easily degradable C molecules. The presence of hardly degradable pine needles in one of the substrates accounted for the lowest increase in alkyl C and the lowest reduction in carbohydrates and carboxyl C as opposite to another substrate characterized by the presence of a highly degradable material such as spent yeast from beer production, which showed the highest increase of the alkyl C/O-alkyl C ratio. The highest increase of COOH deriving by the oxidative degradation of cellulose was shown by a substrate composed by about 50% of plant residues. The smallest increases in alkyl C/O-alkyl C ratio and in polysaccharides were associated to the degradation of proteins and lipids which are major components of sewage sludge. Results obtained were related to the different composition of fresh organic substrates and provided evidence of different OM evolution patterns as a function of the initial substrate composition.

  17. In Situ Determination of Fructose Isomer Concentrations in Wine Using (13)C Quantitative Nuclear Magnetic Resonance Spectroscopy.

    PubMed

    Colombo, Cinzia; Aupic, Clara; Lewis, Andrew R; Pinto, B Mario

    2015-09-30

    A practical method for simultaneously quantifying fructose and ethanol contents in wines using (13)C quantitative nuclear magnetic resonance (qNMR) spectroscopy is reported. Less than 0.6 mL of wine is needed, and the method leaves an unmodified sample available for subsequent testing or additional analyses. The relative ratios of the five known fructose isomers in ethanolic solutions at different pH and their variations with the temperature are also reported. The data are correlated with the sweetness of wines. The technique was applied to commercially available wines, and the results are compared to other methods. Sugar levels above 0.6 g/L can also be measured. A simple adaptation of the method permits measurement of different carbohydrates using integration of single peaks for each compound, in combination with an external reference (13)C qNMR spectrum of a sample with a known concentration. The method can be applied at all stages of wine production, including grape must, during fermentation, and before and after bottling.

  18. Observation of cytoplasmic and vacuolar malate in maize root tips by sup 13 C-NMR spectroscopy. [Zea mays L

    SciTech Connect

    Chang, K.; Roberts, J.K.M. )

    1989-01-01

    The accumulation of malate by maize (Zea mays L.) root tips perfused with KH{sup 13}CO{sub 3} was followed by {sup 13}C nuclear magnetic resonance spectroscopy. In vivo nuclear magnetic resonance spectra contained distinct signals from two pools of malate in maize root tips, one at a pH {approximately}5.3 (assigned to the vacuole) and one at a pH > 6.5 (assigned to the cytoplasm). The ratio of cytoplasmic to vacuolar malate was lower in 12 millimeter long root tips than in 2 millimeter root tips. The relatively broad width of the signals from C1- and C4-labeled vacuolar malate indicated heterogeneity in vacuolar pH. During the 3 hour KH{sup 13}CO{sub 3} treatment, {sup 13}C-malate accumulated first primarily in the cytoplasm, increasing to a fairly constant level of {approximately}6 millimolar by 1 hour. After a lag, vacuolar malate increased throughout the experiment.

  19. Solid state 13C NMR and FT-IR spectroscopy of the cocoon silk of two common spiders

    NASA Astrophysics Data System (ADS)

    Bramanti, Emilia; Catalano, Donata; Forte, Claudia; Giovanneschi, Mario; Masetti, Massimo; Veracini, Carlo Alberto

    2005-11-01

    The structure of the silk from cocoons of two common spiders, Araneus diadematus (family Araneidae) and Achaearanea tepidariorum (family Theridiidae) was investigated by means of 13C solid state NMR and FT-IR spectroscopies. The combined use of these two techniques allowed us to highlight differences in the two samples. The cocoon silk of Achaearanea tepidariorum is essentially constituted by helical and β-sheet structures, whereas that of Araneus diadematus shows a more complex structure, containing also β-strands and β-turns. Moreover, the former silk is essentially crystalline while the latter contains more mobile domains. The structural differences of the two cocoon silks are ascribed to the different habitat of the two species.

  20. Humic acids as proxies for assessing different Mediterranean forest soils signatures using solid-state CPMAS 13C NMR spectroscopy.

    PubMed

    Duarte, Regina M B O; Fernández-Getino, Ana P; Duarte, Armando C

    2013-06-01

    Humic acids (HAs) of four representative forest soils profiles from Central Spain (two with different vegetation - pine and oak - but same parent material - granitie, and two with same vegetation - holm oak - but different parent material - granite and limestone) were investigated by solid-state cross polarization with magic angle spinning (13)C nuclear magnetic resonance (NMR) spectroscopy. The objectives included the investigation of the impact of different forest properties on HA composition, assessing how the structural characteristics of the HA vary with soil depth, and evaluating the role of HA as surrogates for mapping the different forest soils signatures using structural data derived from (13)C NMR spectroscopy. On average, alkyl C is the dominant C constituent (38-48% of the total NMR peak area) in all HA samples, followed by aromatic (12-22%) and O-alkyl C (12-19%), and finally carboxyl C (7.0-10%). The NMR data also indicated that HA composition is likely to be differently affected by the soil physico-chemical properties and type of forest vegetation. The structural characteristics of the HA from soil under oak did not differ broadly downward in the profile, whereas soil HA under pine forest exhibits a somewhat higher recalcitrant nature as a consequence of a higher degree of decomposition. The soil HA from holm oak forests differed from the other two forest soils, exhibiting a progressive decomposition of the alkyl C structures with increasing depth, while the carbohydrate-like indicator (O-alkyl C) is apparently being protected from mineralization in the horizons below the ground level. Overall, these differences in soil HA NMR signatures are an important diagnostic tool for understanding the role of different soil environmental factors on the structural composition of HA from Mediterranean forest soils. PMID:23332874

  1. Humic acids as proxies for assessing different Mediterranean forest soils signatures using solid-state CPMAS 13C NMR spectroscopy.

    PubMed

    Duarte, Regina M B O; Fernández-Getino, Ana P; Duarte, Armando C

    2013-06-01

    Humic acids (HAs) of four representative forest soils profiles from Central Spain (two with different vegetation - pine and oak - but same parent material - granitie, and two with same vegetation - holm oak - but different parent material - granite and limestone) were investigated by solid-state cross polarization with magic angle spinning (13)C nuclear magnetic resonance (NMR) spectroscopy. The objectives included the investigation of the impact of different forest properties on HA composition, assessing how the structural characteristics of the HA vary with soil depth, and evaluating the role of HA as surrogates for mapping the different forest soils signatures using structural data derived from (13)C NMR spectroscopy. On average, alkyl C is the dominant C constituent (38-48% of the total NMR peak area) in all HA samples, followed by aromatic (12-22%) and O-alkyl C (12-19%), and finally carboxyl C (7.0-10%). The NMR data also indicated that HA composition is likely to be differently affected by the soil physico-chemical properties and type of forest vegetation. The structural characteristics of the HA from soil under oak did not differ broadly downward in the profile, whereas soil HA under pine forest exhibits a somewhat higher recalcitrant nature as a consequence of a higher degree of decomposition. The soil HA from holm oak forests differed from the other two forest soils, exhibiting a progressive decomposition of the alkyl C structures with increasing depth, while the carbohydrate-like indicator (O-alkyl C) is apparently being protected from mineralization in the horizons below the ground level. Overall, these differences in soil HA NMR signatures are an important diagnostic tool for understanding the role of different soil environmental factors on the structural composition of HA from Mediterranean forest soils.

  2. Heteronuclear Cross Polarization for Enhanced Sensitivity of in Vivo13C MR Spectroscopy on a Clinical 1.5 T MR System

    NASA Astrophysics Data System (ADS)

    van den Bergh, Adrianus J.; van den Boogert, Hendrikus J.; Heerschap, Arend

    1998-11-01

    The potential of heteronuclear {1H-13C} cross polarization was studied for optimization of the signal-to-noise ratio inin vivo13C MR spectroscopy at the clinical field strength of 1.5 T. Experiments on the human calf showed a significant chemical-shift selective signal enhancement on triglyceride signals of 3.9 by heteronuclear cross polarization, compared to a standard pulse-acquire sequence. Studies on a neonatal piglet brain showed an enhancement by cross polarization of 2.2 for the detection of13C-1-glucose. This enhancement allowed a fourfold improvement in time resolution in dynamic13C MR of13C-1-glucose inflow in piglet brain. Phantom experiments demonstrated the efficiency of this technique for interleaved detection of two spectral regions. Tests with a volume coil showed the feasibility of signal enhancement by cross polarization over a large volume of interest.

  3. 15N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH

    PubMed Central

    2016-01-01

    NMR signal amplification by reversible exchange (SABRE) is a NMR hyperpolarization technique that enables nuclear spin polarization enhancement of molecules via concurrent chemical exchange of a target substrate and parahydrogen (the source of spin order) on an iridium catalyst. Recently, we demonstrated that conducting SABRE in microtesla fields provided by a magnetic shield enables up to 10% 15N-polarization (Theis, T.; et al. J. Am. Chem. Soc.2015, 137, 1404). Hyperpolarization on 15N (and heteronuclei in general) may be advantageous because of the long-lived nature of the hyperpolarization on 15N relative to the short-lived hyperpolarization of protons conventionally hyperpolarized by SABRE, in addition to wider chemical shift dispersion and absence of background signal. Here we show that these unprecedented polarization levels enable 15N magnetic resonance imaging. We also present a theoretical model for the hyperpolarization transfer to heteronuclei, and detail key parameters that should be optimized for efficient 15N-hyperpolarization. The effects of parahydrogen pressure, flow rate, sample temperature, catalyst-to-substrate ratio, relaxation time (T1), and reversible oxygen quenching are studied on a test system of 15N-pyridine in methanol-d4. Moreover, we demonstrate the first proof-of-principle 13C-hyperpolarization using this method. This simple hyperpolarization scheme only requires access to parahydrogen and a magnetic shield, and it provides large enough signal gains to enable one of the first 15N images (2 × 2 mm2 resolution). Importantly, this method enables hyperpolarization of molecular sites with NMR T1 relaxation times suitable for biomedical imaging and spectroscopy. PMID:25960823

  4. Hydration properties of regioselectively etherified celluloses monitored by 2H and 13C solid-state MAS NMR spectroscopy.

    PubMed

    Larsen, Flemming H; Schöbitz, Michael; Schaller, Jens

    2012-06-20

    The hydration properties of 2,3-O-hydroxypropylcellulose (HPC) and 2,3-O-hydroxyethylcellulose (HEC) were analyzed by multi-nuclear solid-state MAS NMR spectroscopy. By 13C single-pulse (SP) MAS and cross-polarization (CP) MAS NMR, differences between the immobile regions and all parts of the polysaccharides were detected as a function of hydration. Complementary information about the water environments was observed by 2H MAS NMR. By this approach it was demonstrated that side chains in 2,3-O-HPC and 2,3-O-HEC were easier to hydrate than the cellulose backbone. Furthermore the motion of water was more restricted (slower) in 2,3-O-HPC than in 2,3-O-HEC. For both polysaccharides the hydration could be explained by a two-step process: in step one increased ordering of the immobile regions occurs after which the entire polymer is hydrated in step two.

  5. Using 13C-labeled benzene and Raman gas spectroscopy to investigate respiration and biodegradation kinetics following soil contamination

    NASA Astrophysics Data System (ADS)

    Jochum, Tobias; Popp, Juergen; Frosch, Torsten

    2016-04-01

    Soil and groundwater contamination with benzene can cause serious environmental damages. However, many soil microorganisms are capable to adapt and known to strongly control the fate of organic contamination. Cavity enhanced Raman gas spectroscopy (CERS) was applied to investigate the short-term response of indigenous soil bacteria to a sudden surface contamination with benzene regarding the temporal variations of gas products and their exchange rates with the adjacent atmosphere. 13C-labeled benzene was spiked on a silty-loamy soil column (sampled from Hainich National Park, Germany) in order to track and separate the changes in heterotrophic soil respiration - involving 12CO2 and O2 - from the microbial process of benzene degradation, which ultimately forms 13CO2.1 The respiratory quotient (RQ) of 0.98 decreased significantly after the spiking and increased again within 33 hours to a value of 0.72. This coincided with maximum 13CO2 concentration rates (0.63 μ mol m-2 s-1), indicating highest benzene degradation at 33 hours after the spiking event. The diffusion of benzene in the headspace and the biodegradation into 13CO2 were simultaneously monitored and 12 days after the benzene spiking no measurable degradation was detected anymore.1 The RQ finally returned to a value of 0.96 demonstrating the reestablished aerobic respiration. In summary, this study shows the potential of combining Raman gas spectroscopy and stable isotopes to follow soil microbial biodegradation dynamics while simultaneously monitoring the underlying respiration behavior. Support by the Collaborative Research Center 1076 Aqua Diva is kindly acknowledged. We thank Beate Michalzik for soil analysis and discussion. 1. T. Jochum, B. Michalzik, A. Bachmann, J. Popp and T. Frosch, Analyst, 2015, 140, 3143-3149.

  6. Diode laser spectroscopy of the fundamental bands of 12C14N, 13C14N, 12C15N, 13C15N free radicals in the ground 2 Sigma+ electronic state.

    PubMed

    Hübner, M; Castillo, M; Davies, P B; Röpcke, J

    2005-01-01

    Rotationally resolved spectra of the fundamental band of the CN free radical in four isotopic forms have been measured using tunable diode laser absorption spectroscopy. The source of the radical was a microwave discharge in a mixture of isotopically selected methane and nitrogen diluted with argon. The lines were measured to an accuracy of 5 x 10(-4) cm(-1) and fitted to the formula for the vibration rotation spectrum of a diatomic molecule, including quartic distortion constants. The band origins of each of the isotopomers from the five parameter fits were found to be 12C14N: 2042.42115(38) cm(-1), 13C14N: 2000.08479(23) cm(-1), 12C15N: 2011.25594(25) cm(-1), 13C15N: 1968.22093(33) cm(-1) with one standard deviation from the fit given in parenthesis. Some of the lines showed a resolved splitting due to the spin rotation interaction. This was averaged for fitting purposes. The average equilibrium internuclear distance derived from the upsilon = 0 and 1 rotational constants of the four isotopomers is 1.171800(6) A which is in good agreement with the value determined from microwave spectroscopy.

  7. Characterization of pyrogenic organic matter by 2-dimenstional HETeronucleus CORelation solid-state 13C NMR (HETCOR) spectroscopy

    NASA Astrophysics Data System (ADS)

    Knicker, Heike

    2016-04-01

    technique was used for monitoring the chemical changes occurring during charring of biomass derived from model compounds, fire-affected and unaffected NOM. The 2D 13C HETCOR NMR spectrum of the fire- unaffected soils revealed that most of the carboxyl C occurs as ester or amide. Aside from cross peaks typically seen in spectra of NOM, the spectrum of the respective fire-affected counterpart shows additional signals assignable to PyOM.

  8. The use of dynamic nuclear polarization 13C-pyruvate MRS in cancer

    PubMed Central

    Gutte, Henrik; Hansen, Adam Espe; Johannesen, Helle Hjorth; Clemmensen, Andreas Ettrup; Ardenkjær-Larsen, Jan Henrik; Nielsen, Carsten Haagen; Kjær, Andreas

    2015-01-01

    In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is 13C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized 13C-pyruvate results in appearance of 13C-lactate, 13C-alanine and 13C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced 13C-pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized 13C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated 13C-lactate/13C-pyruvate ratio in regions of biopsy

  9. 1H and 13C resonance designation of antimycin A1 by two-dimensional NMR spectroscopy

    USGS Publications Warehouse

    Abidi, S.L.; Adams, B.R.

    1987-01-01

    Complete 1H and 13C resonance assignments of antimycin A1 were accomplished by two-dimensional NMR techniques, viz. 1H homonuclear COSY correlation, heteronuclear 13C-1H chemical shift correlation and long-range heteronuclear 13C-1H COLOC correlation. Antimycin A1 was found to consist of two isomeric components in a 2:1 ratio based on NMR spectroscopic evidence. The structure of the major component was newly assigned as the 8-isopentanoic acid ester. The spectra of the minor component were consistent with the known structure of antimycin A1.

  10. Use of In Vivo 13C Nuclear Magnetic Resonance Spectroscopy To Elucidate l-Arabinose Metabolism in Yeasts▿

    PubMed Central

    Fonseca, César; Neves, Ana Rute; Antunes, Alexandra M. M.; Noronha, João Paulo; Hahn-Hägerdal, Bärbel; Santos, Helena; Spencer-Martins, Isabel

    2008-01-01

    Candida arabinofermentans PYCC 5603T and Pichia guilliermondii PYCC 3012 were shown to grow well on l-arabinose, albeit exhibiting distinct features that justify an in-depth comparative study of their respective pentose catabolism. Carbon-13 labeling experiments coupled with in vivo nuclear magnetic resonance (NMR) spectroscopy were used to investigate l-arabinose metabolism in these yeasts, thereby complementing recently reported physiological and enzymatic data. The label supplied in l-[2-13C]arabinose to nongrowing cells, under aerobic conditions, was found on C-1 and C-2 of arabitol and ribitol, on C-2 of xylitol, and on C-1, C-2, and C-3 of trehalose. The detection of labeled arabitol and xylitol constitutes additional evidence for the operation in yeast of the redox catabolic pathway, which is widespread among filamentous fungi. Furthermore, labeling at position C-1 of trehalose and arabitol demonstrates that glucose-6-phosphate is recycled through the oxidative pentose phosphate pathway (PPP). This result was interpreted as a metabolic strategy to regenerate NADPH, the cofactor essential for sustaining l-arabinose catabolism at the level of l-arabinose reductase and l-xylulose reductase. Moreover, the observed synthesis of d-arabitol and ribitol provides a route with which to supply NAD+ under oxygen-limiting conditions. In P. guilliermondii PYCC 3012, the strong accumulation of l-arabitol (intracellular concentration of up to 0.4 M) during aerobic l-arabinose metabolism indicates the existence of a bottleneck at the level of l-arabitol 4-dehydrogenase. This report provides the first experimental evidence for a link between l-arabinose metabolism in fungi and the oxidative branch of the PPP and suggests rational guidelines for the design of strategies for the production of new and efficient l-arabinose-fermenting yeasts. PMID:18245253

  11. Discovering [superscript 13]C NMR, [superscript 1]H NMR, and IR Spectroscopy in the General Chemistry Laboratory through a Sequence of Guided-Inquiry Exercises

    ERIC Educational Resources Information Center

    Iler, H. Darrell; Justice, David; Brauer, Shari; Landis, Amanda

    2012-01-01

    This sequence of three guided-inquiry labs is designed for a second-semester general chemistry course and challenges students to discover basic theoretical principles associated with [superscript 13]C NMR, [superscript 1]H NMR, and IR spectroscopy. Students learn to identify and explain basic concepts of magnetic resonance and vibrational…

  12. Identification of Li-Ion Battery SEI Compounds through (7)Li and (13)C Solid-State MAS NMR Spectroscopy and MALDI-TOF Mass Spectrometry.

    PubMed

    Huff, Laura A; Tavassol, Hadi; Esbenshade, Jennifer L; Xing, Wenting; Chiang, Yet-Ming; Gewirth, Andrew A

    2016-01-13

    Solid-state (7)Li and (13)C MAS NMR spectra of cycled graphitic Li-ion anodes demonstrate SEI compound formation upon lithiation that is followed by changes in the SEI upon delithiation. Solid-state (13)C DPMAS NMR shows changes in peaks associated with organic solvent compounds (ethylene carbonate and dimethyl carbonate, EC/DMC) upon electrochemical cycling due to the formation of and subsequent changes in the SEI compounds. Solid-state (13)C NMR spin-lattice (T1) relaxation time measurements of lithiated Li-ion anodes and reference poly(ethylene oxide) (PEO) powders, along with MALDI-TOF mass spectrometry results, indicate that large-molecular-weight polymers are formed in the SEI layers of the discharged anodes. MALDI-TOF MS and NMR spectroscopy results additionally indicate that delithiated anodes exhibit a larger number of SEI products than is found in lithiated anodes. PMID:26653886

  13. High-field 13C NMR spectroscopy of tissue in Vivo. A double-resonance surface-coil probe

    NASA Astrophysics Data System (ADS)

    Reo, Nicholas V.; Ewy, Coleen S.; Siegfried, Barry A.; Ackerman, Joseph J. H.

    A double-resonance surface-coil NMR probe is described for performance of high-field (8.5 T) proton decoupled carbon-13 experiments with tissue in vivo. The probe may be accommodated in standard, 89 mm i.d. clear bore, commercial spectrometers and is suitable for studies utilizing small laboratory animals such as mice, hamsters, and rats. A coaxial coil design is employed (10 mm diameter 13C coil, 20 mm diameter 1H coil) which provides ca. 40 dB attenuation between the 13C observe and 1H decouple channels. The inherent efficiency of the surface-coil configuration provides a sensitivity comparable to a commercial probe of the same nominal dimension (10 mm Helmholtz coil) and assures adequate decoupling in conductive samples with ca. 3-5 W power. In the absence of 13C isotopic enrichment, NMR spectra of rat leg, liver, and brain in vivo provide signalto-noise sufficient for 10 min time resolution. Administration of 100 mg of 90% 13C-labeled glucose into a peripheral vein of a ca. 300 g rat resulted in a liver glucose resonance which could be monitored with good signal-to-noise and 3 min time resolution.

  14. Studies on the mechanism of the peroxyoxalate chemiluminescence reaction: part 2. Further identification of intermediates using 2D EXSY 13C nuclear magnetic resonance spectroscopy.

    PubMed

    Tonkin, Sarah A; Bos, Richard; Dyson, Gail A; Lim, Kieran F; Russell, Richard A; Watson, Simon P; Hindson, Christopher M; Barnett, Neil W

    2008-05-01

    Further consideration has been given to the reaction pathway of a model peroxyoxalate chemiluminescence system. Again utilising doubly labelled oxalyl chloride and anhydrous hydrogen peroxide, 2D EXSY (13)C nuclear magnetic resonance (NMR) spectroscopy experiments allowed for the characterisation of unknown products and key intermediate species on the dark side of the peroxyoxalate chemiluminescence reaction. Exchange spectroscopy afforded elucidation of a scheme comprised of two distinct mechanistic pathways, one of which contributes to chemiluminescence. (13)C NMR experiments carried out at varied reagent molar ratios demonstrated that excess amounts of hydrogen peroxide favoured formation of 1,2-dioxetanedione: the intermediate that, upon thermolysis, has been long thought to interact with a fluorophore to produce light. PMID:18420048

  15. Chemical composition of the essential oil from Corsican Mentha aquatica--combined analysis by GC(RI), GC-MS and 13C NMR spectroscopy.

    PubMed

    Sutour, Sylvain; Tomi, Félix; Bradesi, Pascale; Casanova, Joseph

    2011-10-01

    The essential oil (EO) of M. aquatica L. growing wild in Corsica was isolated by dry vapor distillation and submitted to combined analysis by column chromatography over silica gel, GC(RI), GC-MS and 13C NMR spectroscopy. The composition was dominated byoxygenated monoterpenes and characterized by the occurrence of menthofuran (50.7%) as the major component. In parallel, seven laboratory-distilled oil samples isolated from individual plants collected in Corsica were analyzed by GC(RI) and 13C NMR spectroscopy. Onlyquantitative differences were observed between the samples. Beside the usual terpenes, various p-menthane lactones (mintlactone, isomintlactone, hydroxymintlactone, menthofurolactone and epimenthofurolactone) have been identified in all the oil samples.

  16. Reproducibility and absolute quantification of muscle glycogen in patients with glycogen storage disease by 13C NMR spectroscopy at 7 Tesla.

    PubMed

    Heinicke, Katja; Dimitrov, Ivan E; Romain, Nadine; Cheshkov, Sergey; Ren, Jimin; Malloy, Craig R; Haller, Ronald G

    2014-01-01

    Carbon-13 magnetic resonance spectroscopy (13C MRS) offers a noninvasive method to assess glycogen levels in skeletal muscle and to identify excess glycogen accumulation in patients with glycogen storage disease (GSD). Despite the clinical potential of the method, it is currently not widely used for diagnosis or for follow-up of treatment. While it is possible to perform acceptable 13C MRS at lower fields, the low natural abundance of 13C and the inherently low signal-to-noise ratio of 13C MRS makes it desirable to utilize the advantage of increased signal strength offered by ultra-high fields for more accurate measurements. Concomitant with this advantage, however, ultra-high fields present unique technical challenges that need to be addressed when studying glycogen. In particular, the question of measurement reproducibility needs to be answered so as to give investigators insight into meaningful inter-subject glycogen differences. We measured muscle glycogen levels in vivo in the calf muscle in three patients with McArdle disease (MD), one patient with phosphofructokinase deficiency (PFKD) and four healthy controls by performing 13C MRS at 7T. Absolute quantification of the MRS signal was achieved by using a reference phantom with known concentration of metabolites. Muscle glycogen concentration was increased in GSD patients (31.5±2.9 g/kg w. w.) compared with controls (12.4±2.2 g/kg w. w.). In three GSD patients glycogen was also determined biochemically in muscle homogenates from needle biopsies and showed a similar 2.5-fold increase in muscle glycogen concentration in GSD patients compared with controls. Repeated inter-subject glycogen measurements yield a coefficient of variability of 5.18%, while repeated phantom measurements yield a lower 3.2% system variability. We conclude that noninvasive ultra-high field 13C MRS provides a valuable, highly reproducible tool for quantitative assessment of glycogen levels in health and disease.

  17. Determination of the structural changes by Raman and {sup 13}C CP/MAS NMR spectroscopy on native corn starch with plasticizers

    SciTech Connect

    Cozar, O.; Filip, C.; Tripon, C.; Cioica, N.; Coţa, C.; Nagy, E. M.

    2013-11-13

    The plasticizing - antiplasticizing effect of water and glycerol contents on native corn starch samples is investigated by FT-Raman and {sup 13}C CP/MAS NMR spectroscopy. The presence of both amorphous and crystalline structural phases was evidenced in pure native corn starch and also in the samples containing plasticizers. Among the crystalline starch structures, the A- and V- types were suggested by CP/MAS NMR spectra.

  18. Direct identification and quantitative determination of costunolide and dehydrocostuslactone in the fixed oil of Laurus novocanariensis by 13C-NMR spectroscopy.

    PubMed

    Ferrari, Bernard; Castilho, Paula; Tomi, Félix; Rodrigues, Ana Isabel; do Ceu Costa, Maria; Casanova, Joseph

    2005-01-01

    The fixed oil of Laurus novocanariensis (previously L. azorica) contains mostly glycerides together with minor non-saponifiable compounds. The direct identification and quantitative determination of costunolide and dehydrocostuslactone, two sesquiterpene lactones components of the oil that exhibit biological activities, is described. The analysis was carried out using 13C-NMR spectroscopy (signal acquisition with inverse gated decoupling of protons; diglyme as internal standard) without separation, derivatisation or any sample preparation.

  19. High-Resolution Correlation Spectroscopy of 13C Spins Near a Nitrogen-Vacancy Center in Diamond

    NASA Astrophysics Data System (ADS)

    Meriles, Carlos; Laraoui, Abdelghani; Dolde, Florian; Wracthrup, Joerg; Reinhard, Friedemann; Burk, Christian

    2013-03-01

    We use a pulse protocol to monitor the time evolution of the 13C ensemble in the vicinity of a NV center. We observe time correlations in the nuclear spin dynamics that extend over several milliseconds exceeding the color center coherence lifetime by more than an order of magnitude. Upon Fourier transform, we separate 13C spins exhibiting differing coupling constants with a frequency resolution inversely proportional to the NV spin-lattice relaxation time. Further, we use the nuclear spin of the host nitrogen as a quantum register during the correlation interval and demonstrate that hyperfine-shifted resonances in this spectrum can be separated from the bare carbon peak upon proper initialization of the NV. Intriguingly, we find that the amplitude of the correlation signal exhibits a sharp dependence on the applied magnetic field, virtually disappearing below a critical field common to all centers. The value of this transition field can be `tuned' by properly adjusting the timing within our correlation scheme. We discuss these observations in the context of the `quantum-to-classical' transition proposed recently to explain the combined dynamics of the NV spin and the 13C bath at variable magnetic field. A.L. and C.A.M. acknowledge support from Research Corp., the von Humboldt Foundation, and NSF. F.D., C.B., F.R. and J.W. acknowledge support from the EU, the DFG, and the Volkswagen Foundation.

  20. /sup 13/C NMR spectroscopy in the analysis of conjugate metabolites in the bile of fish exposed to petroleum

    SciTech Connect

    Hellou, J.; Banoub, J.H.; Payne, J.F.

    1986-01-01

    The first natural abundance /sup 13/C NMR investigation of a complex mixture of conjugate metabolites obtained from the gall bladder bile of fish exposed to hydrocarbons is presented. Cunners were exposed to water accommodated No. 2 fuel oil containing about 68% saturates and 22% aromatics. Spectral analysis indicated that the hydrocarbon derivatives were present predominantly as ..beta..-glucuronides, with the oxygen at carbon-1 of glucuronic acid preferentially attached to an aliphatic carbon. The conjugate metabolites were enriched in aromatic-type carbons when compared to the fuel oil or the aromatic fraction of oil.

  1. High-resolution solid-state 13C NMR spectroscopy of the paramagnetic metal-organic frameworks, STAM-1 and HKUST-1.

    PubMed

    Dawson, Daniel M; Jamieson, Lauren E; Mohideen, M Infas H; McKinlay, Alistair C; Smellie, Iain A; Cadou, Romain; Keddie, Neil S; Morris, Russell E; Ashbrook, Sharon E

    2013-01-21

    Solid-state (13)C magic-angle spinning (MAS) NMR spectroscopy is used to investigate the structure of the Cu(II)-based metal-organic frameworks (MOFs), HKUST-1 and STAM-1, and the structural changes occurring within these MOFs upon activation (dehydration). NMR spectroscopy is an attractive technique for the investigation of these materials, owing to its high sensitivity to local structure, without any requirement for longer-range order. However, interactions between nuclei and unpaired electrons in paramagnetic systems (e.g., Cu(II)-based MOFs) pose a considerable challenge, not only for spectral acquisition, but also in the assignment and interpretation of the spectral resonances. Here, we exploit the rapid T(1) relaxation of these materials to obtain (13)C NMR spectra using a spin-echo pulse sequence at natural abundance levels, and employ frequency-stepped acquisition to ensure uniform excitation of resonances over a wide frequency range. We then utilise selective (13)C isotopic labelling of the organic linker molecules to enable an unambiguous assignment of NMR spectra of both MOFs for the first time. We show that the monomethylated linker can be recovered from STAM-1 intact, demonstrating not only the interesting use of this MOF as a protecting group, but also the ability (for both STAM-1 and HKUST-1) to recover isotopically-enriched linkers, thereby reducing significantly the overall cost of the approach.

  2. FTIR and NDIR spectroscopies as valuable alternatives to IRMS spectrometry for the δ(13)C analysis of food.

    PubMed

    Pironti, Concetta; Proto, Antonio; Camin, Federica; Cucciniello, Raffaele; Zarrella, Ilaria; Motta, Oriana

    2016-11-01

    The (13)C/(12)C carbon isotope ratio is a chemical parameter with many important applications in several scientific area and the technique of choice currently used for the δ(13)C determination is the isotope ratio mass spectrometry (IRMS). This latter is highly accurate (0.1‰) and sensitive (up to 0.01‰), but at the same time expensive and complex. The objective of this work was to assess the reliability of FTIR and NDIRS techniques for the measurement of carbon stable isotope ratio of food sample, in comparison to IRMS. IRMS, NDIRS and FTIR were used to analyze samples of food, such as oil, durum, cocoa, pasta and sugar, in order to determine the natural abundance isotopic ratio of carbon in a parallel way. The results were comparable, showing a close relationship among the three techniques. The main advantage in using FTIR and NDIRS is related to their cheapness and easy-to-operate in comparison to IRMS. PMID:27591614

  3. Trace level detection of compounds related to the chemical weapons convention by 1H-detected 13C NMR spectroscopy executed with a sensitivity-enhanced, cryogenic probehead.

    PubMed

    Cullinan, David B; Hondrogiannis, George; Henderson, Terry J

    2008-04-15

    Two-dimensional 1H-13C HSQC (heteronuclear single quantum correlation) and fast-HMQC (heteronuclear multiple quantum correlation) pulse sequences were implemented using a sensitivity-enhanced, cryogenic probehead for detecting compounds relevant to the Chemical Weapons Convention present in complex mixtures. The resulting methods demonstrated exceptional sensitivity for detecting the analytes at trace level concentrations. 1H-13C correlations of target analytes at < or = 25 microg/mL were easily detected in a sample where the 1H solvent signal was approximately 58,000-fold more intense than the analyte 1H signals. The problem of overlapping signals typically observed in conventional 1H spectroscopy was essentially eliminated, while 1H and 13C chemical shift information could be derived quickly and simultaneously from the resulting spectra. The fast-HMQC pulse sequences generated magnitude mode spectra suitable for detailed analysis in approximately 4.5 h and can be used in experiments to efficiently screen a large number of samples. The HSQC pulse sequences, on the other hand, required roughly twice the data acquisition time to produce suitable spectra. These spectra, however, were phase-sensitive, contained considerably more resolution in both dimensions, and proved to be superior for detecting analyte 1H-13C correlations. Furthermore, a HSQC spectrum collected with a multiplicity-edited pulse sequence provided additional structural information valuable for identifying target analytes. The HSQC pulse sequences are ideal for collecting high-quality data sets with overnight acquisitions and logically follow the use of fast-HMQC pulse sequences to rapidly screen samples for potential target analytes. Use of the pulse sequences considerably improves the performance of NMR spectroscopy as a complimentary technique for the screening, identification, and validation of chemical warfare agents and other small-molecule analytes present in complex mixtures and environmental

  4. A magnetic tunnel to shelter hyperpolarized fluids

    SciTech Connect

    Milani, Jonas Vuichoud, Basile; Bornet, Aurélien; Miéville, Pascal; Mottier, Roger; Jannin, Sami; Bodenhausen, Geoffrey

    2015-02-15

    To shield solutions carrying hyperpolarized nuclear magnetization from rapid relaxation during transfer through low fields, the transfer duct can be threaded through an array of permanent magnets. The advantages are illustrated for solutions containing hyperpolarized {sup 1}H and {sup 13}C nuclei in a variety of molecules.

  5. Quantification of taxanes in a leaf and twig extract from Taxus baccata L. using 13C NMR spectroscopy.

    PubMed

    Paoli, Mathieu; Bighelli, Ange; Castola, Vincent; Tomi, Félix; Casanova, Joseph

    2013-11-01

    In the course of our ongoing work on the chemical characterization of Taxus baccata L. growing wild in Corsica, we have developed and validated a method for direct quantification of taxane derivatives by (13)C NMR using 10-deacetylbaccatin III as reference compound and 1,6-hexanediol as internal standard. We have observed good accuracy (relative errors between 0.3% and 3.5%), linearity (R(2) = 0.999) and precision (reproducibility 8.5 mg ± 1.1%) of the measurements. The experimental procedure was applied to the quantification of six identified taxanes in a fraction of chromatography of a methanol extract of T. baccata leaves. This method can be applied to other compounds bearing the taxane skeleton.

  6. Comprehensive determination of protein tyrosine pKa values for photoactive yellow protein using indirect 13C NMR spectroscopy.

    PubMed

    Oktaviani, Nur Alia; Pool, Trijntje J; Kamikubo, Hironari; Slager, Jelle; Scheek, Ruud M; Kataoka, Mikio; Mulder, Frans A A

    2012-02-01

    Upon blue-light irradiation, the bacterium Halorhodospira halophila is able to modulate the activity of its flagellar motor and thereby evade potentially harmful UV radiation. The 14 kDa soluble cytosolic photoactive yellow protein (PYP) is believed to be the primary mediator of this photophobic response, and yields a UV/Vis absorption spectrum that closely matches the bacterium's motility spectrum. In the electronic ground state, the para-coumaric acid (pCA) chromophore of PYP is negatively charged and forms two short hydrogen bonds to the side chains of Glu-46 and Tyr-42. The resulting acid triad is central to the marked pH dependence of the optical-absorption relaxation kinetics of PYP. Here, we describe an NMR approach to sequence-specifically follow all tyrosine side-chain protonation states in PYP from pH 3.41 to 11.24. The indirect observation of the nonprotonated (13)C(γ) resonances in sensitive and well-resolved two-dimensional (13)C-(1)H spectra proved to be pivotal in this effort, as observation of other ring-system resonances was hampered by spectral congestion and line-broadening due to ring flips. We observe three classes of tyrosine residues in PYP that exhibit very different pK(a) values depending on whether the phenolic side chain is solvent-exposed, buried, or hydrogen-bonded. In particular, our data show that Tyr-42 remains fully protonated in the pH range of 3.41-11.24, and that pH-induced changes observed in the photocycle kinetics of PYP cannot be caused by changes in the charge state of Tyr-42. It is therefore very unlikely that the pCA chromophore undergoes changes in its electrostatic interactions in the electronic ground state. PMID:22325281

  7. Glucuronoxylomannan of Cryptococcus neoformans serotype B: structural analysis by gas-liquid chromatography-mass spectrometry and 13C-nuclear magnetic resonance spectroscopy.

    PubMed

    Turner, S H; Cherniak, R

    1991-04-01

    The major extracellular polysaccharide (glucuronoxylomannan, GXM) from six strains of Cryptococcus neoformans serotype B was characterized by gas-liquid chromatography (g.l.c.), g.l.c.-mass spectrometry (g.l.c.-m.s.), and nuclear magnetic resonance (n.m.r.) spectroscopy. Ultrasonic irradiation (u.i.) was used to reduce the mol.wt. of native GXM from 9.75 x 10(5) to 1.15 x 10(5) without apparent change in its composition (GXM-S). The Xylp:Manp:GlcpA molar ratio of the GXM and GXM-S from the six strains of C. neoformans serotype B is approximately 3.5:3.0:0.6. GXM-S was O-deacetylated (GXM-D) by treatment with NH4OH. The 13C-n.m.r. analysis of GXM-D gave spectra that served as characteristic fingerprints of the structure and also facilitated the assignment of the anomeric carbon resonances to specific structural moieties present in GXM-D. The GXM-D from each serotype B strain was found to be similar by 13C-n.m.r. spectroscopy. The structure contains a linear (1----3)-alpha-D-Manp backbone substituted with 2-O-beta-GlcpA and 2-O-beta-Xylp. beta-Xylp is also O-4 linked to the Manp substituted with GlcpA. In addition, a model for the disposition of the Xylp and GlcpA side chain substituents along the mannopyranan backbone is proposed, based upon results from the combination of g.l.c.-m.s. and 13C-n.m.r. spectroscopy. PMID:1773425

  8. Conformational mapping of the N-terminal segment of surfactant protein B in lipid using 13C-enhanced Fourier transform infrared spectroscopy.

    PubMed

    Gordon, L M; Lee, K Y; Lipp, M M; Zasadzinski, J A; Walther, F J; Sherman, M A; Waring, A J

    2000-04-01

    Synthetic peptides based on the N-terminal domain of human surfactant protein B (SP-B1-25; 25 amino acid residues; NH2-FPIPLPYCWLCRALIKRIQAMIPKG) retain important lung activities of the full-length, 79-residue protein. Here, we used physical techniques to examine the secondary conformation of SP-B1-25 in aqueous, lipid and structure-promoting environments. Circular dichroism and conventional, 12C-Fourier transform infrared (FTIR) spectroscopy each indicated a predominate alpha-helical conformation for SP-B1-25 in phosphate-buffered saline, liposomes of 1-palmitoyl-2-oleoyl phosphatidylglycerol and the structure-promoting solvent hexafluoroisopropanol; FTIR spectra also showed significant beta- and random conformations for peptide in these three environments. In further experiments designed to map secondary structure to specific residues, isotope-enhanced FTIR spectroscopy was performed with 1-palmitoyl-2-oleoyl phosphatidylglycerol liposomes and a suite of SP-B1-25 peptides labeled with 13C-carbonyl groups at either single or multiple sites. Combining these 13C-enhanced FTIR results with energy minimizations and molecular simulations indicated the following model for SP-B1-25 in 1-palmitoyl-2-oleoyl phosphatidylglycerol: beta-sheet (residues 1-6), alpha-helix (residues 8-22) and random (residues 23-25) conformations. Analogous structural motifs are observed in the corresponding homologous N-terminal regions of several proteins that also share the 'saposin-like' (i.e. 5-helix bundle) folding pattern of full-length, human SP-B. In future studies, 13C-enhanced FTIR spectroscopy and energy minimizations may be of general use in defining backbone conformations at amino acid resolution, particularly for peptides or proteins in membrane environments.

  9. Hydrogen bonding induced distortion of CO3 units and kinetic stabilization of amorphous calcium carbonate: results from 2D (13)C NMR spectroscopy.

    PubMed

    Sen, Sabyasachi; Kaseman, Derrick C; Colas, Bruno; Jacob, Dorrit E; Clark, Simon M

    2016-07-27

    Systematic correlation in alkaline-earth carbonate compounds between the deviation of the CO3 units from the perfect D3h symmetry and their (13)C nuclear magnetic resonance (NMR) chemical shift anisotropy (CSA) parameters is established. The (13)C NMR CSA parameters of amorphous calcium carbonate (ACC) are measured using two-dimensional (13)C phase adjusted spinning sidebands (PASS) NMR spectroscopy and are analyzed on the basis of this correlation. The results indicate a distortion of the CO3 units in ACC in the form of an in-plane displacement of the C atom away from the centroid of the O3 triangle, resulting from hydrogen bonding with the surrounding H2O molecules, without significant out-of-plane displacement. Similar distortion for all C atoms in the structure of ACC suggests a uniform spatial disposition of H2O molecules around the CO3 units forming a hydrogen-bonded amorphous network. This amorphous network is stabilized against crystallization by steric frustration, while additives such as Mg presumably provide further stabilization by increasing the energy of dehydration. PMID:27276013

  10. Solid-state /sup 13/C nuclear magnetic resonance spectroscopy of simultaneously metabolized acetate and phenol in a soil Pseudomonas sp

    SciTech Connect

    Heiman, A.S.; Copper, W.T.

    1987-01-01

    An investigation was made of the concentration-dependent primary and secondary substrate relationships in the simultaneous metabolism of the ubiquitous pollutant phenol and the naturally occurring substrate acetate by a Pseudomonas sp. soil isolate capable of utilizing either substance as a sole source of carbon and energy. In addition to conventional analytical techniques, solid-state /sup 13/C nuclear magnetic resonance spectroscopy was used to follow the cellular distribution of (1-/sup 13/C)acetate in the presence of unlabeled phenol. These results suggest that, when phenol is present as the primary substrate, acetate is preferentially shuttled into fatty acyl chain synthesis, whereas phenol carbon is funnelled into the tricarboxylic acid cycle. Thus, simultaneous use of a xenobiotic compound and a natural substrate apparently does occur, and the relative concentrations of the two substrates do influence the rate and manner in which the compounds are utilized. These results also demonstrate the unique advantage of using solid-state nuclear magnetic resonance techniques combined with /sup 13/C labeling of specific sites in substrates when doing microbial degradation studies. In this work, the entire cellular biomass was examined directly without extensive extraction, fractionation, or isolation of subcellular units; thus, there is no uncertainty about chemical alteration of substrate metabolites as a result of these often harsh treatments.

  11. FT-IR spectroscopy and density functional theory calculations of 13C isotopologues of the helical peptide Z-Aib6-OtBu.

    PubMed

    Zeko, Timothy; Hannigan, Steven F; Jacisin, Timothy; Guberman-Pfeffer, Matthew J; Falcone, Eric R; Guildford, Melissa J; Szabo, Christopher; Cole, Kathryn E; Placido, Jessica; Daly, Erin; Kubasik, Matthew A

    2014-01-01

    Isotope-edited FT-IR spectroscopy is a combined synthetic and spectroscopic method used to characterize local (e.g., residue-level) vibrational environments of biomolecules. We have prepared the 3(10) helical peptide Z-Aib6-OtBu and seven (13)C-enriched analogues that vary only in the number and position(s) of (13)C═O isotopic enrichment. FT-IR spectra of these eight peptides solvated in the nonpolar aprotic solvent dichloromethane have been collected and compared to frequency, intensity, and normal mode results of DFT calculations. Single (13)C enrichment of amide functional groups tends to localize amide I vibrational eigenmodes, providing residue-specific information regarding the local environment (e.g., hydrogen bonding or solvent exposure) of the peptide bond. Double (13)C enrichment of Z-Aib6-OtBu allows for examination of interamide coupling between two labeled amide functional groups, providing experimental evidence of interamide coupling in the context of 3(10) helical structure. Although the calculated and observed interamide couplings of Z-Aib6-OtBu are a few cm(-1) and less, the eight peptides exhibit distinct infrared spectra, revealing details of interamide coupling and residue level vibrational environments.

  12. Selective 13C labeling of nucleotides for large RNA NMR spectroscopy using an E. coli strain disabled in the TCA cycle

    PubMed Central

    Thakur, Chandar S.; Sama, Jacob N.; Jackson, Melantha E.; Chen, Bin

    2010-01-01

    Escherichia coli (E. coli) is an ideal organism to tailor-make labeled nucleotides for biophysical studies of RNA. Recently, we showed that adding labeled formate enhanced the isotopic enrichment at protonated carbon sites in nucleotides. In this paper, we show that growth of a mutant E. coli strain DL323 (lacking succinate and malate dehydrogenases) on 13C-2-glycerol and 13C-1,3-glycerol enables selective labeling at many useful sites for RNA NMR spectroscopy. For DL323 E. coli grown in 13C-2-glycerol without labeled formate, all the ribose carbon atoms are labeled except the C3′ and C5′ carbon positions. Consequently the C1′, C2′ and C4′ positions remain singlet. In addition, only the pyrimidine base C6 atoms are substantially labeled to ~96% whereas the C2 and C8 atoms of purine are labeled to ~5%. Supplementing the growth media with 13C-formate increases the labeling at C8 to ~88%, but not C2. Not unexpectedly, addition of exogenous formate is unnecessary for attaining the high enrichment levels of ~88% for the C2 and C8 purine positions in a 13C-1,3-glycerol based growth. Furthermore, the ribose ring is labeled in all but the C4′ carbon position, such that the C2′ and C3′ positions suffer from multiplet splitting but the C5′ position remains singlet and the C1′ position shows a small amount of residual C1′–C2′ coupling. As expected, all the protonated base atoms, except C6, are labeled to ~90%. In addition, labeling with 13C-1,3-glycerol affords an isolated methylene ribose with high enrichment at the C5′ position (~90%) that makes it particularly attractive for NMR applications involving CH2-TROSY modules without the need for decoupling the C4′ carbon. To simulate the tumbling of large RNA molecules, perdeuterated glycerol was added to a mixture of the four nucleotides, and the methylene TROSY experiment recorded at various temperatures. Even under conditions of slow tumbling, all the expected carbon correlations were observed

  13. Real-time analysis of δ13C- and δD-CH4 in ambient air with laser spectroscopy: method development and first intercomparison results

    NASA Astrophysics Data System (ADS)

    Eyer, S.; Tuzson, B.; Popa, M. E.; van der Veen, C.; Röckmann, T.; Rothe, M.; Brand, W. A.; Fisher, R.; Lowry, D.; Nisbet, E. G.; Brennwald, M. S.; Harris, E.; Zellweger, C.; Emmenegger, L.; Fischer, H.; Mohn, J.

    2015-08-01

    In situ and simultaneous measurement of the three most abundant isotopologues of methane using mid-infrared laser absorption spectroscopy is demonstrated. A field-deployable, autonomous platform is realized by coupling a compact quantum cascade laser absorption spectrometer (QCLAS) to a preconcentration unit, called TRace gas EXtractor (TREX). This unit enhances CH4 mole fractions by a factor of up to 500 above ambient levels and quantitatively separates interfering trace gases such as N2O and CO2. The analytical precision of the QCLAS isotope measurement on the preconcentrated (750 ppm, parts-per-million, μmole/mole) methane is 0.1 and 0.5 ‰ for δ13C- and δD-CH4 at 10 min averaging time. Based on replicate measurements of compressed air during a two-week intercomparison campaign, the repeatability of the TREX-QCLAS was determined to be 0.19 and 1.9 ‰ for δ13C and δD-CH4, respectively. In this intercomparison campaign the new in situ technique is compared to isotope-ratio mass-spectrometry (IRMS) based on glass flask and bag sampling and real time CH4 isotope analysis by two commercially available laser spectrometers. Both laser-based analyzers were limited to methane mole fraction and δ13C-CH4 analysis, and only one of them, a cavity ring down spectrometer, was capable to deliver meaningful data for the isotopic composition. After correcting for scale offsets, the average difference between TREX-QCLAS data and bag/flask sampling-IRMS values are within the extended WMO compatibility goals of 0.2 and 5 ‰ for δ13C- and δD-CH4, respectively. Thus, the intercomparison also reveals the need for reference air samples with accurately determined isotopic composition of CH4 to further improve the interlaboratory compatibility.

  14. Noninvasive measurements of glycogen in perfused mouse livers using chemical exchange saturation transfer NMR and comparison to (13)C NMR spectroscopy.

    PubMed

    Miller, Corin O; Cao, Jin; Chekmenev, Eduard Y; Damon, Bruce M; Cherrington, Alan D; Gore, John C

    2015-06-01

    Liver glycogen represents an important physiological form of energy storage. It plays a key role in the regulation of blood glucose concentrations, and dysregulations in hepatic glycogen metabolism are linked to many diseases including diabetes and insulin resistance. In this work, we develop, optimize, and validate a noninvasive protocol to measure glycogen levels in isolated perfused mouse livers using chemical exchange saturation transfer (CEST) NMR spectroscopy. Model glycogen solutions were used to determine optimal saturation pulse parameters which were then applied to intact perfused mouse livers of varying glycogen content. Glycogen measurements from serially acquired CEST Z-spectra of livers were compared with measurements from interleaved natural abundance (13)C NMR spectra. Experimental data revealed that CEST-based glycogen measurements were highly correlated with (13)C NMR glycogen spectra. Monte Carlo simulations were then used to investigate the inherent (i.e., signal-to-noise-based) errors in the quantification of glycogen with each technique. This revealed that CEST was intrinsically more precise than (13)C NMR, although in practice may be prone to other errors induced by variations in experimental conditions. We also observed that the CEST signal from glycogen in liver was significantly less than that observed from identical amounts in solution. Our results demonstrate that CEST provides an accurate, precise, and readily accessible method to noninvasively measure liver glycogen levels and their changes. Furthermore, this technique can be used to map glycogen distributions via conventional proton magnetic resonance imaging, a capability universally available on clinical and preclinical magnetic resonance imaging (MRI) scanners vs (13)C detection, which is limited to a small fraction of clinical-scale MRI scanners. PMID:25946616

  15. Noninvasive measurements of glycogen in perfused mouse livers using chemical exchange saturation transfer NMR and comparison to (13)C NMR spectroscopy.

    PubMed

    Miller, Corin O; Cao, Jin; Chekmenev, Eduard Y; Damon, Bruce M; Cherrington, Alan D; Gore, John C

    2015-06-01

    Liver glycogen represents an important physiological form of energy storage. It plays a key role in the regulation of blood glucose concentrations, and dysregulations in hepatic glycogen metabolism are linked to many diseases including diabetes and insulin resistance. In this work, we develop, optimize, and validate a noninvasive protocol to measure glycogen levels in isolated perfused mouse livers using chemical exchange saturation transfer (CEST) NMR spectroscopy. Model glycogen solutions were used to determine optimal saturation pulse parameters which were then applied to intact perfused mouse livers of varying glycogen content. Glycogen measurements from serially acquired CEST Z-spectra of livers were compared with measurements from interleaved natural abundance (13)C NMR spectra. Experimental data revealed that CEST-based glycogen measurements were highly correlated with (13)C NMR glycogen spectra. Monte Carlo simulations were then used to investigate the inherent (i.e., signal-to-noise-based) errors in the quantification of glycogen with each technique. This revealed that CEST was intrinsically more precise than (13)C NMR, although in practice may be prone to other errors induced by variations in experimental conditions. We also observed that the CEST signal from glycogen in liver was significantly less than that observed from identical amounts in solution. Our results demonstrate that CEST provides an accurate, precise, and readily accessible method to noninvasively measure liver glycogen levels and their changes. Furthermore, this technique can be used to map glycogen distributions via conventional proton magnetic resonance imaging, a capability universally available on clinical and preclinical magnetic resonance imaging (MRI) scanners vs (13)C detection, which is limited to a small fraction of clinical-scale MRI scanners.

  16. High-Precision Measurement of 13C/12C Isotopic Ratio Using Gas Chromatography-Combustion-Cavity Ring-Down Spectroscopy

    NASA Astrophysics Data System (ADS)

    Saad, N.; Kuramoto, D. S.; Haase, C.; Crosson, E.; Tan, S.; Zare, R. N.

    2009-12-01

    Light stable isotope analysis, and in particular, compound specific isotopic analysis (CSIA), is a valuable tool to elucidate pathways and provide a better insight into biological, ecological, and geological systems. We present here the results of compound-specific isotopic carbon analysis of short chain hydrocarbons using the world’s first combination of gas chromatography, combustion interface, and cavity ring-down spectroscopy (GC-C-CRDS). Cavity ring-down spectroscopy (CRDS) is a highly sensitive optical spectroscopy, one application of which is to measure the stable isotopic ratios in small molecules. Because it uses a highly reflective optical cavity with many kilometers effective path length, CRDS provides some of the most sensitive and precise optical absorption measurements. Most optical spectroscopy isotopic analysis measures the quantities of each isotopologue independently using their distinct ro-vibrational spectra. The most common isotopes measured with optical spectroscopy are 13C and 12C in carbon dioxide. However, the isotopes of hydrogen, oxygen, and sulfur have also been measured. Unlike isotope ratio mass spectrometry (IRMS), optical spectroscopy can distinguish among isobars, which have essentially identical m/z ratios. The combination of chemical separation, chemical conversion, and CRDS makes a nearly universal tool for isotopic analysis of mixtures. In addition, CRDS can tolerate a variety of compounds mixed with the target. For example, CRDS can measure carbon dioxide and its isotopic 13C/12C ratio in the presence of oxygen. Using the novel GC-C-CRDS system, we injected a 75-microliter mixture of approximately equal quantities of methane, ethane, and propane into a gas chromatograph using helium as carrier gas. The methane, ethane, and propane were separated in time by 100 to 200 seconds after the chromatograph. Oxygen gas was added, and the hydrocarbons were combusted in a catalytic combustor with platinum and nickel, held at 1150oC. The

  17. The mobility of chondroitin sulfate in articular and artificial cartilage characterized by 13C magic-angle spinning NMR spectroscopy.

    PubMed

    Scheidt, Holger A; Schibur, Stephanie; Magalhães, Alvicler; de Azevedo, Eduardo R; Bonagamba, Tito J; Pascui, Ovidiu; Schulz, Ronny; Reichert, Detlef; Huster, Daniel

    2010-06-01

    We have studied the molecular dynamics of one of the major macromolecules in articular cartilage, chondroitin sulfate. Applying (13)C high-resolution magic-angle spinning NMR techniques, the NMR signals of all rigid macromolecules in cartilage can be suppressed, allowing the exclusive detection of the highly mobile chondroitin sulfate. The technique is also used to detect the chondroitin sulfate in artificial tissue-engineered cartilage. The tissue-engineered material that is based on matrix producing chondrocytes cultured in a collagen gel should provide properties as close as possible to those of the natural cartilage. Nuclear relaxation times of the chondroitin sulfate were determined for both tissues. Although T(1) relaxation times are rather similar, the T(2) relaxation in tissue-engineered cartilage is significantly shorter. This suggests that the motions of chondroitin sulfate in natural and artificial cartilage are different. The nuclear relaxation times of chondroitin sulfate in natural and tissue-engineered cartilage were modeled using a broad distribution function for the motional correlation times. Although the description of the microscopic molecular dynamics of the chondroitin sulfate in natural and artificial cartilage required the identical broad distribution functions for the correlation times of motion, significant differences in the correlation times of motion that are extracted from the model indicate that the artificial tissue does not fully meet the standards of the natural ideal. This could also be confirmed by macroscopic biomechanical elasticity measurements. Nevertheless, these results suggest that NMR is a useful tool for the investigation of the quality of artificially engineered tissue. PMID:20091673

  18. Detection of modifications in the glucose metabolism induced by genetic mutations in Saccharomyces cerevisiae by 13C- and H-NMR spectroscopy.

    PubMed

    Herve, M; Buffin-Meyer, B; Bouet, F; Son, T D

    2000-06-01

    NMR spectroscopy may offer a suitable technique to characterize the glucose metabolism in response to genetic mutations in cells. The effects of various genetic modifications in Saccharomyces cerevisiae yeast were investigated using 13C- and 1H-NMR spectroscopy associated with biochemical techniques. Cells were incubated with [1-13C]glucose in order to study glucose consumption and the formation of various end-products (ethanol, trehalose, glycerol, glutamate and amino acids) as a function of time. Two types of genetic modifications were studied in S. cerevisiae. A genetic modification deleted the N-terminal part of the TFC7 protein which is the smallest subunit (tau55) of the TFIIIC transcription factor. One secondary effect of this mutation was a large deletion of mitochondrial DNA giving the rho-phenotype. The other genetic modification corresponded to the disruption of the HUF gene; the mutated cells were rho+ like the reference strain. Both mutations increase the glycolysis rate and glycerol synthesis and decrease trehalose production. The most modified cells, which contain both TFC7 deletion and HUF gene disruption, utilize glucose in the most extreme manner as in these cells the largest production of the two glycolytic products (ethanol and glycerol) and the smallest trehalose formation occur. The HUF gene disruption serves as a positive modulator of glycolysis and respiration. However, the TFC7 deletion, associated with the phenotype rho-, induces the most damage in the cellular function, dramatically altering the behaviour of the Krebs cycle. The cycle becomes blocked at the level of 2-oxoglutarate, detected by a characteristic pattern of the 13C-NMR glutamate spectra. These NMR spectra corroborate the phenotypic data, the rho-phenotype corresponding to deletions of mitochondria DNA which block all mitochondria protein synthesis and render the cells unable to derive energy from respiration. Moreover, as a consequence of the Krebs cycle blocking, alanine

  19. The binding of amide substrate analogues to phospholipase A2. Studies by 13C-nuclear-magnetic-resonance and infrared spectroscopy.

    PubMed Central

    Slaich, P K; Primrose, W U; Robinson, D H; Wharton, C W; White, A J; Drabble, K; Roberts, G C

    1992-01-01

    (R)-(2-dodecanamidoisohexyl)phosphocholine (DAHPC), labelled with 13C at the amide carbonyl group, has been synthesized and its binding to bovine pancreatic phospholipase A2 (PLA2) studied by n.m.r. and i.r. spectroscopy. Two-dimensional 1H-n.m.r. spectra show that, in the presence of Ca2+, DAHPC binds to the active site of the enzyme in a similar manner to other phospholipid amide substrate analogues. The environment of the labelled carbonyl group has been investigated by a combination of 13C n.m.r. and difference-Fourier-transform i.r. spectroscopy. The carbonyl resonance shifts 3 p.p.m. downfield on the binding of DAHPC to PLA2. The carbonyl absorption frequency decreases by 14-18 cm-1, accompanied by a marked sharpening of the absorption band. These results indicate that the carbonyl bond undergoes significant polarization in the enzyme-ligand complex, facilitated by the enzyme-bound Ca2+ ion. This suggests that ground-state strain is likely to promote catalysis in the case of substrate binding. Simple calculations, based on the i.r. data, indicate that the carbonyl bond is weakened by 5-9 kJ.mol-1. This is the first report of observation of the amide vibration of a bound ligand against the strong background of protein amide vibrations. PMID:1445261

  20. Studies of nitrogen metabolism using /sup 13/C NMR spectroscopy. 3. Synthesis of DL-(3-/sup 13/C,2-/sup 15/N)Lysine and its incorporation into streptothricin F/sup 1/

    SciTech Connect

    Gould, S.J.; Thiruvengadam, T.K.

    1981-11-04

    A scheme for the synthesis of DL-(3-/sup 13/C, 2-/sup 15/N)Lysine, I, is presented. Data are also reported to show that the mutase reaction occurring in the biosynthesis of I occurs with an intramolecular migration of nitrogen from C-2 to C-3. (BLM)

  1. Real-time analysis of δ13C- and δD-CH4 by high precision laser spectroscopy

    NASA Astrophysics Data System (ADS)

    Eyer, Simon; Emmenegger, Lukas; Tuzson, Béla; Fischer, Hubertus; Mohn, Joachim

    2014-05-01

    analysis of CH4 isotopologues. The infrared radiation emitted by the two cw-QC laser sources are combined and coupled into a 0.5 L astigmatic multipass absorption cell with an optical path length of 76 m. An Allan variance minimum of the isotope ratio time-series of 0.1 o for δ13C-CH4 and 0.3 o for δD-CH4 has been achieved using 300 s integration time. First experiments of the developed analytical technique demonstrate its potential with respect to field-applicability and temporal resolving power. References: [1] WMO, Greenhouse Gas Bulletin No. 9, 2013, WMO GAW, pp. 4. [2] H. Fischer, M. Behrens, M. Bock, U. Richter, J. Schmitt, L. Loulergue, J. Chappellaz, R. Spahni, T. Blunier, M. Leuenberger and T. F. Stocker, Nature, 2008, 452, 864-867. [3] J. Mohn, B. Tuzson, A. Manninen, N. Yoshida, S. Toyoda, W. A. Brand, and L. Emmenegger, Atmos. Meas. Tech., 2012, 5, 1601-1609. [4] Tuzson, B., Hiller, R. V., Zeyer, K., Eugster, W., Neftel, A., Ammann, C., and L. Emmenegger, Atmos. Meas. Tech., 2010, 3,1519-1531.

  2. The 'Nuts and Bolts' of 13C NMR Spectroscopy at Elevated-Pressures and -Temperatures for Monitoring In Situ CO2 Conversion to Metal Carbonates

    NASA Astrophysics Data System (ADS)

    Moore, J. K.; Surface, J. A.; Skemer, P. A.; Conradi, M. S.; Hayes, S. E.

    2013-12-01

    characterization of multiple metastable mineral phases in pure forms and in mixtures. Notably, NMR spectroscopy is able to observe signals from amorphous materials, and mixtures of both crystalline and amorphous species can be analyzed. NMR results are verified through a combination of Raman spectroscopy and powder XRD (of crystalline species). Further, we have examined the effects on mineralization reactions of pH gradients in the sample--also monitored in situ by NMR--and these results will be presented. Reference: 'In Situ Measurement of Magnesium Carbonate Formation from CO2 Using Static High-Pressure and -Temperature 13C NMR' J. Andrew Surface, Philip Skemer, Sophia E. Hayes, and Mark S. Conradi, Environ. Sci. Technol. 2013, 47, 119-125. DOI: 10.1021/es301287n

  3. Probing polymorphism and reactivity in the organic solid state using 13C NMR spectroscopy: Studies of p-Formyl- trans-cinnamic acid

    NASA Astrophysics Data System (ADS)

    Harris, Kenneth D. M.; Thomas, John M.

    1991-09-01

    p-Formyl- trans-cinnamic acid (p-FCA) is known to exist in two different crystal phases (denoted β and γ). When crystals of the β phase of p-FCA are exposed to UV radiation, a solid state dimerization reaction occurs to produce 4,4'-diformyl-β-truxinic acid. In contrast, crystals of the γ phase of p-FCA are photostable. It is shown in this paper that high resolution solid state 13C NMR spectroscopy is a sensitive technique for distinguishing the β and γ phases of p-FCA, and can be used to investigate, in detail, the chemical transformation that occurs upon UV irradiation of the β phase. Specifically, the 13C NMR spectra presented here were recorded using the TOSS (total suppression of sidebands) pulse sequence; this is based upon the standard 13C CPMAS (cross polarization/magic angle sample spinning/high power 1H decoupling) method, but has the additional feature that all orders of spinning sidebands are eliminated from the spectrum. The photoproduct obtained from UV irradiation of β-p-FCA contains a significant noncrystalline component (assessed via powder X-ray diffraction), and our NMR studies suggest that this noncrystalline component of the photoproduct contains some amount of the γ phase of the monomer p-FCA. A mechanism is proposed to explain the fact that UV irradiation of β-p-FCA can generate, in addition to the expected photodimer, an impurity amount of the γ phase of p-FCA.

  4. Backbone dynamics of a model membrane protein: 13C NMR spectroscopy of alanine methyl groups in detergent-solubilized M13 coat protein.

    PubMed

    Henry, G D; Weiner, J H; Sykes, B D

    1986-02-11

    The filamentous coliphage M13 possesses multiple copies of a 50-residue coat protein which is inserted into the inner membrane of Escherichia coli during infection. 13C nuclear magnetic resonance (NMR) spectroscopy has been used to probe the structure and dynamics of M13 coat protein solubilized in detergent micelles. A comparison of backbone dynamics within the hydrophobic core region and the hydrophilic terminal domains was obtained by biosynthetic incorporation of [3-13C]alanine. Alanine is distributed throughout the protein and accounts for 10 residues (i.e., 20% of the total). Similar 13C NMR spectra of the protein have been obtained in two anionic detergents, sodium deoxycholate and sodium dodecyl sulfate, although the structures and physical properties of these solubilizing agents are quite different. The N-terminal alanine residues, assigned by pH titration, and the penultimate residue, assigned by carboxypeptidase A digestion, give rise to analogous peaks in both detergent systems. The pKa of Ala-1 (approximately 8.8) and the relaxation parameters of individual carbon atoms (T1, T2, and the nuclear Overhauser enhancement) are also generally similar, suggesting a similarity in the overall protein structure. Relaxation data have been analyzed according to the model-free approach of Lipari and Szabo [Lipari, G., & Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546-4559]. The overall correlation times were obtained by fitting the three experimental relaxation values for a given well-resolved single carbon atom to obtain a unique value for the generalized order parameter, S2, and the effective correlation time, tau e. The former parameter reflects the spatial restriction of motion, and the latter, the rate.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Structural characterization and molecular order of rodlike mesogens with three- and four-ring core by XRD and 13C NMR spectroscopy.

    PubMed

    Reddy, M Kesava; Reddy, K Subramanyam; Yoga, K; Prakash, M; Narasimhaswamy, T; Mandal, A B; Lobo, Nitin P; Ramanathan, K V; Rao, D S Shankar; Prasad, S Krishna

    2013-05-01

    Structural characterizations using XRD and (13)C NMR spectroscopy of two rodlike mesogens consisting of (i) three phenyl ring core with a polar cyano terminal and (ii) four phenyl ring core with flexible dodecyl terminal chain are presented. The three-ring-core mesogen with cyano terminal exhibits enantiotropic smectic A phase while the four-ring mesogen reveals polymesomorphism and shows enantiotropic nematic, smectic C, and tilted hexatic phases. The molecular organization in the three-ring mesogen is found to be partial bilayer smectic Ad type, and the interdigitation of the molecules in the neighboring layers is attributed to the presence of the polar terminal group. For the four-ring mesogen, the XRD results confirm the existence of the smectic C and the tilted hexatic mesophases. A thermal variation of the layer spacing across the smectic C phase followed by a discrete jump at the transition to the tilted hexatic phase is also observed. The tilt angles have been estimated to be about 45° in the smectic C phase and about 40° in tilted hexatic phase. (13)C NMR results indicate that in the mesophase the molecules are aligned parallel to the magnetic field. From the (13)C-(1)H dipolar couplings determined from the 2D experiments, the overall order parameter for the three-ring mesogen in its smectic A phase has been estimated to be 0.72 while values ranging from 0.88 to 0.44 have been obtained for the four-ring mesogen as it passes from the tilted hexatic to the nematic phase. The orientations of the different rings of the core unit with respect to each other and also with respect to the long axis of the molecule have also been obtained. PMID:23627902

  6. Estimates of Oil and Gas Potential of Source Rock by 13C Nuclear Magnetic Resonance (NMR) Spectroscopy

    NASA Astrophysics Data System (ADS)

    Longbottom, T. L.; Hockaday, W. C.; Boling, K. S.; Dworkin, S. I.

    2014-12-01

    Kerogen is defined as the insoluble fraction of organic matter preserved in sediments. Due to its structural complexity, kerogen is poorly understood, yet it holds vast economic importance as petroleum source rock, and represents the largest organic carbon pool on earth. Kerogen originates from a mixture of organic biomolecules and tends to be dominated by the polymeric components of cell walls and cellular membranes, which undergo interactions with sedimentary minerals at elevated temperature and pressure upon burial. Due to the importance of burial diagenesis to petroleum formation, much of our knowledge of chemical properties of kerogens is related to diagenetic and catagenetic effects. The more common geochemical evaluations of the oil and gas potentials of source rock are based upon proximate analyses such as hydrogen and oxygen indices and thermal stability indices, such as those provided by Fisher assay and Rock Eval®. However, proximate analyses provide limited information regarding the chemical structure of kerogens, and therefore provide little insight to the processes of kerogen formation. NMR spectra of kerogen have been previously shown to be useful in estimating oil and gas potential, and the proposed study seeks to refine nuclear magnetic resonance spectroscopy as a tool in kerogen characterization, specifically for the purpose of oil and gas potential calculations.

  7. Real-time analysis of δ13C- and δD-CH4 in ambient air with laser spectroscopy: Method development and intercomparison

    NASA Astrophysics Data System (ADS)

    Harris, E. J.; Eyer, S.; Mohn, J.; Röckmann, T.; Popa, E.; Lowry, D.; Nisbet, E. G.; Fisher, R. E.; Brennwald, M. S.; Fischer, H.; Emmenegger, L.; Tuzson, B.; Zellweger, C.

    2015-12-01

    Methane (CH4) is the second most important anthropogenically emitted greenhouse gas after carbon dioxide (CO2). Its mole fraction has increased from around 722 ppb in pre-industrial times to 1824 ppb in 2013 and the anthropogenic fraction is estimated to be 60 % of the total emissions. A promising approach to improve the understanding of the CH4 budget is the use of isotopologues to distinguish between various CH4 source processes. In the presented study in situ and simultaneous measurement of the three most abundant isotopologues of methane using mid-infrared laser absorption spectroscopy is demonstrated. A field-deployable, autonomous platform is realized by coupling a compact quantum cascade laser absorption spectrometer (QCLAS) to a preconcentration unit, called TRace gas EXtractor (TREX). This unit enhances CH4 mole fractions by a factor of up to 500 above ambient levels and quantitatively separates interfering trace gases such as N2O and CO2. The analytical precision of the QCLAS isotope measurement on the preconcentrated (750 ppm, parts-per-million, mmole/mole) methane is 0.1‰ and 0.5 ‰ for δ13C- and δD-CH4 at 10 min averaging time. [1] Based on replicate measurements of compressed air during a two-week intercomparison campaign, the repeatability of the TREX-QCLAS was determined to be 0.19 ‰ and 1.9 ‰ for δ13C and δD-CH4, respectively. In this intercomparison campaign the new in situ technique is compared to IRMS based on glass flask and bag sampling and real time CH4 isotope analysis by two commercially available laser spectrometers (Figure). Both laser-based analyzers were limited to methane mole fraction and δ13C-CH4 analysis, and only one of them, a cavity ring down spectrometer, was capable to deliver meaningful data for the isotopic composition. After correcting for scale offsets, the average difference between TREX-QCLAS data and bag/flask sampling-IRMS values are within the extended WMO compatibility goals of 0.2 and 5 ‰ for δ13C- and

  8. A simple mathematical model and practical approach for evaluating citric acid cycle fluxes in perfused rat hearts by 13C-NMR and 1H-NMR spectroscopy.

    PubMed

    Tran-Dinh, S; Hoerter, J A; Mateo, P; Bouet, F; Herve, M

    1997-04-15

    We propose a simple mathematical model and a practical approach for evaluating the flux constant and the absolute value of flux in the citric acid cycle in perfused organs by 13C-NMR and 1H-NMR spectroscopy. We demonstrate that 13C-NMR glutamate spectra are independent of the relative sizes of the mitochondrial and cytosolic compartments and the exchange rates of glutamates, unless there is a difference in 13C chemical shifts of glutamate carbons between the two compartments. Wistar rat hearts (five beating and four KCl-arrested hearts) were aerobically perfused with 100% enriched [2-(13)C]acetate and the kinetics of glutamate carbon labeling from perchloric acid extracts were studied at various perfusion times. Under our experimental conditions, the citric acid cycle flux constant, which represents the fraction of glutamate in exchange with the citric acid cycle per unit time, is about 0.350 +/- 0.003 min(-1) for beating hearts and 0.0741 +/- 0.004 min(-1) for KCl-arrested hearts. The absolute values of the citric acid flux for beating hearts and for KCl-arrested hearts are 1.06 +/- 0.06 micromol x min(-1) x mg(-1) and 0.21 +/- 0.02 micromol x min(-1) x g(-1), respectively. The fraction of unlabeled acetate determined from the proton signal of the methyl group is small and essentially the same in beating and arrested hearts (7.4 +/- 1.7% and 8.8 +/- 2.1%, respectively). Thus, the large difference in the Glu C2/C4 between beating and arrested hearts is not due to the important contribution from anaplerotic sources in arrested hearts but simply to a substantial difference in citric acid cycle fluxes. Our model fits the experimental data well, indicating a fast exchange between 2-oxoglutarate and glutamate in the mitochondria of rat hearts. Analysis of the flux constant, calculated from the half-time of glutamate C4 labeling given in the literature, allows for a comparison of the citric acid flux for various working conditions in different animal species.

  9. Kinetic analysis of reactions of Si-based epoxy resins by near-infrared spectroscopy, 13C NMR and soft-hard modelling.

    PubMed

    Garrido, Mariano; Larrechi, Maria Soledad; Rius, F Xavier; Mercado, Luis Adolfo; Galià, Marina

    2007-02-01

    Soft- and hard-modelling strategy was applied to near-infrared spectroscopy data obtained from monitoring the reaction between glycidyloxydimethylphenyl silane, a silicon-based epoxy monomer, and aniline. On the basis of the pure soft-modelling approach and previous chemical knowledge, a kinetic model for the reaction was proposed. Then, multivariate curve resolution-alternating least squares optimization was carried out under a hard constraint, that compels the concentration profiles to fulfil the proposed kinetic model at each iteration of the optimization process. In this way, the concentration profiles of each species and the corresponding kinetic rate constants of the reaction, unpublished until now, were obtained. The results obtained were contrasted with 13C NMR. The joint interval test of slope and intercept for detecting bias was not significant (alpha=5%).

  10. Site-specific thermodynamic stability and unfolding of a de novo designed protein structural motif mapped by 13C isotopically edited IR spectroscopy.

    PubMed

    Kubelka, Ginka S; Kubelka, Jan

    2014-04-23

    The mechanism of protein folding remains poorly understood, in part due to limited experimental information available about partially folded states. Isotopically edited infrared (IR) spectroscopy has emerged as a promising method for studying protein structural changes with site-specific resolution, but its full potential to systematically probe folding at multiple protein sites has not yet been realized. We have used (13)C isotopically edited IR spectroscopy to investigate the site-specific thermal unfolding at seven different locations in the de novo designed helix-turn-helix protein αtα. As one of the few stable helix-turn-helix motifs, αtα is an excellent model for studying the roles of secondary and tertiary interactions in folding. Circular dichroism (CD) experiments on the full αtα motif and its two peptide fragments show that interhelical tertiary contacts are critical for stabilization of the secondary structure. The site-specific thermal unfolding probed by (13)C isotopically edited IR is likewise consistent with primarily tertiary stabilization of the local structure. The least thermally stable part of the αtα motif is near the turn where the interhelical contacts are rather loose, while the motif's center with best established core packing has the highest stability. Similar correlation between the local thermal stability and tertiary contacts was found previously for a naturally occurring helix-turn-helix motif. These results underline the importance of native-like tertiary stabilizing interactions in folding, in agreement with recent state-of-the art folding simulations as well as simplified, native-centric models.

  11. Adaptation of continuous-flow cavity ring-down spectroscopy for batch analysis of δ13C of CO2 and comparison with isotope ratio mass spectrometry.

    PubMed

    Berryman, E M; Marshall, J D; Rahn, T; Cook, S P; Litvak, M

    2011-08-30

    Measurements of δ(13)C in CO(2) have traditionally relied on samples stored in sealed vessels and subsequently analyzed using magnetic sector isotope ratio mass spectrometry (IRMS), an accurate but expensive and high-maintenance analytical method. Recent developments in optical spectroscopy have yielded instruments that can measure δ(13)CO(2) in continuous streams of air with precision and accuracy approaching those of IRMS, but at a fraction of the cost. However, continuous sampling is unsuited for certain applications, creating a need for conversion of these instruments for batch operation. Here, we present a flask (syringe) adaptor that allows the collection and storage of small aliquots (20-30 mL air) for injection into the cavity ring-down spectroscopy (CRDS) instrument. We demonstrate that the adaptor's precision is similar to that of traditional IRMS (standard deviation of 0.3‰ for 385 ppm CO(2) standard gas). In addition, the concentration precision (±0.3% of sample concentration) was higher for CRDS than for IRMS (±7% of sample concentration). Using the adaptor in conjunction with CRDS, we sampled soil chambers and found that soil-respired δ(13)C varied between two different locations in a piñon-juniper woodland. In a second experiment, we found no significant discrimination between the respiration of a small beetle (~5 mm) and its diet. Our work shows that the CRDS system is flexible enough to be used for the analysis of batch samples as well as for continuous sampling. This flexibility broadens the range of applications for which CRDS has the potential to replace magnetic sector IRMS.

  12. Unilateral NMR, 13C CPMAS NMR spectroscopy and micro-analytical techniques for studying the materials and state of conservation of an ancient Egyptian wooden sarcophagus.

    PubMed

    Proietti, Noemi; Presciutti, Federica; Di Tullio, Valeria; Doherty, Brenda; Marinelli, Anna Maria; Provinciali, Barbara; Macchioni, Nicola; Capitani, Donatella; Miliani, Costanza

    2011-03-01

    A multi-technique approach was employed to study a decorated Egyptian wooden sarcophagus (XXV-XXVI dynasty, Third Intermediate Period), belonging to the Museo del Vicino Oriente of the Sapienza University of Rome. Portable non-invasive unilateral NMR was applied to evaluate the conservation state of the sarcophagus. Moreover, using unilateral NMR, a non-invasive analytical protocol was established to detect the presence of organic substances on the surface and/or embedded in the wooden matrix. This protocol allowed for an educated sampling campaign aimed at further investigating the state of degradation of the wood and the presence of organic substances by (13)C cross polarization magic angle spinning (CPMAS) NMR spectroscopy. The composition of the painted layer was analysed by optical microscopy (OM), scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), Raman and surface enhanced (resonance) Raman spectroscopy (SERS/SERRS), infrared and GC-MS techniques, evidencing original components such as clay minerals, Egyptian green, indigo, natural gums, and also highlighting restoration pigments and alteration compounds. The identification of the wood, of great value for the reconstruction of the history of the artwork, was achieved by means of optical microscopy.

  13. Characterization of the humic substances isolated from postfire soils of scotch pine forest in Togljatty city, Samara region by the 13C-NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Maksimova, Ekaterina; Abakumov, Evgeny

    2016-04-01

    Postpyrogenic soil dynamics is an informative tool for studying of soil elementary processes in extreme temperature conditions and for predicting of short time environmental changes in conditions of catastrophic landscape changes. Soil organic matter (SOM) system evolution is the most rapid process of postpyrogenic soil development. In this relation the evaluation of humus accumulation rates and humification trend were conducted with use of the classical chemical and modern spectroscopy methods. Soil restoration after spontaneous forest fires near Togljatty city (Samara region, Russia) was abandoned in 2010, and further monitoring over the next four years was organized to evaluate the speed of biogenic processes and humus accumulation dynamics. Three key soil plots were studied for estimating SOM quality changes under the forest fire effect: surface forest fire, crown forest fire and control. Total carbon and nitrogen content as well as Cha/Cfa ratios (content of humic acids/ content of fulvic acids), were estimated to assess the dynamics of soil restoration. Humic acid powders were extracted and analyzed by elemental composition and 13C-NMR spectroscopy to assess changes in humic substance structure and composition. The data obtained indicate that burning of a forest floor and sod (humic) horizon led to humus losses and decreases in total carbon stocks. As a result of the fires, the content of humic acids in the pyrogenic horizon increased, leading alterations of humus type. Greater increases in the degree of organic matter humification were observed for surface fires than crown fires. It was shown that the humus molecular composition was substantially affected by the wildfires. The data show an increase in aromaticity, a loss of oxygen-containing groups and dehydrogenation of humic acids. Humic acids in the soils of the control plots and after wildfires were significantly different, especially in the ratios of hydrogen, oxygen and carbon. The increase in the

  14. Sampling Hyperpolarized Molecules Utilizing a 1 Tesla Permanent Magnetic Field.

    PubMed

    Tee, Sui Seng; DiGialleonardo, Valentina; Eskandari, Roozbeh; Jeong, Sangmoo; Granlund, Kristin L; Miloushev, Vesselin; Poot, Alex J; Truong, Steven; Alvarez, Julio A; Aldeborgh, Hannah N; Keshari, Kayvan R

    2016-01-01

    Hyperpolarized magnetic resonance spectroscopy (HP MRS) using dynamic nuclear polarization (DNP) is a technique that has greatly enhanced the sensitivity of detecting (13)C nuclei. However, the HP MRS polarization decays in the liquid state according to the spin-lattice relaxation time (T1) of the nucleus. Sampling of the signal also destroys polarization, resulting in a limited temporal ability to observe biologically interesting reactions. In this study, we demonstrate that sampling hyperpolarized signals using a permanent magnet at 1 Tesla (1T) is a simple and cost-effective method to increase T1s without sacrificing signal-to-noise. Biologically-relevant information may be obtained with a permanent magnet using enzyme solutions and in whole cells. Of significance, our findings indicate that changes in pyruvate metabolism can also be quantified in a xenograft model at this field strength. PMID:27597137

  15. Sampling Hyperpolarized Molecules Utilizing a 1 Tesla Permanent Magnetic Field

    NASA Astrophysics Data System (ADS)

    Tee, Sui Seng; Digialleonardo, Valentina; Eskandari, Roozbeh; Jeong, Sangmoo; Granlund, Kristin L.; Miloushev, Vesselin; Poot, Alex J.; Truong, Steven; Alvarez, Julio A.; Aldeborgh, Hannah N.; Keshari, Kayvan R.

    2016-09-01

    Hyperpolarized magnetic resonance spectroscopy (HP MRS) using dynamic nuclear polarization (DNP) is a technique that has greatly enhanced the sensitivity of detecting 13C nuclei. However, the HP MRS polarization decays in the liquid state according to the spin-lattice relaxation time (T1) of the nucleus. Sampling of the signal also destroys polarization, resulting in a limited temporal ability to observe biologically interesting reactions. In this study, we demonstrate that sampling hyperpolarized signals using a permanent magnet at 1 Tesla (1T) is a simple and cost-effective method to increase T1s without sacrificing signal-to-noise. Biologically-relevant information may be obtained with a permanent magnet using enzyme solutions and in whole cells. Of significance, our findings indicate that changes in pyruvate metabolism can also be quantified in a xenograft model at this field strength.

  16. Sampling Hyperpolarized Molecules Utilizing a 1 Tesla Permanent Magnetic Field.

    PubMed

    Tee, Sui Seng; DiGialleonardo, Valentina; Eskandari, Roozbeh; Jeong, Sangmoo; Granlund, Kristin L; Miloushev, Vesselin; Poot, Alex J; Truong, Steven; Alvarez, Julio A; Aldeborgh, Hannah N; Keshari, Kayvan R

    2016-09-06

    Hyperpolarized magnetic resonance spectroscopy (HP MRS) using dynamic nuclear polarization (DNP) is a technique that has greatly enhanced the sensitivity of detecting (13)C nuclei. However, the HP MRS polarization decays in the liquid state according to the spin-lattice relaxation time (T1) of the nucleus. Sampling of the signal also destroys polarization, resulting in a limited temporal ability to observe biologically interesting reactions. In this study, we demonstrate that sampling hyperpolarized signals using a permanent magnet at 1 Tesla (1T) is a simple and cost-effective method to increase T1s without sacrificing signal-to-noise. Biologically-relevant information may be obtained with a permanent magnet using enzyme solutions and in whole cells. Of significance, our findings indicate that changes in pyruvate metabolism can also be quantified in a xenograft model at this field strength.

  17. Sampling Hyperpolarized Molecules Utilizing a 1 Tesla Permanent Magnetic Field

    PubMed Central

    Tee, Sui Seng; DiGialleonardo, Valentina; Eskandari, Roozbeh; Jeong, Sangmoo; Granlund, Kristin L.; Miloushev, Vesselin; Poot, Alex J.; Truong, Steven; Alvarez, Julio A.; Aldeborgh, Hannah N.; Keshari, Kayvan R.

    2016-01-01

    Hyperpolarized magnetic resonance spectroscopy (HP MRS) using dynamic nuclear polarization (DNP) is a technique that has greatly enhanced the sensitivity of detecting 13C nuclei. However, the HP MRS polarization decays in the liquid state according to the spin-lattice relaxation time (T1) of the nucleus. Sampling of the signal also destroys polarization, resulting in a limited temporal ability to observe biologically interesting reactions. In this study, we demonstrate that sampling hyperpolarized signals using a permanent magnet at 1 Tesla (1T) is a simple and cost-effective method to increase T1s without sacrificing signal-to-noise. Biologically-relevant information may be obtained with a permanent magnet using enzyme solutions and in whole cells. Of significance, our findings indicate that changes in pyruvate metabolism can also be quantified in a xenograft model at this field strength. PMID:27597137

  18. On-site analysis of d13C- and dD-CH4 by laser spectroscopy for the allocation of source processes

    NASA Astrophysics Data System (ADS)

    Eyer, Simon; Tuzson, Béla; Popa, Elena; van der Veen, Carina; Röckmann, Thomas; Brand, Willi A.; Fisher, Rebecca; Lowry, David; Nisbet, Euan G.; Brennwald, Matthias S.; Harris, Eliza; Emmenegger, Lukas; Fischer, Hubertus; Mohn, Joachim

    2015-04-01

    Analysis of the most abundant methane isotopologues 12CH4, 13CH4 and 12CH3D can be used to disentangle source/sink processes (Fischer et al. 2008) and to develop target oriented reduction strategies. Isotopic analysis of CH4 is accomplished by isotope-ratio mass-spectrometry (IRMS) and more recently by mid-infrared laser spectroscopy. For high precision measurements in ambient air, however, both techniques rely on preconcentration of the target gas (Eyer et al. 2014). We developed a field-deployable analyser for real-time, on-site analysis of CH4 isotopologues which is based on a dual quantum cascade laser absorption spectrometer (QCLAS) in combination with an innovative preconcentration technique named trace gas extractor (TREX). The core part of the 19 ″ rack-mounted preconcentration unit is a highly efficient adsorbent trap attached to the cold end of a Stirling cooler. The system achieves preconcentration factors >500. For fast desorption and optimal heat management, the trap is decoupled from the cooler during desorption. The QCLAS has been developed based on a previously described instrument (Tuzson 2010). It comprises two cw-QC laser sources combined and coupled into an astigmatic multipass absorption cell with 76 m optical path. The developed technique reaches an unsurpassed precision of 0.1‰ for d13C-CH4 and <0.5‰ for dD-CH4 at 600 s spectral averaging. The potential of the new analytical system for field applications has been shown in June 2014, where the system has achieved an overall repeatability of 0.19‰ for d13C and 1.7‰ for dD-CH4 for repeated target gas measurements. Compatibility of TREX - QCLAS with flask sampling - IRMS for analysis of ambient CH4 fulfilled the extended WMO/GAW compatibility goals of 0.2‰ for d13C-CH4 and 5‰ for dD-CH4. References: Fischer, H., Behrens, M., Bock, M., Richter, U., Schmitt, J., Loulergue, L., Chappellaz, J., Spahni, R., Blunier, T., Leuenberger, M., Stocker, T. F. (2008) Nature 452: 864-867. Eyer, S

  19. Unique Backbone-Water Interaction Detected in Sphingomyelin Bilayers with 1H/31P and 1H/13C HETCOR MAS NMR Spectroscopy

    PubMed Central

    Holland, Gregory P.; Alam, Todd M.

    2008-01-01

    Two-dimensional 1H/31P dipolar heteronuclear correlation (HETCOR) magic-angle spinning nuclear magnetic resonance (NMR) is used to investigate the correlation of the lipid headgroup with various intra- and intermolecular proton environments. Cross-polarization NMR techniques involving 31P have not been previously pursued to a great extent in lipid bilayers due to the long 1H-31P distances and high degree of headgroup mobility that averages the dipolar coupling in the liquid crystalline phase. The results presented herein show that this approach is very promising and yields information not readily available with other experimental methods. Of particular interest is the detection of a unique lipid backbone-water intermolecular interaction in egg sphingomyelin (SM) that is not observed in lipids with glycerol backbones like phosphatidylcholines. This backbone-water interaction in SM is probed when a mixing period allowing magnetization exchange between different 1H environments via the nuclear Overhauser effect (NOE) is included in the NMR pulse sequence. The molecular information provided by these 1H/31P dipolar HETCOR experiments with NOE mixing differ from those previously obtained by conventional NOE spectroscopy and heteronuclear NOE spectroscopy NMR experiments. In addition, two-dimensional 1H/13C INEPT HETCOR experiments with NOE mixing support the 1H/31P dipolar HETCOR results and confirm the presence of a H2O environment that has nonvanishing dipolar interactions with the SM backbone. PMID:18390621

  20. Solution Structures of the Prototypical 18 kDa Translocator Protein Ligand, PK 11195, Elucidated with 1H/13C NMR Spectroscopy and Quantum Chemistry

    PubMed Central

    2012-01-01

    Eighteen kilodalton translocator protein (TSPO) is an important target for drug discovery and for clinical molecular imaging of brain and peripheral inflammatory processes. PK 11195 [1a; 1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide] is the major prototypical high-affinity ligand for TSPO. Elucidation of the solution structure of 1a is of interest for understanding small-molecule ligand interactions with the lipophilic binding site of TSPO. Dynamic 1H/13C NMR spectroscopy of 1a revealed four quite stable but interconverting rotamers, due to amide bond and 2-chlorophenyl group rotation. These rotamers have been neglected in previous descriptions of the structure of 1a and of the binding of 1a to TSPO. Here, we used quantum chemistry at the level of B3LYP/6-311+G(2d,p) to calculate 13C and 1H chemical shifts for the rotamers of 1a and for the very weak TSPO ligand, N-desmethyl-PK 11195 (1b). These data, plus experimental NMR data, were then used to characterize the structures of rotamers of 1a and 1b in organic solution. Energy barriers for both the amide bond and 2′-chlorophenyl group rotation of 1a were determined from dynamic 1H NMR to be similar (ca.17 to 18 kcal/mol), and they compared well with those calculated at the level of B3LYP/6-31G*. Furthermore, the computed barrier for Z to E rotation is considerably lower in 1a(18.7 kcal/mol) than in 1b (25.4 kcal/mol). NMR (NOE) unequivocally demonstrated that the E rotamer of 1a is the more stable in solution by about 0.4 kcal/mol. These detailed structural findings will aid future TSPO ligand design and support the notion that TSPO prefers to bind ligands as amide E-rotamers. PMID:22860199

  1. /sup 18/O isotope effect in /sup 13/C nuclear magnetic resonance spectroscopy. Part 9. Hydrolysis of benzyl phosphate by phosphatase enzymes and in acidic aqueous solutions

    SciTech Connect

    Parente, J.E.; Risley, J.M.; Van Etten, R.L.

    1984-12-26

    The /sup 18/O isotope-induced shifts in /sup 13/C and /sup 31/P nuclear magnetic resonance (NMR) spectroscopy were used to establish the position of bond cleavage in the phosphatase-catalyzed and acid-catalyzed hydrolysis reactions of benzyl phosphate. The application of the /sup 18/O-isotope effect in NMR spectroscopy affords a continuous, nondestructive assay method for following the kinetics and position of bond cleavage in the hydrolytic process. The technique provides advantages over most discontinuous methods in which the reaction components must be isolated and converted to volatile derivatives prior to analysis. In the present study, (..cap alpha..-/sup 13/C,ester-/sup 18/O)benzyl phosphate and (ester-/sup 18/O)benzyl phosphate were synthesized for use in enzymatic and nonenzymatic studies. Hydrolysis reactions catalyzed by the alkaline phosphatase from E. coli and by the acid phosphatases isolated from human prostate and human liver were all accompanied by cleavage of the substrate phosphorus-oxygen bond consistent with previously postulated mechanisms involving covalent phosphoenzyme intermediates. An extensive study of the acid-catalyzed hydrolysis of benzyl phosphate at 75/sup 0/C revealed that the site of bond cleavage is dependent on pH. At pH less than or equal to 1.3, the hydrolysis proceeds with C-O bond cleavage; at 1.3 < pH < 2.0, there is a mixture of C-O and P-O bond scission, the latter progressively predominating as the pH is raised; at pH greater than or equal to 2.0, the hydrolysis proceeds with exclusive P-O bond scission. (S)-(+)-(..cap alpha..-/sup 2/H)Benzyl phosphate was also synthesized. Hydrolysis of this chiral benzyl derivative demonstrated that the acid-catalyzed C-O bond scission of benzyl phosphate proceeds by an A-1 (S/sub N/1) mechanism with 70% racemization and 30% inversion at carbon. 37 references, 4 figures, 2 tables.

  2. Stability and biodegradability of organic matter from Arctic soils of Western Siberia: Insights from 13C-NMR spectroscopy and elemental analysis

    NASA Astrophysics Data System (ADS)

    Ejarque, Elisabet; Abakumov, Evgeny

    2016-04-01

    Arctic soils contain large amounts of organic matter which, globally, exceed the amount of carbon stored in vegetation biomass and in the atmosphere. Recent studies emphasize the potential sensitivity for this soil organic matter (SOM) to be mineralised when faced with increasing ambient temperatures. In order to better refine the predictions about the response of SOM to climate warming, there is a need to increase the spatial coverage of empirical data on SOM quantity and quality in the Arctic area. This study provides, for the first time, a characterisation of SOM from the Gydan Peninsula in the Yamal Region, Western Siberia, Russia. On the one hand, soil humic acids and their humification state were characterised by measuring the elemental composition and diversity of functional groups using solid-state 13C-NMR spectroscopy. Also, the total mineralisable carbon was measured. Our results show that there is a predominance of aliphatic carbon structures, with a distribution of functional groups that has a minimal variation both regionally and within soil depth. Such vertical homogeneity and low level of aromaticity reflects the accumulation in soil of lowly decomposed organic matter due to cold temperatures. Mineralisation rates were found to be independent of SOM quality, and to be mainly explained solely by the total carbon content. Overall, our results provide further evidence on the sensitivity that the soils of Western Siberia may have to increasing ambient temperatures and highlight the important role that this region can play in the global carbon balance under the effects of climate warming.

  3. Magnetic resonance spectroscopy and metabolism. Applications of proton and 13C NMR to the study of glutamate metabolism in cultured glial cells and human brain in vivo.

    PubMed

    Portais, J C; Pianet, I; Allard, M; Merle, M; Raffard, G; Kien, P; Biran, M; Labouesse, J; Caille, J M; Canioni, P

    1991-01-01

    Nuclear magnetic resonance (NMR) spectroscopy was used to study the metabolism of cells from the central nervous system both in vitro on perchloric acid extracts obtained either from cultured tumoral cells (C6 rat glioma) or rat astrocytes in primary culture, and in vivo within the human brain. Analysis of carbon 13 NMR spectra of perchloric acid extracts prepared from cultured cells in the presence of NMR [1-13C] glucose as substrate allowed determination of the glutamate and glutamine enrichments in both normal and tumoral cells. Preliminary results indicated large changes in the metabolism of these amino acids (and also of aspartate and alanine) in the C6 cell as compared to its normal counterpart. Localized proton NMR spectra of the human brain in vivo were obtained at 1.5 T, in order to evaluate the content of various metabolites, including glutamate, in peritumoral edema from a selected volume of 2 x 2 x 2 cm3. N-acetyl aspartate, glutamate, phosphocreatine, creatine, choline and inositol derivative resonances were observed in 15 min spectra. N-acetyl-aspartate was found to be at a lower level in contrast to glutamate which was detected at a higher level in the injured area as compared to the contralateral unaffected side. PMID:1674432

  4. Comparisons of sorption of aquatic humic matter by DAX-8 and XAD-8 resins from solid-state (13)C NMR spectroscopy's point of view.

    PubMed

    Peuravuori, J; Ingman, P; Pihlaja, K; Koivikko, R

    2001-10-31

    Aquatic humic solutes were separated in parallel by the non-ionic macroporous DAX-8 and XAD-8 resins from four different fresh water sources. On average, the sorptive power of the DAX-8 resin does not differ systematically from that of the XAD-8 resin. The DAX-8 resin seems to have more precise column characteristics compared with the XAD-8 resin. There was no significant difference between the major elemental compositions of the parallel humic-solute bulks obtained by these two resins. According to the (13)C NMR spectroscopy the content and quality of aliphatic carbons, especially those representing terminal methyl groups or methylene carbons, were the most systematic and powerful discriminating factors between the humic extracts obtained by these two resins. Generally speaking the DAX-8 and XAD-8 resins seem to isolate humic-solute bulks almost equally, although the content of aliphatics is slightly greater for the former, producing mixtures with similar structural compositions for general purposes. The structural composition and quantity of the humic-solute mixture isolable with a weakly basic DEAE-cellulose anion exchange resin differs partially from any humic fraction obtained by non-ionic sorbing solids. The environmental impact was also visible on the quality of the structural fine-chemistry of the different humic isolates obtained both by the DAX-8 and XAD-8 resins. PMID:18968420

  5. Chemical structures of coal lithotypes before and after CO2 adsorption as investigated by advanced solid-state 13C nuclear magnetic resonance spectroscopy

    USGS Publications Warehouse

    Cao, X.; Mastalerz, Maria; Chappell, M.A.; Miller, L.F.; Li, Y.; Mao, J.

    2011-01-01

    Four lithotypes (vitrain, bright clarain, clarain, and fusain) of a high volatile bituminous Springfield Coal from the Illinois Basin were characterized using advanced solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. The NMR techniques included quantitative direct polarization/magic angle spinning (DP/MAS), cross polarization/total sideband suppression (CP/TOSS), dipolar dephasing, CHn selection, and recoupled C-H long-range dipolar dephasing techniques. The lithotypes that experienced high-pressure CO2 adsorption isotherm analysis were also analyzed to determine possible changes in coal structure as a result of CO2 saturation at high pressure and subsequent evacuation. The main carbon functionalities present in original vitrain, bright clarain, clarain and fusain were aromatic carbons (65.9%-86.1%), nonpolar alkyl groups (9.0%-28.9%), and aromatic C-O carbons (4.1%-9.5%). Among these lithotypes, aromaticity increased in the order of clarain, bright clarain, vitrain, and fusain, whereas the fraction of alkyl carbons decreased in the same order. Fusain was distinct from other three lithotypes in respect to its highest aromatic composition (86.1%) and remarkably small fraction of alkyl carbons (11.0%). The aromatic cluster size in fusain was larger than that in bright clarain. The lithotypes studied responded differently to high pressure CO2 saturation. After exposure to high pressure CO2, vitrain and fusain showed a decrease in aromaticity but an increase in the fraction of alkyl carbons, whereas bright clarain and clarain displayed an increase in aromaticity but a decrease in the fraction of alkyl carbons. Aromatic fused-rings were larger for bright clarain but smaller for fusain in the post-CO2 adsorption samples compared to the original lithotypes. These observations suggested chemical CO2-coal interactions at high pressure and the selectivity of lithotypes in response to CO2 adsorption. ?? 2011 Elsevier B.V.

  6. Hyperpolarized NMR of plant and cancer cell extracts at natural abundance.

    PubMed

    Dumez, Jean-Nicolas; Milani, Jonas; Vuichoud, Basile; Bornet, Aurélien; Lalande-Martin, Julie; Tea, Illa; Yon, Maxime; Maucourt, Mickaël; Deborde, Catherine; Moing, Annick; Frydman, Lucio; Bodenhausen, Geoffrey; Jannin, Sami; Giraudeau, Patrick

    2015-09-01

    Natural abundance (13)C NMR spectra of biological extracts are recorded in a single scan provided that the samples are hyperpolarized by dissolution dynamic nuclear polarization combined with cross polarization. Heteronuclear 2D correlation spectra of hyperpolarized breast cancer cell extracts can also be obtained in a single scan. Hyperpolarized NMR of extracts opens many perspectives for metabolomics. PMID:26215673

  7. Aromatic spectral editing techniques for magic-angle-spinning solid-state NMR spectroscopy of uniformly (13)C-labeled proteins.

    PubMed

    Williams, Jonathan K; Schmidt-Rohr, Klaus; Hong, Mei

    2015-11-01

    The four aromatic amino acids in proteins, namely histidine, phenylalanine, tyrosine, and tryptophan, have strongly overlapping (13)C chemical shift ranges between 100 and 160ppm, and have so far been largely neglected in solid-state NMR determination of protein structures. Yet aromatic residues play important roles in biology through π-π and cation-π interactions. To better resolve and assign aromatic residues' (13)C signals in magic-angle-spinning (MAS) solid-state NMR spectra, we introduce two spectral editing techniques. The first method uses gated (1)H decoupling in a proton-driven spin-diffusion (PDSD) experiment to remove all protonated (13)C signals and retain only non-protonated carbon signals in the aromatic region of the (13)C spectra. The second technique uses chemical shift filters and (1)H-(13)C dipolar dephasing to selectively detect the Cα, Cβ and CO cross peaks of aromatic residues while suppressing the signals of all aliphatic residues. We demonstrate these two techniques on amino acids, a model peptide, and the microcrystalline protein GB1, and show that they significantly simplify the 2D NMR spectra and both reveal and permit the ready assignment of the aromatic residues' signals.

  8. Rapid adaptation of rat brain and liver metabolism to a ketogenic diet: an integrated study using 1H- and 13C-NMR spectroscopy

    PubMed Central

    Roy, Maggie; Beauvieux, Marie-Christine; Naulin, Jérôme; El Hamrani, Dounia; Gallis, Jean-Louis; Cunnane, Stephen C; Bouzier-Sore, Anne-Karine

    2015-01-01

    The ketogenic diet (KD) is an effective alternative treatment for refractory epilepsy in children, but the mechanisms by which it reduces seizures are poorly understood. To investigate how the KD modifies brain metabolism, we infused control (CT) and 7-day KD rats with either [1-13C]glucose (Glc) or [2,4-13C2]β-hydroxybutyrate (β-HB). Specific enrichments of amino acids (AAs) measured by 1H- and 13C-NMR in total brain perchloric acid extracts were similar between CT and KD rats after [1-13C]Glc infusion whereas they were higher in KD rats after [2,4-13C2]β-HB infusion. This suggests better metabolic efficiency of ketone body utilization on the KD. The relative rapid metabolic adaptation to the KD included (1) 11%-higher brain γ-amino butyric acid (GABA)/glutamate (Glu) ratio versus CT, (2) liver accumulation of the ketogenic branched-chain AAs (BCAAs) leucine (Leu) and isoleucine (ILeu), which were never detected in CT, and (3) higher brain Leu and ILeu contents. Since Glu and GABA are excitatory and inhibitory neurotransmitters, respectively, higher brain GABA/Glu ratio could contribute to the mechanism by which the KD reduces seizures in epilepsy. Increased BCAA on the KD may also contribute to better seizure control. PMID:25785828

  9. FOURIER TRANSFORM EMISSION SPECTROSCOPY OF THE B {sup 2}{Sigma}{sup +}-X {sup 2}{Sigma}{sup +} (VIOLET) SYSTEM OF {sup 13}C{sup 14}N

    SciTech Connect

    Ram, R. S.; Bernath, P. F.

    2011-06-01

    Emission spectra of the B {sup 2}{Sigma}{sup +}-X {sup 2}{Sigma}{sup +} transition of {sup 13}C{sup 14}N have been observed at high resolution using the Fourier transform spectrometer associated with the McMath-Pierce Solar Telescope of the National Solar Observatory. The spectra have been measured in the 21000-30000 cm{sup -1} region and a total of 52 vibrational bands involving vibrational levels up to v = 15 of the ground and excited states have been rotationally analyzed to provide a much improved set of spectroscopic constants. An experimental line list and calculated term values are provided. The results of the present analysis should prove useful in the identification of additional {sup 13}C{sup 14}N lines in comets and cool stars, and will help in the determination of the {sup 12}C/{sup 13}C abundance ratio.

  10. Simultaneous two-voxel localized 1H-observed 13C-edited spectroscopy for in vivo MRS on rat brain at 9.4 T: Application to the investigation of excitotoxic lesions

    NASA Astrophysics Data System (ADS)

    Doan, Bich-Thuy; Autret, Gwennhael; Mispelter, Joël; Méric, Philippe; Même, William; Montécot-Dubourg, Céline; Corrèze, Jean-Loup; Szeremeta, Frédéric; Gillet, Brigitte; Beloeil, Jean-Claude

    2009-05-01

    13C spectroscopy combined with the injection of 13C-labeled substrates is a powerful method for the study of brain metabolism in vivo. Since highly localized measurements are required in a heterogeneous organ such as the brain, it is of interest to augment the sensitivity of 13C spectroscopy by proton acquisition. Furthermore, as focal cerebral lesions are often encountered in animal models of disorders in which the two brain hemispheres are compared, we wished to develop a bi-voxel localized sequence for the simultaneous bilateral investigation of rat brain metabolism, with no need for external additional references. Two sequences were developed at 9.4 T: a bi-voxel 1H-( 13C) STEAM-POCE (Proton Observed Carbon Edited) sequence and a bi-voxel 1H-( 13C) PRESS-POCE adiabatically decoupled sequence with Hadamard encoding. Hadamard encoding allows both voxels to be recorded simultaneously, with the same acquisition time as that required for a single voxel. The method was validated in a biological investigation into the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions. Following an excitotoxic quinolinate-induced localized lesion in the rat cortex and the infusion of U- 13C glucose, two 1H-( 13C) spectra of distinct (4 × 4 × 4 mm 3) voxels, one centred on the injured hemisphere and the other on the contralateral hemisphere, were recorded simultaneously. Two 1H bi-voxel spectra were also recorded and showed a significant decrease in N-acetyl aspartate, and an accumulation of lactate in the ipsilateral hemisphere. The 1H-( 13C) spectra could be recorded dynamically as a function of time, and showed a fall in the glutamate/glutamine ratio and the presence of a stable glutamine pool, with a permanent increase of lactate in the ipsilateral hemisphere. This bi-voxel 1H-( 13C) method can be used to investigate simultaneously both brain hemispheres, and to perform dynamic studies. We report here the neuronal damage and the

  11. Applying the diode laser spectroscopy method for high sensitivity on-line control of 13C contained in the gaseous mixture with 12C

    NASA Astrophysics Data System (ADS)

    Kireev, S. V.; Kondrashov, A. A.; Shnyrev, S. L.

    2016-06-01

    This letter details the development of an on-line control method for carbon dioxide molecules of various isotopes contained in gaseous media on the basis of a tunable diode laser operating in the 4860-4880 cm-1 range. It shows that the sensitivity of 13C registering may amount to ~1012 cm-3.

  12. 1H-13C HSQC NMR spectroscopy for estimating procyanidin/prodelphinidin and cis/trans flavan-3-ol ratios of condensed tannin samples: correlation with thiolysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies with a diverse array of 22 condensed tannin (CT) fractions from 9 plant species demonstrated that procyanidin/prodelphinidin (PC/PD) and cis/trans flavan-3-ol ratios can be appraised by 1H-13C HSQC NMR. The method was developed from fractions containing 44 to ~100% CT, PC/PD ratios ranging f...

  13. Estimation of procyanidin/prodelphinidin and cis/trans flavanol ratios of condensed tannin fractions by 1H-13C HSQC NMR spectroscopy: Correlation with thiolysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Integration of cross-peak contours of H/C-2’,6’ signals from prodelphinidin (PD) and of H/C-6’ signals from procyanidin (PC) units in 1H-13C HSQC nuclear magnetic resonance (NMR) spectra of condensed tannins yielded nuclei-adjusted PC/PD estimates that were highly correlated with PC/PD ratios obtain...

  14. Rovibrational constants of the ground state and v8 = 1 state of 13C2HD3 by high-resolution FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Ng, L. L.; Tan, T. L.

    2016-06-01

    The Fourier transform infrared (FTIR) spectrum of the c-type ν8 band of 13C2HD3 was recorded for the first time at a unapodized resolution of 0.0063 cm-1 in the wavenumber region of 830-1000 cm-1. Through the fitting of a total of 1057 assigned infrared transitions using Watson's A-reduced Hamiltonian in the Ir representation, rovibrational constants for the upper state (v8 = 1) up to five quartic centrifugal distortion terms were derived for the first time with a root-mean-square (rms) deviation of 0.00073 cm-1. The band center of ν8 of 13C2HD3 was found to be 913.011021(55) cm-1. Ground state rovibrational constants up to five quartic terms of 13C2HD3 were also determined from a fit of 453 ground state combination-differences from the present infrared measurements with an rms deviation of 0.00072 cm-1 for the first time. The uncertainty of the measured infrared lines was estimated to be ±0.0012 cm-1. From the ground state rotational constants, the inertial defect of 13C2HD3 was calculated to be 0.06973(16) uÅ2, showing the high planarity of the molecule.

  15. Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy

    SciTech Connect

    Fox, Matthew S.; Ouriadov, Alexei; Hegarty, Elaine; Thind, Kundan; Wong, Eugene; Hope, Andrew; Santyr, Giles E.

    2014-07-15

    Purpose: Radiation induced lung injury (RILI) is a common side effect for patients undergoing thoracic radiation therapy (RT). RILI can lead to temporary or permanent loss of lung function and in extreme cases, death. Combining functional lung imaging information with conventional radiation treatment plans may lead to more desirable treatment plans that reduce lung toxicity and improve the quality of life for lung cancer survivors. Magnetic Resonance Imaging of the lung following inhalation of hyperpolarized{sup 129}Xe may provide a useful nonionizing approach for probing changes in lung function and structure associated with RILI before, during, or after RT (early and late time-points). Methods: In this study, dynamic{sup 129}Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (T{sub Tr-tissue} and T{sub Tr-RBC}) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a {sup 60}Co source. A separate group of six healthy age-matched rats served as a control group. Results: T{sub Tr-tissue} values at two weeks post-irradiation (51.6 ± 6.8 ms) were found to be significantly elevated (p < 0.05) with respect to the healthy control group (37.2 ± 4.8 ms). T{sub Tr-RBC} did not show any significant changes between groups. T{sub Tr-tissue} was strongly correlated with T{sub Tr-RBC} in the control group (r = 0.9601 p < 0.05) and uncorrelated in the irradiated groups. Measurements of arterial partial pressure of oxygen obtained by arterial blood sampling were found to be significantly decreased (p < 0.05) in the two-week group (54.2 ± 12.3 mm Hg) compared to those from a representative control group (85.0 ± 10.0 mm Hg). Histology of a separate group of similarly irradiated animals confirmed the presence of inflammation due to radiation exposure with alveolar wall thicknesses that were significantly different (p < 0.05). At six weeks post

  16. Hyperpolarized nanodiamond with long spin-relaxation times

    PubMed Central

    Rej, Ewa; Gaebel, Torsten; Boele, Thomas; Waddington, David E.J.; Reilly, David J.

    2015-01-01

    The use of hyperpolarized agents in magnetic resonance, such as 13C-labelled compounds, enables powerful new imaging and detection modalities that stem from a 10,000-fold boost in signal. A major challenge for the future of the hyperpolarization technique is the inherently short spin-relaxation times, typically <60 s for 13C liquid-state compounds, which limit the time that the signal remains boosted. Here we demonstrate that 1.1% natural abundance 13C spins in synthetic nanodiamond can be hyperpolarized at cryogenic and room temperature without the use of free radicals, and, owing to their solid-state environment, exhibit relaxation times exceeding 1 h. Combined with the already established applications of nanodiamonds in the life sciences as inexpensive fluorescent markers and non-cytotoxic substrates for gene and drug delivery, these results extend the theranostic capabilities of nanoscale diamonds into the domain of hyperpolarized magnetic resonance. PMID:26450570

  17. Mathematical model for evaluating the Krebs cycle flux with non-constant glutamate-pool size by 13C-NMR spectroscopy. Evidence for the existence of two types of Krebs cycles in cells.

    PubMed

    Tran-Dinh, S; Beganton, F; Nguyen, T T; Bouet, F; Herve, M

    1996-12-01

    A practical method using matrix operations is proposed for studying the isotopic transformation of glutamate, or any other metabolite isotopomers, in the Krebs cycle. Two mathematical models were constructed for evaluating the Krebs cycle flux where the enrichment of [2-13C]acetyl-CoA is not 100% and the total glutamate concentration remains constant or varies during incubation. A comparative study of [1-13C]glucose metabolism was subsequently carried out using Saccharomyces cerevisiae cells from two different strains (ATCC-9763 and NCYC-239) by 13C-NMR spectroscopy and biochemical techniques. The results show that there are two types of Krebs cycles in cells. The first is represented by the ATCC cells which contain a small amount of 2-oxoglutarate dehydrogenase and hence the flux in the Krebs cycle is negligible. With [1-13C]glucose as a carbon source, the 13C-NMR spectra of glutamate exhibit the C2 and C4 resonances that are almost equivalent and much greater than that of the C3. Labeled metabolites derived from [1-13C]glucose enter the Krebs cycle at two points: oxaloacetate and citrate. The second cell type is represented by NCYC-239. The C2 and C3 areas are equivalent and smaller than the C4 resonance. The results suggest that labeled metabolites enter the Krebs cycle only at the citrate level via acetyl-CoA, 2-oxoglutarate dehydrogenase is present but pyruvate carboxylase is virtually absent or inactivated. When both are incubated with glucose, the total concentration of glutamate was found to decrease with the incubation time. The fraction of glutamate in isotopic exchange with the Krebs cycle in NCYC-239 cells is about 2.6% and the reduction in glutamate concentration is about 0.5%/min. Using our model, with a variable glutamate pool size, good agreement between the theoretical and experimental data is obtained.

  18. High-Resolution Spectroscopy of the A^1Π(v'=0-10)-X^1Σ^+(v''=0) Bands in 13C18O

    NASA Astrophysics Data System (ADS)

    Lemaire, Jean Louis; Eidelsberg, Michele; Heays, Alan; Gavilan, Lisseth; Federman, Steven; Stark, Glenn; Lyons, James R.; de Oliveira, Nelson; Joyeux, Denis

    2016-06-01

    Ultraviolet spectrographs on space-borne astronomical facilities are used to study CO photochemistry primarily through observations of the A-X Fourth Positive Band System. Absorption from 12C16O, 13C16O, 12C18O, and 12C17O in diffuse interstellar clouds has been detected to date. While the necessary spectroscopic data are available to identify the isotopologues, measurements of oscillator strengths only exist for the most abundant variant, 12C16O. In our ongoing experiments on the DESIRS beam-line at the SOLEIL Synchrotron, we are acquiring the necessary data on oscillator strengths and term values for other isotopologues. Here we present our latest results involving A-X bands in 13C18O.

  19. High resolution spectroscopy and chemical shift imaging of hyperpolarized 129Xe dissolved in the human brain in vivo at 1.5 tesla

    PubMed Central

    Rao, Madhwesha; Stewart, Neil J.; Norquay, Graham; Griffiths, Paul D.

    2016-01-01

    Purpose Upon inhalation, xenon diffuses into the bloodstream and is transported to the brain, where it dissolves in various compartments of the brain. Although up to five chemically distinct peaks have been previously observed in 129Xe rat head spectra, to date only three peaks have been reported in the human head. This study demonstrates high resolution spectroscopy and chemical shift imaging (CSI) of 129Xe dissolved in the human head at 1.5 Tesla. Methods A 129Xe radiofrequency coil was built in‐house and 129Xe gas was polarized using spin‐exchange optical pumping. Following the inhalation of 129Xe gas, NMR spectroscopy was performed with spectral resolution of 0.033 ppm. Two‐dimensional CSI in all three anatomical planes was performed with spectral resolution of 2.1 ppm and voxel size 20 mm × 20 mm. Results Spectra of hyperpolarized 129Xe dissolved in the human head showed five distinct peaks at 188 ppm, 192 ppm, 196 ppm, 200 ppm, and 217 ppm. Assignment of these peaks was consistent with earlier studies. Conclusion High resolution spectroscopy and CSI of hyperpolarized 129Xe dissolved in the human head has been demonstrated. For the first time, five distinct NMR peaks have been observed in 129Xe spectra from the human head in vivo. Magn Reson Med 75:2227–2234, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27080441

  20. Identification and quantitative determination of eudesmane-type acids from the essential oil of Dittrichia viscosa sp. viscosa using 13C-NMR spectroscopy.

    PubMed

    Blanc, Marie-Cécile; Bradesi, Pascale; Casanova, Joseph

    2005-01-01

    A procedure that allows the identification and quantitative determination of eudesmane-type acids in the acidic part of the essential oil of Dittrichia viscosa sp. viscosa is described. The method involves the computer-aided analysis of the 13C-NMR spectrum of the mixture without the requirement of previous separation or derivatisation. The quantitative procedure was verified with costic acid standard and applied to three other acids which possess the same eudesmane framework.

  1. Substrate affinities for membrane transport proteins determined by 13C cross-polarization magic-angle spinning nuclear magnetic resonance spectroscopy.

    PubMed

    Patching, Simon G; Brough, Adrian R; Herbert, Richard B; Rajakarier, J Anton; Henderson, Peter J F; Middleton, David A

    2004-03-17

    We have devised methods in which cross-polarization magic-angle spinning (CP-MAS) solid-state NMR is exploited to measure rigorous parameters for binding of (13)C-labeled substrates to membrane transport proteins. The methods were applied to two proteins from Escherichia coli: a nucleoside transporter, NupC, and a glucuronide transporter, GusB. A substantial signal for the binding of methyl [1-(13)C]-beta-d-glucuronide to GusB overexpressed in native membranes was achieved with a sample that contained as little as 20 nmol of GusB protein. The data were fitted to yield a K(D) value of 4.17 mM for the labeled ligand and 0.42 mM for an unlabeled ligand, p-nitrophenyl beta-d-glucuronide, which displaced the labeled compound. CP-MAS was also used to measure binding of [1'-(13)C]uridine to overexpressed NupC. The spectrum of NupC-enriched membranes containing [1'-(13)C]uridine exhibited a large peak from substrate bound to undefined sites other than the transport site, which obscured the signal from substrate bound to NupC. In a novel application of a cross-polarization/polarization-inversion (CPPI) NMR experiment, the signal from undefined binding was eliminated by use of appropriate inversion pulse lengths. By use of CPPI in a titration experiment, a K(D) value of 2.6 mM was determined for uridine bound to NupC. These approaches are broadly applicable to quantifying binding of substrates, inhibitors, drugs, and antibiotics to numerous membrane proteins. PMID:15012136

  2. Combined Parallel and Partial Fourier MR Reconstruction for Accelerated 8-Channel Hyperpolarized Carbon-13 In Vivo Magnetic Resonance Spectroscopic Imaging (MRSI)

    PubMed Central

    Ohliger, Michael A.; Larson, Peder E.Z.; Bok, Robert A.; Shin, Peter; Hu, Simon; Tropp, James; Robb, Fraser; Carvajal, Lucas; Nelson, Sarah J.; Kurhanewicz, John; Vigneron, Daniel B.

    2013-01-01

    Purpose To implement and evaluate combined parallel magnetic resonance imaging (MRI) and partial Fourier acquisition and reconstruction for rapid hyperpolarized carbon-13 (13C) spectroscopic imaging. Short acquisition times mitigate hyperpolarized signal losses that occur due to T1 decay, metabolism, and radiofrequency (RF) saturation. Human applications additionally require rapid imaging to permit breath-holding and to minimize the effects of physiologic motion. Materials and Methods Numerical simulations were employed to validate and characterize the reconstruction. In vivo MR spectroscopic images were obtained from a rat following injection of hyperpolarized 13C pyruvate using an 8-channel array of carbon-tuned receive elements. Results For small spectroscopic matrix sizes, combined parallel imaging and partial Fourier undersampling resulted primarily in decreased spatial resolution, with relatively less visible spatial aliasing. Parallel reconstruction qualitatively restored lost image detail, although some pixel spectra had persistent numerical error. With this technique, a 30 × 10 × 16 matrix of 4800 3D MR spectroscopy imaging voxels from a whole rat with isotropic 8 mm3 resolution was acquired within 11 seconds. Conclusion Parallel MRI and partial Fourier acquisitions can provide the shorter imaging times and wider spatial coverage that will be necessary as hyperpolarized 13C techniques move toward human clinical applications. PMID:23293097

  3. Carbanion substituent effects on 1-disubstituted 4-(4'-pyridyl)pyridinium methylide structures using 13C NMR spectroscopy and DFT method

    NASA Astrophysics Data System (ADS)

    Depature, Ludovic; Surpateanu, Gheorghe

    2003-11-01

    The structure of 1-disubstituted 4-(4'-pyridyl)pyridinium methylides or 4,4'-bipyridinium monoylides ( 2- 5) with a wide range of carbanion substituents, were determined using 13C NMR signals in dimethylsufoxide (DMSO- d6) solution. For the first time, we developed a systematic determination of 13C NMR chemical shifts of the ylidic carbon using a long-range correlated ( 1H- 13C) HMBC experiments. The chemical shift values are discussed in terms of magnetic and/or electronic effects of the ylidic carbon substituents. From the extracted NMR parameters and the results of accompanying quantum chemical DFT calculations for a three-dimensional (3D)-structure representation, we found a long distance electronic effect where the aromatic heterocycle C2C6 and C4 centers are perturbed according to the electron acceptor strengths of ylidic carbon substituents in all monoylides ( 2- 5c) capable to stabilize in a planar conformation. No significant perturbation on C2C6 and C4 centers are found in all other monoylides ( 2- 5a, b) that adopted a non-planar conformation. Good similar linear dependences of the chemical shift variation Δ (calculated by the differences of analogous C2C6 and C4 chemical shifts in non-planar and planar monoylides) with the ylidic carbon chemical shifts modulated by the strength of electron acceptor substituents pointed out the resonance interaction or the delocalization phenomena of the ylidic carbon charge on the heterocycle.

  4. Secondary structure and side-chain sup 1 H and sup 13 C resonance assignments of calmodulin in solution by heteronuclear multidimensional NMR spectroscopy

    SciTech Connect

    Ikura, Mitsuhiko; Spera, S.; Barbato, G.; Kay, L.E.; Bax, A. ); Krinks, M. )

    1991-09-24

    Heteronuclear 2D and 3D NMR experiments were carried out on recombinant Drosophila calmodulin (CaM), a protein of 148 residues and with molecular mass of 16.7 kDa, that is uniformly labeled with {sup 15}N and {sup 13}C to a level of > 95%. Nearly complete {sup 1}H and {sup 13}C side-chain assignments for all amino acid residues are obtained by using the 3D HCCH-COSY and HCCH-TOCSY experiments that rely on large heteronuclear one-bond scalar couplings to transfer magnetization and establish through-bond connectivities. The secondary structure of this protein in solution has been elucidated by a qualitative interpretation of nuclear Overhauser effects, hydrogen exchange data, and {sup 3}J{sub HNH{alpha}} coupling constants. A clear correlation between the {sup 13}C{alpha} chemical shift and secondary structure is found. The secondary structure in the two globular domains of Drosophila CaM in solution is essentially identical with that of the X-ray crystal structure of mammalian CaM which consists of two pairs of a helix-loop-helix motif in each globular domain. The existence of a short antiparallel {beta}-sheet between the two loops in each domain has been confirmed. The eight {alpha}-helix segments identified from the NMR data are located at Glu-6 to Phe-19, thr-29 to Ser-38, Glu-45 to Glu-54, Phe-65 to Lys-77, Glu-82 to Asp-93, Ala-102 to Asn-111, Asp-118 to Glu-127, and Tyr-138 to Thr-146. Although the crystal structure has a long central helix from Phe-65 to Phe-92 that connects the two globular domains, NMR data indicate that residues Asp-78 to Ser-81 of this central helix adopt a nonhelical conformation with considerable flexibility.

  5. Mathematical models for determining metabolic fluxes through the citric acid and the glyoxylate cycles in Saccharomyces cerevisiae by 13C-NMR spectroscopy.

    PubMed

    Tran-Dinh, S; Bouet, F; Huynh, Q T; Herve, M

    1996-12-15

    We propose, first, a practical method for studying the isotopic transformation of glutamate or any other metabolite isotopomers in the citric acid and the glyoxylate cycles; second, two mathematical models, one for evaluating the flux through the citric acid cycle and the other for evaluating the flux through the latter coupled to the glyoxylate cycle in yeast. These models are based on the analysis of 13C-NMR spectra of glutamate obtained from Saccharomyces cerevisiae, NCYC strain, fed with 100% enriched [2-13C]acetate. The population of each glutamate isotopomer, the change in intensity of each multiplet component or the enrichment of any glutamate carbon is expressed by a specific analytical equation from which the flux in the citric acid and the glyoxylate cycles can be deduced. The aerobic metabolism of 100% [2-13C]acetate in acetate-grown S. cerevisiae cells was studied as a function of time using 13C-NMR. 1H-NMR and biochemical techniques. The C1 and C6 doublet and singlet of labeled trehalose increase continuously with time indicating that there is no isotopic transformation between trehalose isotopomers even though the corresponding formation rates are different. By contrast, the glutamate C4 singlet increases then decreases with time. The C4 doublet, which is lower than the singlet for t < 60 min, increases continuously and becomes higher than the singlet for t > 90 min. A similar observation was made for the C2 resonance singlet and doublet. In addition, the glutamate C2 multiplet consists of only seven instead of nine peaks as in random labeling. These results agree well with our models and demonstrate that, in the presence of acetate, anaplerotic carbon sources involved in the synthesis of acetyl-CoA are negligible in yeast. The flux in the citric acid cycle was deduced from a plot of the C4 area versus incubation time, while the flux within the glyoxylate cycle was determined from the relative intensity of the glutamate C4 doublet and singlet. The

  6. Residue specific hydration of primary cell wall potato pectin identified by solid-state 13C single-pulse MAS and CP/MAS NMR spectroscopy.

    PubMed

    Larsen, Flemming H; Byg, Inge; Damager, Iben; Diaz, Jerome; Engelsen, Søren B; Ulvskov, Peter

    2011-05-01

    Hydration of rhamnogalacturonan-I (RG-I) derived from potato cell wall was analyzed by (13)C single-pulse (SP) magic-angle-spinning (MAS) and (13)C cross-polarization (CP) MAS nuclear magnetic resonance (NMR) and supported by (2)H SP/MAS NMR experiments. The study shows that the arabinan side chains hydrate more readily than the galactan side chains and suggests that the overall hydration properties can be controlled by modifying the ratio of these side chains. Enzymatic modification of native (NA) RG-I provided samples with reduced content of arabinan (sample DA), galactan (sample DG), or both side chains (sample DB). Results of these samples suggested that hydration properties were determined by the length and character of the side chains. NA and DA exhibited similar hydration characteristics, whereas DG and DB were difficult to hydrate because of the less hydrophilic properties of the rhamnose-galacturonic acid (Rha-GalA) backbone in RG-I. Potential food ingredient uses of RG-I by tailoring of its structure are discussed.

  7. Spectroscopy of {sup 13}B via the {sup 13}C(t,{sup 3}He) reaction at 115A MeV

    SciTech Connect

    Guess, C. J.; Zegers, R. G. T.; Brown, B. A.; Deaven, J. M.; Hitt, G. W.; Meharchand, R.; Austin, Sam M.; Perdikakis, G.; Tur, C.; Bazin, D.; Grinyer, G. F.; Caesar, C.; Herlitzius, C.; Noji, S.; Sakai, H.; Shimbara, Y.

    2009-08-15

    Gamow-Teller and dipole transitions to final states in {sup 13}B were studied via the {sup 13}C(t,{sup 3}He) reaction at E{sub t}=115A MeV. In addition to the strong Gamow-Teller transition to the {sup 13}B ground state, a weaker Gamow-Teller transition to a state at 3.6 MeV was found. This state was assigned a spin-parity of 3/2{sup -} by comparison with shell-model calculations using the WBP and WBT interactions which were modified to allow for mixing between n({Dirac_h}/2{pi}){omega} and (n+2)({Dirac_h}/2{pi}){omega} configurations. This assignment agrees with a recent result from a lifetime measurement of excited states in {sup 13}B. The shell-model calculations also explained the relatively large spectroscopic strength measured for a low-lying 1/2{sup +} state at 4.83 MeV in {sup 13}B. The cross sections for dipole transitions up to E{sub x}({sup 13}B)=20 MeV excited via the {sup 13}C(t,{sup 3}He) reaction were also compared with the shell-model calculations. The theoretical cross sections exceeded the data by a factor of about 1.8, which might indicate that the dipole excitations are ''quenched''. Uncertainties in the reaction calculations complicate that interpretation.

  8. Short hydrogen bonds in salts of dicarboxylic acids; structural correlations from solid-state 13C and 2H NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Kalsbeek, Nicoline; Schaumburg, Kjeld; Larsen, Sine

    1993-10-01

    Solid-state 13C and 2H NMR spectra are found to very suitable for characterizing the short Osbnd H...O hydrogen bonds observed in acid salts of dicarboxylic acids. The majority of the investigated compounds are acid salts of malonic, succinic and tartaric acid with monovalent cations derived from alkali metals and small aliphatic amines. They include systems with symmetric and asymmetric hydrogen bonds. Accurate structural information about their geometry is available from low-temperature X-ray diffraction data. The 13C chemical shifts of the C atoms in the different carboxy groups display a linear variation with the absolute difference between the two Csbnd O bond lengths. Theoretical ab initio calculations for model systems showed that the nuclear quadrupole coupling constant NQCC for 2H increases with increasing asymmetry of the hydrogen-bonded system. NQCC values for 2H in the short symmetric hydrogen-bonded systems are in the range 53-59 kHz compared with the larger values of up to 166kHz found in systems with longer asymmetric hydrogen bonds. The 2H NQCC values display a perfect linear dependence on the asymmetry of the hydrogen bond. 2H NQCC decreases with decreasing temperature in the symmetric hydrogen bonds showing that the corresponding potential has a single well.

  9. Conformations of solid 2-methyl-4-( p-X-phenylazo)imidazoles by 13C CP MAS NMR spectroscopy and PM3 semi-empirical calculations

    NASA Astrophysics Data System (ADS)

    Maciejewska, Dorota

    1999-03-01

    Solid 2-methyl-4-( p-X-phenylazo)imidazoles form hydrogen bonded chains with N-H⋯N bonds and C-H⋯O or C-H⋯N interaction. Depending on the nature and orientation of the substituents X it was possible to identify one tautomer if XH ( 2), Br ( 3), NO 2 ( 4) and the two, a- and b-tautomers in the crystal unit if XOCH 3 ( 1). The 13C CP MAS NMR spectra of ( 4) indicate the presence of phenyl ring dynamics. A preferred structure present in the solid state is that with different lengths of C1'-N and C4-N bonds and with higher dipole moment.

  10. Chemical and nanometer-scale structure of kerogen and its change during thermal maturation investigated by advanced solid-state 13C NMR spectroscopy

    USGS Publications Warehouse

    Mao, J.; Fang, X.; Lan, Y.; Schimmelmann, A.; Mastalerz, Maria; Xu, L.; Schmidt-Rohr, K.

    2010-01-01

    We have used advanced and quantitative solid-state nuclear magnetic resonance (NMR) techniques to investigate structural changes in a series of type II kerogen samples from the New Albany Shale across a range of maturity (vitrinite reflectance R0 from 0.29% to 1.27%). Specific functional groups such as CH3, CH2, alkyl CH, aromatic CH, aromatic C-O, and other nonprotonated aromatics, as well as "oil prone" and "gas prone" carbons, have been quantified by 13C NMR; atomic H/C and O/C ratios calculated from the NMR data agree with elemental analysis. Relationships between NMR structural parameters and vitrinite reflectance, a proxy for thermal maturity, were evaluated. The aromatic cluster size is probed in terms of the fraction of aromatic carbons that are protonated (???30%) and the average distance of aromatic C from the nearest protons in long-range H-C dephasing, both of which do not increase much with maturation, in spite of a great increase in aromaticity. The aromatic clusters in the most mature sample consist of ???30 carbons, and of ???20 carbons in the least mature samples. Proof of many links between alkyl chains and aromatic rings is provided by short-range and long-range 1H-13C correlation NMR. The alkyl segments provide most H in the samples; even at a carbon aromaticity of 83%, the fraction of aromatic H is only 38%. While aromaticity increases with thermal maturity, most other NMR structural parameters, including the aromatic C-O fractions, decrease. Aromaticity is confirmed as an excellent NMR structural parameter for assessing thermal maturity. In this series of samples, thermal maturation mostly increases aromaticity by reducing the length of the alkyl chains attached to the aromatic cores, not by pronounced growth of the size of the fused aromatic ring clusters. ?? 2010 Elsevier Ltd. All rights reserved.

  11. Vanadium bisimide bonding investigated by X-ray crystallography, 51V and 13C nuclear magnetic resonance spectroscopy, and V L(3,2)-edge X-ray absorption near-edge structure spectroscopy.

    PubMed

    La Pierre, Henry S; Minasian, Stefan G; Abubekerov, Mark; Kozimor, Stosh A; Shuh, David K; Tyliszczak, Tolek; Arnold, John; Bergman, Robert G; Toste, F Dean

    2013-10-01

    Syntheses of neutral halide and aryl vanadium bisimides are described. Treatment of VCl2(NtBu)[NTMS(N(t)Bu)], 2, with PMe3, PEt3, PMe2Ph, or pyridine gave vanadium bisimides via TMSCl elimination in good yield: VCl(PMe3)2(N(t)Bu)2 3, VCl(PEt3)2(N(t)Bu)2 4, VCl(PMe2Ph)2(N(t)Bu)2 5, and VCl(Py)2(N(t)Bu)2 6. The halide series (Cl-I) was synthesized by use of TMSBr and TMSI to give VBr(PMe3)2(N(t)Bu)2 7 and VI(PMe3)2(N(t)Bu)2 8. The phenyl derivative was obtained by reaction of 3 with MgPh2 to give VPh(PMe3)2(N(t)Bu)2 9. These neutral complexes are compared to the previously reported cationic bisimides [V(PMe3)3(N(t)Bu)2][Al(PFTB)4] 10, [V(PEt3)2(N(t)Bu)2][Al(PFTB)4] 11, and [V(DMAP)(PEt3)2(N(t)Bu)2][Al(PFTB)4] 12 (DMAP = dimethylaminopyridine, PFTB = perfluoro-tert-butoxide). Characterization of the complexes by X-ray diffraction, (13)C NMR, (51)V NMR, and V L(3,2)-edge X-ray absorption near-edge structure (XANES) spectroscopy provides a description of the electronic structure in comparison to group 6 bisimides and the bent metallocene analogues. The electronic structure is dominated by π bonding to the imides, and localization of electron density at the nitrogen atoms of the imides is dictated by the cone angle and donating ability of the axial neutral supporting ligands. This phenomenon is clearly seen in the sensitivity of (51)V NMR shift, (13)C NMR Δδ(αβ), and L3-edge energy to the nature of the supporting phosphine ligand, which defines the parameters for designing cationic group 5 bisimides that would be capable of breaking stronger σ bonds. Conversely, all three methods show little dependence on the variable equatorial halide ligand. Furthermore, this analysis allows for quantification of the electronic differences between vanadium bisimides and the structurally analogous mixed Cp/imide system CpV(N(t)Bu)X2 (Cp = C5H5(1-)). PMID:24024833

  12. New insights into the structure and chemistry of Titan's tholins via 13C and 15N solid state nuclear magnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Derenne, S.; Coelho, C.; Anquetil, C.; Szopa, C.; Quirico, E.; Bonhomme, C.

    2012-09-01

    Titan, the largest moon of Saturn, is characterized by a dense atmosphere, mainly composed of N2 (ca. 97 %) and CH4 (ca. 2 %). In the upper atmosphere, methane and nitrogen molecules undergo dissociation under the influence of solar UV radiation and electron impacts, followed by recombination reactions leading to a large variety of organic molecules. Some of these compounds form a thick, orange-coloured haze composed of solid organic aerosols that subsequently fall to the surface or remain in suspension in the atmosphere. To gain insight into the chemical composition and structural nature of these complex organic compounds, analogous materials, termed Titan's tholins, are produced in the laboratory, in particular using plasma discharge in gaseous N2 - CH4 mixtures with similar proportions as in Titan's atmosphere. Titan's tholins have been analysed using a wide variety of techniques which provided a wealth of information about potential functional groups and structural building blocks present within the tholin samples. Taken together, the results converge on a structure based on a CxHyNz chemistry that can contain a variety of C-C, C-N, N-H etc single or multiple bonds. It is now necessary to build on that information to refine the chemical and structural models for the Titan's tholins. Here we used solid state NMR techniques to investigate the carbon and nitrogen bonding environments in a 13C- and 15Nenriched sample.

  13. Insight into the packing pattern of β2 fibrils: a model study of glutamic acid rich oligomers with 13C isotopic edited vibrational spectroscopy.

    PubMed

    Chi, Heng; Welch, William R W; Kubelka, Jan; Keiderling, Timothy A

    2013-11-11

    Polyglutamic acid at low pH forms aggregates and self-assembles into a spiral, fibril-like superstructure formed as a β2-type sheet conformation that has a more compact intersheet packing than commonly found. This is stabilized by three-centered bifurcated hydrogen bonding of the amide carbonyl involving the protonated glutamic acid side chain. We report vibrational spectroscopic results and analyses for oligopeptides rich in glutamic acid enhanced with (13)C isotope labeling in a study modeling low pH poly-Glu self-assembly. Our results indicate bifurcated H-bonding and β2 aggregation can be attained in these model decamers, confirming they have the same conformations as poly-Glu. We also prepared conventional β1-sheet aggregates by rapid precipitation from the residual peptides in the higher pH supernatant. By comparing the isotope-enhanced IR and VCD spectra with theoretical predictions, we deduced that the oligo-Glu β2 structure is based on stacked, twisted, antiparallel β-sheets. The best fit to theoretical predictions was obtained for the strands being out of register, sequentially stepped by one residue, in a ladder-like fashion. The alternate β1 conformer for this oligopeptide was similarly shown to be antiparallel but was less ordered and apparently had a different registry in its aggregate structure.

  14. Abnormalities in hyperpolarized (129)Xe magnetic resonance imaging and spectroscopy in two patients with pulmonary vascular disease.

    PubMed

    Dahhan, Talal; Kaushik, Shiv S; He, Mu; Mammarappallil, Joseph G; Tapson, Victor F; McAdams, Holman P; Sporn, Thomas A; Driehuys, Bastiaan; Rajagopal, Sudarshan

    2016-03-01

    The diagnosis of pulmonary vascular disease (PVD) is usually based on hemodynamic and/or clinical criteria. Noninvasive imaging of the heart and proximal vasculature can also provide useful information. An alternate approach to such criteria in the diagnosis of PVD is to image the vascular abnormalities in the lungs themselves. Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) is a novel technique for assessing abnormalities in ventilation and gas exchange in the lungs. We applied this technique to two patients for whom there was clinical suspicion of PVD. Two patients who had significant hypoxemia and dyspnea with no significant abnormalities on computed tomography imaging or ventilation-perfusion scan and only mild or borderline pulmonary arterial hypertension at catheterization were evaluated. They underwent HP (129)Xe imaging and subsequently had tissue diagnosis obtained from lung pathology. In both patients, HP (129)Xe imaging demonstrated normal ventilation but markedly decreased gas transfer to red blood cells with focal defects on imaging, a pattern distinct from those previously described for idiopathic pulmonary fibrosis or obstructive lung disease. Pathology on both patients later demonstrated severe PVD. These findings suggest that HP (129)Xe MRI may be useful in the diagnosis of PVD and monitoring response to therapy. Further studies are required to determine its sensitivity and specificity in these settings. PMID:27162620

  15. High Resolution Laser Spectroscopy of Mg12C12CD, Mg13C13CH and Mg12C_4H

    NASA Astrophysics Data System (ADS)

    Forthomme, D.; Linton, C.; Tokaryk, D. W.; Adam, A. G.; Granger, A. D.

    2010-06-01

    Carbon and magnesium are abundant elements in the interstellar medium, so it is possible that carbon chain molecules containing a magnesium atom may exist in this environment. With this in mind, radical molecules of the form MgC2nH (n = 1,2,3) have been frequent subjects of both experimental and theoretical studies In this presentation we will discuss our high-resolution experiments of the ~A2Π-~X2Σ+ transitions in the isotopologues Mg12C12CD and Mg13C13CH, which complement our earlier investigation of this spectrum in Mg12C12CH^b. The data permit us to determine the lengths of individual bonds to high precision. In addition, we have expanded on previous studies of the ~A2Π-~X2Σ+ transition of Mg12C_4H, conducted at medium resolution. The parameters obtained from our high-resolution spectra are compared with those obtained from theoretical structure calculations. H. Ding, C. Apetrei, L. Chacaga, J. P. Maier, Astrophys. J. 677 (2008) 348-352 D. W. Tokaryk, A. G. Adam, W. S. Hopkins, J. Mol. Spectrosc. 230 (2005) 54-61 D. E. Woon, Chem. Phys. Lett. 274 (1997) 299-305 C. A. Thompson and L. Andrews, J. Am. Chem. Soc. 118 (1996) 10242-10249 X. Guo, J. Zhang, J. Li, L. Jiang, J. Zhang, Chem. Phys 360 (2009) 27-31 E. Chasovskikh, E. B. Jochnowitz, J. P. Maier, J. Phys. Chem. A. 112 (2008) 8686-8689.

  16. Carbonation of C–S–H and C–A–S–H samples studied by {sup 13}C, {sup 27}Al and {sup 29}Si MAS NMR spectroscopy

    SciTech Connect

    Sevelsted, Tine F.; Skibsted, Jørgen

    2015-05-15

    Synthesized calcium silicate hydrate (C–S–H) samples with Ca/Si ratios of 0.66, 1.0, and 1.5 have been exposed to atmospheric CO{sub 2} at room temperature and high relative humidity and studied after one to 12 weeks. {sup 29}Si NMR reveals that the decomposition of C–S–H caused by carbonation involves two steps and that the decomposition rate decreases with increasing Ca/Si ratio. The first step is a gradual decalcification of the C–S–H where calcium is removed from the interlayer and defect sites in the silicate chains until Ca/Si = 0.67 is reached, ideally corresponding to infinite silicate chains. In the seconds step, calcium from the principal layers is consumed, resulting in the final decomposition of the C–S–H and the formation of an amorphous silica phase composed of Q{sup 3} and Q{sup 4} silicate tetrahedra. The amount of solid carbonates and of carbonate ions in a hydrous environment increases with increasing Ca/Si ratio for the C–S–H, as shown by {sup 13}C NMR. For C–A–S–H samples with Ca/Si = 1.0 and 1.5, {sup 27}Al NMR demonstrates that all aluminium sites associated with the C–S–H are consumed during the carbonation reactions and incorporated mainly as tetrahedral Al(–OSi){sub 4} units in the amorphous silica phase. A small amount of penta-coordinated Al sites has also been identified in the silica phase.

  17. Studies of low-lying triplet states in 1,3-C4F6, c-C4F6 and 2-C4F6 by electron energy-loss spectroscopy and ab initio calculations

    NASA Astrophysics Data System (ADS)

    Limão-Vieira, P.; Duflot, D.; Anzai, K.; Kato, H.; Hoshino, M.; Silva, F. Ferreira da; Mogi, D.; Tanioka, T.; Tanaka, H.

    2013-06-01

    This Letter reports on the first measurements of the lowest lying triplet states as studied by electron energy loss spectroscopy for C4F6 isomers, hexafluoro-1,3-butadiene (1,3-C4F6), hexafluorocyclobutene (c-C4F6) and hexafluoro-2-butyne (2-C4F6). This study has been performed at an incident electron energy of 30 eV, 30°, whilst sweeping the energy loss over the range 2.0-15.0 eV. The electronic state spectroscopy has been investigated and the assignments supported by multi-reference quantum chemical calculations. The transition to the steepest electronic excited potential energy curve, is suggested to be dominant for 2-C4F6, due to the large broadening in its energy profile.

  18. Probing alanine transaminase catalysis with hyperpolarized 13CD3-pyruvate

    NASA Astrophysics Data System (ADS)

    Barb, A. W.; Hekmatyar, S. K.; Glushka, J. N.; Prestegard, J. H.

    2013-03-01

    Hyperpolarized metabolites offer a tremendous sensitivity advantage (>104 fold) when measuring flux and enzyme activity in living tissues by magnetic resonance methods. These sensitivity gains can also be applied to mechanistic studies that impose time and metabolite concentration limitations. Here we explore the use of hyperpolarization by dissolution dynamic nuclear polarization (DNP) in mechanistic studies of alanine transaminase (ALT), a well-established biomarker of liver disease and cancer that converts pyruvate to alanine using glutamate as a nitrogen donor. A specific deuterated, 13C-enriched analog of pyruvic acid, 13C3D3-pyruvic acid, is demonstrated to have advantages in terms of detection by both direct 13C observation and indirect observation through methyl protons introduced by ALT-catalyzed H-D exchange. Exchange on injecting hyperpolarized 13C3D3-pyruvate into ALT dissolved in buffered 1H2O, combined with an experimental approach to measure proton incorporation, provided information on mechanistic details of transaminase action on a 1.5 s timescale. ALT introduced, on average, 0.8 new protons into the methyl group of the alanine produced, indicating the presence of an off-pathway enamine intermediate. The opportunities for exploiting mechanism-dependent molecular signatures as well as indirect detection of hyperpolarized 13C3-pyruvate and products in imaging applications are discussed.

  19. Simultaneous estimation of T₁ and the flip angle in hyperpolarized NMR experiments using acquisition at non-regular time intervals.

    PubMed

    Puckeridge, Max; Pagès, Guilhem; Kuchel, Philip W

    2012-09-01

    In NMR spectroscopy of the liquid state T(1) is typically measured using an inversion recovery pulse sequence; but with hyperpolarized spins use is made of a sequence of multiple small radiofrequency (RF) induced nutations, α. Depending on the values of α and τ, the time interval between the pulses, the estimate of T(1) can be artifactually smaller than the real value; so without knowing the value of α the estimate of T(1) can be incorrect. Thus, we propose a method that involves a series of pulses with timing governed by a geometric sequence (or in general, any mathematically specified non-uniformly spaced sequence). This approach enables the simultaneous estimation of both the intrinsic T(1) value and α. The method was successfully applied to obtain T(1)=(44.9 ± 0.3)s and α=(4.0 ± 0.2)° (n=3) for a sample of hyperpolarized (13)C-urea in solution, matching with the inversion recovery pulse sequence estimate of T(1)=44 ± 2s using non-hyperpolarized (13)C-urea in solution.

  20. Following Metabolism in Living Microorganisms by Hyperpolarized (1)H NMR.

    PubMed

    Dzien, Piotr; Fages, Anne; Jona, Ghil; Brindle, Kevin M; Schwaiger, Markus; Frydman, Lucio

    2016-09-21

    Dissolution dynamic nuclear polarization (dDNP) is used to enhance the sensitivity of nuclear magnetic resonance (NMR), enabling monitoring of metabolism and specific enzymatic reactions in vivo. dDNP involves rapid sample dissolution and transfer to a spectrometer/scanner for subsequent signal detection. So far, most biologically oriented dDNP studies have relied on hyperpolarizing long-lived nuclear spin species such as (13)C in small molecules. While advantages could also arise from observing hyperpolarized (1)H, short relaxation times limit the utility of prepolarizing this sensitive but fast relaxing nucleus. Recently, it has been reported that (1)H NMR peaks in solution-phase experiments could be hyperpolarized by spontaneous magnetization transfers from bound (13)C nuclei following dDNP. This work demonstrates the potential of this sensitivity-enhancing approach to probe the enzymatic process that could not be suitably resolved by (13)C dDNP MR. Here we measured, in microorganisms, the action of pyruvate decarboxylase (PDC) and pyruvate formate lyase (PFL)-enzymes that catalyze the decarboxylation of pyruvate to form acetaldehyde and formate, respectively. While (13)C NMR did not possess the resolution to distinguish the starting pyruvate precursor from the carbonyl resonances in the resulting products, these processes could be monitored by (1)H NMR at 500 MHz. These observations were possible in both yeast and bacteria in minute-long kinetic measurements where the hyperpolarized (13)C enhanced, via (13)C → (1)H cross-relaxation, the signals of protons binding to the (13)C over the course of enzymatic reactions. In addition to these spontaneous heteronuclear enhancement experiments, single-shot acquisitions based on J-driven (13)C → (1)H polarization transfers were also carried out. These resulted in higher signal enhancements of the (1)H resonances but were not suitable for multishot kinetic studies. The potential of these (1)H-based approaches for

  1. Strategies for the Hyperpolarization of Acetonitrile and Related Ligands by SABRE

    PubMed Central

    2014-01-01

    We report on a strategy for using SABRE (signal amplification by reversible exchange) for polarizing 1H and 13C nuclei of weakly interacting ligands which possess biologically relevant and nonaromatic motifs. We first demonstrate this via the polarization of acetonitrile, using Ir(IMes)(COD)Cl as the catalyst precursor, and confirm that the route to hyperpolarization transfer is via the J-coupling network. We extend this work to the polarization of propionitrile, benzylnitrile, benzonitrile, and trans-3-hexenedinitrile in order to assess its generality. In the 1H NMR spectrum, the signal for acetonitrile is enhanced 8-fold over its thermal counterpart when [Ir(H)2(IMes)(MeCN)3]+ is the catalyst. Upon addition of pyridine or pyridine-d5, the active catalyst changes to [Ir(H)2(IMes)(py)2(MeCN)]+ and the resulting acetonitrile 1H signal enhancement increases to 20- and 60-fold, respectively. In 13C NMR studies, polarization transfers optimally to the quaternary 13C nucleus of MeCN while the methyl 13C is hardly polarized. Transfer to 13C is shown to occur first via the 1H–1H coupling between the hydrides and the methyl protons and then via either the 2J or 1J couplings to the respective 13Cs, of which the 2J route is more efficient. These experimental results are rationalized through a theoretical treatment which shows excellent agreement with experiment. In the case of MeCN, longitudinal two-spin orders between pairs of 1H nuclei in the three-spin methyl group are created. Two-spin order states, between the 1H and 13C nuclei, are also created, and their existence is confirmed for Me13CN in both the 1H and 13C NMR spectra using the Only Parahydrogen Spectroscopy protocol. PMID:25539423

  2. Strategies for the hyperpolarization of acetonitrile and related ligands by SABRE.

    PubMed

    Mewis, Ryan E; Green, Richard A; Cockett, Martin C R; Cowley, Michael J; Duckett, Simon B; Green, Gary G R; John, Richard O; Rayner, Peter J; Williamson, David C

    2015-01-29

    We report on a strategy for using SABRE (signal amplification by reversible exchange) for polarizing (1)H and (13)C nuclei of weakly interacting ligands which possess biologically relevant and nonaromatic motifs. We first demonstrate this via the polarization of acetonitrile, using Ir(IMes)(COD)Cl as the catalyst precursor, and confirm that the route to hyperpolarization transfer is via the J-coupling network. We extend this work to the polarization of propionitrile, benzylnitrile, benzonitrile, and trans-3-hexenedinitrile in order to assess its generality. In the (1)H NMR spectrum, the signal for acetonitrile is enhanced 8-fold over its thermal counterpart when [Ir(H)2(IMes)(MeCN)3](+) is the catalyst. Upon addition of pyridine or pyridine-d5, the active catalyst changes to [Ir(H)2(IMes)(py)2(MeCN)](+) and the resulting acetonitrile (1)H signal enhancement increases to 20- and 60-fold, respectively. In (13)C NMR studies, polarization transfers optimally to the quaternary (13)C nucleus of MeCN while the methyl (13)C is hardly polarized. Transfer to (13)C is shown to occur first via the (1)H-(1)H coupling between the hydrides and the methyl protons and then via either the (2)J or (1)J couplings to the respective (13)Cs, of which the (2)J route is more efficient. These experimental results are rationalized through a theoretical treatment which shows excellent agreement with experiment. In the case of MeCN, longitudinal two-spin orders between pairs of (1)H nuclei in the three-spin methyl group are created. Two-spin order states, between the (1)H and (13)C nuclei, are also created, and their existence is confirmed for Me(13)CN in both the (1)H and (13)C NMR spectra using the Only Parahydrogen Spectroscopy protocol.

  3. Room-temperature in situ nuclear spin hyperpolarization from optically pumped nitrogen vacancy centres in diamond

    SciTech Connect

    King, Jonathan P.; Jeong, Keunhong; Vassiliou, Christophoros C.; Shin, Chang S.; Page, Ralph H.; Avalos, Claudia E.; Wang, Hai-Jing; Pines, Alexander

    2015-12-07

    Low detection sensitivity stemming from the weak polarization of nuclear spins is a primary limitation of magnetic resonance spectroscopy and imaging. Methods have been developed to enhance nuclear spin polarization but they typically require high magnetic fields, cryogenic temperatures or sample transfer between magnets. Here we report bulk, room-temperature hyperpolarization of 13C nuclear spins observed via high-field magnetic resonance. The technique harnesses the high optically induced spin polarization of diamond nitrogen vacancy centres at room temperature in combination with dynamic nuclear polarization. We observe bulk nuclear spin polarization of 6%, an enhancement of ~170,000 over thermal equilibrium. The signal of the hyperpolarized spins was detected in situ with a standard nuclear magnetic resonance probe without the need for sample shuttling or precise crystal orientation. In conclusion, hyperpolarization via optical pumping/dynamic nuclear polarization should function at arbitrary magnetic fields enabling orders of magnitude sensitivity enhancement for nuclear magnetic resonance of solids and liquids under ambient conditions.

  4. Room-temperature in situ nuclear spin hyperpolarization from optically pumped nitrogen vacancy centres in diamond

    DOE PAGESBeta

    King, Jonathan P.; Jeong, Keunhong; Vassiliou, Christophoros C.; Shin, Chang S.; Page, Ralph H.; Avalos, Claudia E.; Wang, Hai-Jing; Pines, Alexander

    2015-12-07

    Low detection sensitivity stemming from the weak polarization of nuclear spins is a primary limitation of magnetic resonance spectroscopy and imaging. Methods have been developed to enhance nuclear spin polarization but they typically require high magnetic fields, cryogenic temperatures or sample transfer between magnets. Here we report bulk, room-temperature hyperpolarization of 13C nuclear spins observed via high-field magnetic resonance. The technique harnesses the high optically induced spin polarization of diamond nitrogen vacancy centres at room temperature in combination with dynamic nuclear polarization. We observe bulk nuclear spin polarization of 6%, an enhancement of ~170,000 over thermal equilibrium. The signal ofmore » the hyperpolarized spins was detected in situ with a standard nuclear magnetic resonance probe without the need for sample shuttling or precise crystal orientation. In conclusion, hyperpolarization via optical pumping/dynamic nuclear polarization should function at arbitrary magnetic fields enabling orders of magnitude sensitivity enhancement for nuclear magnetic resonance of solids and liquids under ambient conditions.« less

  5. Hyperpolarized functional magnetic resonance of murine skeletal muscle enabled by multiple tracer-paradigm synchronizations.

    PubMed

    Leftin, Avigdor; Roussel, Tangi; Frydman, Lucio

    2014-01-01

    Measuring metabolism's time- and space-dependent responses upon stimulation lies at the core of functional magnetic resonance imaging. While focusing on water's sole resonance, further insight could arise from monitoring the temporal responses arising from the metabolites themselves, in what is known as functional magnetic resonance spectroscopy. Performing these measurements in real time, however, is severely challenged by the short functional timescales and low concentrations of natural metabolites. Dissolution dynamic nuclear polarization is an emerging technique that can potentially alleviate this, as it provides a massive sensitivity enhancement allowing one to probe low-concentration tracers and products in a single-scan. Still, conventional implementations of this hyperpolarization approach are not immediately amenable to the repeated acquisitions needed in real-time functional settings. This work proposes a strategy for functional magnetic resonance of hyperpolarized metabolites that bypasses this limitation, and enables the observation of real-time metabolic changes through the synchronization of stimuli-triggered, multiple-bolus injections of the metabolic tracer 13C1-pyruvate. This new approach is demonstrated with paradigms tailored to reveal in vivo thresholds of murine hind-limb skeletal muscle activation, involving the conversion of 13C1-pyruvate to 13C1-lactate and 13C1-alanine. These functional hind-limb studies revealed that graded skeletal muscle stimulation causes commensurate increases in glycolytic metabolism in a frequency- and amplitude-dependent fashion, that can be monitored on the seconds/minutes timescale using dissolution dynamic nuclear polarization. Spectroscopic imaging further allowed the in vivo visualization of uptake, transformation and distribution of the tracer and products, in fast-twitch glycolytic and in slow-twitch oxidative muscle fiber groups. While these studies open vistas in time and sensitivity for metabolic

  6. Hyperpolarized Functional Magnetic Resonance of Murine Skeletal Muscle Enabled by Multiple Tracer-Paradigm Synchronizations

    PubMed Central

    Leftin, Avigdor; Roussel, Tangi; Frydman, Lucio

    2014-01-01

    Measuring metabolism's time- and space-dependent responses upon stimulation lies at the core of functional magnetic resonance imaging. While focusing on water's sole resonance, further insight could arise from monitoring the temporal responses arising from the metabolites themselves, in what is known as functional magnetic resonance spectroscopy. Performing these measurements in real time, however, is severely challenged by the short functional timescales and low concentrations of natural metabolites. Dissolution dynamic nuclear polarization is an emerging technique that can potentially alleviate this, as it provides a massive sensitivity enhancement allowing one to probe low-concentration tracers and products in a single-scan. Still, conventional implementations of this hyperpolarization approach are not immediately amenable to the repeated acquisitions needed in real-time functional settings. This work proposes a strategy for functional magnetic resonance of hyperpolarized metabolites that bypasses this limitation, and enables the observation of real-time metabolic changes through the synchronization of stimuli-triggered, multiple-bolus injections of the metabolic tracer 13C1-pyruvate. This new approach is demonstrated with paradigms tailored to reveal in vivo thresholds of murine hind-limb skeletal muscle activation, involving the conversion of 13C1-pyruvate to 13C1-lactate and 13C1-alanine. These functional hind-limb studies revealed that graded skeletal muscle stimulation causes commensurate increases in glycolytic metabolism in a frequency- and amplitude-dependent fashion, that can be monitored on the seconds/minutes timescale using dissolution dynamic nuclear polarization. Spectroscopic imaging further allowed the in vivo visualization of uptake, transformation and distribution of the tracer and products, in fast-twitch glycolytic and in slow-twitch oxidative muscle fiber groups. While these studies open vistas in time and sensitivity for metabolic

  7. Cardiovascular applications of hyperpolarized contrast media and metabolic tracers.

    PubMed

    Bhattacharya, Pratip; Ross, Brian D; Bünger, Rolf

    2009-12-01

    Modern hyperpolarization technology enhances the recordable magnetic resonance signal four to five orders of magnitude, making in vivo assessments of tracer pathways and metabolic compartments feasible. Existing hyperpolarization instrumentation and previous tracer studies using hydroxyethylpropionate (HEP) as an extracellular marker and 14-carbon label pyruvate as examples are described and reviewed as applicable to the working heart. Future metabolic imaging based on the use of hyperpolarized pyruvate needs to consider extra- and intra-cellular label dilution due to glycolysis, lactate oxidation and protein degradation. This dilution can substantially decrease the recordable signals from PDH flux (oxidative decarboxylation of pyruvate) and other pyruvate pathways. The review of previous literature and data suggests that the (13)C-alanine signal is a better index of mitochondrially oxidized pyruvate than L-lactate. These facts and considerations will help in the interpretation of the in vivo recorded hyperpolarization signals of metabolic tracers and contrast media. PMID:19934362

  8. Hyperpolarized NMR Probes for Biological Assays

    PubMed Central

    Meier, Sebastian; Jensen, Pernille R.; Karlsson, Magnus; Lerche, Mathilde H.

    2014-01-01

    During the last decade, the development of nuclear spin polarization enhanced (hyperpolarized) molecular probes has opened up new opportunities for studying the inner workings of living cells in real time. The hyperpolarized probes are produced ex situ, introduced into biological systems and detected with high sensitivity and contrast against background signals using high resolution NMR spectroscopy. A variety of natural, derivatized and designed hyperpolarized probes has emerged for diverse biological studies including assays of intracellular reaction progression, pathway kinetics, probe uptake and export, pH, redox state, reactive oxygen species, ion concentrations, drug efficacy or oncogenic signaling. These probes are readily used directly under natural conditions in biofluids and are often directly developed and optimized for cellular assays, thus leaving little doubt about their specificity and utility under biologically relevant conditions. Hyperpolarized molecular probes for biological NMR spectroscopy enable the unbiased detection of complex processes by virtue of the high spectral resolution, structural specificity and quantifiability of NMR signals. Here, we provide a survey of strategies used for the selection, design and use of hyperpolarized NMR probes in biological assays, and describe current limitations and developments. PMID:24441771

  9. Hyperpolarized NMR probes for biological assays.

    PubMed

    Meier, Sebastian; Jensen, Pernille R; Karlsson, Magnus; Lerche, Mathilde H

    2014-01-16

    During the last decade, the development of nuclear spin polarization enhanced (hyperpolarized) molecular probes has opened up new opportunities for studying the inner workings of living cells in real time. The hyperpolarized probes are produced ex situ, introduced into biological systems and detected with high sensitivity and contrast against background signals using high resolution NMR spectroscopy. A variety of natural, derivatized and designed hyperpolarized probes has emerged for diverse biological studies including assays of intracellular reaction progression, pathway kinetics, probe uptake and export, pH, redox state, reactive oxygen species, ion concentrations, drug efficacy or oncogenic signaling. These probes are readily used directly under natural conditions in biofluids and are often directly developed and optimized for cellular assays, thus leaving little doubt about their specificity and utility under biologically relevant conditions. Hyperpolarized molecular probes for biological NMR spectroscopy enable the unbiased detection of complex processes by virtue of the high spectral resolution, structural specificity and quantifiability of NMR signals. Here, we provide a survey of strategies used for the selection, design and use of hyperpolarized NMR probes in biological assays, and describe current limitations and developments.

  10. Effect of ionic interaction between a hyperpolarized magnetic resonance chemical probe and a gadolinium contrast agent for the hyperpolarized lifetime after dissolution

    NASA Astrophysics Data System (ADS)

    Takakusagi, Yoichi; Inoue, Kaori; Naganuma, Tatsuya; Hyodo, Fuminori; Ichikawa, Kazuhiro

    2016-09-01

    In hyperpolarization of 13C-enriched magnetic resonance chemical probes in the solid-state, a trace amount of gadolinium (Gd) contrast agent can be used to maximize polarization of the 13C nuclear spins. Here, we report systematic measurement of the spin-lattice relaxation time (T1) and enhancement level of 13C-enriched chemical probes in the presence of various Gd contrast agents in the liquid-state after dissolution. Using two different 13C probes having opposite electric charges at neutral pH, we clearly show the T1 of hyperpolarized 13C was barely affected by the use of a Gd complex that displays repulsive interaction with the 13C probe in solution, whilst T1 was drastically shortened when there was ionic attraction between probe and complex.

  11. Transfer of hyperpolarization from long T 1 storage nuclei to short T 1 neighbors using FLOPSY-8

    NASA Astrophysics Data System (ADS)

    Moreno, Karlos X.; Harrison, Crystal; Dean Sherry, A.; Malloy, Craig R.; Merritt, Matthew E.

    2011-12-01

    Nuclei with long T 1s are optimal targets for dynamic nuclear polarization (DNP). Therefore, most of the agents used in metabolic imaging and spectroscopy studies are based on carboxylic acid moieties that lack protons, a strong source of dipolar relaxation. Metabolic flux information encoded into spectra of small molecule metabolites in the form of the 13C isotopomer data cannot be accessed using standard 13C hyperpolarization methods because protonated carbons relax too quickly through T 1 dipolar relaxation. It is shown here that the longitudinal mixing sequence FLOPSY-8 can be used to transfer polarization from a long T 1 storage nucleus to adjacent protonated carbons so that they may be detected with high sensitivity. We demonstrate that FLOPSY-8 allows a direct readout of isotopomer populations in butyrate and glutamate in vitro.

  12. Study of the interactions between sucrose and metal ions (Mg2+ and K+) and their simultaneous quantification in ternary mixture by mid-infrared and 13C nuclear magnetic resonance spectroscopies.

    PubMed

    Rondeau, Philippe; Jhurry, Dhanjay; Sers, Sandrine; Cadet, Frédéric

    2004-07-01

    In this paper, a ternary aqueous mixture of sucrose and two metal ions (Mg(2+) and K(+)) has been examined by mid-infrared spectroscopy coupled with principal component analysis (PCA) and the partial least-squares regression method (PLS). PCA was first used for the description of Fourier transform mid-infrared (mid-FTIR) spectral data of the complex samples. The resulting factorial map, set up with the two most influential component axes, features distinct concentration distribution specific to each component. Prediction equations that linked sucrose, magnesium, and potassium concentrations to the spectral data were established by the partial least-squares regression method. A quite good correlation was obtained between the first 5 axes and the concentration variables, with coefficient values ranging from 0.984 to 0.997. It was thus possible to predict specifically both metal ion concentrations in the ternary mixture with relatively good accuracy. The ternary mixtures of sucrose, Mg(2+), and K(+) were also subjected to (13)C NMR (nuclear magnetic resonance) analysis. From the relative displacements of chemical shifts of the carbon atoms of sucrose, it was possible to determine the influence of each metal ion present in the mixture. PMID:15282047

  13. Detection of kestoses and kestose-related oligosaccharides in extracts of Festuca arundinacea, Dactylis glomerate L. , and Asparagus officinalis L. root cultures and invertase by sup 13 C and sup 1 H nuclear magnetic resonance spectroscopy

    SciTech Connect

    Forsythe, K.L.; Feather, M.S.; Gracz, H.; Wong, T.C. )

    1990-04-01

    Previous studies show that {sup 13}C nuclear magnetic resonance spectroscopy can be used to detect and identify mixtures of 1-kestose and neokestose after conversion to the acetate derivatives. In this study, unequivocal assignments are made for the anomeric carbon and proton signals for the above two trisaccharide acetates as well as for 6-kestose hendecaacetate and for nystose tetradecaacetate (a 1-kestose-derived tetrasaccharide). A number of oligosaccharide fractions were isolated from several plant species, converted to the acetates, and nuclear magnetic resonance spectra obtained. Using the above reference data, the following information was obtained. The trisaccharide fraction from Dactylis gomerata L. stem tissue and Asparagus officinalis L. roots contain both 1-kestose and neokestose, and the tetrasaccharide fractions contain three components, one of which is nystose. Penta- and hexasaccharide acetates were also isolated from A. officinalis L. roots and were found to contain, respectively, four and at least five components. All components of both of the above species appear to contain a kestose residue and to be produced by the sequential addition of fructofuranosyl units to these. The trisaccharide fraction from Festuca arundinacea is complex, and contains at least five different components, two of which appear to be 1-kestose and neokestose.

  14. Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry

    PubMed Central

    Reed, Galen D.; von Morze, Cornelius; Verkman, Alan S.; Koelsch, Bertram L.; Chaumeil, Myriam M.; Lustig, Michael; Ronen, Sabrina M.; Bok, Robert A.; Sands, Jeff M.; Larson, Peder E. Z.; Wang, Zhen J.; Larsen, Jan Henrik Ardenkjær; Kurhanewicz, John; Vigneron, Daniel B.

    2016-01-01

    In vivo spin spin relaxation time (T2) heterogeneity of hyperpolarized [13C,15N2]urea in the rat kidney was investigated. Selective quenching of the vascular hyperpolarized 13C signal with a macromolecular relaxation agent revealed that a long-T2 component of the [13C,15N2]urea signal originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the [13C,15N2]urea to be distinguished via multi-exponential analysis. The T2 response to induced diuresis and antidiuresis was performed with two imaging agents: hyperpolarized [13C,15N2]urea and a control agent hyperpolarized bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-2H8. Large T2 increases in the inner-medullar and papilla were observed with the former agent and not the latter during antidiuresis. Therefore, [13C,15N2]urea relaxometry is sensitive to two steps of the renal urea handling process: glomerular filtration and the inner-medullary urea transporter (UT)-A1 and UT-A3 mediated urea concentrating process. Simple motion correction and subspace denoising algorithms are presented to aid in the multi exponential data analysis. Furthermore, a T2-edited, ultra long echo time sequence was developed for sub-2 mm3 resolution 3D encoding of urea by exploiting relaxation differences in the vascular and filtrate pools. PMID:27570835

  15. Study of stereospecificity of 1H, 13C, 15N and 77Se shielding constants in the configurational isomers of the selenophene-2-carbaldehyde azine by NMR spectroscopy and MP2-GIAO calculations.

    PubMed

    Afonin, Andrei V; Pavlov, Dmitry V; Albanov, Alexander I; Levanova, Ekaterina P; Levkovskaya, Galina G

    2011-11-01

    In the (1)H and (13)C NMR spectra of selenophene-2-carbaldehyde azine, the (1)H-5, (13)C-3 and (13)C-5 signals of the selenophene ring are shifted to higher frequencies, whereas those of the (1)H-1, (13)C-1, (13)C-2 and (13)C-4 are shifted to lower frequencies on going from the EE to ZZ isomer or from the E moiety to the Z moiety of EZ isomer. The (15)N chemical shift is significantly larger in the EE isomer relative to the ZZ isomer and in the E moiety relative to the Z moiety of EZ isomer. A very pronounced difference (60-65 mg/g) between the (77)Se resonance positions is revealed in the studied azine isomers, the (77)Se peak being shifted to higher frequencies in the ZZ isomer and in the Z moiety of EZ isomer. The trends in the changes of the measured chemical shifts are reasonably reproduced by the GIAO calculations at the MP2 level of the (1)H, (13)C, (15)N and (77)Se shielding constants in the energy-favorable conformation with the syn orientation of both selenophene rings relative to the C = N groups. The NBO analysis suggests that such an arrangement of the selenophene rings may take place because of a higher energy of some intramolecular interactions. PMID:22002712

  16. (13)C MRS and LC-MS Flux Analysis of Tumor Intermediary Metabolism.

    PubMed

    Shestov, Alexander A; Lee, Seung-Cheol; Nath, Kavindra; Guo, Lili; Nelson, David S; Roman, Jeffrey C; Leeper, Dennis B; Wasik, Mariusz A; Blair, Ian A; Glickson, Jerry D

    2016-01-01

    We present the first validated metabolic network model for analysis of flux through key pathways of tumor intermediary metabolism, including glycolysis, the oxidative and non-oxidative arms of the pentose pyrophosphate shunt, the TCA cycle as well as its anaplerotic pathways, pyruvate-malate shuttling, glutaminolysis, and fatty acid biosynthesis and oxidation. The model that is called Bonded Cumomer Analysis for application to (13)C magnetic resonance spectroscopy ((13)C MRS) data and Fragmented Cumomer Analysis for mass spectrometric data is a refined and efficient form of isotopomer analysis that can readily be expanded to incorporate glycogen, phospholipid, and other pathways thereby encompassing all the key pathways of tumor intermediary metabolism. Validation was achieved by demonstrating agreement of experimental measurements of the metabolic rates of oxygen consumption, glucose consumption, lactate production, and glutamate pool size with independent measurements of these parameters in cultured human DB-1 melanoma cells. These cumomer models have been applied to studies of DB-1 melanoma and DLCL2 human diffuse large B-cell lymphoma cells in culture and as xenografts in nude mice at 9.4 T. The latter studies demonstrate the potential translation of these methods to in situ studies of human tumor metabolism by MRS with stable (13)C isotopically labeled substrates on instruments operating at high magnetic fields (≥7 T). The melanoma studies indicate that this tumor line obtains 51% of its ATP by mitochondrial metabolism and 49% by glycolytic metabolism under both euglycemic (5 mM glucose) and hyperglycemic conditions (26 mM glucose). While a high level of glutamine uptake is detected corresponding to ~50% of TCA cycle flux under hyperglycemic conditions, and ~100% of TCA cycle flux under euglycemic conditions, glutaminolysis flux and its contributions to ATP synthesis were very small. Studies of human lymphoma cells demonstrated that inhibition of

  17. 13C MRS and LC–MS Flux Analysis of Tumor Intermediary Metabolism

    PubMed Central

    Shestov, Alexander A.; Lee, Seung-Cheol; Nath, Kavindra; Guo, Lili; Nelson, David S.; Roman, Jeffrey C.; Leeper, Dennis B.; Wasik, Mariusz A.; Blair, Ian A.; Glickson, Jerry D.

    2016-01-01

    We present the first validated metabolic network model for analysis of flux through key pathways of tumor intermediary metabolism, including glycolysis, the oxidative and non-oxidative arms of the pentose pyrophosphate shunt, the TCA cycle as well as its anaplerotic pathways, pyruvate–malate shuttling, glutaminolysis, and fatty acid biosynthesis and oxidation. The model that is called Bonded Cumomer Analysis for application to 13C magnetic resonance spectroscopy (13C MRS) data and Fragmented Cumomer Analysis for mass spectrometric data is a refined and efficient form of isotopomer analysis that can readily be expanded to incorporate glycogen, phospholipid, and other pathways thereby encompassing all the key pathways of tumor intermediary metabolism. Validation was achieved by demonstrating agreement of experimental measurements of the metabolic rates of oxygen consumption, glucose consumption, lactate production, and glutamate pool size with independent measurements of these parameters in cultured human DB-1 melanoma cells. These cumomer models have been applied to studies of DB-1 melanoma and DLCL2 human diffuse large B-cell lymphoma cells in culture and as xenografts in nude mice at 9.4 T. The latter studies demonstrate the potential translation of these methods to in situ studies of human tumor metabolism by MRS with stable 13C isotopically labeled substrates on instruments operating at high magnetic fields (≥7 T). The melanoma studies indicate that this tumor line obtains 51% of its ATP by mitochondrial metabolism and 49% by glycolytic metabolism under both euglycemic (5 mM glucose) and hyperglycemic conditions (26 mM glucose). While a high level of glutamine uptake is detected corresponding to ~50% of TCA cycle flux under hyperglycemic conditions, and ~100% of TCA cycle flux under euglycemic conditions, glutaminolysis flux and its contributions to ATP synthesis were very small. Studies of human lymphoma cells demonstrated that inhibition of

  18. Optoacoustic 13C-breath test analyzer

    NASA Astrophysics Data System (ADS)

    Harde, Hermann; Helmrich, Günther; Wolff, Marcus

    2010-02-01

    The composition and concentration of exhaled volatile gases reflects the physical ability of a patient. Therefore, a breath analysis allows to recognize an infectious disease in an organ or even to identify a tumor. One of the most prominent breath tests is the 13C-urea-breath test, applied to ascertain the presence of the bacterium helicobacter pylori in the stomach wall as an indication of a gastric ulcer. In this contribution we present a new optical analyzer that employs a compact and simple set-up based on photoacoustic spectroscopy. It consists of two identical photoacoustic cells containing two breath samples, one taken before and one after capturing an isotope-marked substrate, where the most common isotope 12C is replaced to a large extent by 13C. The analyzer measures simultaneously the relative CO2 isotopologue concentrations in both samples by exciting the molecules on specially selected absorption lines with a semiconductor laser operating at a wavelength of 2.744 μm. For a reliable diagnosis changes of the 13CO2 concentration of 1% in the exhaled breath have to be detected at a concentration level of this isotope in the breath of about 500 ppm.

  19. Study of Urban environmental quality through Isotopes δ13C

    NASA Astrophysics Data System (ADS)

    González-Sosa, E.; Mastachi-Loza, C.; Becerril-Piña, R.; Ramos-Salinas, N. M.

    2012-04-01

    Usually, trees with similar pH values on their bark develop epiphytes of similar species, the acidity to be a factor for growth. The aim of the study was evaluate the air quality through isotope δ13C in order to define the levels of environmental quality in the city of Queretaro, Mexico. In this work were collected at least 4 epiphytes positioned in trees of the species Prosopis Laevigata at 25 sites of Queretaro City. The samples were analyzed for trace elements with an inductively coupled plasma atomic emission spectroscopy (ICP). The collecting took place during dry period, in May and early rain June 2011 period, and on four sectors to identify the spatial distribution of pollution, using isotopic analysis of concentration of δ 13C. According with the results there are significant differences among the species in each of the sampled areas. The 5 February Avenue presented greater diversity and richness of δ13C, followed by those who were surveyed in the proximity of the UAQ and finally in the middle-east area. An average value of δ13C-17.92%, followed by those surveyed in the vicinity of the UAQ that correspond to sector I and II with an concentration of δ13C-17.55% and δ13C-17.22%, and finally the samples collected in trees scattered in the East-Sector II and IV with a value of δ13C-17.02% and δ13C-15.62%, respectively. Also were observed differences between the dry and wet period. It is likely that these results of δ 13C in moist period reflect the drag of the isotopes due to rain events that could mark a trend in the dilution of this element, however there is a trend in terms of abundance and composition of finding more impact in those species sampled in dry period, in May and early June 2011.

  20. Combined analysis of the essential oil of Chenopodium ambrosioides by GC, GC-MS and 13C-NMR spectroscopy: quantitative determination of ascaridole, a heat-sensitive compound.

    PubMed

    Cavalli, Jean-François; Tomi, Félix; Bernardini, Antoine-François; Casanova, Joseph

    2004-01-01

    A commercial sample of the essential oil of Chenopodium ambrosioides L. from Madagascar was analysed by GC, GC-MS and 13C-NMR. By GC analysis, the major constituents were found to be ascaridole (1) (41.8%), isoascaridole (2) (18.1%), p-cymene (16.2%), alpha-terpinene (9.7%) and limonene (3.8%). However, ascaridole undergoes a partial thermal isomerisation to 2 and hence the amount of 1 is under-estimated by GC analysis. The actual contents of 1 and 2 (55.3 and 4.6%, respectively) were obtained following combined analysis of the sample by GC and 13C-NMR. Several hydroxy- and polyhydroxy-menthanes were identified by 13C-NMR.

  1. Characterization of polysulfone and polysulfone/vanillin microcapsules by 1H NMR spectroscopy, solid-state 13C CP/MAS-NMR spectroscopy, and N2 adsorption-desorption analyses.

    PubMed

    Peña, Brisa; de Ménorval, Louis-Charles; Garcia-Valls, Ricard; Gumí, Tània

    2011-11-01

    Textile detergent and softener industries have incorporated perfume microencapsulation technology to improve their products. Perfume encapsulation allows perfume protection until use and provides a long-lasting fragrance release. But, certain industrial microcapsules show low encapsulation capacity and low material stability. Polysulfone capsules have been already proposed to solve these drawbacks. Among them, PSf/Vanillin capsules were considered as a desirable system. They present both good material stability and high encapsulation capacity. However, several factors such as the final location of the perfume in the polymeric matrix, the aggregation state that it has in the capsule and its interaction with the capsule components have not been studied yet. These factors can provide vast information about the capsule performance and its improvement. With the aim to characterize these parameters, the physical and chemical properties of PSf/Vanillin capsules have been investigated by nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and N(2) adsorption-desorption measurements. AFM micrograph and N(2) isotherms confirm that the presence of vanillin modify the physical structure of PSf/Vanillin microcapsules as it is trapped in the capsule porosity. NMR results show that vanillin is present in solid state in PSf/Vanillin microcapsules.

  2. The Semiquinone at the Qi Site of the bc1 Complex Explored Using HYSCORE Spectroscopy and Specific Isotopic Labeling of Ubiquinone in Rhodobacter sphaeroides via 13C Methionine and Construction of a Methionine Auxotroph

    PubMed Central

    2015-01-01

    Specific isotopic labeling at the residue or substituent level extends the scope of different spectroscopic approaches to the atomistic level. Here we describe 13C isotopic labeling of the methyl and methoxy ring substituents of ubiquinone, achieved through construction of a methionine auxotroph in Rhodobacter sphaeroides strain BC17 supplemented with l-methionine with the side chain methyl group 13C-labeled. Two-dimensional electron spin echo envelope modulation (HYSCORE) was applied to study the 13C methyl and methoxy hyperfine couplings in the semiquinone generated in situ at the Qi site of the bc1 complex in its membrane environment. The data were used to characterize the distribution of unpaired spin density and the conformations of the methoxy substituents based on density functional theory calculations of 13C hyperfine tensors in the semiquinone of the geometry-optimized X-ray structure of the bc1 complex (Protein Data Bank entry 1PP9) with the highest available resolution. Comparison with other proteins indicates individual orientations of the methoxy groups in each particular case are always different from the methoxy conformations in the anion radical prepared in a frozen alcohol solution. The protocol used in the generation of the methionine auxotroph is more generally applicable and, because it introduces a gene deletion using a suicide plasmid, can be applied repeatedly. PMID:25184535

  3. Single crystal to single crystal topochemical photoreactions: measuring the degree of disorder in the [2+2] photodimerization of trans-cinnamic acid using single-crystal 13C NMR spectroscopy.

    PubMed

    Nieuwendaal, Ryan C; Mattler, Sarah J; Bertmer, Marko; Hayes, Sophia E

    2011-05-19

    A single crystal of α-trans-cinnamic acid was synthesized with a (13)C-label at the β-carbon position and photoreacted to yield the [2+2] cycloaddition product, α-truxillic acid. (13)C{(1)H} cross-polarization (CP) single-crystal NMR experiments were performed on the unreacted and sequentially photoreacted samples for different goniometer orientations, and the spectra were simulated using the SIMMOL and SIMPSON software packages. Atomic coordinates from single-crystal X-ray diffraction data were used as inputs in the simulations, which allowed the chemical shift tensor to be precisely measured and related to the unit cell (or molecular) reference frame of cinnamic acid. The line widths of the (13)C resonances observed at different goniometer rotations were utilized to estimate the orientational dispersion of the cinnamic acid species, which ultimately provides a measure of disorder in the single crystal. The photoreacted sample, a solid solution of cinnamic and truxillic acids, maintained its single-crystal nature, even up to 44% conversion to truxillic acid, keeping its P2(1)/n symmetry. Upon photoirradiation, however, a slight loss of order was observed in the cinnamic acid species as evidenced by an increase in the (13)C NMR line widths, demonstrating that NMR can be used to monitor subtle orientational imperfections in single crystal to single crystal photoreactions.

  4. A large volume double channel 1H-X RF probe for hyperpolarized magnetic resonance at 0.0475 T.

    PubMed

    Coffey, Aaron M; Shchepin, Roman V; Wilkens, Ken; Waddell, Kevin W; Chekmenev, Eduard Y

    2012-07-01

    In this work we describe a large volume 340 mL (1)H-X magnetic resonance (MR) probe for studies of hyperpolarized compounds at 0.0475 T. (1)H/(13)C and (1)H/(15)N probe configurations are demonstrated with the potential for extension to (1)H/(129)Xe. The primary applications of this probe are preparation and quality assurance of (13)C and (15)N hyperpolarized contrast agents using PASADENA (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) and other parahydrogen-based methods of hyperpolarization. The probe is efficient and permits 62 μs (13)C excitation pulses at 5.3 W, making it suitable for portable operation. The sensitivity and detection limits of this probe, tuned to (13)C, are compared with a commercial radio frequency (RF) coil operating at 4.7 T. We demonstrate that low field MR of hyperpolarized contrast agents could be as sensitive as conventional high field detection and outline potential improvements and optimization of the probe design for preclinical in vivo MRI. PASADENA application of this low-power probe is exemplified with (13)C hyperpolarized 2-hydroxyethyl propionate-1-(13)C,2,3,3-d(3).

  5. 13C-1H dipolar-driven 13C-13C recoupling without 13C rf irradiation in nuclear magnetic resonance of rotating solids

    NASA Astrophysics Data System (ADS)

    Takegoshi, K.; Nakamura, Shinji; Terao, Takehiko

    2003-02-01

    Two recently proposed 13C-13C recoupling methods under magic angle spinning (MAS), resonant interference recoupling (RIR), and 13C-1H dipolar-assisted rotational resonance (DARR), are examined on a common theoretical foundation using the average Hamiltonian theory. In both methods, a rf field is applied on not 13C but 1H to recouple the 13C-1H dipolar interactions, and spectral overlap necessary to conserve energy for 13C-13C polarization transfer is achieved by the 13C-1H dipolar line broadening. While DARR employs time-independent 13C-1H interactions recoupled by suitable rf irradiation to 1H spins, RIR uses time-dependent 13C-1H interactions modulated appropriately by 1H rf irradiation. There are two distinct cases where 13C-1H line broadening realizes 13C-13C spectral overlap. For a pair of a carbonyl or aromatic carbon and an aliphatic carbon, spectral overlap can be achieved between one of the spinning sidebands of the former 13C resonance and the 13C-1H dipolar powder pattern of the latter. On the other hand for a pair of spins with a small chemical shift difference, the two center bands are overlapped with each other due to 13C-1H dipolar broadening. For the former, we show that both RIR and DARR occur in the first order, while for the latter, DARR recoupling is appreciable for time-independent 13C-1H interactions. We refer to the former DARR as the first-order DARR recoupling and the latter as the second-order DARR. Experimentally, we examined the following 13C-1H recoupling methods for DARR: 1H CW irradiation fulfilling a rotary-resonance condition or a modulatory-resonance condition, and 1H π pulses applied synchronously to MAS. For RIR, the FSLG-m2m¯m sequence is applied to 1H. Several one-dimensional DARR and RIR experiments were done for N-acetyl[1,2-13C, 15N] DL-valine, and [2,3-13C] L-alanine. It was found that the polarization transfer rate for RIR is larger than that for DARR except for fast spinning, while the rate for DARR is less sensitive to

  6. Synthesis and applications of {sup 13}C glycerol

    SciTech Connect

    Stocking, E.; Khalsa, O.; Martinez, R.A.; Silks, L.A. III

    1994-12-01

    Due in part to the use of labeled glycerol for the {sup 13}C enrichment of biomolecules, we are currently developing new synthetic routes to various isotopomers of glycerol. Judging from our experience, traditional methods of glycerol synthesis are not easily adapted for isotopic enrichment and/or have poor overall yields (12 to 15%). Furthermore, the use of glycerol for enrichment can be prohibitively expensive and its availability is limited by the level of demand. We are presently developing a short de novo synthesis of glycerol from carbon dioxide ({approximately}53% overall yield for four steps) and are examining the feasibility of synthesizing site-specific {sup 13}C-labeled glycerol and dihydroxyacetone (DHA) from labeled methanol and carbon dioxide. One application of {sup 13}C glycerol we have examined is enzymatic conversion of glycerol to glyceraldehyde-3-monophosphate or dihydroxyacetone monophosphate (DHAP) with yields ranging from 25 to 50% (as determined by NMR spectroscopy). We are also pursuing the chemical conversion of {sup 13}C-labeled DHA to DHAP. We are especially interested in {sup 13}C-labeled DHAP because we are investigating its use as a chemo-enzymatic precursor for both labeled 2-deoxyribose and 2-deoxyribonucleic acids.

  7. Regenerative hyperpolarization in rods.

    PubMed Central

    Werblin, F S

    1975-01-01

    1. The electrical properties of the rods in Necturus maculosus were studied at the cell body and the outer segments in dark and light under current and voltage clamp with a pair of intracellular electrodes separated by about 1 mum. 2. The membrane resistance in the dark was voltage- and time-dependent both for the cell body and the outer segment. Slight depolarizations in the cell body reduced the slope resistance from 60 to 10 M omega with a time constant of about 1 sec. Polarization in either direction, at the outer segment, when greater than about 20 mV, reduced the slope resistance from 60 to 30 M omega. The dark potential in the cell body was typically -30 to -35 m V; at the outer segment it was typically only -10 to -15 mV. 3. The light-elicited voltage response in both the cell body and the outer segment was largest with the membrane near the dark potential level. In both regions, the response was reduced when the membrane was polarized in either direction. 4. Under voltage-clamp conditions, a reversal potential for the light response near + 10 mV was measured at the outer segment. At the cell body no reversal potential for the light response was measured; there the clamping current required during the light response was almost of the same magnitude at all potential levels. 5. When the membrane at the cell body was hyperpolarized in the dark under voltage clamp, a transient outward current, typically about one-half the magnitude of the initial inward clamping current was required to maintain the membrane at the clamped potential level. This outward current transient was associated with a decrease in membrane resistance with similar time course. The transient outward current reversed and became inward when the membrane was clamped to potentials more negative than -80 mV. Thus, the transient outward current appears to involve a transient activation initiated by hyperpolarization. I is regenerative in that it is initiated by hyperpolarization and tends to

  8. Impact of Ho(3+)-doping on (13)C dynamic nuclear polarization using trityl OX063 free radical.

    PubMed

    Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Kaur, Pavanjeet; Martins, André; Fidelino, Leila; Khemtong, Chalermchai; Song, Likai; Sherry, A Dean; Lumata, Lloyd

    2016-08-21

    We have investigated the effects of Ho-DOTA doping on the dynamic nuclear polarization (DNP) of [1-(13)C] sodium acetate using trityl OX063 free radical at 3.35 T and 1.2 K. Our results indicate that addition of 2 mM Ho-DOTA on 3 M [1-(13)C] sodium acetate sample in 1 : 1 v/v glycerol : water with 15 mM trityl OX063 improves the DNP-enhanced (13)C solid-state nuclear polarization by a factor of around 2.7-fold. Similar to the Gd(3+) doping effect on (13)C DNP, the locations of the positive and negative (13)C maximum polarization peaks in the (13)C microwave DNP sweep are shifted towards each other with the addition of Ho-DOTA on the DNP sample. W-band electron spin resonance (ESR) studies have revealed that while the shape and linewidth of the trityl OX063 ESR spectrum was not affected by Ho(3+)-doping, the electron spin-lattice relaxation time T1 of trityl OX063 was prominently reduced at cryogenic temperatures. The reduction of trityl OX063 electron T1 by Ho-doping is linked to the (13)C DNP improvement in light of the thermodynamic picture of DNP. Moreover, the presence of Ho-DOTA in the dissolution liquid at room temperature has negligible reduction effect on liquid-state (13)C T1, in contrast to Gd(3+)-doping which drastically reduces the (13)C T1. The results here suggest that Ho(3+)-doping is advantageous over Gd(3+) in terms of preservation of hyperpolarized state-an important aspect to consider for in vitro and in vivo NMR or imaging (MRI) experiments where a considerable preparation time is needed to administer the hyperpolarized (13)C liquid.

  9. Impact of Ho(3+)-doping on (13)C dynamic nuclear polarization using trityl OX063 free radical.

    PubMed

    Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Kaur, Pavanjeet; Martins, André; Fidelino, Leila; Khemtong, Chalermchai; Song, Likai; Sherry, A Dean; Lumata, Lloyd

    2016-08-21

    We have investigated the effects of Ho-DOTA doping on the dynamic nuclear polarization (DNP) of [1-(13)C] sodium acetate using trityl OX063 free radical at 3.35 T and 1.2 K. Our results indicate that addition of 2 mM Ho-DOTA on 3 M [1-(13)C] sodium acetate sample in 1 : 1 v/v glycerol : water with 15 mM trityl OX063 improves the DNP-enhanced (13)C solid-state nuclear polarization by a factor of around 2.7-fold. Similar to the Gd(3+) doping effect on (13)C DNP, the locations of the positive and negative (13)C maximum polarization peaks in the (13)C microwave DNP sweep are shifted towards each other with the addition of Ho-DOTA on the DNP sample. W-band electron spin resonance (ESR) studies have revealed that while the shape and linewidth of the trityl OX063 ESR spectrum was not affected by Ho(3+)-doping, the electron spin-lattice relaxation time T1 of trityl OX063 was prominently reduced at cryogenic temperatures. The reduction of trityl OX063 electron T1 by Ho-doping is linked to the (13)C DNP improvement in light of the thermodynamic picture of DNP. Moreover, the presence of Ho-DOTA in the dissolution liquid at room temperature has negligible reduction effect on liquid-state (13)C T1, in contrast to Gd(3+)-doping which drastically reduces the (13)C T1. The results here suggest that Ho(3+)-doping is advantageous over Gd(3+) in terms of preservation of hyperpolarized state-an important aspect to consider for in vitro and in vivo NMR or imaging (MRI) experiments where a considerable preparation time is needed to administer the hyperpolarized (13)C liquid. PMID:27424954

  10. New guidelines for δ13C measurements

    USGS Publications Warehouse

    Coplen, Tyler B.; Brand, Willi A.; Gehre, Matthias; Groning, Manfred; Meijer, Harro A. J.; Toman, Blaza; Verkouteren, R. Michael

    2006-01-01

    Consistency of δ13C measurements can be improved 39−47% by anchoring the δ13C scale with two isotopic reference materials differing substantially in 13C/12C. It is recommended thatδ13C values of both organic and inorganic materials be measured and expressed relative to VPDB (Vienna Peedee belemnite) on a scale normalized by assigning consensus values of −46.6‰ to L-SVEC lithium carbonate and +1.95‰ to NBS 19 calcium carbonate. Uncertainties of other reference material values on this scale are improved by factors up to two or more, and the values of some have been notably shifted:  the δ13C of NBS 22 oil is −30.03%.

  11. Relaxation Mechanisms in Hyperpolarized Polycrystalline ^129Xe

    NASA Astrophysics Data System (ADS)

    Samuelson, G.; Su, T.; Saam, B.

    2002-10-01

    Through spin exchange with optically polarized Rb vapor, it is possible to achieve upwards of 30% nuclear spin polarization in ^129Xe and a corresponding NMR signal some 5 orders of magnitude stronger than typical thermally polarized ^129Xe. Due to such a strong signal, hyperpolarized ^129Xe is being used for several leading-edge technologies (eg. biochemical spectroscopy, MRI, and polarization transfer). We have measured the nuclear spin relaxation rate of polycrystalline hyperpolarized ^129Xe at 77K (well below the freezing point of 160K) in a magnetic field of only a few Gauss and have observed that the hyperpolarization completely survives the freezing process. Furthermore, in this regime we have observed non-exponential spin relaxation that depends strongly on magnetic field, isotopic concentration (between ^129Xe and ^131Xe) and differences in crystallite formation. We present a simple spin-diffusion model that fits and explains the features of the data. Our results agree with the hypothesis that at low fields and temperatures the dominant spin relaxation mechanism is cross-relaxation with ^131Xe on the surface of the crystallites (Gatzke, et al., PRL b70, 690 (1993)).

  12. Hyperpolarized xenon magnetic resonance of the lung and the brain

    NASA Astrophysics Data System (ADS)

    Venkatesh, Arvind Krishnamachari

    2001-04-01

    Hyperpolarized noble gas Magnetic Resonance Imaging (MRI) is a new diagnostic modality that has been used successfully for lung imaging. Xenon is soluble in blood and inhaled xenon is transported to the brain via circulating blood. Xenon also accumulates in the lipid rich white matter of the brain. Hyperpolarized xenon can hence be used as a tissue- sensitive probe of brain function. The goals of this study were to identify the NMR resonances of xenon in the rat brain and evaluate the role of hyperpolarized xenon for brain MRI. We have developed systems to produce sufficient volumes of hyperpolarized xenon for in vivo brain experiments. The specialized instrumentation developed include an apparatus for optical pump-cell manufacture and high purity gas manifolds for filling cells. A hyperpolarized gas delivery system was designed to ventilate small animals with hyperpolarized xenon for transport to the brain. The T1 of xenon dissolved in blood indicates that the lifetime of xenon in the blood is sufficient for significant magnetization to be transferred to distal tissues. A variety of carrier agents for intravenous delivery of hyperpolarized xenon were tested for transport to distal tissues. Using our new gas delivery system, high SNR 129Xe images of rat lungs were obtained. Spectroscopy with hyperpolarized xenon indicated that xenon was transported from the lungs to the blood and tissues with intact magnetization. After preliminary studies that indicated the feasibility for in vivo rat brain studies, experiments were performed with adult rats and young rats with different stages of white matter development. Both in vivo and in vitro experiments showed the prominence of one peak from xenon in the rat brain, which was assigned to brain lipids. Cerebral brain perfusion was calculated from the wash-out of the hyperpolarized xenon signal in the brain. An increase in brain perfusion during maturation was observed. These experiments showed that hyperpolarized xenon MRI

  13. Producing over 100 ml of highly concentrated hyperpolarized solution by means of dissolution DNP

    PubMed Central

    Comment, A.; Rentsch, J.; Kurdzesau, F.; Jannin, S.; Uffmann, K.; van Heeswijk, R. B.; Hautle, P.; Konter, J. A.; van den Brandt, B.; van der Klink, J. J.

    2008-01-01

    New low-temperature inserts compatible with an existing hyperpolarizer were developed to dynamically polarize nuclei in large samples. The performance of the system was tested on 8 ml glassy frozen solutions containing 13C-labeled molecules and doped with nitroxyl free radicals. The obtained 13C low-temperature polarization was comparable to the one measured on 20 times smaller sample volume with only 3–4 times higher microwave power. By using a dissolution insert that fits to the new design, it was possible to obtain about 120 ml of room-temperature hyperpolarized solution. The polarization as well as the molecule concentration was comparable to the values obtained in standard size hyperpolarized samples. Such large samples are interesting for future studies on larger animals and possibly for potential clinical applications. PMID:18595751

  14. High-Resolution Stimulated Raman Spectroscopy and Analysis of ν_2 and ν_3 Bands of of 13C_2H_4 Using the D2h Top Data System

    NASA Astrophysics Data System (ADS)

    Alkadrou, Abdulsamee; Rotger, Maud; Bermejo, Dionisio; Domenech, Jose Luis; Boudon, Vincent

    2016-06-01

    High resolution stimulated Raman spectra of 13C_2H_4 in the regions of the ν_2 and ν_3 Raman active modes have been recorded at at two temperatures (145 and 296 K) based on the quasi continuous-wave (cw) stimulated Raman spectrometer at Instituto de Estructura de la Materia (CSIC) in Madrid. A tensorial formalism adapted to X2Y4 planar asymmetric tops with D2h symmetry has been developed in Dijon and a program suite called D2hTDS (now part of the XTDS/SPVIEW spectroscopic software was proposed to calculate their high-resolution spectra. The effective Hamiltonian operator, involving a polyad structure, and transition moment (dipole moment and polarizability) operators can be systematically expanded to carry out global analyses of many rovibrational bands. A total of 103 and 51 lines corresponding to ν_2 and ν_3 Raman active modes have been assigned and fitted in frequency with a global root mean square deviation of 0.54 × 10-3 cm-1 and 0.36 × 10-3 cm-1, respectively. The figures below shows the stimulated Raman spectrum of the ν_2 and ν_3 bands of 13C_2H_4, compared to the simulation at 296 K. Raballand W, Rotger M, Boudon V, Loëte M. J Mol Spectrosc 2003;217:239-48. Wenger Ch, Boudon V, Rotger M, Champion JP, Sanzharov M. J Mol Spectrosc 2008;251:102-13.

  15. Producing Radical-Free Hyperpolarized Perfusion Agents for In Vivo Magnetic Resonance Using Spin-Labeled Thermoresponsive Hydrogel.

    PubMed

    Cheng, Tian; Mishkovsky, Mor; Junk, Matthias J N; Münnemann, Kerstin; Comment, Arnaud

    2016-07-01

    Dissolution dynamic nuclear polarization (DNP) provides a way to tremendously improve the sensitivity of nuclear magnetic resonance experiments. Once the spins are hyperpolarized by dissolution DNP, the radicals used as polarizing agents become undesirable since their presence is an additional source of nuclear spin relaxation and their toxicity might be an issue. This study demonstrates the feasibility of preparing a hyperpolarized [1-(13) C]2-methylpropan-2-ol (tert-butanol) solution free of persistent radicals by using spin-labeled thermoresponsive hydrophilic polymer networks as polarizing agents. The hyperpolarized (13) C signal can be detected for up to 5 min before the spins fully relax to their thermal equilibrium. This approach extends the applicability of spin-labeled thermoresponsive hydrogel to the dissolution DNP field and highlights its potential as polarizing agent for preparing neat slowly relaxing contrast agents. The hydrogels are especially suited to hyperpolarize deuterated alcohols which can be used for in vivo perfusion imaging. PMID:27184565

  16. Static and dynamic interaction between π and d electrons in organic superconductor β″-(BEDT-TTF)4[(H3O ) Fe (C2O4)3] .C6H5Br studied by 13C NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Ihara, Y.; Futami, Y.; Kawamoto, A.; Matsui, K.; Goto, T.; Sasaki, T.; Benmansour, S.; Gómez-García, C. J.

    2016-08-01

    We present the results of 13C NMR experiments in an organic superconductor with localized Fe spins β″-(BEDT-TTF) 4[(H3O ) Fe (C2O4)3] .C6H5Br . We reveal the antiferromagnetic coupling between Fe d spins and π spins, which creates an exchange field antiparallel to the external field direction at the π electrons. In addition to the static effects of Fe spins, we show from the nuclear spin-lattice relaxation rate measurement that the magnetic fluctuations generated by Fe spins are suppressed at low temperatures and high magnetic fields. These conditions are suitable to stabilize the field-induced superconductivity by the field compensation mechanism. After the suppression of Fe-spin dynamics by a magnetic field of 19 T, we observed the underlying π -electron contribution. We discuss a possible anomaly in the π -electron system.

  17. NMR Hyperpolarization Techniques for Biomedicine

    PubMed Central

    Nikolaou, Panayiotis; Goodson, Boyd M.

    2015-01-01

    Recent developments in NMR hyperpolarization have enabled a wide array of new in vivo molecular imaging modalities—ranging from functional imaging of the lungs to metabolic imaging of cancer. This Concept article explores selected advances in methods for the preparation and use of hyperpolarized contrast agents, many of which are already at or near the phase of their clinical validation in patients. PMID:25470566

  18. Hyperpolarized singlet lifetimes of pyruvate in human blood and in the mouse.

    PubMed

    Marco-Rius, Irene; Tayler, Michael C D; Kettunen, Mikko I; Larkin, Timothy J; Timm, Kerstin N; Serrao, Eva M; Rodrigues, Tiago B; Pileio, Giuseppe; Ardenkjaer-Larsen, Jan Henrik; Levitt, Malcolm H; Brindle, Kevin M

    2013-12-01

    Hyperpolarized NMR is a promising technique for non-invasive imaging of tissue metabolism in vivo. However, the pathways that can be studied are limited by the fast T1 decay of the nuclear spin order. In metabolites containing pairs of coupled nuclear spins-1/2, the spin order may be maintained by exploiting the non-magnetic singlet (spin-0) state of the pair. This may allow preservation of the hyperpolarization in vivo during transport to tissues of interest, such as tumors, or to detect slower metabolic reactions. We show here that in human blood and in a mouse in vivo at millitesla fields the (13)C singlet lifetime of [1,2-(13)C2]pyruvate was significantly longer than the (13)C T1, although it was shorter than the T1 at field strengths of several tesla. We also examine the singlet-derived NMR spectrum observed for hyperpolarized [1,2-(13)C2]lactate, originating from the metabolism of [1,2-(13)C2]pyruvate.

  19. Hyperpolarized singlet lifetimes of pyruvate in human blood and in the mouse

    PubMed Central

    Marco-Rius, Irene; Tayler, Michael C D; Kettunen, Mikko I; Larkin, Timothy J; Timm, Kerstin N; Serrao, Eva M; Rodrigues, Tiago B; Pileio, Giuseppe; Ardenkjaer-Larsen, Jan Henrik; Levitt, Malcolm H; Brindle, Kevin M

    2013-01-01

    Hyperpolarized NMR is a promising technique for non-invasive imaging of tissue metabolism in vivo. However, the pathways that can be studied are limited by the fast T1 decay of the nuclear spin order. In metabolites containing pairs of coupled nuclear spins-1/2, the spin order may be maintained by exploiting the non-magnetic singlet (spin-0) state of the pair. This may allow preservation of the hyperpolarization in vivo during transport to tissues of interest, such as tumors, or to detect slower metabolic reactions. We show here that in human blood and in a mouse in vivo at millitesla fields the 13C singlet lifetime of [1,2-13C2]pyruvate was significantly longer than the 13C T1, although it was shorter than the T1 at field strengths of several tesla. We also examine the singlet-derived NMR spectrum observed for hyperpolarized [1,2-13C2]lactate, originating from the metabolism of [1,2-13C2]pyruvate. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. PMID:23946252

  20. A rapid method for direct detection of metabolic conversion and magnetization exchange with application to hyperpolarized substrates

    NASA Astrophysics Data System (ADS)

    Larson, Peder E. Z.; Kerr, Adam B.; Leon Swisher, Christine; Pauly, John M.; Vigneron, Daniel B.

    2012-12-01

    In this work, we present a new MR spectroscopy approach for directly observing nuclear spins that undergo exchange, metabolic conversion, or, generally, any frequency shift during a mixing time. Unlike conventional approaches to observe these processes, such as exchange spectroscopy (EXSY), this rapid approach requires only a single encoding step and thus is readily applicable to hyperpolarized MR in which the magnetization is not replenished after T1 decay and RF excitations. This method is based on stimulated-echoes and uses phase-sensitive detection in conjunction with precisely chosen echo times in order to separate spins generated during the mixing time from those present prior to mixing. We are calling the method Metabolic Activity Decomposition Stimulated-echo Acquisition Mode or MAD-STEAM. We have validated this approach as well as applied it in vivo to normal mice and a transgenic prostate cancer mouse model for observing pyruvate-lactate conversion, which has been shown to be elevated in numerous tumor types. In this application, it provides an improved measure of cellular metabolism by separating [1-13C]-lactate produced in tissue by metabolic conversion from [1-13C]-lactate that has flowed into the tissue or is in the blood. Generally, MAD-STEAM can be applied to any system in which spins undergo a frequency shift.

  1. Determination of methyl 13C-15N dipolar couplings in peptides and proteins by three-dimensional and four-dimensional magic-angle spinning solid-state NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Helmus, Jonathan J.; Nadaud, Philippe S.; Höfer, Nicole; Jaroniec, Christopher P.

    2008-02-01

    We describe three- and four-dimensional semiconstant-time transferred echo double resonance (SCT-TEDOR) magic-angle spinning solid-state nuclear magnetic resonance (NMR) experiments for the simultaneous measurement of multiple long-range N15-Cmethyl13 dipolar couplings in uniformly C13, N15-enriched peptides and proteins with high resolution and sensitivity. The methods take advantage of C13 spin topologies characteristic of the side-chain methyl groups in amino acids alanine, isoleucine, leucine, methionine, threonine, and valine to encode up to three distinct frequencies (N15-Cmethyl13 dipolar coupling, N15 chemical shift, and Cmethyl13 chemical shift) within a single SCT evolution period of initial duration ˜1/JCC1 (where JCC1≈35Hz, is the one-bond Cmethyl13-C13 J-coupling) while concurrently suppressing the modulation of NMR coherences due to C13-C13 and N15-C13 J-couplings and transverse relaxation. The SCT-TEDOR schemes offer several important advantages over previous methods of this type. First, significant (approximately twofold to threefold) gains in experimental sensitivity can be realized for weak N15-Cmethyl13 dipolar couplings (corresponding to structurally interesting, ˜3.5Å or longer, distances) and typical Cmethyl13 transverse relaxation rates. Second, the entire SCT evolution period can be used for Cmethyl13 and/or N15 frequency encoding, leading to increased spectral resolution with minimal additional coherence decay. Third, the experiments are inherently "methyl selective," which results in simplified NMR spectra and obviates the use of frequency-selective pulses or other spectral filtering techniques. Finally, the N15-C13 cross-peak buildup trajectories are purely dipolar in nature (i.e., not influenced by J-couplings or relaxation), which enables the straightforward extraction of N15-Cmethyl13 distances using an analytical model. The SCT-TEDOR experiments are demonstrated on a uniformly C13, N15-labeled peptide, N-acetyl-valine, and a 56

  2. Hyperpolarized 89Y complexes as pH sensitive NMR probes.

    PubMed

    Jindal, Ashish K; Merritt, Matthew E; Suh, Eul Hyun; Malloy, Craig R; Sherry, A Dean; Kovács, Zoltán

    2010-02-17

    Hyperpolarization can increase the sensitivity of NMR/MRI experiments, but the primary limitation is the T(1) decay of magnetization. Due to its long T(1), the hyperpolarized (89)Y nucleus makes an excellent candidate as an in vivo spectroscopy/imaging probe. Here we report the (89)Y chemical shift dependence upon pH for two hyperpolarized (89)Y(III) complexes and demonstrate how such complexes can be used as sensitive spectroscopy/imaging agents to measure pH.

  3. Astroglial Contribution to Brain Energy Metabolism in Humans Revealed by 13C Nuclear Magnetic Resonance Spectroscopy: Elucidation of the Dominant Pathway for Neurotransmitter Glutamate Repletion and Measurement of Astrocytic Oxidative Metabolism

    PubMed Central

    Lebon, Vincent; Petersen, Kitt F.; Cline, Gary W.; Shen, Jun; Mason, Graeme F.; Dufour, Sylvie; Behar, Kevin L.; Shulman, Gerald I.; Rothman, Douglas L.

    2010-01-01

    Increasing evidence supports a crucial role for glial metabolism in maintaining proper synaptic function and in the etiology of neurological disease. However, the study of glial metabolism in humans has been hampered by the lack of noninvasive methods. To specifically measure the contribution of astroglia to brain energy metabolism in humans, we used a novel noninvasive nuclear magnetic resonance spectroscopic approach. We measured carbon 13 incorporation into brain glutamate and glutamine in eight volunteers during an intravenous infusion of [2-13C] acetate, which has been shown in animal models to be metabolized specifically in astroglia. Mathematical modeling of the three established pathways for neurotransmitter glutamate repletion indicates that the glutamate/glutamine neurotransmitter cycle between astroglia and neurons (0.32 ± 0.07 μmol · gm−1 · min−1) is the major pathway for neuronal glutamate repletion and that the astroglial TCA cycle flux (0.14 ± 0.06 μmol · gm−1 · min−1) accounts for ~14% of brain oxygen consumption. Up to 30% of the glutamine transferred to the neurons by the cycle may derive from replacement of oxidized glutamate by anaplerosis. The further application of this approach could potentially enlighten the role of astroglia in supporting brain glutamatergic activity and in neurological and psychiatric disease. PMID:11880482

  4. Measuring long-lived 13C2 state lifetimes at natural abundance

    NASA Astrophysics Data System (ADS)

    Claytor, Kevin; Theis, Thomas; Feng, Yesu; Warren, Warren

    2014-02-01

    Long-lived disconnected eigenstates (for example, the singlet state in a system with two nearly equivalent carbons, or the singlet-singlet state in a system with two chemically equivalent carbons and two chemically equivalent hydrogens) hold the potential to drastically extend the lifetime of hyperpolarization in molecular tracers for in vivo magnetic resonance imaging (MRI). However, a first-principles calculation of the expected lifetime (and thus selection of potential imaging agents) is made very difficult because of the large variety of relevant intra- and intermolecular relaxation mechanisms. As a result, all previous measurements relied on costly and time consuming syntheses of 13C labeled compounds. Here we show that it is possible to determine 13C singlet state lifetimes by detecting the naturally abundant doubly-labeled species. This approach allows for rapid and low cost screening of potential molecular biomarkers bearing long-lived states.

  5. A 13C-NMR study of exopolysaccharide synthesis in Rhizobium meliloti Su47 strain

    NASA Astrophysics Data System (ADS)

    Tavernier, P.; Portais, J.-C.; Besson, I.; Courtois, J.; Courtois, B.; Barbotin, J.-N.

    1998-02-01

    Metabolic pathways implied in the synthesis of succinoglycan produced by the Su47 strain of R. meliloti were evaluated by 13C-NMR spectroscopy after incubation with [1{-}13C] or [2{-}13C] glucose. The biosynthesis of this polymer by R. meliloti from glucose occurred by a direct polymerisation of the introduced glucose and by the pentose phosphate pathway. Les voies métaboliques impliquées dans la synthèse du succinoglycane produit par la souche Su47 de R. meliloti ont été évaluées par la spectroscopie de RMN du carbone 13 après incubation des cellules avec du [1{-}13C] ou [2{-}13C] glucose. La biosynthèse de ce polymère à partir du glucose se produit par polymérisation directe du glucose et par la voie des pentoses phosphate.

  6. Study of conformations and hydrogen bonds in the configurational isomers of pyrrole-2-carbaldehyde oxime by 1H, 13C and 15N NMR spectroscopy combined with MP2 and DFT calculations and NBO analysis.

    PubMed

    Afonin, Andrei V; Ushakov, Igor A; Pavlov, Dmitry V; Ivanov, Andrei V; Mikhaleva, Al'bina I

    2010-09-01

    The (1)H, (13)C and (15)N NMR studies have shown that the E and Z isomers of pyrrole-2-carbaldehyde oxime adopt preferable conformation with the syn orientation of the oxime group with respect to the pyrrole ring. The syn conformation of E and Z isomers of pyrrole-2-carbaldehyde oxime is stabilized by the N-H...N and N-H...O intramolecular hydrogen bonds, respectively. The N-H...N hydrogen bond in the E isomer causes the high-frequency shift of the bridge proton signal by about 1 ppm and increase the (1)J(N, H) coupling by approximately 3 Hz. The bridge proton shows further deshielding and higher increase of the (1)J(N, H) coupling constant due to the strengthening of the N-H...O hydrogen bond in the Z isomer. The MP2 calculations indicate that the syn conformation of E and Z isomers is by approximately 3.5 kcal/mol energetically less favorable than the anti conformation. The calculations of (1)H shielding and (1)J(N, H) coupling in the syn and anti conformations allow the contribution to these constants from the N-H...N and N-H...O hydrogen bondings to be estimated. The NBO analysis suggests that the N-H...N hydrogen bond in the E isomer is a pure electrostatic interaction while the charge transfer from the oxygen lone pair to the antibonding orbital of the N-H bond through the N-H...O hydrogen bond occurs in the Z isomer. PMID:20623827

  7. Synthesis Of [2h, 13c] And [2h3, 13c]Methyl Aryl Sulfides

    DOEpatents

    Martinez, Rodolfo A.; Alvarez, Marc A.; Silks, III, Louis A.; Unkefer, Clifford J.

    2004-03-30

    The present invention is directed to labeled compounds, [.sup.2 H.sub.1, .sup.13 C], [.sup.2 H.sub.2, .sup.13 C] and [.sup.2 H.sub.3, .sup.13 C]methyl aryl sulfides wherein the .sup.13 C methyl group attached to the sulfur of the sulfide includes exactly one, two or three deuterium atoms and the aryl group is selected from the group consisting of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are each independently, hydrogen, a C.sub.1 -C.sub.4 lower alkyl, a halogen, an amino group from the group consisting of NH.sub.2, NHR and NRR' where R and R' are each a C.sub.1 -C.sub.4 lower alkyl, a phenyl, or an alkoxy group. The present invention is also directed to processes of preparing [.sup.2 H.sub.1, .sup.13 C], [.sup.2 H.sub.2,.sup.13 C] and [.sup.2 H.sub.3, .sup.13 C]methyl aryl sulfides wherein the .sup.13 C methyl group attached to the sulfur of the sulfide includes exactly one, two or three deuterium atoms. The present invention is also directed to the labeled compounds of [.sup.2 H.sub.1, .sup.13 C]methyl iodide and [.sup.2 H.sub.2, .sup.13 C]methyl iodide.

  8. Assignment of the ferriheme resonances of high- and low-spin forms of the symmetrical hemin-reconstituted nitrophorins 1-4 by 1H and 13C NMR spectroscopy: the dynamics of heme ruffling deformations.

    PubMed

    Shokhireva, Tatiana K; Shokhirev, Nikolai V; Berry, Robert E; Zhang, Hongjun; Walker, F Ann

    2008-08-01

    The four major nitrophorins (NPs) of the adult blood-sucking insect Rhodnius prolixus have been reconstituted with the "symmetrical hemin" 2,4-dimethyldeuterohemin, and their NMR spectra have been investigated as the high-spin (S=5/2) aqua and low-spin (S=1/2) N-methylimidazole (NMeIm) and cyanide complexes. The NMeIm complexes allow assignment of the high-spin hemin resonances by saturation transfer difference spectroscopy. The cyanide complexes were investigated as paramagnetic analogues of the NO complexes. It is shown that the hemin ring is highly distorted from planarity, much more so for NP2 than for NP1 and NP4 (with ruffling being the major distortion mode), for both high- and low-spin forms. For the cyanide complexes, the conformation of the distorted ring changes on the NMR timescale to yield chemical exchange (exchange spectroscopy, EXSY) cross peaks for NP1sym(CN), NP3sym(CN) and NP4sym(CN) but not for NP2sym(CN). These changes in nonplanar conformation are visualized as a "rolling" of the ruffled macrocycle ridges through some number of degrees, the lowest-energy ruffling mode. This probably occurs in response to slow protein dynamics that cause the I120 and L132 side chains in the distal heme pocket to move in opposite directions (up and away vs. down and toward the hemin ring). This in turn changes the out-of-plane displacements of the 2M and 3M of the symmetrical hemin on the NMR timescale. Two other types of dynamics, i.e., changes in heme seating and NMeIm rotation, are also observed. The highly distorted heme and the dynamics it causes are unique to the NPs and a few other heme proteins with highly distorted macrocycles. PMID:18458965

  9. {sup 13}C-{sup 1}H and {sup 13}C-{sup 13}C spin couplings in [2`-{sup 13}C]2`-deoxyribonucleosides: Correlations with molecular structure

    SciTech Connect

    Bandyopadhyay, T.; Stripe, W.A.; Carmichael, I.; Serianni, A.S.; Wu, J.

    1997-02-19

    2`-Deoxyribonucleosides (2`-deoxyadenosine (1), 2`-depoxycytidine (2), thymidine (3)) singly enriched with {sup 13}C at C2` have been prepared and used to obtain one-, two-, and three-bond {sup 13}C-{sup 1}H and {sup 13}C-{sup 13}C spin-coupling constants involving C2`. Spin couplings in 1-3 involving C1` and C2`are also compared to corresponding values in ribonucleosides in order to assess the effects of nucleoside structure and conformation on J values within the furanose ring. {sup 1}J{sub C2`,H2`R} and {sup 1}J{sub C2`,H2`S} in 1-3 and {sup 1}J{sub C2`,H2`} in ribonucleosides depend on C-H bond orientation: {sup 1}J{sub C1`,H1`} in 1-3 and in ribonucleosides exhibits a similar dependence. The latter couplings appear to be essentially unaffected by N-glycoside torsion. {sup 1}J{sub CC} values depend on the number and distribution of electronegative substituents on the C-C fragment. A modified projection curve is proposed to aid in the interpretation of {sup 2}J{sub C2`,H1`} values; the presence of N substitution at C1` caused a shift to more negative couplings relative to the O-substituted analog. In contrast, {sup 2}J{sub C1`,H2`} is essentially unaffected by the same change in the electronegative substituent at C1`. {sup 2}J{sub CC} values within the furanose ring are determined buy two coupling pathways; in one case (i.e., {sup 2}J{sub C1`,C3`}), the observed coupling is shown to be the algebraic sum of the two couplings arising from each pathway. 41 refs., 4 figs., 2 tabs.

  10. Apparatus for preparing a solution of a hyperpolarized noble gas for NMR and MRI analysis

    DOEpatents

    Pines, Alexander; Budinger, Thomas; Navon, Gil; Song, Yi-Qiao; Appelt, Stephan; Bifone, Angelo; Taylor, Rebecca; Goodson, Boyd; Seydoux, Roberto; Room, Toomas; Pietrass, Tanja

    2008-06-10

    The present invention relates generally to nuclear magnetic resonance (NMR) techniques for both spectroscopy and imaging. More particularly, the present invention relates to methods in which hyperpolarized noble gases (e.g., Xe and He) are used to enhance and improve NMR and MRI. Additionally, the hyperpolarized gas solutions of the invention are useful both in vitro and in vivo to study the dynamics or structure of a system. When used with biological systems, either in vivo or in vitro, it is within the scope of the invention to target the hyperpolarized gas and deliver it to specific regions within the system.

  11. Enhancement of NMR and MRI in the presence of hyperpolarized noble gases

    DOEpatents

    Pines, Alexander; Budinger, Thomas; Navon, Gil; Song, Yi-Qiao; Appelt, Stephan; Bifone, Angelo; Taylor, Rebecca; Goodson, Boyd; Seydoux, Roberto; Room, Toomas; Pietrass, Tanja

    2004-11-16

    The present invention relates generally to nuclear magnetic resonance (NMR) techniques for both spectroscopy and imaging. More particularly, the present invention relates to methods in which hyperpolarized noble gases (e.g., Xe and He) are used to enhance and improve NMR and MRI. Additionally, the hyperpolarized gas solutions of the invention are useful both in vitro and in vivo to study the dynamics or structure of a system. When used with biological systems, either in vivo or in vitro, it is within the scope of the invention to target the hyperpolarized gas and deliver it to specific regions within the system.

  12. Refined Analysis of Brain Energy Metabolism Using In Vivo Dynamic Enrichment of 13C Multiplets

    PubMed Central

    Dehghani M., Masoumeh; Duarte, João M. N.; Kunz, Nicolas; Gruetter, Rolf

    2016-01-01

    Carbon-13 nuclear magnetic resonance spectroscopy in combination with the infusion of 13C-labeled precursors is a unique approach to study in vivo brain energy metabolism. Incorporating the maximum information available from in vivo localized 13C spectra is of importance to get broader knowledge on cerebral metabolic pathways. Metabolic rates can be quantitatively determined from the rate of 13C incorporation into amino acid neurotransmitters such as glutamate and glutamine using suitable mathematical models. The time course of multiplets arising from 13C-13C coupling between adjacent carbon atoms was expected to provide additional information for metabolic modeling leading to potential improvements in the estimation of metabolic parameters. The aim of the present study was to extend two-compartment neuronal/glial modeling to include dynamics of 13C isotopomers available from fine structure multiplets in 13C spectra of glutamate and glutamine measured in vivo in rats brain at 14.1 T, termed bonded cumomer approach. Incorporating the labeling time courses of 13C multiplets of glutamate and glutamine resulted in elevated precision of the estimated fluxes in rat brain as well as reduced correlations between them. PMID:26969691

  13. Earth's magnetic field enabled scalar coupling relaxation of 13C nuclei bound to fast-relaxing quadrupolar 14N in amide groups

    NASA Astrophysics Data System (ADS)

    Chiavazza, Enrico; Kubala, Eugen; Gringeri, Concetta V.; Düwel, Stephan; Durst, Markus; Schulte, Rolf F.; Menzel, Marion I.

    2013-02-01

    Scalar coupling relaxation, which is usually only associated with closely resonant nuclei (e.g., 79Br-13C), can be a very effective relaxation mechanism. While working on hyperpolarized [5-13C]glutamine, fast liquid-state polarization decay during transfer to the MRI scanner was observed. This behavior could hypothetically be explained by substantial T1 shortening due to a scalar coupling contribution (type II) to the relaxation caused by the fast-relaxing quadrupolar 14N adjacent to the 13C nucleus in the amide group. This contribution is only effective in low magnetic fields (i.e., less than 800 μT) and prevents the use of molecules bearing the 13C-amide group as hyperpolarized MRS/MRI probes. In the present work, this hypothesis is explored both theoretically and experimentally. The results show that high hyperpolarization levels can be retained using either a 15N-labeled amide or by applying a magnetic field during transfer of the sample from the polarizer to the MRI scanner.

  14. Optimal variable flip angle schemes for dynamic acquisition of exchanging hyperpolarized substrates

    NASA Astrophysics Data System (ADS)

    Xing, Yan; Reed, Galen D.; Pauly, John M.; Kerr, Adam B.; Larson, Peder E. Z.

    2013-09-01

    In metabolic MRI with hyperpolarized contrast agents, the signal levels vary over time due to T1 decay, T2 decay following RF excitations, and metabolic conversion. Efficient usage of the nonrenewable hyperpolarized magnetization requires specialized RF pulse schemes. In this work, we introduce two novel variable flip angle schemes for dynamic hyperpolarized MRI in which the flip angle is varied between excitations and between metabolites. These were optimized to distribute the magnetization relatively evenly throughout the acquisition by accounting for T1 decay, prior RF excitations, and metabolic conversion. Simulation results are presented to confirm the flip angle designs and evaluate the variability of signal dynamics across typical ranges of T1 and metabolic conversion. They were implemented using multiband spectral-spatial RF pulses to independently modulate the flip angle at various chemical shift frequencies. With these schemes we observed increased SNR of [1-13C]lactate generated from [1-13C]pyruvate, particularly at later time points. This will allow for improved characterization of tissue perfusion and metabolic profiles in dynamic hyperpolarized MRI.

  15. Perfusion Imaging with a Freely Diffusible Hyperpolarized Contrast Agent

    PubMed Central

    Grant, Aaron K.; Vinogradov, Elena; Wang, Xiaoen; Lenkinski, Robert E.; Alsop, David C.

    2011-01-01

    Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized 13C labeled 2-methylpropan-2-ol (also known as dimethylethanol, tertiary butyl alcohol and tert-butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic 13C images acquired in rat brain with a balanced steady-state free precession (bSSFP) sequence following administration of hyperpolarized 2-methylpropan-2-ol show that this agent can be imaged with 2–4s temporal resolution, 2mm slice thickness, and 700 micron in-plane resolution while retaining adequate signal-to-noise ratio. 13C relaxation measurements on 2-methylpropan-2-ol in blood at 9.4T yield T1=46±4s and T2=0.55±0.03s. In the rat brain at 4.7T, analysis of the temporal dynamics of the bSSFP image intensity in tissue and venous blood indicate that 2-methylpropan-2-ol has a T2 of roughly 2–4s and a T1 of 43±24s. In addition, the images indicate that 2-methylpropan-2-ol is freely diffusible in brain and hence has a long residence time in tissue; this in turn makes it possible to image the agent continuously for tens of seconds. These characteristics show that 2-methylpropan-2-ol is a promising agent for robust and quantitative perfusion imaging in the brain and body. PMID:21432901

  16. Synthesis Of 2h- And 13c-Substituted Dithanes

    DOEpatents

    Martinez, Rodolfo A.; Alvarez, Marc A.; Silks, III, Louis A.; Unkefer, Clifford J.

    2004-05-04

    The present invention is directed to labeled compounds, [2-.sup.13 C]dithane wherein the .sup.13 C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to processes of preparing [2-.sup.13 C]dithane wherein the .sup.13 C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to labeled compounds, e.g., [.sup.2 H.sub.1-2, .sup.13 C]methanol (arylthio)-, acetates wherein the .sup.13 C atom is directly bonded to exactly one or two deuterium atoms.

  17. Synthesis of 2H- and 13C-substituted dithanes

    DOEpatents

    Martinez, Rodolfo A.; Alvarez, Marc A.; Silks, III, Louis A.; Unkefer, Clifford J.

    2003-01-01

    The present invention is directed to labeled compounds, [2-.sup.13 C]dithiane wherein the .sup.13 C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to processes of preparing [2-.sup.13 C]dithiane wherein the .sup.13 C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to labeled compounds, e.g., [.sup.2 H.sub.1-2, .sup.13 C]methanol (arylthio)-, acetates wherein the .sup.13 C atom is directly bonded to exactly one or two deuterium atoms.

  18. Calculation of total meal d13C from individual food d13C.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Variations in the isotopic signature of carbon in biological samples can be used to distinguish dietary patterns and monitor shifts in metabolism. But for these variations to have meaning, the isotopic signature of the diet must be known. We sought to determine if knowledge of the 13C isotopic abund...

  19. In vivo dynamic turnover of cerebral 13C isotopomers from [U- 13C]glucose

    NASA Astrophysics Data System (ADS)

    Xu, Su; Shen, Jun

    2006-10-01

    An INEPT-based 13C MRS method and a cost-effective and widely available 11.7 Tesla 89-mm bore vertical magnet were used to detect dynamic 13C isotopomer turnover from intravenously infused [U- 13C]glucose in a 211 μL voxel located in the adult rat brain. The INEPT-based 1H → 13C polarization transfer method is mostly adiabatic and therefore minimizes signal loss due to B 1 inhomogeneity of the surface coils used. High quality and reproducible data were acquired as a result of combined use of outer volume suppression, ISIS, and the single-shot three-dimensional localization scheme built in the INEPT pulse sequence. Isotopomer patterns of both glutamate C4 at 34.00 ppm and glutamine C4 at 31.38 ppm are dominated first by a doublet originated from labeling at C4 and C5 but not at C3 (with 1JC4C5 = 51 Hz) and then by a quartet originated from labeling at C3, C4, and C5 (with 1JC3C4 = 35 Hz). A lag in the transition of glutamine C4 pattern from doublet-dominance to quartet dominance as compared to glutamate C4 was observed, which provides an independent verification of the precursor-product relationship between neuronal glutamate and glial glutamine and a significant intercompartmental cerebral glutamate-glutamine cycle between neurons and glial cells.

  20. Preparation of 13C/15N-labeled oligomers using the polymerase chain reaction

    DOEpatents

    Chen, Xian; Gupta, Goutam; Bradbury, E. Morton

    2001-01-01

    Preparation of .sup.13 C/.sup.15 N-labeled DNA oligomers using the polymerase chain reaction (PCR). A PCR based method for uniform (.sup.13 C/.sup.15 N)-labeling of DNA duplexes is described. Multiple copies of a blunt-ended duplex are cloned into a plasmid, each copy containing the sequence of interest and restriction Hinc II sequences at both the 5' and 3' ends. PCR using bi-directional primers and uniformly .sup.13 C/.sup.15 N-labeled dNTP precursors generates labeled DNA duplexes containing multiple copies of the sequence of interest. Twenty-four cycles of PCR, followed by restriction and purification, gave the uniformly .sup.13 C/.sup.15 N-labeled duplex sequence with a 30% yield. Such labeled duplexes find significant applications in multinuclear magnetic resonance spectroscopy.

  1. Nuclear hyperpolarization comes of age

    NASA Astrophysics Data System (ADS)

    Jeschke, Gunnar; Frydman, Lucio

    2016-03-01

    The last decade has seen transformative developments and previously unthinkable opportunities opening in the fields of solid-state, solution and imaging NMR, thanks to the advent of methods for hyperpolarizing the nuclear spins. Probably since the introduction of the Fourier Transform, and to some extent for similar reasons, few single concepts have had the potential to affect so many areas of magnetic resonance, as the dissemination of these sensitivity-enhancing methods. The generality of these methods, particularly those based on dynamic nuclear polarization (DNP), has triggered exciting new research over a wide range of applications ranging from material sciences and structural biology to metabolic analysis, biochemistry, biology and clinical diagnosis. This excitement has been accompanied by concurrent efforts to better understand the physical basis of nuclear hyperpolarization to optimize the instrumentation that will achieve higher levels of nuclear polarization over a wide range of conditions, and with new NMR and MRI sequences and experiments that will better fit the particular demands of these experiments. This concentrated attention has also brought in close synergy the electron and nuclear magnetic resonance communities, particularly as the former showed the latter that electrons could be exploited via DNP to originate nuclear hyperpolarization over a wide range of solution and solid state systems. Such "DNP revolution" also rekindled similar searches based on alternatives such as para-Hydrogen induced polarization and optical pumping. The kind of NMR enhancement that all these techniques could provide would have been unreachable by traditional approaches, for instance further optimizations of the NMR receiving hardware or increasing the NMR/MRI observation fields.

  2. Medical Imaging of Hyperpolarized Gases

    SciTech Connect

    Miller, G. Wilson

    2009-08-04

    Since the introduction of hyperpolarized {sup 3}He and {sup 129}Xe as gaseous MRI contrast agents more than a decade ago, a rich variety of imaging techniques and medical applications have been developed. Magnetic resonance imaging of the inhaled gas depicts ventilated lung airspaces with unprecedented detail, and allows one to track airflow and pulmonary mechanics during respiration. Information about lung structure and function can also be obtained using the physical properties of the gas, including spin relaxation in the presence of oxygen, restricted diffusion inside the alveolar airspaces, and the NMR frequency shift of xenon dissolved in blood and tissue.

  3. 500-fold enhancement of in situ (13)C liquid state NMR using gyrotron-driven temperature-jump DNP.

    PubMed

    Yoon, Dongyoung; Soundararajan, Murari; Caspers, Christian; Braunmueller, Falk; Genoud, Jérémy; Alberti, Stefano; Ansermet, Jean-Philippe

    2016-09-01

    A 550-fold increase in the liquid state (13)C NMR signal of a 50μL sample was obtained by first hyperpolarizing the sample at 20K using a gyrotron (260GHz), then, switching its frequency in order to apply 100W for 1.5s so as to melt the sample, finally, turning off the gyrotron to acquire the (13)C NMR signal. The sample stays in its NMR resonator, so the sequence can be repeated with rapid cooling as the entire cryostat stays cold. DNP and thawing of the sample are performed only by the switchable and tunable gyrotron without external devices. Rapid transition from DNP to thawing in one second time scale was necessary especially in order to enhance liquid (1)H NMR signal. PMID:27490302

  4. 500-fold enhancement of in situ 13C liquid state NMR using gyrotron-driven temperature-jump DNP

    NASA Astrophysics Data System (ADS)

    Yoon, Dongyoung; Soundararajan, Murari; Caspers, Christian; Braunmueller, Falk; Genoud, Jérémy; Alberti, Stefano; Ansermet, Jean-Philippe

    2016-09-01

    A 550-fold increase in the liquid state 13C NMR signal of a 50 μL sample was obtained by first hyperpolarizing the sample at 20 K using a gyrotron (260 GHz), then, switching its frequency in order to apply 100 W for 1.5 s so as to melt the sample, finally, turning off the gyrotron to acquire the 13C NMR signal. The sample stays in its NMR resonator, so the sequence can be repeated with rapid cooling as the entire cryostat stays cold. DNP and thawing of the sample are performed only by the switchable and tunable gyrotron without external devices. Rapid transition from DNP to thawing in one second time scale was necessary especially in order to enhance liquid 1H NMR signal.

  5. 13C isotopic fractionation during biodegradation of agricultural wastes.

    PubMed

    Chalk, Phillip M; Inácio, Caio T; Urquiaga, Segundo; Chen, Deli

    2015-01-01

    Significant differences in δ(13)C signatures occur within and between plant tissues and their constituent biochemical entities, and also within and between heterotrophic bacteria and fungi and their metabolic products. Furthermore, (13)C isotopic fractionation occurs during the biodegradation of organic molecules as seen in the substrate, respired CO(2) and the microbial biomass, which could be related to substrate composition and/or microbial metabolism. The (13)C isotopic fractionation observed during the decomposition of a single defined C substrate appears to be due to the intra-molecular heterogeneity in (13)C in the substrate and to (13)C isotopic fractionation during microbial metabolism. Very limited data suggest that the latter may be quantitatively more important than the former. Studies with defined fungi in culture media have highlighted the complexities associated with the interpretation of the observed patterns of (13)C isotopic fractionation when a single defined C source is added to the culture medium which itself contains one or more C sources. Techniques involving (13)C enrichment or paired treatments involving an equivalent C(3)- and C(4)-derived substrate have been devised to overcome the problem of background C in the culture medium and (13)C isotopic fractionation during metabolism. Studies with complex substrates have shown an initial (13)C depletion phase in respired CO(2) followed by a (13)C enrichment phase which may or may not be followed by another (13)C depletion phase. Basic studies involving an integrated approach are required to gain a new insight into (13)C isotopic fractionation during organic residue decomposition, by simultaneous measurements of δ(13)C in all C moieties. New analytical tools to measure real-time changes in δ(13)CO(2) and the intra-molecular δ(13)C distribution within plant biochemical entities offer new opportunities for unravelling the complex interactions between substrate and microbial metabolism with

  6. Conditions for (13)C NMR detection of 2-hydroxyglutarate in tissue extracts from isocitrate dehydrogenase-mutated gliomas.

    PubMed

    Pichumani, Kumar; Mashimo, Tomoyuki; Baek, Hyeon-Man; Ratnakar, James; Mickey, Bruce; DeBerardinis, Ralph J; Maher, Elizabeth A; Bachoo, Robert M; Malloy, Craig R; Kovacs, Zoltan

    2015-07-15

    (13)C NMR (nuclear magnetic resonance) spectroscopy of extracts from patient tumor samples provides rich information about metabolism. However, in isocitrate dehydrogenase (IDH)-mutant gliomas, (13)C labeling is obscured in oncometabolite 2-hydroxyglutaric acid (2 HG) by glutamate and glutamine, prompting development of a simple method to resolve the metabolites. J-coupled multiplets in 2 HG were similar to glutamate and glutamine and could be clearly resolved at pH 6. A cryogenically cooled (13)C probe, but not J-resolved heteronuclear single quantum coherence spectroscopy, significantly improved detection of 2 HG. These methods enable the monitoring of (13)C-(13)C spin-spin couplings in 2 HG expressing IDH-mutant gliomas.

  7. Time resolved spectroscopic NMR imaging using hyperpolarized 129Xe.

    PubMed

    Han, S; Kühn, H; Häsing, F W; Münnemann, K; Blümich, B; Appelt, S

    2004-04-01

    We have visualized the melting and dissolution processes of xenon (Xe) ice into different solvents using the methods of nuclear magnetic resonance (NMR) spectroscopy, imaging, and time resolved spectroscopic imaging by means of hyperpolarized 129Xe. Starting from the initial condition of a hyperpolarized solid Xe layer frozen on top of an ethanol (ethanol/water) ice block we measured the Xe phase transitions as a function of time and temperature. In the pure ethanol sample, pieces of Xe ice first fall through the viscous ethanol to the bottom of the sample tube and then form a thin layer of liquid Xe/ethanol. The xenon atoms are trapped in this liquid layer up to room temperature and keep their magnetization over a time period of 11 min. In the ethanol/water mixture (80 vol%/20%), most of the polarized Xe liquid first stays on top of the ethanol/water ice block and then starts to penetrate into the pores and cracks of the ethanol/water ice block. In the final stage, nearly all the Xe polarization is in the gas phase above the liquid and trapped inside the pores. NMR spectra of homogeneous samples of pure ethanol containing thermally polarized Xe and the spectroscopic images of the melting process show that very high concentrations of hyperpolarized Xe (about half of the density of liquid Xe) can be stored or delivered in pure ethanol. PMID:15040986

  8. The Fate of Oral Glucosamine Traced by 13C Labeling in the Dog

    PubMed Central

    Dodge, George R.; Regatte, Ravinder R.; Noyszewski, Elizabeth A.; Hall, Jeffery O.; Sharma, Akella V.; Callaway, D. Allen; Reddy, Ravinder

    2011-01-01

    Objective: It has remained ambiguous as to whether oral dosing of glucosamine (GlcN) would make its way to the joint and affect changes in the cartilage, particularly the integrity of cartilage and chondrocyte function. The objective of this study was to trace the fate of orally dosed GlcN and determine definitively if GlcN was incorporated into cartilage proteoglycans. Design: Two dogs were treated with 13C-GlcN-HCl by oral dosing (500 mg/dog/d for 2 weeks and 250 mg/dog/d for 3 weeks). Cartilage was harvested from the tibial plateau and femoral condyles along with tissue specimens from the liver, spleen, heart, kidney, skin, skeletal muscle, lung, and costal cartilage. Percentages of 13C and 13C-GlcN present in each tissue sample were determined by inductively coupled plasma mass spectroscopy (ICP-MS) and nuclear magnetic resonance spectroscopy, respectively. Results: In the case of dog 1 (2-week treatment), there was an increase of 2.3% of 13C present in the articular cartilage compared to the control and an increase of 1.6% of 13C in dog 2 compared to control. As to be expected, the highest percentage of 13C in the other tissues tested was found in the liver, and the remaining tissues had percentages of 13C less than that of articular cartilage. Conclusion: The results are definitive and for the first time provide conclusive evidence that orally given GlcN can make its way through the digestive tract and be used by chondrocytes in joint cartilage, thereby potentially having an effect on the available GlcN for proteoglycan biosynthesis. PMID:26069586

  9. Analysis of Cancer Metabolism by Imaging Hyperpolarized Nuclei: Prospects for Translation to Clinical Research

    PubMed Central

    Kurhanewicz, John; Vigneron, Daniel B; Brindle, Kevin; Chekmenev, Eduard Y; Comment, Arnaud; Cunningham, Charles H; DeBerardinis, Ralph J; Green, Gary G; Leach, Martin O; Rajan, Sunder S; Rizi, Rahim R; Ross, Brian D; Warren, Warren S; Malloy, Craig R

    2011-01-01

    A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as 13C or 15N with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism—poor sensitivity—while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care. PMID:21403835

  10. sup 13 C-enriched ribonucleosides: Synthesis and application of sup 13 C- sup 1 H and sup 13 C- sup 13 C spin-coupling constants to assess furanose and N-glycoside bond conformations

    SciTech Connect

    Kline, P.C.; Serianni, A.S. )

    1990-09-26

    Adenosine (1), cytidine (2), guanosine (3), and uridine (4) have been prepared chemically with {sup 13}C enrichment (99 atom %) at C1{prime} and C2{prime} of the ribose ring. Reliable synthetic protocols have been developed to permit access to millimole quantities of labeled ribonucleosides required for structural studies of stable isotopically labeled oligonucleotides and for in vivo metabolism studies. High-resolution {sup 1}H and {sup 13}C NMR spectra of the enriched ribonucleosides have been obtained, and {sup 13}C-{sup 13}C and {sup 13}C-{sup 1}H spin-coupling constants have been measured for pathways within the {beta}-D-ribofuranose ring and across the N-glycoside bond. Related couplings were determined in methyl {alpha}- and {beta}-D-riboruanosides (5,6), and in two conformationally constrained nucleosides, 2,2{prime}-anhydro-(1-{beta}-D-arabinofuranosyl)uracil (7) and 2{prime},3{prime}-O-isopropylidene-2,5{prime}-O-cyclouridine (8). The latter data were used to construct a crude Karplus curve for the {sup 13}C-C-N-{sup 13}C coupling pathway across the N-glycoside bond in 1-4. {sup 1}H-{sup 1}H, {sup 13}C-{sup 1}H, and {sup 13}C-{sup 13}C coupling data are used to evaluate current models describing the conformational dynamics of 1-4 in aqueous solution.

  11. Membrane hyperpolarization during human sperm capacitation

    PubMed Central

    López-González, I.; Torres-Rodríguez, P.; Sánchez-Carranza, O.; Solís-López, A.; Santi, C.M.; Darszon, A.; Treviño, C.L.

    2014-01-01

    Sperm capacitation is a complex and indispensable physiological process that spermatozoa must undergo in order to acquire fertilization capability. Spermatozoa from several mammalian species, including mice, exhibit a capacitation-associated plasma membrane hyperpolarization, which is necessary for the acrosome reaction to occur. Despite its importance, this hyperpolarization event has not been adequately examined in human sperm. In this report we used flow cytometry to show that a subpopulation of human sperm indeed undergo a plasma membrane hyperpolarization upon in vitro capacitation. This hyperpolarization correlated with two other well-characterized capacitation parameters, namely an increase in intracellular pH and Ca2+ concentration, measured also by flow cytometry. We found that sperm membrane hyperpolarization was completely abolished in the presence of a high external K+ concentration (60 mM), indicating the participation of K+ channels. In order to identify, which of the potential K+ channels were involved in this hyperpolarization, we used different K+ channel inhibitors including charybdotoxin, slotoxin and iberiotoxin (which target Slo1) and clofilium (a more specific blocker for Slo3). All these K+ channel antagonists inhibited membrane hyperpolarization to a similar extent, suggesting that both members of the Slo family may potentially participate. Two very recent papers recorded K+ currents in human sperm electrophysiologically, with some contradictory results. In the present work, we show through immunoblotting that Slo3 channels are present in the human sperm membrane. In addition, we found that human Slo3 channels expressed in CHO cells were sensitive to clofilium (50 μM). Considered altogether, our data indicate that Slo1 and Slo3 could share the preponderant role in the capacitation-associated hyperpolarization of human sperm in contrast to what has been previously reported for mouse sperm, where Slo3 channels are the main contributors to the

  12. Membrane hyperpolarization during human sperm capacitation.

    PubMed

    López-González, I; Torres-Rodríguez, P; Sánchez-Carranza, O; Solís-López, A; Santi, C M; Darszon, A; Treviño, C L

    2014-07-01

    Sperm capacitation is a complex and indispensable physiological process that spermatozoa must undergo in order to acquire fertilization capability. Spermatozoa from several mammalian species, including mice, exhibit a capacitation-associated plasma membrane hyperpolarization, which is necessary for the acrosome reaction to occur. Despite its importance, this hyperpolarization event has not been adequately examined in human sperm. In this report we used flow cytometry to show that a subpopulation of human sperm indeed undergo a plasma membrane hyperpolarization upon in vitro capacitation. This hyperpolarization correlated with two other well-characterized capacitation parameters, namely an increase in intracellular pH and Ca(2+) concentration, measured also by flow cytometry. We found that sperm membrane hyperpolarization was completely abolished in the presence of a high external K(+) concentration (60 mM), indicating the participation of K(+) channels. In order to identify, which of the potential K(+) channels were involved in this hyperpolarization, we used different K(+) channel inhibitors including charybdotoxin, slotoxin and iberiotoxin (which target Slo1) and clofilium (a more specific blocker for Slo3). All these K(+) channel antagonists inhibited membrane hyperpolarization to a similar extent, suggesting that both members of the Slo family may potentially participate. Two very recent papers recorded K(+) currents in human sperm electrophysiologically, with some contradictory results. In the present work, we show through immunoblotting that Slo3 channels are present in the human sperm membrane. In addition, we found that human Slo3 channels expressed in CHO cells were sensitive to clofilium (50 μM). Considered altogether, our data indicate that Slo1 and Slo3 could share the preponderant role in the capacitation-associated hyperpolarization of human sperm in contrast to what has been previously reported for mouse sperm, where Slo3 channels are the main

  13. Synthesis Of [2h, 13c]M [2h2m 13c], And [2h3,, 13c] Methyl Aryl Sulfones And Sulfoxides

    DOEpatents

    Martinez, Rodolfo A.; Alvarez, Marc A.; Silks, III, Louis A.; Unkefer, Clifford J.; Schmidt, Jurgen G.

    2004-07-20

    The present invention is directed to labeled compounds, [.sup.2 H.sub.1, .sup.13 C], [.sup.2 H.sub.2, .sup.13 C] and [.sup.2 H.sub.3, .sup.13 C]methyl aryl sulfones and [.sup.2 H.sub.1, .sup.13 C], [.sup.2 H.sub.2, .sup.13 C] and [.sup.2 H.sub.3, .sup.13 C]methyl aryl sulfoxides, wherein the .sup.13 C methyl group attached to the sulfur of the sulfone or sulfoxide includes exactly one, two or three deuterium atoms and the aryl group is selected from the group consisting of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently, hydrogen, a C.sub.1 -C.sub.4 lower alkyl, a halogen, an amino group from the group consisting of NH.sub.2, NHR and NRR' where R and R' are each a C.sub.1 -C.sub.4 lower alkyl, a phenyl, or an alkoxy group. The present invention is also directed to processes of preparing methyl aryl sulfones and methyl aryl sulfoxides.

  14. Nearly 10(6)-fold enhancements in intermolecular (1)H double-quantum NMR experiments by nuclear hyperpolarization.

    PubMed

    Mishkovsky, Mor; Eliav, Uzi; Navon, Gil; Frydman, Lucio

    2009-09-01

    Intermolecular Multiple-Quantum Coherences (iMQCs) can yield interesting NMR information of high potential usefulness in spectroscopy and imaging - provided their associated sensitivity limitations can be overcome. A recent study demonstrated that ex situ dynamic nuclear polarization (DNP) could assist in overcoming sensitivity problems for iMQC-based experiments on (13)C nuclei. In the present work we show that a similar approach is possible when targeting the protons of a hyperpolarized solvent. It was found that although the DNP procedure enhances single-quantum (1)H signals by about 600, which is significantly less than in optimized low-gamma liquid-state counterparts, the non-linear dependence of iMQC-derived signals on polarization can yield very large enhancements approaching 10(6). Cleary no practical amount of data averaging can match this kind of sensitivity gains. The fact that DNP endows iMQC-based (1)H NMR spectra with a sensitivity that amply exceeds that of their thermally polarized single-quantum counterpart, is confirmed in a number of simple single-scan 2D imaging experiments.

  15. /sup 13/C nuclear magnetic resonance studies of cardiac metabolism

    SciTech Connect

    Seeholzer, S.H.

    1985-01-01

    The last decade has witnessed the increasing use of Nuclear Magnetic Resonance (NMR) techniques for following the metabolic fate of compounds specifically labeled with /sup 13/C. The goals of the present study are: (1) to develop reliable quantitative procedures for measuring the /sup 13/C enrichment of specific carbon sites in compounds enriched by the metabolism of /sup 13/C-labeled substrates in rat heart, and (2) to use these quantitative measurements of fractional /sup 13/C enrichment within the context of a mathematical flux model describing the carbon flow through the TCA cycle and ancillary pathways, as a means for obtaining unknown flux parameters. Rat hearts have been perfused in vitro with various combinations of glucose, acetate, pyruvate, and propionate to achieve steady state flux conditions, followed by perfusion with the same substrates labeled with /sup 13/C in specific carbon sites. The hearts were frozen at different times after addition of /sup 13/C-labeled substrates and neutralized perchloric acid extracts were used to obtain high resolution proton-decoupled /sup 13/C NMR spectra at 90.55 MHz. The fractional /sup 13/C enrichment (F.E.) of individual carbon sites in different metabolites was calculated from the area of the resolved resonances after correction for saturation and nuclear Overhauser effects. These F.E. measurements by /sup 13/C NMR were validated by the analysis of /sup 13/C-/sup 1/H scalar coupling patterns observed in /sup 1/H NMR spectra of the extracted metabolites. The results obtained from perfusion of hearts glucose plus either (2-/sup 13/C) acetate or (3-/sup 13/C) pyruvate are similar to those obtained by previous investigators using /sup 14/C-labeled substrates.

  16. Nondestructive determination of the 13C content in isotopic diamond by nuclear resonance fluorescence

    NASA Astrophysics Data System (ADS)

    Beck, O.; Ruf, T.; Finkelstein, Y.; Cardona, M.; Anthony, T. R.; Belic, D.; Eckert, T.; Jäger, D.; Kneissl, U.; Maser, H.; Moreh, R.; Nord, A.; Pitz, H. H.; Wolpert, A.

    1998-05-01

    Nuclear resonance fluorescence excited with continuous electron bremsstrahlung from the 4.3 MV Stuttgart Dynamitron accelerator is used as a nondestructive method to determine the 13C content x of bulk isotopic diamonds (12C1-x13Cx). The smallest detectable amount of 13C in carbon or low Z matrices is on the order of 0.5 mg. The relative accuracy of absolute mass determinations is about ±7%. Errors are mainly due to uncertainties in the natural widths Γ of the 13C nuclear levels at 3089 and 3684 keV used in the measurements. The results confirm a previous calibration which is based on Raman scattering and the destructive determination of x by mass spectroscopy.

  17. Following Glycolysis Using 13C NMR: An Experiment Adaptable to Different Undergraduate Levels

    NASA Astrophysics Data System (ADS)

    Mega, T. L.; Carlson, C. B.; Cleary, D. A.

    1997-12-01

    This paper describes a laboratory exercise where the glycolysis of [1-13C] glucose under anaerobic conditions was followed using 13C NMR spectroscopy. The exercise is described in terms of its suitability for a variety of different undergraduate levels, although the emphasis in this paper is on its use in a n advanced chemistry laboratory course. The kinetics of the loss of glucose and the production of ethanol were investigated and found not to fit simple first or second order kinetics. In addition, the relative reaction rates of the two anomeric forms of glucose were analyzed, and it was determined that the a anomeric form reacted faster than the β anomeric form. Using proton-coupled 13C NMR, some of the metabolites were identified including ethanol (major) and glycerol (minor). Reaction and spectroscopic details are included.

  18. New optical analyzer for 13C-breath test

    NASA Astrophysics Data System (ADS)

    Harde, Hermann; Dressler, Matthias; Helmrich, Günther; Wolff, Marcus; Groninga, Hinrich

    2008-04-01

    Medical breath tests are well established diagnostic tools, predominantly for gastroenterological inspections, but also for many other examinations. Since the composition and concentration of exhaled volatile gases reflect the physical condition of a patient, a breath analysis allows one to recognize an infectious disease in an organ or even to identify a tumor. One of the most prominent breath tests is the 13C-urea-breath test, applied to ascertain the presence of the bacterium helicobacter pylori in the stomach wall as an indication of a gastric ulcer. In this contribution we present a new optical analyzer that is based on photoacoustic spectroscopy and uses a DFB diode laser at 2.744 μm. The concentration ratio of the CO II isotopologues is determined by measuring the absorption on a 13CO II line in comparison to a 12CO II line. In the specially selected spectral range the lines have similar strengths, although the concentrations differ by a factor of 90. Therefore, the signals are well comparable. Due to an excellent signal-noise-ratio isotope variations of less than 1% can be resolved as required for the breath test.

  19. Stable isotopic signatures (δ13C, δD) of methane from European landfill sites

    NASA Astrophysics Data System (ADS)

    Bergamaschi, P.; Lubina, C.; KöNigstedt, R.; Fischer, H.; Veltkamp, A. C.; Zwaagstra, O.

    1998-04-01

    The stable isotopic signatures (δ13C, δD) of CH4 from four German and Dutch landfill sites have been characterized using different techniques for isotope analysis (tunable diode laser absorption spectroscopy and isotope ratio mass spectrometry). Samples taken directly from the gas collection systems show fairly uniform, biogenic δ13C-δD isotopic signatures [δ13C = (-59.0±2.2)‰ VPDB (n = 104); δD = (-304±10)‰ VSMOW (n = 46)]. In contrast, emission samples taken with static chambers on soil-covered landfill areas exhibit a considerable δ13C-δD variability, mainly due to the influence of aerobic bacterial CH4 oxidation, which occurs when the biogas CH4 encounters atmospheric oxygen available in the uppermost region of the cover soil. Soil gas samples from the landfill covers clearly show the progressive isotopic enrichment within the aerobic regions of the soil. Isotope fractionation factors due to CH4 oxidation were determined to be α(δ13C) = 1.008±0.004 and α(δD) = 1.039±0.026. On average, about 80% (70-97%) of CH4 is oxidized during the transport through cover soils, while no significant CH4 oxidation was found in uncovered areas consisting of freshly dumped waste. Area-integrated δ13C values of total emissions were derived from upwind-downwind measurements around the landfill and show very little temporal and site-to-site variation (δ13C = (-55.4±1.4)‰ VPDB (n = 13; four different landfills)). CH4 budgets were established for two landfill sites, indicating that projected CH4 surface emissions from uncovered and covered areas are significantly lower compared to total CH4 production (for a landfill without gas collection) or compared to the difference between CH4 production and recovery (for a landfill with a gas collection system). For these two landfill sites the overall fraction of CH4 oxidation is estimated to be 46 and 39% (53%) of total CH4 production (minus recovery). Furthermore, the δ13C balance (comparing the δ13C values of the

  20. Construction and 13C NMR signal-amplification efficiency of a dynamic nuclear polarizer at 6.4 T and 1.4 K

    NASA Astrophysics Data System (ADS)

    Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Ferguson, Sarah; Taylor, David; McDonald, George; Lumata, Lloyd

    Dissolution dynamic nuclear polarization (DNP) is a rapidly emerging technique in biomedical and metabolic imaging since it amplifies the liquid-state nuclear magnetic resonance (NMR) and imaging (MRI) signals by >10,000-fold. Originally used in nuclear scattering experiments, DNP works by creating a non-Boltzmann nuclear spin distribution by transferring the high electron (γ = 28,000 MHz/T) thermal polarization to the nuclear spins via microwave irradiation of the sample at high magnetic field and low temperature. A dissolution device is used to rapidly dissolve the frozen sample and consequently produces an injectable ``hyperpolarized'' liquid at physiologically-tolerable temperature. Here we report the construction and performance evaluation of a dissolution DNP hyperpolarizer at 6.4 T and 1.4 K using a continuous-flow cryostat. The solid and liquid-state 13C NMR signal enhancement levels of 13C acetate samples doped with trityl OX063 and 4-oxo-TEMPO free radicals will be discussed and compared with the results from the 3.35 T commercial hyperpolarizer. This work is supported by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

  1. A comparison of quantitative methods for clinical imaging with hyperpolarized 13C‐pyruvate

    PubMed Central

    Daniels, Charlie J.; McLean, Mary A.; Schulte, Rolf F.; Robb, Fraser J.; Gill, Andrew B.; McGlashan, Nicholas; Graves, Martin J.; Schwaiger, Markus; Lomas, David J.; Brindle, Kevin M.

    2016-01-01

    Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized 13C‐labelled molecules, such as the conversion of [1‐13C]pyruvate to [1‐13C]lactate, to be dynamically and non‐invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model‐free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two‐way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time‐to‐peak and the lactate‐to‐pyruvate area under the curve ratio were simple model‐free approaches that accurately represented the full reaction, with the time‐to‐peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized 13C data. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID:27414749

  2. Determination of glucan phosphorylation using heteronuclear 1H, 13C double and 1H, 13C, 31P triple-resonance NMR spectra.

    PubMed

    Schmieder, Peter; Nitschke, Felix; Steup, Martin; Mallow, Keven; Specker, Edgar

    2013-10-01

    Phosphorylation and dephosphorylation of starch and glycogen are important for their physicochemical properties and also their physiological functions. It is therefore desirable to reliably determine the phosphorylation sites. Heteronuclear multidimensional NMR-spectroscopy is in principle a straightforward analytical approach even for complex carbohydrate molecules. With heterogeneous samples from natural sources, however, the task becomes more difficult because a full assignment of the resonances of the carbohydrates is impossible to obtain. Here, we show that the combination of heteronuclear (1) H,(13) C and (1) H,(13) C,(31) P techniques and information derived from spectra of a set of reference compounds can lead to an unambiguous determination of the phosphorylation sites even in heterogeneous samples. PMID:23913630

  3. Determination of glucan phosphorylation using heteronuclear 1H, 13C double and 1H, 13C, 31P triple-resonance NMR spectra.

    PubMed

    Schmieder, Peter; Nitschke, Felix; Steup, Martin; Mallow, Keven; Specker, Edgar

    2013-10-01

    Phosphorylation and dephosphorylation of starch and glycogen are important for their physicochemical properties and also their physiological functions. It is therefore desirable to reliably determine the phosphorylation sites. Heteronuclear multidimensional NMR-spectroscopy is in principle a straightforward analytical approach even for complex carbohydrate molecules. With heterogeneous samples from natural sources, however, the task becomes more difficult because a full assignment of the resonances of the carbohydrates is impossible to obtain. Here, we show that the combination of heteronuclear (1) H,(13) C and (1) H,(13) C,(31) P techniques and information derived from spectra of a set of reference compounds can lead to an unambiguous determination of the phosphorylation sites even in heterogeneous samples.

  4. Whole-core analysis by sup 13 C NMR

    SciTech Connect

    Vinegar, H.J.; Tutunjian, P.N. ); Edelstein, W.A.; Roemer, P.B. )

    1991-06-01

    This paper reports on a whole-core nuclear magnetic resonance (NMR) system that was used to obtain natural abundance {sup 13}C spectra. The system enables rapid, nondestructive measurements of bulk volume of movable oil, aliphatic/aromatic ratio, oil viscosity, and organic vs. carbonate carbon. {sup 13}C NMR can be used in cores where the {sup 1}H NMR spectrum is too broad to resolve oil and water resonances separately. A 5 1/4-in. {sup 13}C/{sup 1}H NMR coil was installed on a General Electric (GE) CSI-2T NMR imager/spectrometer. With a 4-in.-OD whole core, good {sup 13}C signal/noise ratio (SNR) is obtained within minutes, while {sup 1}H spectra are obtained in seconds. NMR measurements have been made of the {sup 13}C and {sup 1}H density of crude oils with a wide range of API gravities. For light- and medium-gravity oils, the {sup 13}C and {sup 1}H signal per unit volume is constant within about 3.5%. For heavy crudes, the {sup 13}C and {sup 1}H density measured by NMR is reduced by the shortening of spin-spin relaxation time. {sup 13}C and {sup 1}H NMR spin-lattice relaxation times were measured on a suite of Cannon viscosity standards, crude oils (4 to 60{degrees} API), and alkanes (C{sub 5} through C{sub 16}) with viscosities at 77{degrees}F ranging from 0.5 cp to 2.5 {times} 10{sup 7} cp. The {sup 13}C and {sup 1}H relaxation times show a similar correlation with viscosity from which oil viscosity can be estimated accurately for viscosities up to 100 cp. The {sup 13}C surface relaxation rate for oils on water-wet rocks is very low. Nonproton decoupled {sup 13}C NMR is shown to be insensitive to kerogen; thus, {sup 13}C NMR measures only the movable hydrocarbon content of the cores. In carbonates, the {sup 13}C spectrum also contains a carbonate powder pattern useful in quantifying inorganic carbon and distinguishing organic from carbonate carbon.

  5. NMR structure analysis of uniformly 13C-labeled carbohydrates.

    PubMed

    Fontana, Carolina; Kovacs, Helena; Widmalm, Göran

    2014-06-01

    In this study, a set of nuclear magnetic resonance experiments, some of them commonly used in the study of (13)C-labeled proteins and/or nucleic acids, is applied for the structure determination of uniformly (13)C-enriched carbohydrates. Two model substances were employed: one compound of low molecular weight [(UL-(13)C)-sucrose, 342 Da] and one compound of medium molecular weight ((13)C-enriched O-antigenic polysaccharide isolated from Escherichia coli O142, ~10 kDa). The first step in this approach involves the assignment of the carbon resonances in each monosaccharide spin system using the anomeric carbon signal as the starting point. The (13)C resonances are traced using (13)C-(13)C correlations from homonuclear experiments, such as (H)CC-CT-COSY, (H)CC-NOESY, CC-CT-TOCSY and/or virtually decoupled (H)CC-TOCSY. Based on the assignment of the (13)C resonances, the (1)H chemical shifts are derived in a straightforward manner using one-bond (1)H-(13)C correlations from heteronuclear experiments (HC-CT-HSQC). In order to avoid the (1) J CC splitting of the (13)C resonances and to improve the resolution, either constant-time (CT) in the indirect dimension or virtual decoupling in the direct dimension were used. The monosaccharide sequence and linkage positions in oligosaccharides were determined using either (13)C or (1)H detected experiments, namely CC-CT-COSY, band-selective (H)CC-TOCSY, HC-CT-HSQC-NOESY or long-range HC-CT-HSQC. However, due to the short T2 relaxation time associated with larger polysaccharides, the sequential information in the O-antigen polysaccharide from E. coli O142 could only be elucidated using the (1)H-detected experiments. Exchanging protons of hydroxyl groups and N-acetyl amides in the (13)C-enriched polysaccharide were assigned by using HC-H2BC spectra. The assignment of the N-acetyl groups with (15)N at natural abundance was completed by using HN-SOFAST-HMQC, HNCA, HNCO and (13)C-detected (H)CACO spectra.

  6. NMR structure analysis of uniformly 13C-labeled carbohydrates.

    PubMed

    Fontana, Carolina; Kovacs, Helena; Widmalm, Göran

    2014-06-01

    In this study, a set of nuclear magnetic resonance experiments, some of them commonly used in the study of (13)C-labeled proteins and/or nucleic acids, is applied for the structure determination of uniformly (13)C-enriched carbohydrates. Two model substances were employed: one compound of low molecular weight [(UL-(13)C)-sucrose, 342 Da] and one compound of medium molecular weight ((13)C-enriched O-antigenic polysaccharide isolated from Escherichia coli O142, ~10 kDa). The first step in this approach involves the assignment of the carbon resonances in each monosaccharide spin system using the anomeric carbon signal as the starting point. The (13)C resonances are traced using (13)C-(13)C correlations from homonuclear experiments, such as (H)CC-CT-COSY, (H)CC-NOESY, CC-CT-TOCSY and/or virtually decoupled (H)CC-TOCSY. Based on the assignment of the (13)C resonances, the (1)H chemical shifts are derived in a straightforward manner using one-bond (1)H-(13)C correlations from heteronuclear experiments (HC-CT-HSQC). In order to avoid the (1) J CC splitting of the (13)C resonances and to improve the resolution, either constant-time (CT) in the indirect dimension or virtual decoupling in the direct dimension were used. The monosaccharide sequence and linkage positions in oligosaccharides were determined using either (13)C or (1)H detected experiments, namely CC-CT-COSY, band-selective (H)CC-TOCSY, HC-CT-HSQC-NOESY or long-range HC-CT-HSQC. However, due to the short T2 relaxation time associated with larger polysaccharides, the sequential information in the O-antigen polysaccharide from E. coli O142 could only be elucidated using the (1)H-detected experiments. Exchanging protons of hydroxyl groups and N-acetyl amides in the (13)C-enriched polysaccharide were assigned by using HC-H2BC spectra. The assignment of the N-acetyl groups with (15)N at natural abundance was completed by using HN-SOFAST-HMQC, HNCA, HNCO and (13)C-detected (H)CACO spectra. PMID:24771296

  7. Neuroprotective effects of caffeine in MPTP model of Parkinson's disease: A (13)C NMR study.

    PubMed

    Bagga, Puneet; Chugani, Anup N; Patel, Anant B

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons with an accompanying neuroinflammation leading to loss of dopamine in the basal ganglia. Caffeine, a well-known A2A receptor antagonist is reported to slow down the neuroinflammation caused by activated microglia and reduce the extracellular glutamate in the brain. In this study, we have evaluated the neuroprotective effect of caffeine in the MPTP model of PD by monitoring the region specific cerebral energy metabolism. Adult C57BL6 mice were treated with caffeine (30 mg/kg, i.p.) 30 min prior to MPTP (25 mg/kg, i.p.) administration for 8 days. The paw grip strength of mice was assessed in order to evaluate the motor function after various treatments. For metabolic studies, mice were infused with [1,6-(13)C2]glucose, and (13)C labeling of amino acids was monitored using ex vivo(1)H-[(13)C]-NMR spectroscopy. The paw grip strength was found to be reduced following the MPTP treatment. The caffeine pretreatment showed significant protection against the reduction of paw grip strength in MPTP treated mice. The levels of GABA and myo-inositol were found to be elevated in the striatum of MPTP treated mice. The (13)C labeling of GluC4, GABAC2 and GlnC4 from [1,6-(13)C2]glucose was decreased in the cerebral cortex, striatum, olfactory bulb, thalamus and cerebellum suggesting impaired glutamatergic and GABAergic neuronal activity and neurotransmission of the MPTP treated mice. Most interestingly, the pretreatment of caffeine maintained the (13)C labeling of amino acids to the control values in cortical, olfactory bulb and cerebellum regions while it partially retained in striatal and thalamic regions in MPTP treated mice. The pretreatment of caffeine provides a partial neuro-protection against severe striatal degeneration in the MPTP model of PD.

  8. Measuring Level Alignment at the Metal–Molecule Interface by In Situ Electrochemical 13C NMR

    SciTech Connect

    Li, Ying; Zelakiewicz, Brian S.; Allison, Thomas C.; Tong, Yu ye J.

    2015-03-16

    A new technique to measure energy-level alignment at a metal–molecule interface between the Fermi level of the metal and the frontier orbitals of the molecule is proposed and experimentally demonstrated. The method, which combines the electrochemistry of organo-ligand-stabilized Au nanoparticles with 13C NMR spectroscopy (i.e. in situ electrochemical NMR), enables measuring both occupied and unoccupied states.

  9. Biosynthetic uniform 13C,15N-labelling of zervamicin IIB. Complete 13C and 15N NMR assignment.

    PubMed

    Ovchinnikova, Tatyana V; Shenkarev, Zakhar O; Yakimenko, Zoya A; Svishcheva, Natalia V; Tagaev, Andrey A; Skladnev, Dmitry A; Arseniev, Alexander S

    2003-01-01

    Zervamicin IIB is a member of the alpha-aminoisobutyric acid containing peptaibol antibiotics. A new procedure for the biosynthetic preparation of the uniformly 13C- and 15N-enriched peptaibol is described This compound was isolated from the biomass of the fungus-producer Emericellopsis salmosynnemata strain 336 IMI 58330 obtained upon cultivation in the totally 13C, 15N-labelled complete medium. To prepare such a medium the autolysed biomass and the exopolysaccharides of the obligate methylotrophic bacterium Methylobacillus flagellatus KT were used. This microorganism was grown in totally 13C, 15N-labelled minimal medium containing 13C-methanol and 15N-ammonium chloride as the only carbon and nitrogen sources. Preliminary NMR spectroscopic analysis indicated a high extent of isotope incorporation (> 90%) and led to the complete 13C- and 15N-NMR assignment including the stereospecific assignment of Aib residues methyl groups. The observed pattern of the structurally important secondary chemical shifts of 1H(alpha), 13C=O and 13C(alpha) agrees well with the previously determined structure of zervamicin IIB in methanol solution. PMID:14658801

  10. Structure of B sub 13 C sub 2

    SciTech Connect

    Bylander, D.M.; Kleinman, L. )

    1991-01-15

    By comparing calculated lattice constants with x-ray data as well as by comparison of calculated free energies, we find that the correct structure of B{sub 13}C{sub 2} is B{sub 12}(CBC) rather than B{sub 11}C(BBC), as had been suggested. We also show that B{sub 12}C{sub 3} is stable against 13B{sub 12}C{sub 3}{r arrow}12B{sub 13}C{sub 2}+15C as is B{sub 13}C{sub 2} against 3B{sub 13}C{sub 2}{r arrow}2B{sub 12}C{sub 3}+15B.

  11. Anomalous 13C enrichment in modern marine organic carbon

    USGS Publications Warehouse

    Arthur, M.A.; Dean, W.E.; Claypool, G.E.

    1985-01-01

    Marine organic carbon is heavier isotopically (13C enriched) than most land-plant or terrestrial organic C1. Accordingly, ??13C values of organic C in modern marine sediments are routinely interpreted in terms of the relative proportions of marine and terrestrial sources of the preserved organic matter2,3. When independent geochemical techniques are used to evaluate the source of organic matter in Cretaceous or older rocks, those rocks containing mostly marine organic C are found typically to have lighter (more-negative) ??13C values than rocks containing mostly terrestrial organic C. Here we conclude that marine photosynthesis in mid-Cretaceous and earlier oceans generally resulted in a greater fractionation of C isotopes and produced organic C having lighter ??13C values. Modern marine photosynthesis may be occurring under unusual geological conditions (higher oceanic primary production rates, lower PCO2) that limit dissolved CO2 availability and minimize carbon isotope fractionation4. ?? 1985 Nature Publishing Group.

  12. Dihydroflavanonols from Cedrus deodara, A (13)C NMR study.

    PubMed

    Agrawal, P K; Agarwal, S K; Rastogi, R P; Osterdahal, B G

    1981-09-01

    High resolution (13)C NMR study of taxifolin, cedeodarin, cedrin and their methyl ethers allowed unambiguous placement of the Me in 5,7-dihydroxyflavanonol nucleus, besides providing other valuable information on the substitution pattern in the molecule.

  13. Double cross polarization /sup 13/C-NMR experiment in solid fossil fuel structure analysis

    SciTech Connect

    Hagaman, E.W.; Woody, M.C.

    1988-01-01

    The Double Cross Polarization /sup 13/C-MAS/NMR experiment has been used to derive a new operational classification of solid fossil fuels based on chemical reactivity. The method requires labeling reactive sites in the organic matrix with a magnetically active isotope not present in the precursor material, and using the local, isolated dipole-dipole interaction between this nucleus and nearby /sup 13/C nuclei to detect via cross polarization the carbon centers in the vicinity of the label. The technique is a marriage of chemistry and spectroscopy and the information content of the DCP spectra is defined by both partners. /sup 1/H-/sup 13/C-/sup 31/P DCP/MAS /sup 13/C-NMR spectroscopy has been used to statistically describe phenolic ortho-substitution patterns of coals via their aryl phosphinate or phosphate derivatives. In these applications of DCP NMR the new, detailed structure and/or reactivity information is realized by detection of carbon resonances one or more bonds removed from the reaction center, but in a volume element of intramolecular dimensions. To the extent that intermolecular contributions to the spectrum are detected, and not recognized as such, the structure/reactivity correlation is weakened. Direct substitution of phosphorus on the aromatic rings in the organic matrix of the coal is not readily accomplished. This environment potentially can be labeled with fluorine in a selective fashion using newly developed reagents. The possibility of determining the changes in average ring substitution patterns as a function of chemical treatment or coal diagenesis emerges. Recent developments in the field of DCP /sup 13/C NMR are presented.

  14. Pulsed polarization transfer for 13C NMR in solids

    NASA Astrophysics Data System (ADS)

    Bax, Ad; Szeverenyi, Nikolaus M.; Maciel, Gary E.

    A new pulsed polarization transfer experiment method is described for the polarization of 13C spins in a solid by magnetization transfer from protons. The method is directly analogous to the INEPT sequence for liquids introduced by Freeman and Morris. As polarization is transferred in PPT between individual 1H 13C pairs, rather than between spin reservoirs, different opportunities exist for structurally selective experiments. Results on p-diethoxybenzene and coronene are presented.

  15. Abundance anomaly of the 13C species of CCH

    NASA Astrophysics Data System (ADS)

    Sakai, N.; Saruwatari, O.; Sakai, T.; Takano, S.; Yamamoto, S.

    2010-03-01

    Aims: We have observed the N = 1-0 lines of CCH and its 13C isotopic species toward a cold dark cloud, TMC-1 and a star-forming region, L1527, to investigate the 13C abundances and formation pathways of CCH. Methods: The observations have been carried out with the IRAM 30 m telescope. Results: We have successfully detected the lines of 13CCH and C13CH toward the both sources and found a significant intensity difference between the two 13C isotopic species. The [C13CH] /[13CCH] abundance ratios are 1.6 ± 0.4 (3σ) and 1.6 ± 0.1 (3σ) for TMC-1 and L1527, respectively. The abundance difference between C13CH and 13CCH means that the two carbon atoms of CCH are not equivalent in the formation pathway. On the other hand, the [CCH]/[C13CH] and [CCH]/[13CCH] ratios are evaluated to be larger than 170 and 250 toward TMC-1, and to be larger than 80 and 135 toward L1527, respectively. Therefore, both of the 13C species are significantly diluted in comparison with the interstellar 12C/13C ratio of 60. The dilution is discussed in terms of a behavior of 13C in molecular clouds.

  16. Do twisted laser beams evoke nuclear hyperpolarization?

    PubMed

    Schmidt, A B; Andrews, D L; Rohrbach, A; Gohn-Kreuz, C; Shatokhin, V N; Kiselev, V G; Hennig, J; von Elverfeldt, D; Hövener, J-B

    2016-07-01

    The hyperpolarization of nuclear spins promises great advances in chemical analysis and medical diagnosis by substantially increasing the sensitivity of nuclear magnetic resonance (NMR). Current methods to produce a hyperpolarized sample, however, are arduous, time-consuming or costly and require elaborate equipment. Recently, a much simpler approach was introduced that holds the potential, if harnessed appropriately, to revolutionize the production of hyperpolarized spins. It was reported that high levels of hyperpolarization in nuclear spins can be created by irradiation with a laser beam carrying orbital angular momentum (twisted light). Aside from these initial reports however, no further experimental verification has been presented. In addition, this effect has so far evaded a critical theoretical examination. In this contribution, we present the first independent attempt to reproduce the effect. We exposed a sample of immersion oil or a fluorocarbon liquid that was placed within a low-field NMR spectrometer to Laguerre-Gaussian and Bessel laser beams at a wavelength of 514.5nm and various topological charges. We acquired (1)H and (19)F NMR free induction decay data, either during or alternating with the irradiation that was parallel to B0. We observed an irregular increase in NMR signal in experiments where the sample was exposed to beams with higher values of the topological charge. However, at no time did the effect reach statistical significance of 95%. Given the measured sensitivity of our setup, we estimate that a possible effect did not exceed a hyperpolarization (at 5mT) of 0.14-6%, depending on the assumed hyperpolarized volume. It should be noted though, that there were some differences between our setup and the previous implementation of the experiment, which may have inhibited the full incidence of this effect. To approach a theoretical description of this effect, we considered the interaction of an electron with a plane wave, which is known to be

  17. Do twisted laser beams evoke nuclear hyperpolarization?

    PubMed

    Schmidt, A B; Andrews, D L; Rohrbach, A; Gohn-Kreuz, C; Shatokhin, V N; Kiselev, V G; Hennig, J; von Elverfeldt, D; Hövener, J-B

    2016-07-01

    The hyperpolarization of nuclear spins promises great advances in chemical analysis and medical diagnosis by substantially increasing the sensitivity of nuclear magnetic resonance (NMR). Current methods to produce a hyperpolarized sample, however, are arduous, time-consuming or costly and require elaborate equipment. Recently, a much simpler approach was introduced that holds the potential, if harnessed appropriately, to revolutionize the production of hyperpolarized spins. It was reported that high levels of hyperpolarization in nuclear spins can be created by irradiation with a laser beam carrying orbital angular momentum (twisted light). Aside from these initial reports however, no further experimental verification has been presented. In addition, this effect has so far evaded a critical theoretical examination. In this contribution, we present the first independent attempt to reproduce the effect. We exposed a sample of immersion oil or a fluorocarbon liquid that was placed within a low-field NMR spectrometer to Laguerre-Gaussian and Bessel laser beams at a wavelength of 514.5nm and various topological charges. We acquired (1)H and (19)F NMR free induction decay data, either during or alternating with the irradiation that was parallel to B0. We observed an irregular increase in NMR signal in experiments where the sample was exposed to beams with higher values of the topological charge. However, at no time did the effect reach statistical significance of 95%. Given the measured sensitivity of our setup, we estimate that a possible effect did not exceed a hyperpolarization (at 5mT) of 0.14-6%, depending on the assumed hyperpolarized volume. It should be noted though, that there were some differences between our setup and the previous implementation of the experiment, which may have inhibited the full incidence of this effect. To approach a theoretical description of this effect, we considered the interaction of an electron with a plane wave, which is known to be

  18. Do twisted laser beams evoke nuclear hyperpolarization?

    NASA Astrophysics Data System (ADS)

    Schmidt, A. B.; Andrews, D. L.; Rohrbach, A.; Gohn-Kreuz, C.; Shatokhin, V. N.; Kiselev, V. G.; Hennig, J.; von Elverfeldt, D.; Hövener, J.-B.

    2016-07-01

    The hyperpolarization of nuclear spins promises great advances in chemical analysis and medical diagnosis by substantially increasing the sensitivity of nuclear magnetic resonance (NMR). Current methods to produce a hyperpolarized sample, however, are arduous, time-consuming or costly and require elaborate equipment. Recently, a much simpler approach was introduced that holds the potential, if harnessed appropriately, to revolutionize the production of hyperpolarized spins. It was reported that high levels of hyperpolarization in nuclear spins can be created by irradiation with a laser beam carrying orbital angular momentum (twisted light). Aside from these initial reports however, no further experimental verification has been presented. In addition, this effect has so far evaded a critical theoretical examination. In this contribution, we present the first independent attempt to reproduce the effect. We exposed a sample of immersion oil or a fluorocarbon liquid that was placed within a low-field NMR spectrometer to Laguerre-Gaussian and Bessel laser beams at a wavelength of 514.5 nm and various topological charges. We acquired 1H and 19F NMR free induction decay data, either during or alternating with the irradiation that was parallel to B0. We observed an irregular increase in NMR signal in experiments where the sample was exposed to beams with higher values of the topological charge. However, at no time did the effect reach statistical significance of 95%. Given the measured sensitivity of our setup, we estimate that a possible effect did not exceed a hyperpolarization (at 5 mT) of 0.14-6%, depending on the assumed hyperpolarized volume. It should be noted though, that there were some differences between our setup and the previous implementation of the experiment, which may have inhibited the full incidence of this effect. To approach a theoretical description of this effect, we considered the interaction of an electron with a plane wave, which is known to be

  19. 13C Tracking after 13CO2 Supply Revealed Diurnal Patterns of Wood Formation in Aspen.

    PubMed

    Mahboubi, Amir; Linden, Pernilla; Hedenström, Mattias; Moritz, Thomas; Niittylä, Totte

    2015-06-01

    Wood of trees is formed from carbon assimilated in the photosynthetic tissues. Determining the temporal dynamics of carbon assimilation, subsequent transport into developing wood, and incorporation to cell walls would further our understanding of wood formation in particular and tree growth in general. To investigate these questions, we designed a (13)CO2 labeling system to study carbon transport and incorporation to developing wood of hybrid aspen (Populus tremula × tremuloides). Tracking of (13)C incorporation to wood over a time course using nuclear magnetic resonance spectroscopy revealed diurnal patterns in wood cell wall biosynthesis. The dark period had a differential effect on (13)C incorporation to lignin and cell wall carbohydrates. No (13)C was incorporated into aromatic amino acids of cell wall proteins in the dark, suggesting that cell wall protein biosynthesis ceased during the night. The results show previously unrecognized temporal patterns in wood cell wall biosynthesis, suggest diurnal cycle as a possible cue in the regulation of carbon incorporation to wood, and establish a unique (13)C labeling method for the analysis of wood formation and secondary growth in trees.

  20. In vivo 13C NMR metabolite profiling: potential for understanding and assessing conifer seed quality.

    PubMed

    Terskikh, Victor V; Feurtado, J Allan; Borchardt, Shane; Giblin, Michael; Abrams, Suzanne R; Kermode, Allison R

    2005-08-01

    High-resolution 13C MAS NMR spectroscopy was used to profile a range of primary and secondary metabolites in vivo in intact whole seeds of eight different conifer species native to North America, including six of the Pinaceae family and two of the Cupressaceae family. In vivo 13C NMR provided information on the total seed oil content and fatty acid composition of the major storage lipids in a non-destructive manner. In addition, a number of monoterpenes were identified in the 13C NMR spectra of conifer seeds containing oleoresin; these compounds showed marked variability in individual seeds of Pacific silver fir within the same seed lot. In imbibed conifer seeds, the 13C NMR spectra showed the presence of considerable amounts of dissolved sucrose presumed to play a protective role in the desiccation-tolerance of seeds. The free amino acids arginine and asparagine, generated as a result of storage protein mobilization, were detected in vivo during seed germination and early seedling growth. The potential for NMR to profile metabolites in a non-destructive manner in single conifer seeds and seed populations is discussed. It is a powerful tool to evaluate seed quality because of its ability to assess reserve accumulation during seed development or at seed maturity; it can also be used to monitor reserve mobilization, which is critical for seedling emergence. PMID:15996983

  1. A 13C-NMR study of azacryptand complexes.

    PubMed

    Wild, Aljoscha A C; Fennell, Kevin; Morgan, Grace G; Hewage, Chandralal M; Malthouse, J Paul G

    2014-09-28

    An azacryptand has been solubilised in aqueous media containing 50% (v/v) dimethyl sulphoxide. (13)C-NMR has been used to determine how the azacryptand is affected by zinc binding at pH 10. Using (13)C-NMR and (13)C-enriched bicarbonate we have been able to observe the formation of 4 different carbamate derivatives of the azacryptand at pH 10. The azacryptand was shown to solubilise zinc or cadmium at alkaline pHs. Two moles of zinc are bound per mole of azacryptand and this complex binds 1 mole of carbonate. By replacing the zinc with cadmium-113 we have shown that the (13)C-NMR signal of the (13)C-enriched carbon of the bound carbonate is split into two triplets at 2.2 °C. This shows that two cadmium complexes are formed and in each of these complexes the carbonate group is bound by two magnetically equivalent metal ions. It also demonstrates that these cadmium complexes are not in fast exchange. From temperature studies we show that in the zinc complexes both complexes are in fast exchange with each other but are in slow exchange with free bicarbonate. HOESY is used to determine the position of the carbonate carbon in the complex. The solution and crystal structures of the zinc-carbonate-azacryptand complexes are compared. PMID:25091182

  2. 13C-based metabolic flux analysis: fundamentals and practice.

    PubMed

    Yang, Tae Hoon

    2013-01-01

    Isotope-based metabolic flux analysis is one of the emerging technologies applied to system level metabolic phenotype characterization in metabolic engineering. Among the developed approaches, (13)C-based metabolic flux analysis has been established as a standard tool and has been widely applied to quantitative pathway characterization of diverse biological systems. To implement (13)C-based metabolic flux analysis in practice, comprehending the underlying mathematical and computational modeling fundamentals is of importance along with carefully conducted experiments and analytical measurements. Such knowledge is also crucial when designing (13)C-labeling experiments and properly acquiring key data sets essential for in vivo flux analysis implementation. In this regard, the modeling fundamentals of (13)C-labeling systems and analytical data processing are the main topics we will deal with in this chapter. Along with this, the relevant numerical optimization techniques are addressed to help implementation of the entire computational procedures aiming at (13)C-based metabolic flux analysis in vivo.

  3. A scientific workflow framework for (13)C metabolic flux analysis.

    PubMed

    Dalman, Tolga; Wiechert, Wolfgang; Nöh, Katharina

    2016-08-20

    Metabolic flux analysis (MFA) with (13)C labeling data is a high-precision technique to quantify intracellular reaction rates (fluxes). One of the major challenges of (13)C MFA is the interactivity of the computational workflow according to which the fluxes are determined from the input data (metabolic network model, labeling data, and physiological rates). Here, the workflow assembly is inevitably determined by the scientist who has to consider interacting biological, experimental, and computational aspects. Decision-making is context dependent and requires expertise, rendering an automated evaluation process hardly possible. Here, we present a scientific workflow framework (SWF) for creating, executing, and controlling on demand (13)C MFA workflows. (13)C MFA-specific tools and libraries, such as the high-performance simulation toolbox 13CFLUX2, are wrapped as web services and thereby integrated into a service-oriented architecture. Besides workflow steering, the SWF features transparent provenance collection and enables full flexibility for ad hoc scripting solutions. To handle compute-intensive tasks, cloud computing is supported. We demonstrate how the challenges posed by (13)C MFA workflows can be solved with our approach on the basis of two proof-of-concept use cases.

  4. A scientific workflow framework for (13)C metabolic flux analysis.

    PubMed

    Dalman, Tolga; Wiechert, Wolfgang; Nöh, Katharina

    2016-08-20

    Metabolic flux analysis (MFA) with (13)C labeling data is a high-precision technique to quantify intracellular reaction rates (fluxes). One of the major challenges of (13)C MFA is the interactivity of the computational workflow according to which the fluxes are determined from the input data (metabolic network model, labeling data, and physiological rates). Here, the workflow assembly is inevitably determined by the scientist who has to consider interacting biological, experimental, and computational aspects. Decision-making is context dependent and requires expertise, rendering an automated evaluation process hardly possible. Here, we present a scientific workflow framework (SWF) for creating, executing, and controlling on demand (13)C MFA workflows. (13)C MFA-specific tools and libraries, such as the high-performance simulation toolbox 13CFLUX2, are wrapped as web services and thereby integrated into a service-oriented architecture. Besides workflow steering, the SWF features transparent provenance collection and enables full flexibility for ad hoc scripting solutions. To handle compute-intensive tasks, cloud computing is supported. We demonstrate how the challenges posed by (13)C MFA workflows can be solved with our approach on the basis of two proof-of-concept use cases. PMID:26721184

  5. Generating Super Stimulated-Echoes in MRI and their Application to Hyperpolarized C-13 Diffusion Metabolic Imaging

    PubMed Central

    Larson, Peder E. Z.; Kerr, Adam B.; Reed, Galen D.; Hurd, Ralph E.; Kurhanewicz, John; Pauly, John M.; Vigneron, Daniel B.

    2011-01-01

    Stimulated-echoes in MR can be used to provide high sensitivity to motion and flow, creating diffusion and perfusion weighting as well as T1 contrast, but conventional approaches inherently suffer from a 50% signal loss. The super stimulated-echo, which uses a specialized radiofrequency (RF) pulse train, has been proposed in order to improve the signal while preserving motion and T1 sensitivity. This paper presents a novel and straightforward method for designing the super stimulated-echo pulse train using inversion pulse design techniques. This method can also create adiabatic designs with an improved response to RF transmit field variations. The scheme was validated in phantom experiments and shown in vivo to improve SNR. We have applied a super stimulated-echo to metabolic MRI with hyperpolarized 13C-labeled molecules. For spectroscopic imaging of hyperpolarized agents, several repetition times are required but only a single stimulated-echo encoding is feasible, which can lead to unwanted motion blurring. To address this, a super stimulated-echo preparation scheme was used in which the diffusion weighting is terminated prior to the acquisition, and we observed a SNR increases of 60% in phantoms and 49% in vivo over a conventional stimulated-echo. Experiments following injection of hyperpolarized [1-13C]-pyruvate in murine transgenic cancer models have shown improved delineation for tumors since signals from metabolites within tumor tissues are retained while those from the vasculature are suppressed by the diffusion preparation scheme. PMID:22027366

  6. {sup 13}C relaxation in an RNA hairpin

    SciTech Connect

    King, G.C. |; Akratos, C.; Xi, Z.; Michnica, M.J.

    1994-12-01

    This initial survey of {sup 13}C relaxation in the {triangle}TAR RNA element has generated a number of interesting results that should prove generally useful for future studies. The most readily comparable study in the literature monitored {sup 13}C relaxation of the methyl groups from unusual bases in tRNA{sup Phe}. The study, which used T{sub 1} and NOE data only, reported order parameters for the methyl group axis that ranged between 0.51 and 0.97-a range similar to that observed here. However, they reported a breakdown of the standard order parameter analysis at higher (118-MHz {sup 13}C) frequencies, which should serve to emphasize the need for a thorough exploration of suitable motional models.

  7. 13C solid-state NMR chemical shift anisotropy analysis of the anomeric carbon in carbohydrates.

    PubMed

    Chen, Ying-Ying; Luo, Shun-Yuan; Hung, Shang-Cheng; Chan, Sunney I; Tzou, Der-Lii M

    2005-03-21

    (13)C NMR solid-state structural analysis of the anomeric center in carbohydrates was performed on six monosaccharides: glucose (Glc), mannose (Man), galactose (Gal), galactosamine hydrochloride (GalN), glucosamine hydrochloride (GlcN), and N-acetyl-glucosamine (GlcNAc). In the 1D (13)C cross-polarization/magic-angle spinning (CP/MAS) spectrum, the anomeric center C-1 of these carbohydrates revealed two well resolved resonances shifted by 3-5ppm, which were readily assigned to the anomeric alpha and beta forms. From this experiment, we also extracted the (13)C chemical shift anisotropy (CSA) tensor elements of the two forms from their spinning sideband intensities, respectively. It was found out that the chemical shift tensor for the alpha anomer was more axially symmetrical than that of the beta form. A strong linear correlation was obtained when the ratio of the axial asymmetry of the (13)C chemical shift tensors of the two anomeric forms was plotted in a semilogarithmic plot against the relative population of the two anomers. Finally, we applied REDOR spectroscopy to discern whether or not there were any differences in the sugar ring conformation between the anomers. Identical two-bond distances of 2.57A (2.48A) were deduced for both the alpha and beta forms in GlcNAc (GlcN), suggesting that the two anomers have essentially identical sugar ring scaffolds in these sugars. In light of these REDOR distance measurements and the strong correlation observed between the ratio of the axial asymmetry parameters of the (13)C chemical shift tensors and the relative population between the two anomeric forms, we concluded that the anomeric effect arises principally from interaction of the electron charge clouds between the C-1-O-5 and the C-1-O-1 bonds in these monosaccharides.

  8. Analysis of Hydroperoxides in Solid Polyethylene by MAS (13)C NMR and EPR

    SciTech Connect

    ASSINK,ROGER A.; CELINA,MATHIAS C.; DUNBAR,TIMOTHY D.; ALAM,TODD M.; CLOUGH,ROGER LEE; GILLEN,KENNETH T.

    1999-11-19

    {sup 13}C-enriched polyethylene was subjected to {gamma}-irradiation in the presence of air at 25 and 80 C for total doses ranging from 71 to 355 kGy. Significant quantities of hydroperoxides were detected in the 25 C irradiated sample by {sup 13}C magic angle spinning NMR spectroscopy. This method of detection was performed on the solid polymer and required no chemical derivatization or addition of solvent. The chemical stability and subsequent products of the hydroperoxide species were studied by annealing the irradiated samples in air at temperatures ranging from 22 to 110 C. A time-temperature superposition analysis provided an activation energy of 108 kJ/mol for the hydroperoxide decomposition process. The primary products of hydroperoxide decomposition were ketones and secondary alcohols with lesser amounts of acids and esters. EPR measurements suggest that the reactive hydroperoxide species reside in the amorphous phase of polyethylene, consistent with degradation occurring in the amorphous phase.

  9. NMR analyses of the cold cataract. III. /sup 13/C acrylamide studies

    SciTech Connect

    Lerman, S.; Megaw, J.M.; Moran, M.N.

    1985-10-01

    /sup 13/C-enriched acrylamide was employed to further delineate the action of this compound in preventing the cold cataract phenomenon when it is incorporated (in vitro) into young human and rabbit lenses. The extent of acrylamide incorporation, in the dark and with concurrent UV exposure, was monitored by /sup 13/C NMR spectroscopy. These studies provide further evidence that UV exposure causes permanent acrylamide photobinding within the lens. In such lenses, the gamma crystallin fraction of the soluble lens proteins is affected to the greatest extent. It appears to become aggregated and/or combined with the alpha and beta fractions resulting in an apparent loss of most of the gamma monomers. There is also an age-related effect with respect to the amount of acrylamide that can be incorporated into the lens. The decrease in acrylamide incorporation with age directly parallels the age-related decline in gamma crystallin levels.

  10. Phenyl galactopyranosides - 13C CPMAS NMR and conformational analysis using genetic algorithm

    NASA Astrophysics Data System (ADS)

    Wałejko, Piotr; Paradowska, Katarzyna; Bukowicki, Jarosław; Witkowski, Stanisław; Wawer, Iwona

    2015-08-01

    Structural analyses of four compounds (phenyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside (1), phenyl β-D-galactopyranoside (2), phenyl 2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside (3) and phenyl α-D-galactopyranoside (4)) have been performed using solid-state 13C MAS NMR spectroscopy and theoretical methods. Conformational analysis involved grid search and genetic algorithm (GAAGS). Low-energy conformers found by GAAGS were further optimized by DFT and chemical shifts were calculated using GIAO/DFT approach. 13C CPMAS NMR chemical shift of carbon C2 is indicative of the glycoside torsional angle. Separated or merged resonances of C2 and C6 suggest free rotation of phenyl ring in the solid phase.

  11. Room temperature hyperpolarization of nuclear spins in bulk

    PubMed Central

    Tateishi, Kenichiro; Negoro, Makoto; Nishida, Shinsuke; Kagawa, Akinori; Morita, Yasushi; Kitagawa, Masahiro

    2014-01-01

    Dynamic nuclear polarization (DNP), a means of transferring spin polarization from electrons to nuclei, can enhance the nuclear spin polarization (hence the NMR sensitivity) in bulk materials at most 660 times for 1H spins, using electron spins in thermal equilibrium as polarizing agents. By using electron spins in photo-excited triplet states instead, DNP can overcome the above limit. We demonstrate a 1H spin polarization of 34%, which gives an enhancement factor of 250,000 in 0.40 T, while maintaining a bulk sample (∼0.6 mg, ∼0.7 × 0.7 × 1 mm3) containing >1019 1H spins at room temperature. Room temperature hyperpolarization achieved with DNP using photo-excited triplet electrons has potentials to be applied to a wide range of fields, including NMR spectroscopy and MRI as well as fundamental physics. PMID:24821773

  12. Measuring doubly 13C-substituted ethane by mass spectrometry

    NASA Astrophysics Data System (ADS)

    Clog, M.; Ling, C.; Eiler, J. M.

    2012-12-01

    Ethane (C2H6) is present in non-negligible amounts in most natural gas reservoirs and is used to produce ethylene for petrochemical industries. It is one of the by-products of lipid metabolism and is the arguably simplest molecule that can manifest multiple 13C substitutions. There are several plausible controls on the relative abundances of 13C2H6 in natural gases: thermodynamically controlled homogeneous isotope exchange reactions analogous to those behind carbonate clumped isotope thermometry; inheritance from larger biomolecules that under thermal degradation to produce natural gas; mixing of natural gases that differ markedly in bulk isotopic composition; or combinations of these and/or other, less expected fractionations. There is little basis for predicting which of these will dominate in natural samples. Here, we focus on an analytical techniques that will provide the avenue for exploring these phenomena. The method is based on high-resolution gas source isotope ratio mass spectrometry, using the Thermo 253-Ultra (a new prototype mass spectrometer). This instrument achieves the mass resolution (M/Δ M) up to 27,000, permitting separation of the isobaric interferences of potential contaminants and isotopologues of an analtye or its fragments which share a cardinal mass. We present techniques to analyze several isotopologues of molecular and fragment ions of C2H6. The critical isobaric separations for our purposes include: discrimination of 13C2H6 from 13C12CDH5 at mass 32 and separation of the 13CH3 fragment from 12CH4 at mass 16, both requiring at least a mass resolution of 20000 to make an adequate measurement. Other obvious interferences are either cleanly separated (e.g., O2, O) or accounted for by peak-stripping (CH3OH on mass 32 and NH2 on mass 16). We focus on a set of measurements which constrain: the doubly-substituted isotopologue, 13C2H6, and the 13CH3/12CH3 ratio of the methyl fragment, which constrains the bulk δ 13C. Similar methods can be

  13. Milli-tesla NMR and spectrophotometry of liquids hyperpolarized by dissolution dynamic nuclear polarization

    NASA Astrophysics Data System (ADS)

    Zhu, Yue; Chen, Chia-Hsiu; Wilson, Zechariah; Savukov, Igor; Hilty, Christian

    2016-09-01

    Hyperpolarization methods offer a unique means of improving low signal strength obtained in low-field NMR. Here, simultaneous measurements of NMR at a field of 0.7 mT and laser optical absorption from samples hyperpolarized by dissolution dynamic nuclear polarization (D-DNP) are reported. The NMR measurement field closely corresponds to a typical field encountered during sample injection in a D-DNP experiment. The optical spectroscopy allows determination of the concentration of the free radical required for DNP. Correlation of radical concentration to NMR measurement of spin polarization and spin-lattice relaxation time allows determination of relaxivity and can be used for optimization of the D-DNP process. Further, the observation of the nuclear Overhauser effect originating from hyperpolarized spins is demonstrated. Signals from 1H and 19F in a mixture of trifluoroethanol and water are detected in a single spectrum, while different atoms of the same type are distinguished by J-coupling patterns. The resulting signal changes of individual peaks are indicative of molecular contact, suggesting a new application area of hyperpolarized low-field NMR for the determination of intermolecular interactions.

  14. Neutron Backgrounds: 13C({alpha}, n) etc

    SciTech Connect

    Mitsui, Tadao

    2005-09-08

    13C({alpha}, n) reaction is the main neutron source in an underground large-volume liquid-scintillator detector KamLAND. {alpha} sources, targets, cross sections, and neutron transport are studied to estimate the backgrounds of v-bare signal.

  15. 1H-detected 13C Photo-CIDNP as a Sensitivity Enhancement Tool in Solution NMR

    PubMed Central

    Lee, Jung Ho; Sekhar, Ashok; Cavagnero, Silvia

    2011-01-01

    NMR is a powerful yet intrinsically insensitive technique. The applicability of NMR to chemical and biological systems would be substantially extended by new approaches going beyond current signal-to-noise capabilities. Here, we exploit the large enhancements arising from 13C photo-chemically induced dynamic nuclear polarization (13C photo-CIDNP) in solution to improve biomolecular NMR sensitivity in the context of heteronuclear correlation spectroscopy. The 13C-PRINT pulse sequence presented here involves an initial 13C nuclear spin polarization via photo-CIDNP followed by conversion to antiphase coherence and transfer to 1H for detection. We observe substantial enhancements, up to ≫200-fold, relative to the dark (laser off) experiment. Resonances of both side-chain and backbone CH pairs are enhanced for the three aromatic residues Trp, His and Tyr and the Trp-containing σ32 peptide. The sensitivity of this experiment, defined as signal-to-noise per unit time (S/N)t, is unprecedented in the NMR polarization enhancement literature dealing with polypeptides in solution. Up to a 16-fold larger (S/N)t than the 1H-13C SE-HSQC reference sequence is achieved, for the σ32 peptide. This gain leads to a reduction in data collection time up to 256-fold, highlighting the advantages of 1H-detected 13C photo-CIDNP in solution NMR. PMID:21548581

  16. 13C and 15N CP/MAS, 1H-15N SCT CP/MAS and FTIR spectroscopy as tools for qualitative detection of the presence of zwitterionic and non-ionic forms of ansa-macrolide 3-formylrifamycin SV and its derivatives in solid state.

    PubMed

    Przybylski, Piotr; Pyta, Krystian; Klich, Katarzyna; Schilf, Wojciech; Kamieński, Bohdan

    2014-01-01

    (13)C, (15)N CP/MAS, including (1)H-(13)C and (1)H-(15)N short contact time CP/MAS experiments, and FTIR methods were applied for detailed structural characterization of ansa-macrolides as 3-formylrifamycin SV (1) and its derivatives (2-6) in crystal and in powder forms. Although HPLC chromatograms for 2/CH3 OH and 2/CH3 CCl3 were the same for rifampicin crystals dissolved in respective solvents, the UV-vis data recorded for them were different in 300-375 nm region. Detailed solid state (13)C and (15)N CP/MAS NMR and FTIR studies revealed that rifampicin (2), in contrast to 3-formylrifamycin SV (1) and its amino derivatives (3-6), can occur in pure non-ionic or zwitterionic forms in crystal and in pure these forms or a mixture of them in a powder. Multinuclear CP/MAS and FTIR studies demonstrated also that 3-6 derivatives were present exclusively in pure zwitterionic forms, both in powder and in crystal. On the basis of the solid state NMR and FTIR studies, two conformers of 3-formylrifamycin SV were detected in powder form due to the different orientations of carbonyl group of amide moiety. The PM6 molecular modeling at the semi-empirical level of theory, allowed visualization the most energetically favorable non-ionic and zwitterionic forms of 1-6 antibiotics, strongly stabilized via intramolecular H-bonds. FTIR studies indicated that the originally adopted forms of these type antibiotics in crystal or in powder are stable in standard laboratory conditions in time. The results presented point to the fact that because of a possible presence of two forms of rifampicin (compound 2), quantification of the content of this antibiotic in relevant pharmaceuticals needs caution. PMID:24347399

  17. 13C and 15N CP/MAS, 1H-15N SCT CP/MAS and FTIR spectroscopy as tools for qualitative detection of the presence of zwitterionic and non-ionic forms of ansa-macrolide 3-formylrifamycin SV and its derivatives in solid state.

    PubMed

    Przybylski, Piotr; Pyta, Krystian; Klich, Katarzyna; Schilf, Wojciech; Kamieński, Bohdan

    2014-01-01

    (13)C, (15)N CP/MAS, including (1)H-(13)C and (1)H-(15)N short contact time CP/MAS experiments, and FTIR methods were applied for detailed structural characterization of ansa-macrolides as 3-formylrifamycin SV (1) and its derivatives (2-6) in crystal and in powder forms. Although HPLC chromatograms for 2/CH3 OH and 2/CH3 CCl3 were the same for rifampicin crystals dissolved in respective solvents, the UV-vis data recorded for them were different in 300-375 nm region. Detailed solid state (13)C and (15)N CP/MAS NMR and FTIR studies revealed that rifampicin (2), in contrast to 3-formylrifamycin SV (1) and its amino derivatives (3-6), can occur in pure non-ionic or zwitterionic forms in crystal and in pure these forms or a mixture of them in a powder. Multinuclear CP/MAS and FTIR studies demonstrated also that 3-6 derivatives were present exclusively in pure zwitterionic forms, both in powder and in crystal. On the basis of the solid state NMR and FTIR studies, two conformers of 3-formylrifamycin SV were detected in powder form due to the different orientations of carbonyl group of amide moiety. The PM6 molecular modeling at the semi-empirical level of theory, allowed visualization the most energetically favorable non-ionic and zwitterionic forms of 1-6 antibiotics, strongly stabilized via intramolecular H-bonds. FTIR studies indicated that the originally adopted forms of these type antibiotics in crystal or in powder are stable in standard laboratory conditions in time. The results presented point to the fact that because of a possible presence of two forms of rifampicin (compound 2), quantification of the content of this antibiotic in relevant pharmaceuticals needs caution.

  18. Does the Shuram δ13C excursion record Ediacaran oxygenation?

    NASA Astrophysics Data System (ADS)

    Husson, J. M.; Maloof, A. C.; Schoene, B.; Higgins, J. A.

    2013-12-01

    The most negative carbon isotope excursion in Earth history is found in carbonate rocks of the Ediacaran Period (635-542 Ma). Known colloquially as the the 'Shuram' excursion, workers have long noted its tantalizing, broad concordance with the rise of abundant macro-scale fossils in the rock record, variously interpreted as animals, giant protists, macro-algae and lichen, and known as the 'Ediacaran Biota.' Thus, the Shuram excursion has been interpreted by many in the context of a dramatically changing redox state of the Ediacaran oceans - e.g., a result of methane cycling in a low O2 atmosphere, the final destruction of a large pool of recalcitrant dissolved organic carbon (DOC), and the step-wise oxidation of the Ediacaran oceans. More recently, diagenetic interpretations of the Shuram excursion - e.g. sedimentary in-growth of very δ13C depleted authigenic carbonates, meteoric alteration of Ediacaran carbonates, late-stage burial diagenesis - have challenged the various Ediacaran redox models. A rigorous geologic context is required to discriminate between these explanatory models, and determine whether the Shuram excursion can be used to evaluate terminal Neoproterozoic oxygenation. Here, we present chemo-stratigraphic data (δ13C, δ18O, δ44/42Ca and redox sensitive trace element abundances) from 12 measured sections of the Ediacaran-aged Wonoka Formation (Fm.) of South Australia that require a syn-depositional age for the extraordinary range of δ13C values (-12 to +4‰) observed in the formation. In some locations, the Wonoka Fm. is ~700 meters (m) of mixed shelf limestones and siliclastics that record the full 16 ‰ δ13C excursion in a remarkably consistent fashion across 100s of square kilometers of basin area. Fabric-altering diagenesis, where present, occurs at the sub-meter vertical scale, only results in sub-permil offsets in δ13C and cannot be used to explain the full δ13C excursion. In other places, the Wonoka Fm. is host to deep (1 km

  19. Use of Isotope Ratio Determination (13C/12C) to Assess the Production Method of Sparkling Wine.

    PubMed

    Rossier, Joël S; Maury, Valérie; Gaillard, Laetitia; Pfammatter, Elmar

    2016-01-01

    The production of a sparkling wine can be performed with different methods taking from a few weeks to several years, which often justifies a difference in added value for the consumer. This paper presents the use of isotope ratio δ(13)C measurements combined with physico-chemical analyses for the determination of mislabelling of sparkling wines produced by 'ancestral', 'traditional', 'closed tank' or 'gasification' methods. This work shows that the isotope composition of CO(2) compared with that of the corresponding dried residue of wine (DRW) can assess whether carbonate CO(2) in a sparkling wine originates from alcohol fermentation or from artificial gas addition. Isotopic ratios expressed as δ(13)C(CO2) and δ(13)C(DRW) measurements have been obtained for each wine by gasbench isotopic ratio mass spectroscopy and cavity ring down infrared spectroscopy, respectively. When the difference between δ(13)C(CO2) and δ(13)C(DRW) is negative, the presence of artificial CO(2) can be undoubtedly inferred, which would exclude the production methods 'ancestral' or 'traditional' for instance. Other parameters such as alcohol content, sugar and acid distributions are also important to complete the analytical panel to aid fraud tracking.

  20. Characterization of cerebral glutamine uptake from blood in the mouse brain: implications for metabolic modeling of 13C NMR data

    PubMed Central

    Bagga, Puneet; Behar, Kevin L; Mason, Graeme F; De Feyter, Henk M; Rothman, Douglas L; Patel, Anant B

    2014-01-01

    13C Nuclear Magnetic Resonance (NMR) studies of rodent and human brain using [1-13C]/[1,6-13C2]glucose as labeled substrate have consistently found a lower enrichment (∼25% to 30%) of glutamine-C4 compared with glutamate-C4 at isotopic steady state. The source of this isotope dilution has not been established experimentally but may potentially arise either from blood/brain exchange of glutamine or from metabolism of unlabeled substrates in astrocytes, where glutamine synthesis occurs. In this study, the contribution of the former was evaluated ex vivo using 1H-[13C]-NMR spectroscopy together with intravenous infusion of [U-13C5]glutamine for 3, 15, 30, and 60 minutes in mice. 13C labeling of brain glutamine was found to be saturated at plasma glutamine levels >1.0 mmol/L. Fitting a blood–astrocyte–neuron metabolic model to the 13C enrichment time courses of glutamate and glutamine yielded the value of glutamine influx, VGln(in), 0.036±0.002 μmol/g per minute for plasma glutamine of 1.8 mmol/L. For physiologic plasma glutamine level (∼0.6 mmol/L), VGln(in) would be ∼0.010 μmol/g per minute, which corresponds to ∼6% of the glutamine synthesis rate and rises to ∼11% for saturating blood glutamine concentrations. Thus, glutamine influx from blood contributes at most ∼20% to the dilution of astroglial glutamine-C4 consistently seen in metabolic studies using [1-13C]glucose. PMID:25074745

  1. The effect of exogenous substrate concentrations on true and apparent metabolism of hyperpolarized pyruvate in the isolated perfused lung.

    PubMed

    Kadlecek, Stephen; Shaghaghi, Hoora; Siddiqui, Sarmad; Profka, Harrilla; Pourfathi, Mehrdad; Rizi, Rahim

    2014-12-01

    Although relatively metabolically inactive, the lung has an important role in maintaining systemic glycolytic intermediate and cytosolic redox balance. Failure to perform this function appropriately may lead to lung disease progression, including systemic aspects of these disorders. In this study, we experimentally probe the response of the isolated, perfused organ to varying glycolytic intermediate (pyruvate and lactate) concentrations, and the effect on the apparent metabolism of hyperpolarized 1-(13)C pyruvate. Twenty-four separate conditions were studied, from sub-physiological to super-physiological concentrations of each metabolite. A three-compartment model is developed, which accurately matches the full range of experiments and includes a full account of evolution of agent concentration and polarization. The model is then refined using a series of approximations which are shown to be applicable to cases of physiological relevance, and which facilitate an intuitive understanding of the saturation and scaling behavior. Perturbations of the model assumptions are used to determine the sensitivity to input parameter estimates, and finally the model is used to examine the relationship between measurements accessible by NMR and the underlying physiological parameters of interest. Based on the observed scaling of lactate labeling with lactate and pyruvate concentrations, we conclude that the level of hyperpolarized lactate signal in the lung is primarily determined by the rate at which NAD(+) is reduced to NADH. Further, although weak dependences on other factors are predicted, the modeled NAD(+) reduction rate is largely governed by the intracellular lactate pool size. Conditions affecting the lactate pool can therefore be expected to display the highest contrast in hyperpolarized (13)C-pyruvate imaging. The work is intended to serve as a basis both to interpret the signal dynamics of hyperpolarized measurements in the normal lung and to understand the cause of

  2. Synthesis of [1-.sup.13C]pyruvic acid], [2-.sup.13C]pyruvic acid], [3-.sup.13C]pyruvic acid] and combinations thereof

    DOEpatents

    Martinez, Rodolfo A.; Unkefer, Clifford J.; Alvarez, Marc A.

    2009-09-01

    The present invention is directed to labeled compounds, of the formulae ##STR00001## wherein C* is each independently selected from the group consisting of .sup.13C and .sup.12C with the proviso that at least one C* is .sup.13C, each hydrogen of the methylene group can independently be either hydrogen or deuterium, the methyl group includes either zero or three deuterium atoms, Q is from the group of sulfide, sulfinyl, and sulfone, Z is an aryl group from the group of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure ##STR00002## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently from the group of hydrogen, a C.sub.1-C.sub.4 lower alkyl, a halogen, and an amino group from the group of NH.sub.2, NHR and NRR' where R and R' are each independently from the group of a C.sub.1-C.sub.4 lower alkyl, a phenyl, and an alkoxy group, and the methyl group can include either zero or three deuterium atoms.

  3. Synthesis of [1-.sup.13C]pyruvic acid], [2-.sup.13C]pyruvic acid], [3-.sup.13C]pyruvic acid] and combinations thereof

    DOEpatents

    Martinez, Rodolfo A. , Unkefer; Clifford J. , Alvarez; Marc A.

    2012-06-12

    The present invention is directed to the labeled compounds, ##STR00001## wherein C* is each either .sup.13C and .sup.12C where at least one C* is .sup.13C, each hydrogen of the methylene group is hydrogen or deuterium, the methyl group includes either zero or three deuterium atoms, Q is sulfide, sulfinyl, or sulfone, Z is an aryl group such as 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, or a phenyl group ##STR00002## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently either hydrogen, a C.sub.1-C.sub.4 lower alkyl, a halogen, and an amino group such as NH.sub.2, NHR and NRR' where R and R' are each independently either a C.sub.1-C.sub.4 lower alkyl, a phenyl, and an alkoxy group, and the methyl group can include either zero or three deuterium atoms. The present invention is also directed to the labeled compounds ##STR00003##

  4. Hyperpolarized Gas MRI: Technique and Applications

    PubMed Central

    McAdams, Holman P.; Kaushik, S. Sivaram; Driehuys, Bastiaan

    2015-01-01

    Synopsis Functional imaging today offers a rich world of information that is more sensitive to changes in lung structure and function than traditionally obtained pulmonary function tests. Hyperpolarized helium (3He) and xenon (129Xe) MR imaging of the lungs provided new sensitive contrast mechanisms to probe changes in pulmonary ventilation, microstructure and gas exchange. With the recent scarcity in the supply of 3He the field of hyperpolarized gas imaging shifted to the use of cheaper and naturally available 129Xe. Xenon is well tolerated and recent technical advances have ensured that the 129Xe image quality is on par with that of 3He. The added advantage of 129Xe is its solubility in pulmonary tissue, which allows exploring specific lung function characteristics involved in gas exchange and alveolar oxygenation. With a plethora of contrast mechanisms, hyperpolarized gases and 129Xe in particular, stands to be an excellent probe of pulmonary structure and function, and provide sensitive and non-invasive biomarkers for a wide variety of pulmonary diseases. PMID:25952516

  5. Improved CRDS δ13C Stability Through New Calibration Application For CO2 And CH4

    NASA Astrophysics Data System (ADS)

    Rella, Chris; Arata, Caleb; Saad, Nabil; Leggett, Graham; Miles, Natasha; Richardson, Scott; Davis, Ken

    2015-04-01

    Stable carbon isotope ratio measurements of CO2 and CH4 provide valuable insight into global and regional sources and sinks of the two most important greenhouse gases. Methodologies based on Cavity Ring-Down Spectroscopy (CRDS) have been developed and are capable of delivering δ13C measurements with a precision better than 0.12 permil for CO2 and 0.4 permil for CH4 (1 hour window, 5 minute average). Here we present a method to further improve this measurement stability. We have developed a two-point calibration method which corrects for δ13C drift due to a dependence on carbon species concentration. This method calibrates for both carbon species concentration as well as δ13C. In addition, we further demonstrate that this added stability is especially valuable when using carbon isotope data in linear regression models such as Keeling plots, where even small amounts of error can be magnified to give inconclusive results. Furthermore, we show how this method is used to validate multiple instruments simultaneously and can be used to create the standard samples needed for field calibrations.

  6. 13C NMR spectra of pyridine chalcone analogs

    NASA Astrophysics Data System (ADS)

    Jovanović, B. Ž.; Mišić-Vuković, M.; Marinković, A. D.; Csanádi, J.

    1999-05-01

    13C NMR spectra of two series of pyridine chalcone analogs were determined in deuterated dimethylsulphoxide (DMSO-d 6). It was established that these compounds were in more stable E-configurations except for the 4-pyridalacetophenone which was in Z-configuration. On the basis of the Hammett correlations of 13C NMR chemical shifts of the ethylenic bond carbon atoms and the σ values for the pyridine "aza" groups, the polarization of ethylenic bonds were discussed. It was established that the opposite effect of the pyridine substituents at the electronic density distribution in pyridalacetophenone and cinnamoylpyridines depends on its direct bonding to the ethylenic carbon or the transmission electronic effects via the carbonyl group, respectively.

  7. Experimental design principles for isotopically instationary 13C labeling experiments.

    PubMed

    Nöh, Katharina; Wiechert, Wolfgang

    2006-06-01

    13C metabolic flux analysis (MFA) is a well-established tool in Metabolic Engineering that found numerous applications in recent years. However, one strong limitation of the current method is the requirement of an-at least approximate-isotopic stationary state at sampling time. This requirement leads to a principle lower limit for the duration of a 13C labeling experiment. A new methodological development is based on repeated sampling during the instationary transient of the 13C labeling dynamics. The statistical and computational treatment of such instationary experiments is a completely new terrain. The computational effort is very high because large differential equations have to be solved and, moreover, the intracellular pool sizes play a significant role. For this reason, the present contribution works out principles and strategies for the experimental design of instationary experiments based on a simple example network. Hereby, the potential of isotopically instationary experiments is investigated in detail. Various statistical results on instationary flux identifiability are presented and possible pitfalls of experimental design are discussed. Finally, a framework for almost optimal experimental design of isotopically instationary experiments is proposed which provides a practical guideline for the analysis of large-scale networks.

  8. High-resolution spectroscopy of the {A}^{1}{\\rm{\\Pi }}(v^{\\prime} =0{--}10){--}{X}^{1}{{\\rm{\\Sigma }}}^{+}(v^{\\prime\\prime} =0) bands in 13C18O: term values, ro-vibrational oscillator strengths and Hönl–London corrections

    NASA Astrophysics Data System (ADS)

    Lemaire, J. L.; Eidelsberg, M.; Heays, A. N.; Gavilan, L.; Federman, S. R.; Stark, G.; Lyons, J. R.; de Oliveira, N.; Joyeux, D.

    2016-08-01

    Our knowledge of astronomical environments containing CO depends on accurate molecular data to reproduce and interpret observations. The constant improvement in UV space instrumentation, both in sensitivity and resolution, requires increasingly detailed laboratory data. Following a long-term experimental campaign at the SOLEIL Synchrotron facility, we have acquired complete datasets on the CO isotopologues in the vacuum ultraviolet. Absorption spectra were recorded using the Fourier-transform spectrometer installed on the DESIRS beamline, providing a resolving power R > 106 in the 8–12 eV range. Such resolution allows the analysis of individual line positions and strengths in electronic transitions and the location of perturbations. We continue our previous work on A–X bands of 12C16O and 13C16O, reporting here measurements for the 13C18O isotopologue. Gas column densities in the differentially-pumped system were calibrated using the B {}1{{{Σ }}}+–X {}1{{{Σ }}}+({v}\\prime =0,v\\prime\\prime =0) band. Absorption bands are analyzed by synthesizing line and band profiles and fitting them to measured spectra. New results for A {}1{{\\Pi }}({v}\\prime =0{--}10)–X {}1{{{Σ }}}+(v\\prime\\prime =0) bands include precise line assignments, term values, band-integrated oscillator strengths as well as individual ro-vibrational oscillator strengths and Hönl–London corrections. For ({v}\\prime =1) our results are compared with earlier studies. The interpretation of mixed perturbing bands, complementing an earlier study, is also presented as well as precise line assignments and term values for the B {}1{{{Σ }}}+–X {}1{{{Σ }}}+(0–0) band calibrator, and the nearby B–X (1–0) and C {}1{{{Σ }}}+–X {}1{{{Σ }}}+(0–0) bands.

  9. Two Techniques for Estimating Deglacial Mean-Ocean δ13 C Change from the Same Set of 493 Benthic δ13C Records

    NASA Astrophysics Data System (ADS)

    Peterson, C. D.; Lisiecki, L. E.; Gebbie, G.

    2013-12-01

    The crux of carbon redistribution over the deglaciation centers on the ocean, where the isotopic signature of terrestrial carbon (δ13C terrestrial carbon = -25‰) is observed as a 0.3-0.7‰ shift in benthic foraminiferal δ13C. Deglacial mean-ocean δ13C estimates vary due to different subsets of benthic δ13C data and different methods of weighting the mean δ13C by volume. Here, we present a detailed 1-to-1 comparison of two methods of calculating mean δ13C change and uncertainty estimates using the same set of 493 benthic Cibicidoides spp. δ13C measurements for the LGM and Late Holocene. The first method divides the ocean into 8 regions, and uses simple line fits to describe the distribution of δ13C data for each timeslice over 0.5-5 km depth. With these line fits, we estimate the δ13C value at 100-meter intervals and weight those estimates by the regional volume at each depth slice. The mean-ocean δ13C is the sum of these volume-weighted regional δ13C estimates and the uncertainty of these mean-ocean δ13C estimates is computed using Monte Carlo simulations. The whole-ocean δ13C change is estimated using extrapolated surface- and deep-ocean δ13C estimates, and an assumed δ13C value for the Southern Ocean. This method yields an estimated LGM-to-Holocene change of 0.38×0.07‰ for 0.5-5km and 0.35×0.16‰ for the whole ocean (Peterson et al., 2013, submitted to Paleoceanography). The second method reconstructs glacial and modern δ13C by combining the same data compilation as above with a steady-state ocean circulation model (Gebbie, 2013, submitted to Paleoceanography). The result is a tracer distribution on a 4-by-4 degree horizontal resolution grid with 23 vertical levels, and an estimate of the distribution's uncertainty that accounts for the distinct modern and glacial water-mass geometries. From both methods, we compare the regional δ13C estimates (0.5-5 km), surface δ13C estimates (0-0.5 km), deep δ13C estimates (>5 km), Southern Ocean

  10. Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization.

    PubMed

    Gajan, David; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Melzi, Roberto; van Kalkeren, Henri A; Veyre, Laurent; Thieuleux, Chloé; Conley, Matthew P; Grüning, Wolfram R; Schwarzwälder, Martin; Lesage, Anne; Copéret, Christophe; Bodenhausen, Geoffrey; Emsley, Lyndon; Jannin, Sami

    2014-10-14

    Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion. PMID:25267650

  11. Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization

    PubMed Central

    Gajan, David; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Melzi, Roberto; van Kalkeren, Henri A.; Veyre, Laurent; Thieuleux, Chloé; Conley, Matthew P.; Grüning, Wolfram R.; Schwarzwälder, Martin; Lesage, Anne; Copéret, Christophe; Bodenhausen, Geoffrey; Emsley, Lyndon; Jannin, Sami

    2014-01-01

    Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion. PMID:25267650

  12. An in vivo 13C magnetic resonance spectroscopic study of the relationship between diet and adipose tissue composition.

    PubMed

    Thomas, E L; Frost, G; Barnard, M L; Bryant, D J; Taylor-Robinson, S D; Simbrunner, J; Coutts, G A; Burl, M; Bloom, S R; Sales, K D; Bell, J D

    1996-02-01

    13C magnetic resonance spectroscopy (MRS) is a noninvasive technique used in the study of lipids. We applied 13C MRS to assess the effects of long-term dietary variation on adipose tissue composition in humans. In vivo 13C MRS was used to analyze the fatty acid composition of adipose tissue in 88 healthy volunteers with significantly different diets (38 vegans, 11 vegetarians, and 39 omnivores) assessed by analysis of dietary records. Results were compared with the serum lipid profile. 13C MRS revealed clear differences in the adipose tissue composition of vegans, which contained more unsaturated (P < 0.01) and fewer saturated fatty acids (P < 0.01) compared with omnivores and vegetarians. The vegan subjects had a significantly lower intake of saturated fatty acids and higher intake of polyunsaturated fatty acids than either the omnivore or the vegetarian groups (P < 0.01). These findings were associated with significantly lower levels of serum total cholesterol and low density lipoprotein-cholesterol in the vegan group compared with the omnivores. Our results demonstrate the use of 13C MRS for the noninvasive study of adipose tissue composition and its application to the study of the interaction between long-term dietary and metabolic risk factors in humans. PMID:8835401

  13. An in vivo 13C magnetic resonance spectroscopic study of the relationship between diet and adipose tissue composition.

    PubMed

    Thomas, E L; Frost, G; Barnard, M L; Bryant, D J; Taylor-Robinson, S D; Simbrunner, J; Coutts, G A; Burl, M; Bloom, S R; Sales, K D; Bell, J D

    1996-02-01

    13C magnetic resonance spectroscopy (MRS) is a noninvasive technique used in the study of lipids. We applied 13C MRS to assess the effects of long-term dietary variation on adipose tissue composition in humans. In vivo 13C MRS was used to analyze the fatty acid composition of adipose tissue in 88 healthy volunteers with significantly different diets (38 vegans, 11 vegetarians, and 39 omnivores) assessed by analysis of dietary records. Results were compared with the serum lipid profile. 13C MRS revealed clear differences in the adipose tissue composition of vegans, which contained more unsaturated (P < 0.01) and fewer saturated fatty acids (P < 0.01) compared with omnivores and vegetarians. The vegan subjects had a significantly lower intake of saturated fatty acids and higher intake of polyunsaturated fatty acids than either the omnivore or the vegetarian groups (P < 0.01). These findings were associated with significantly lower levels of serum total cholesterol and low density lipoprotein-cholesterol in the vegan group compared with the omnivores. Our results demonstrate the use of 13C MRS for the noninvasive study of adipose tissue composition and its application to the study of the interaction between long-term dietary and metabolic risk factors in humans.

  14. Unraveling the 13C NMR Chemical Shifts in Single-Walled Carbon Nanotubes: Dependence on Diameter and Electronic Structure

    SciTech Connect

    Engtrakul, C.; Irurzun, V. M.; Gjersing, E. L.; Holt, J. M.; Larsen, B. A.; Resasco, D. E.; Blackburn, J. L.

    2012-03-14

    The atomic specificity afforded by nuclear magnetic resonance (NMR) spectroscopy could enable detailed mechanistic information about single-walled carbon nanotube (SWCNT) functionalization as well as the noncovalent molecular interactions that dictate ground-state charge transfer and separation by electronic structure and diameter. However, to date, the polydispersity present in as-synthesized SWCNT populations has obscured the dependence of the SWCNT {sup 13}C chemical shift on intrinsic parameters such as diameter and electronic structure, meaning that no information is gleaned for specific SWCNTs with unique chiral indices. In this article, we utilize a combination of {sup 13}C labeling and density gradient ultracentrifugation (DGU) to produce an array of {sup 13}C-labeled SWCNT populations with varying diameter, electronic structure, and chiral angle. We find that the SWCNT isotropic {sup 13}C chemical shift decreases systematically with increasing diameter for semiconducting SWCNTs, in agreement with recent theoretical predictions that have heretofore gone unaddressed. Furthermore, we find that the {sup 13}C chemical shifts for small diameter metallic and semiconducting SWCNTs differ significantly, and that the full-width of the isotropic peak for metallic SWCNTs is much larger than that of semiconducting nanotubes, irrespective of diameter.

  15. Application of 13C Nuclear Magnetic Resonance To Elucidate the Unexpected Biosynthesis of Erythritol by Leuconostoc oenos

    PubMed Central

    Veiga-Da-Cunha, Maria; Firme, Paula; Romão, M. Vitória San; Santos, Helena

    1992-01-01

    Natural-abundance 13C nuclear magnetic resonance (13C-NMR) revealed the production of erythritol and glycerol by nongrowing cells of Leuconostoc oenos metabolizing glucose. The ratio of erythritol to glycerol was strongly influenced by the aeration conditions of the medium. The elucidation of the metabolic pathway responsible for erythritol production was achieved by 13C-NMR and 1H-NMR spectroscopy using specifically 13C-labelled d-glucose. The 1H-NMR spectrum of the cell supernatant resulting from the metabolism of [2-13C]glucose showed that only 75% of the glucose supplied was metabolized heterofermentatively and that the remaining 25% was channelled to the production of erythritol. The synthesis of this polyol resulted from the reduction of the C-4 moiety of the intermediate fructose 6-phosphate. Oxygen has an inhibitory effect on the production of erythritol by L. oenos. Preaeration of a suspension of nongrowing cells of L. oenos resulted in 30% less erythritol and in 70% more glycerol formed during the anaerobic metabolism of glucose. The anaerobic production of erythritol from glucose was also found in growing cultures of L. oenos, although to a smaller extent. PMID:16348738

  16. Study of Nuclear Structure of 13C and 20Ne by Low Energy Nuclear Reactions

    NASA Astrophysics Data System (ADS)

    Lombardo, I.; Campajola, L.; Dell'Aquila, D.; La Commara, M.; Ordine, A.; Rosato, E.; Spadaccini, G.; Vigilante, M.

    2014-12-01

    We report some recent experimental results on the spectroscopy of 13C and 20Ne nuclei by means of low energy nuclear reactions carried out with high resolution electrostatic accelerators. In the case of 13C we investigated the possible existence of a-cluster states above the a emission threshold by means of low energy elastic resonant scattering α+9Be in direct kinematics. Excitation functions show the presence of various resonances that have been reproduced by R-matrix fit. We studied also the structure of 20Ne by means of the 19F(p,α0) reaction at sub-barrier energies. The spectroscopy of 20Ne excited states in the region Ex ≈ 13.5-14.0 MeV can be probed by analyzing experimental angular distributions and excitation functions. This reaction plays an important role also in the CNOF cycle and is an important ingredient to describe hydrogen-induced destruction of fluorine in massive stars. For this reason we investigated the trend of S-factor, that has been compared with results previously reported in the literature.

  17. Hyperpolarization of 29Si by Resonant Nuclear Spin Transfer from Optically Hyperpolarized 31P Donors

    NASA Astrophysics Data System (ADS)

    Dluhy, Phillip; Salvail, Jeff; Saeedi, Kamyar; Thewalt, Mike; Simons, Stephanie

    2014-03-01

    Recent developments in nanomedicine have allowed nanoparticles of silicon containing hyperpolarized 29Si to be imaged in vivo using magnetic resonance imaging. The extremely long relaxation times and isotropy of the Si lattice make polarized 29Si isotopes ideal for these sorts of imaging methods. However, one of the major difficulties standing in the path of widespread adoption of these techniques is the slow rate at which the 29Si is hyperpolarized and the limited maximum hyperpolarization achievable. In this talk, I will describe an effective method for hyperpolarization of the 29Si isotopes using resonant optical pumping of the donor bound exciton transitions to polarize the 31P donor nuclei, and a choice of static magnetic field that conserves energy during spin flip flops between donor nuclear and 29Si spins to facilitate diffusion of this polarization. Using this method, we are able to polarize greater than 10% of the 29Si centers in 64 hours without seeing saturation of the 29Si polarization.

  18. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

    PubMed Central

    2011-01-01

    Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate). The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose phosphates in cytosol. In contrast

  19. Nuclear spin imaging with hyperpolarized nuclei created by brute force method

    NASA Astrophysics Data System (ADS)

    Tanaka, Masayoshi; Kunimatsu, Takayuki; Fujiwara, Mamoru; Kohri, Hideki; Ohta, Takeshi; Utsuro, Masahiko; Yosoi, Masaru; Ono, Satoshi; Fukuda, Kohji; Takamatsu, Kunihiko; Ueda, Kunihiro; Didelez, Jean-P.; Prossati, Giorgio; de Waard, Arlette

    2011-05-01

    We have been developing a polarized HD target for particle physics at the SPring-8 under the leadership of the RCNP, Osaka University for the past 5 years. Nuclear polarizaton is created by means of the brute force method which uses a high magnetic field (~17 T) and a low temperature (~ 10 mK). As one of the promising applications of the brute force method to life sciences we started a new project, "NSI" (Nuclear Spin Imaging), where hyperpolarized nuclei are used for the MRI (Magnetic Resonance Imaging). The candidate nuclei with spin ½hslash are 3He, 13C, 15N, 19F, 29Si, and 31P, which are important elements for the composition of the biomolecules. Since the NMR signals from these isotopes are enhanced by orders of magnitudes, the spacial resolution in the imaging would be much more improved compared to the practical MRI used so far. Another advantage of hyperpolarized MRI is that the MRI is basically free from the radiation, while the problems of radiation exposure caused by the X-ray CT or PET (Positron Emission Tomography) cannot be neglected. In fact, the risk of cancer for Japanese due to the radiation exposure through these diagnoses is exceptionally high among the advanced countries. As the first step of the NSI project, we are developing a system to produce hyperpolarized 3He gas for the diagnosis of serious lung diseases, for example, COPD (Chronic Obstructive Pulmonary Disease). The system employs the same 3He/4He dilution refrigerator and superconducting solenoidal coil as those used for the polarized HD target with some modification allowing the 3He Pomeranchuk cooling and the following rapid melting of the polarized solid 3He to avoid the depolarization. In this report, the present and future steps of our project will be outlined with some latest experimental results.

  20. The 13C nuclear magnetic resonance in graphite intercalation compounds

    NASA Technical Reports Server (NTRS)

    Tsang, T.; Resing, H. A.

    1985-01-01

    The (13)C NMR chemical shifts of graphite intercalation compounds were calculated. For acceptor types, the shifts come mainly from the paramagnetic (Ramsey) intra-atomic terms. They are related to the gross features of the two-dimensional band structures. The calculated anisotropy is about -140 ppm and is independent of the finer details such as charge transfer. For donor types, the carbon 2p pi orbitals are spin-polarized because of mixing with metal conduction electrons, thus there is an additional dipolar contribution which may be correlated with the electronic specific heat. The general agreement with experimental data is satisfactory.

  1. The delta 13C record of Devonian to Permian carbonates

    NASA Astrophysics Data System (ADS)

    Buggisch, W.

    2003-04-01

    A δ13Ccarb curve will be presented for samples spanning the time interval from the Silurian/Devonian to the Permian/Triassic boundary. Reliable data are usually based on analyses of brachiopod shells. Because of the huge reservoir of carbon in carbonates, also whole rock samples are suitable for stable carbon isotope analyses if they are not altered by meteoric water or by incorporation of re-oxidized organic carbon during diagenesis. There are several possibilities to test the quality of the data: (1) comparison of the δ13C record of whole rock samples with samples from brachiopod shells, (2) with the organic record, (3) analyses of the same time interval in different sections. If the same pattern of isotope data is observed in separa-ted palaeogeographic settings, it is probably caused by a change in the global carbon reservoir. Reliable δ13C data will be presented for the Devonian, Mississippian and Middle to Late Permian. During Pennsylvanian and Early Permian most carbonates were affected by meteoric diagenesis due to the large glacio-eustatic sea level changes of the Permo-Carboniferous glaciation. Long term variations (mean values for 10 Ma) are known from literature. Devonian δ13C values are about 0 to 2 ppm (V-PDB) they increase up to 5 to 6 ppm during the Mississippian - Pennsylvanian transition and drop sharply at the Permian Triassic boundary. The Devonian - Carboniferous trend is probably at least partly due to the evolution of land plants. Short term variations in the range of 0.1 to 1 Ma modify the long term trend significantly. Large positive excursions of δ13C up to 5 or 6 ppm are known from the Silurian - Devonian boundary and during the Middle Tournaisian of Laurentia and Europe. Many positive excursions of a magnitude of 2 to 3 ppm are observed, some are verified worldwide as for instance at the Frasnian - Famennian boundary which coincides with one of the largest extinction events in earth history. Short time variations in the isotopic

  2. S-Factor of radiative р 13C capture

    NASA Astrophysics Data System (ADS)

    Dubovichenko, S. B.

    2012-06-01

    The possibility of description of experimental data on the astrophysical S-factor of radiative р 13C capture within the framework of the potential cluster model with forbidden states is analyzed at energies in the range 0.03-0.8 MeV. It is demonstrated that the behavior of the astrophysical S-factor can be explained based on the Е1-transition to the bound 3 P 1 state of the 14N nucleus in the р 13С channel from the 3 S 1 wave of р 13С scattering at resonant energy of 0.55 MeV (l.s.).

  3. Trans and surface membrane bound zervamicin IIB: 13C-MAOSS-NMR at high spinning speed.

    PubMed

    Raap, J; Hollander, J; Ovchinnikova, T V; Swischeva, N V; Skladnev, D; Kiihne, S

    2006-08-01

    Interactions between (15)N-labelled peptides or proteins and lipids can be investigated using membranes aligned on a thin polymer film, which is rolled into a cylinder and inserted into the MAS-NMR rotor. This can be spun at high speed, which is often useful at high field strengths. Unfortuantely, substrate films like commercially available polycarbonate or PEEK produce severe overlap with peptide and protein signals in (13)C-MAOSS NMR spectra. We show that a simple house hold foil support allows clear observation of the carbonyl, aromatic and C(alpha) signals of peptides and proteins as well as the ester carbonyl and choline signals of phosphocholine lipids. The utility of the new substrate is validated in applications to the membrane active peptide zervamicin IIB. The stability and macroscopic ordering of thin PC10 bilayers was compared with that of thicker POPC bilayers, both supported on the household foil. Sidebands in the (31)P-spectra showed a high degree of alignment of both the supported POPC and PC10 lipid molecules. Compared with POPC, the PC10 lipids are slightly more disordered, most likely due to the increased mobilities of the shorter lipid molecules. This mobility prevents PC10 from forming stable vesicles for MAS studies. The (13)C-peptide peaks were selectively detected in a (13)C-detected (1)H-spin diffusion experiment. Qualitative analysis of build-up curves obtained for different mixing times allowed the transmembrane peptide in PC10 to be distinguished from the surface bound topology in POPC. The (13)C-MAOSS results thus independently confirms previous findings from (15)N spectroscopy [Bechinger, B., Skladnev, D.A., Ogrel, A., Li, X., Rogozhkina, E.V., Ovchinnikova, T.V., O'Neil, J.D.J. and Raap, J. (2001) Biochemistry, 40, 9428-9437]. In summary, application of house hold foil opens the possibility of measuring high resolution (13)C-NMR spectra of peptides and proteins in well ordered membranes, which are required to determine the secondary

  4. Detection of Reduced GABA Synthesis Following Inhibition of GABA Transaminase Using in Vivo Magnetic Resonance Signal of [13C]GABA C1

    PubMed Central

    Yang, Jehoon; Johnson, Christopher; Shen, Jun

    2009-01-01

    Previous in vivo magnetic resonance spectroscopy (MRS) studies of gamma-aminobutyric acid (GABA) synthesis have relied on 13C label incorporation into GABA C2 from [1-13C] or [1,6-13C2]glucose. In this study, the [13C]GABA C1 signal at 182.3 ppm in the carboxylic/amide spectral region of localized in vivo 13C spectra was detected. GABA-transaminase of rat brain was inhibited by administration of gabaculine after pre-labeling of GABA C1 and its metabolic precursors with exogenous [2,5-13C2]glucose. A subsequent isotope chase experiment was performed by infusing unlabeled glucose, which revealed a markedly slow change in the labeling of GABA C1 accompanying the blockade of the GABA shunt. This slow labeling of GABA at elevated GABA concentration was attributed to the relatively small intercompartmental GABA-glutamine cycling flux that constitutes the main route of 13C label loss during the isotope chase. Because this study showed that using low RF power broadband stochastic proton decoupling is feasible at very high field strength, it has important implications for the development of carboxylic/amide 13C MRS methods to study brain metabolism and neurotransmission in human subjects at high magnetic fields. PMID:19540876

  5. Design of a sup 13 C (1H) RF probe for monitoring the in vivo metabolism of (1- sup 13 C)glucose in primate brain

    SciTech Connect

    Hammer, B.E.; Sacks, W.; Bigler, R.E.; Hennessy, M.J.; Sacks, S.; Fleischer, A.; Zanzonico, P.B. )

    1990-01-01

    The design of an RF probe suitable for obtaining proton-decoupled {sup 13}C spectra from a subhuman primate brain is described. Two orthogonal saddle coils, one tuned to the resonant frequency of {sup 13}C and the other to the resonant frequency of 1H, were used to monitor the in vivo metabolism of (1-{sup 13}C)glucose in rhesus monkey brain at 2.1 T. Difference spectra showed the appearance of {sup 13}C-enriched glutamate and glutamine 30 to 40 min after a bolus injection of (1-{sup 13}C)glucose.

  6. Analysis of dynamics and mechanism of ligand binding to Artocarpus integrifolia agglutinin. A 13C and 19F NMR study.

    PubMed

    Krishna Sastry, M V; Swamy, M J; Surolia, A

    1988-10-15

    Binding of 13C-labeled N-acetylgalactosamine (13C-GalNAc) and N-trifluoroacetylgalactosamine (19F-GalNAc) to Artocarpus integrifolia agglutinin has been studied using 13C and 19F nuclear magnetic resonance spectroscopy, respectively. Binding of these saccharides resulted in broadening of the resonances, and no change in chemical shift was observed, suggesting that the alpha- and beta-anomers of 13C-GalNAc and 19F-GalNAc experience a magnetically equivalent environment in the lectin combining site. The alpha- and beta-anomers of 13C-GalNAc and 19F-GalNAc were found to be in slow exchange between free and protein bound states. Binding of 13C-GalNAc was studied as a function of temperature. From the temperature dependence of the line broadening, the thermodynamic and kinetic parameters were evaluated. The association rate constants obtained for the alpha-anomers of 13C-GalNAc and 19F-GalNAc (k+1 = 1.01 x 10(5) M-1.s-1 and 0.698 x 10(5) M-1.s-1, respectively) are in close agreement with those obtained for the corresponding beta-anomers (k+1 = 0.95 x 10(5) M-1.s-1 and 0.65 x 10(5) M-1.s-1, respectively), suggesting that the two anomers bind to the lectin by a similar mechanism. In addition these values are several orders of magnitude slower than those obtained for diffusion controlled processes. The dissociation rate constants obtained are 49.9, 56.9, 42, and 43 s-1, respectively, for the alpha- and beta-anomers of 13C-GalNAc and 19F-GalNAc. A two-step mechanism has been proposed for the interaction of 13C-GalNAc and 19F-GalNAc with A. integrifolia lectin in view of the slow association rates and high activation entropies. The thermodynamic parameters obtained for the association and dissociation reactions suggest that the binding process is entropically favored and that there is a small enthalpic contribution.

  7. 13C NMR and isotopic (δ13C) investigations on modern vegetation samples: a tool to understand the soil organic matter degradation dynamics and preferences

    NASA Astrophysics Data System (ADS)

    Rakshit, Subhadeep; Sanyal, Prasanta; Vardhan Gaur, Harsh

    2015-04-01

    Soil organic carbon, one of the largest reservoirs of carbon, is a heterogeneous mixture of organic compounds with dominant contribution derived from decomposition of plants in various stages. Although general ideas about the processes and mechanisms of soil organic matter (SOM) degradation have been developed, a very few study has linked the SOM with its parent material. In this study we aim to generate reference data set of functional groups from modern vegetation samples (C3 and C4plants) to better understand the degradation dynamics and preferences. The carbon functional groups from modern vegetation samples (eight C3 and nine C4 plants collected from Mohanpur, Nadia, West Bengal, India) were examined by solid state 13C CPMAS NMR spectroscopy. Additionally, isotopic investigations (δ13C) has also been carried out on the modern vegetation samples to understand the relationship of bulk isotopic values to the concentration of functional groups. The major functional groups (alkyl C, O-alkyl C, aromatic C, carbonyl C and aldehyde/ketone) of modern vegetation samples form 16%, 65%, 5%, 14% and 1% respectively in C3 plants. Considerable differences has been observed for C4 plants with average values of alkyl C, O-alkyl C, aromatic C, carbonyl C and aldehyde/ketone are 8%, 83%, 3%, 5% and 1% respectively. The concentration of functional groups from the modern vegetational samples can be considered as reference scale to compare with the 13C NMR data derived from the different soil horizons to understand the SOM degradation dynamics. The δ13CV PDB values of modern vegetation samples plotted against the individual concentration of functional groups shows significant correlation in C4 plants, whereas a lack in correlation has been observed for C3 plants. We assume this difference in relationship of δ13CV PDB values with functional groups of C3 and C4plants can be due to the differences in photosynthesis pathways, the fractionation of CO2 and accumulation of the products

  8. 13C and 1H Nuclear Magnetic Resonance Study of Glycogen Futile Cycling in Strains of the Genus Fibrobacter

    PubMed Central

    Matheron, Christelle; Delort, Anne-Marie; Gaudet, Geneviève; Forano, Evelyne; Liptaj, Tibor

    1998-01-01

    We investigated the carbon metabolism of three strains of Fibrobacter succinogenes and one strain of Fibrobacter intestinalis. The four strains produced the same amounts of the metabolites succinate, acetate, and formate in approximately the same ratio (3.7/1/0.3). The four strains similarly stored glycogen during all growth phases, and the glycogen-to-protein ratio was close to 0.6 during the exponential growth phase. 13C nuclear magnetic resonance (NMR) analysis of [1-13C]glucose utilization by resting cells of the four strains revealed a reversal of glycolysis at the triose phosphate level and the same metabolic pathways. Glycogen futile cycling was demonstrated by 13C NMR by following the simultaneous metabolism of labeled [13C]glycogen and exogenous unlabeled glucose. The isotopic dilutions of the CH2 of succinate and the CH3 of acetate when the resting cells were metabolizing [1-13C]glucose and unlabeled glycogen were precisely quantified by using 13C-filtered spin-echo difference 1H NMR spectroscopy. The measured isotopic dilutions were not the same for succinate and acetate; in the case of succinate, the dilutions reflected only the contribution of glycogen futile cycling, while in the case of acetate, another mechanism was also involved. Results obtained in complementary experiments are consistent with reversal of the succinate synthesis pathway. Our results indicated that for all of the strains, from 12 to 16% of the glucose entering the metabolic pathway originated from prestored glycogen. Although genetically diverse, the four Fibrobacter strains studied had very similar carbon metabolism characteristics. PMID:12033219

  9. NMR study of Met-1 human Angiogenin: (1)H, (13)C, (15)N backbone and side-chain resonance assignment.

    PubMed

    Tsika, Aikaterini C; Chatzileontiadou, Demetra S M; Leonidas, Demetres D; Spyroulias, Georgios A

    2016-10-01

    Here, we report the high yield expression and preliminary structural analysis via solution hetero-nuclear NMR spectroscopy of the recombinant Met-1 human Angiogenin. The analysis reveals a well folded as well as, a monomeric polypeptide. Τhe sequence-specific assignment of its (1)H, (15)N and (13)C resonances at high percentage was obtained. Also, using TALOS+ its secondary structure elements were determined.

  10. Σ production from targets of ^4He and ^13C

    NASA Astrophysics Data System (ADS)

    Chrien, R. E.

    1996-10-01

    One of the abiding issues in hypernuclear research has been the question of the formation of nuclear bound states incorporating the Σ-hyperon. The recent increases in beam intensity at the Brookhaven AGS have enabled us to obtain a high statistics study on the production of Σ-hyperons on a ^4He target. Earlier research using stopped kaons at KEK indicated the presence of structure in the (K^-,π^-) reaction, and led to the postulate of a Σ bound state. That structure has now been definitely confirmed in the in-flight kaon experiment at the LESB2 beam line and Moby-Dick spectrometer. An improved measurement of the binding energy of the presumed state will be reported, together with a production cross section. In addition, both (K^-,π^-) and (K^-,π^+) reactions on ^13C have been studied and will be compared to similar measurements on ^9Be.

  11. Millimeter and submillimeter wave spectra of 13C-glycolaldehydes

    NASA Astrophysics Data System (ADS)

    Haykal, I.; Motiyenko, R. A.; Margulès, L.; Huet, T. R.

    2013-01-01

    Context. Glycolaldehyde (CH2OHCHO) is the simplest sugar and an important intermediate in the path toward forming more complex biologically relevant molecules. Astronomical surveys of interstellar molecules, such as those available with the very sensitive ALMA telescope, require preliminary laboratory investigations of the microwave and submillimeter-wave spectra of molecular species including new isotopologs - to identify these in the interstellar media. Aims: To achieve the detection of the 13C isotopologs of glycolaldehyde in the interstellar medium, their rotational spectra in the millimeter and submillimeter-wave regions were studied. Methods: The spectra of 13CH2OHCHO and CH2OH13CHO were recorded in the 150-945 GHz spectral range in the laboratory using a solid-state submillimeter-wave spectrometer in Lille. The observed line frequencies were measured with an accuracy of 30 kHz up to 700 GHz and of 50 kHz above 700 GHz. We analyzed the spectra with a standard Watson Hamiltonian. Results: About 10 000 new lines were identified for each isotopolog. The spectroscopic parameters were determined for the ground- and the three lowest vibrational states up to 945 and 630 GHz. Previous microwave assignments of 13CH2OHCHO were not confirmed. Conclusions: The provided line-lists and sets of molecular parameters meet the needs for a first astrophysical search of 13C-glycolaldehydes. Full Tables 3 and 4 are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/549/A96

  12. Approaches to studies on neuronal/glial relationships by 13C-MRS analysis.

    PubMed

    Taylor, A; McLean, M; Morris, P; Bachelard, H

    1996-01-01

    The use of different 13C-labelled precursors alone or in combination ([1-13C]glucose, [2-13C]glucose, [1-13C]acetate, [2-13C]acetate and [1,2-13C2]acetate) to study neuronal/glial metabolic relationships by MRS is discussed. Glutamine and citrate resonances represent glial metabolism if a combination of [1-13C]glucose + [2-13C]acetate is used, but only for short time periods. A combination of [2-13C]glucose + [2-13C]acetate will label -COO- groups from glucose and -CH2 groups from acetate, respectively, which distinguish well in theory. However, this approach is severely limited by the long T1S of -COO- groups and low S/N. Contributions of the anaplerotic pathway can be assessed using [2-13C]glucose, but again can be limited by the long T1S of -COO- groups. Labelling of glycerol-3-phosphate (believed to be produced in glia) from [1-13C]glucose is difficult to see under normal conditions but has proved useful in, e.g., hypoxia. We believe the most promising approach is the use of [1-13C] glucose with [1,2-13C2]acetate, by analysis of the multiplets ('isotopomers') of the amino acid resonances.

  13. 1H-NMR and 13C-NMR lipid profiles of human renal tissues.

    PubMed

    Tugnoli, V; Bottura, G; Fini, G; Reggiani, A; Tinti, A; Trinchero, A; Tosi, M R

    2003-01-01

    Lipids from human renal tissues are studied by means of (1)H- and (13)C-NMR spectroscopy. The total lipid fractions obtained from healthy kidneys, malignant renal cell carcinomas, and benign oncocytomas are characterized and analyzed to elucidate the main differences between the functional and neoplastic tissues. In all cases the lipid components are well identified. The healthy kidney is characterized by high amounts of triglycerides and the presence of cholesterol in its free form. On the contrary, renal cell carcinomas contain high amounts of cholesterol that are almost completely esterified as oleate, suggesting an intracellular localization of the cholesteryl esters synthesis. Cholesteryl esters are considered markers of renal cell carcinomas, thus supporting recent theories that these compounds play a leading role in cell proliferation. Oncocytomas are particularly rich in phosphatidylcholine and, analogous to the healthy kidney, are completely lacking in cholesteryl esters. Healthy kidneys and oncocytomas appear to have other similarities if compared with renal cell carcinomas: a very high fatty acyl/cholesterol ratio, the presence of dolichols, and a higher grade of unsaturation. The (13)C data suggest a new method for the direct evaluation of the saturated/unsaturated fatty acyl ratio.

  14. Incomplete fusion reactions at low energies in 13C+169Tm system

    NASA Astrophysics Data System (ADS)

    Sharma, Vijay R.; Yadav, Abhishek; Singh, Devendra P.; Singh, Pushpendra P.; Bala, Indu; Kumar, R.; Sharma, M. K.; Gupta, S.; Murlithar, S.; Singh, R. P.; Singh, B. P.; Prasad, R.

    2014-03-01

    Aiming to investigate the incomplete fusion processes at low projectile energies, experiments have been carried out for the 13C + 169Tm system at ≈ 4-7 MeV/A. Excitation functions for several heavy residues likely to be populated via complete and incomplete fusion processes have been measured using heavy recoil residue catcher technique followed by γ- ray spectroscopy. The measured cross-sections for the complete fusion (xn and pxn) channels are compared with the statistical model code PACE4, consistently using the same set of parameters. The complete fusion channels are found to be consistent with the model calculations. However, the cross-sections for all the measured α-emitting channels are found to be significantly enhanced over the calculations. Analysis of data indicate a significant fraction of incomplete fusion even at energies as low as 17% above barrier. The present results are discussed in light of the Morgenstern's systematics. Incomplete fusion strength function is found to be relatively large for alpha cluster projectile i.e. for 12C as compared to one neutron excess 13C projectile.

  15. Hyperpolarized 129Xe MRI of the Human Lung

    PubMed Central

    Mugler, John P.; Altes, Talissa A.

    2012-01-01

    By permitting direct visualization of the airspaces of the lung, MR imaging using hyperpolarized gases provides unique strategies for evaluating pulmonary structure and function. Although the vast majority of research in humans has been performed using hyperpolarized 3He, recent contraction in the supply of 3He and consequent increases in price have turned attention to the alternative agent, hyperpolarized 129Xe. Compared to 3He, 129Xe yields reduced signal due to its smaller magnetic moment. Nonetheless, taking advantage of advances in gas-polarization technology, recent studies in humans using techniques for measuring ventilation, diffusion, and partial pressure of oxygen have demonstrated results for hyperpolarized 129Xe comparable to those previously demonstrated using hyperpolarized 3He. In addition, xenon has the advantage of readily dissolving in lung tissue and blood following inhalation, which makes hyperpolarized 129Xe particularly attractive for exploring certain characteristics of lung function, such as gas exchange and uptake, which cannot be accessed using 3He. Preliminary results from methods for imaging 129Xe dissolved in the human lung suggest that these approaches will provide new opportunities for quantifying relationships among gas delivery, exchange, and transport, and thus show substantial potential to broaden our understanding of lung disease. Finally, recent changes in the commercial landscape of the hyperpolarized-gas field now make it possible for this innovative technology to move beyond the research lab. PMID:23355432

  16. The First in Vivo Observation of 13C- 15N Coupling in Mammalian Brain

    NASA Astrophysics Data System (ADS)

    Kanamori, Keiko; Ross, Brian D.

    2001-12-01

    [5-13C,15N]Glutamine, with 1J(13C-15N) of 16 Hz, was observed in vivo in the brain of spontaneously breathing rats by 13C MRS at 4.7 T. The brain [5-13C]glutamine peak consisted of the doublet from [5-13C,15N]glutamine and the center [5-13C,14N]glutamine peak, resulting in an apparent triplet with a separation of 8 Hz. The time course of formation of brain [5-13C,15N]glutamine was monitored in vivo with a time resolution of 20-35 min. This [5-13C,15N]glutamine was formed by glial uptake of released neurotransmitter [5-13C]glutamate and its reaction with 15NH3 catalyzed by the glia-specific glutamine synthetase. The neurotransmitter glutamate C5 was selectively13C-enriched by intravenous [2,5-13C]glucose infusion to 13C-label whole-brain glutamate C5, followed by [12C]glucose infusion to chase 13C from the small and rapidly turning-over glial glutamate pool, leaving 13C mainly in the neurotransmitter [5-13C]glutamate pool, which is sequestered in vesicles until release. Hence, the observed [5-13C,15N]glutamine arises from a coupling between 13C of neuronal origin and 15N of glial origin. Measurement of the rate of brain [5-13C,15N]glutamine formation provides a novel noninvasive method of studying the kinetics of neurotransmitter uptake into glia in vivo, a process that is crucial for protecting the brain from glutamate excitotoxicity.

  17. Microwave spectra for the three 13C1 isotopologues of propene and new rotational constants for propene and its 13C1 isotopologues

    NASA Astrophysics Data System (ADS)

    Craig, Norman C.; Groner, Peter; Conrad, Andrew R.; Gurusinghe, Ranil; Tubergen, Michael J.

    2016-10-01

    New measurements of microwave lines (A and E) of propene and its three 13C1 isotopologues have been made in the 10-22 GHz region with FT accuracy. The revised lines for propene along with many hundreds from the literature were fitted with the ERHAM program for internal rotors to give improved rotational constants. The new constants are A0 = 46280.2904(16), B0 = 9305.24260(30), and C0 = 8134.22685(28) MHz. Lines for the 3-13C1 species were observed in a pure sample; lines for the 1-13C1 and 2-13C1 species were observed in natural abundance. In fitting the limited sets of lines for the 13C1 species, many of the centrifugal distortion constants and most of the tunneling parameters were transferred from the fit of propene itself with 27 parameters. Improved rotational constants for the 13C1 species are reported.

  18. Detection of tobacco smoke deposition by hyperpolarized krypton-83 MRI.

    PubMed

    Cleveland, Zackary I; Pavlovskaya, Galina E; Stupic, Karl F; Wooten, Jan B; Repine, John E; Meersmann, Thomas

    2008-02-01

    Despite the importance of the tobacco smoke particulate matter in the lungs to the etiology of pulmonary disease in cigarette smokers, little is currently known about the spatial distribution of particle deposition or the persistence of the resulting deposits in humans, and no satisfactory technique currently exists to directly observe tobacco smoke condensate in airways. In this proof-of-principle work, hyperpolarized (hp) 83Kr MRI and NMR spectroscopy are introduced as probes for tobacco smoke deposition in porous media. A reduction in the hp-83Kr longitudinal (T1) relaxation of up to 95% under near-ambient humidity, pressure and temperature conditions was observed when the krypton gas was brought into contact with surfaces that had been exposed to cigarette smoke. This smoke-induced acceleration of the 83Kr self-relaxation was observed for model glass surfaces that, in some experiments, were coated with bovine lung surfactant extract. However, a similar effect was not observed with hp-(129)Xe indicating that the 83Kr sensitivity to smoke deposition was not caused by paramagnetic species but rather by quadrupolar relaxation due to high adsorption affinity for the smoke deposits. The 83Kr T1 differences between smoke-treated and untreated surfaces were sufficient to produce a strong contrast in variable flip angle FLASH hp-83Kr MRI, suggesting that hp-83Kr may be a promising contrast agent for in vivo pulmonary MRI.

  19. Light Adaptation in Pecten Hyperpolarizing Photoreceptors

    PubMed Central

    Gomez, Maria del Pilar; Nasi, Enrico

    1997-01-01

    The ability of scallop hyperpolarizing photoreceptors to respond without attenuation to repetitive flashes, together with their low light sensitivity, lack of resolvable quantum bumps and fast photoresponse kinetics, had prompted the suggestion that these cells may be constitutively in a state akin to light adaptation. We here demonstrate that their photocurrent displays all manifestations of sensory adaptation: (a) The response amplitude to a test flash is decreased in a graded way by background or conditioning lights. This attenuation of the response develops with a time constant of 200–800 ms, inversely related to background intensity. (b) Adapting stimuli shift the stimulus-response curve and reduce the size of the saturating photocurrent. (c) The fall kinetics of the photoresponse are accelerated by light adaptation, and the roll-off of the modulation transfer function is displaced to higher frequencies. This light-induced desensitization exhibits a rapid recovery, on the order of a few seconds. Based on the notion that Ca mediates light adaptation in other cells, we examined the consequences of manipulating this ion. Removal of external Ca reversibly increased the photocurrent amplitude, without affecting light sensitivity, photoresponse kinetics, or susceptibility to background adaptation; the effect, therefore, concerns ion permeation, rather than the regulation of the visual response. Intracellular dialysis with 10 mM BAPTA did not reduce the peak-to-plateau decay of the photocurrent elicited by prolonged light steps, not the background-induced compression of the response amplitude range and the acceleration of its kinetics. Conversely, high levels of buffered free [Ca]i (10 μM) only marginally shifted the sensitivity curve (Δσ = 0.3 log) and spared all manifestations of light adaptation. These results indicate that hyperpolarizing invertebrate photoreceptors adapt to light, but the underlying mechanisms must utilize pathways that are largely

  20. A high resolution δ13C record in a modern Porites lobata coral: Insights into controls on skeletal δ13C

    NASA Astrophysics Data System (ADS)

    Allison, Nicola; Finch, Adrian A.; EIMF

    2012-05-01

    δ13C was determined at a high spatial resolution by secondary ion mass spectrometry (SIMS) across a 1 year section of a modern Porites lobata coral skeleton from Hawaii. Skeletal δ13C is dominated by large oscillations of 5-7‰ that typically cover skeletal distances equivalent to periods of ˜14-40 days. These variations do not reflect seawater temperature and it is unlikely that they reflect variations in the δ13C of local seawater. We observe no correlation between skeletal δ13C and the pH of the calcification fluid (estimated from previous measurements of skeletal δ11B). We conclude that either the proportion of skeletal carbon derived from metabolic CO2 is not reflected by estimated ECF pH (as the [CO2] in the overlying coral tissue varies) and/or the δ13C composition of the metabolic CO2 is highly variable. We also observe no correlation between skeletal δ13C and previous δ18O SIMS measurements. Variations in skeletal δ13C and δ18O do not have a common timing, providing no evidence that skeletal δ13C and δ18O vary in response to a single factor. This suggests that skeletal δ13C is principally driven by variations in the δ13C composition of metabolic CO2 rather than by the abundance of metabolic CO2, which would also affect skeletal δ18O. The δ13C composition of metabolic CO2 reflects the processes of photosynthesis, heterotrophic feeding and respiration in the overlying coral tissue. Corals catabolise stored lipid reserves to meet energetic demands when photosynthesis conditions are sub-optimal. Variations in the amounts and types of reserves utilised could induce changes in the δ13C composition of metabolic CO2 and the resultant skeleton which are temporally offset from skeletal δ18O records.

  1. Structural Characterization of Humic Materials Using ^13C NMR Techniques: A Comparison of Solution- and Solid-State Methods

    NASA Astrophysics Data System (ADS)

    Clewett, Catherine; Alam, Todd; Osantowski, Eric; Pullin, Michael

    2011-10-01

    The analysis of the carbon type distribution and chemical structure of natural organic matter (NOM) by ^13C NMR spectroscopy is an important technique for understanding its origins and reactivity. While prior work has used solution-state NMR techniques, solid-state NMR has the potential to provide this information using less instrument time and sample manipulation, while providing an array of advanced filtering techniques. Analyses of four isolated humic materials with ^13C solid-state magic angle spinning (MAS) NMR techniques are described, including three commercially available samples and one fulvic acid sample isolated from the Rio Grande in New Mexico. This study demonstrates the utility of solid-state ^13C NMR for aquatic NOM structural characterization, comparing these results to the existing solution-state determinations. The solid-state ^13C MAS NMR results are used to determine % carbon distribution, estimates of elemental composition (%C, %H, %(O+N)), aromatic fraction (fa), nonprotonated aromatic fraction (faN), an estimate of aromatic cluster size, and ratio of sp^2 to sp^3 carbons. A Gaussian deconvolution method is introduced that allows for a detailed analysis of carbon type.

  2. 13C Tracking after 13CO2 Supply Revealed Diurnal Patterns of Wood Formation in Aspen1

    PubMed Central

    Mahboubi, Amir; Linden, Pernilla; Moritz, Thomas

    2015-01-01

    Wood of trees is formed from carbon assimilated in the photosynthetic tissues. Determining the temporal dynamics of carbon assimilation, subsequent transport into developing wood, and incorporation to cell walls would further our understanding of wood formation in particular and tree growth in general. To investigate these questions, we designed a 13CO2 labeling system to study carbon transport and incorporation to developing wood of hybrid aspen (Populus tremula × tremuloides). Tracking of 13C incorporation to wood over a time course using nuclear magnetic resonance spectroscopy revealed diurnal patterns in wood cell wall biosynthesis. The dark period had a differential effect on 13C incorporation to lignin and cell wall carbohydrates. No 13C was incorporated into aromatic amino acids of cell wall proteins in the dark, suggesting that cell wall protein biosynthesis ceased during the night. The results show previously unrecognized temporal patterns in wood cell wall biosynthesis, suggest diurnal cycle as a possible cue in the regulation of carbon incorporation to wood, and establish a unique 13C labeling method for the analysis of wood formation and secondary growth in trees. PMID:25931520

  3. (13)C-labeled biochemical probes for the study of cancer metabolism with dynamic nuclear polarization-enhanced magnetic resonance imaging.

    PubMed

    Salamanca-Cardona, Lucia; Keshari, Kayvan R

    2015-01-01

    In recent years, advances in metabolic imaging have become dependable tools for the diagnosis and treatment assessment in cancer. Dynamic nuclear polarization (DNP) has recently emerged as a promising technology in hyperpolarized (HP) magnetic resonance imaging (MRI) and has reached clinical relevance with the successful visualization of [1-(13)C] pyruvate as a molecular imaging probe in human prostate cancer. This review focuses on introducing representative compounds relevant to metabolism that are characteristic of cancer tissue: aerobic glycolysis and pyruvate metabolism, glutamine addiction and glutamine/glutamate metabolism, and the redox state and ascorbate/dehydroascorbate metabolism. In addition, a brief introduction of probes that can be used to trace necrosis, pH changes, and other pathways relevant to cancer is presented to demonstrate the potential that HP MRI has to revolutionize the use of molecular imaging for diagnosis and assessment of treatments in cancer.

  4. 13C Solid State Nuclear Magnetic Resonance and µ-Raman Spectroscopic Characterization of Sicilian Amber.

    PubMed

    Barone, Germana; Capitani, Donatella; Mazzoleni, Paolo; Proietti, Noemi; Raneri, Simona; Longobardo, Ugo; Di Tullio, Valeria

    2016-08-01

    (13)C cross-polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR) and µ-Raman spectroscopy were applied to characterize Sicilian amber samples. The main goal of this work was to supply a complete study of simetite, highlighting discriminating criteria useful to distinguish Sicilian amber from fossil resins from other regions and laying the foundations for building a spectroscopic database of Sicilian amber. With this aim, a private collection of unrefined simetite samples and fossil resins from the Baltic region and Dominican Republic was analyzed. Overall, the obtained spectra permitted simetite to be distinguished from the other resins. In addition, principal component analysis (PCA) was applied to the spectroscopic data, allowing the clustering of simetite samples with respect to the Baltic and Dominican samples and to group the simetite samples in two sets, depending on their maturity. Finally, the analysis of loadings allowed for a better understanding of the spectral features that mainly influenced the discriminating characteristics of the investigated ambers.

  5. Simulation of 13C nuclear magnetic resonance spectra for isodon terpenoid

    NASA Astrophysics Data System (ADS)

    Yang, Guochen; Tong, Jianbo; Liu, Shuling

    2008-11-01

    A quantitative structure spectroscopy relationship (QSSR) model of 13C nuclear magnetic resonance (NMR) of 7000 carbon atoms in 350 isodon terpenoid compounds has been developed using atomic electronegativity distance vector (AEDV) and atomic hybridization state index (AHSI). The prediction correlation coefficient ( R) value of the QSSR model based on multiple linear regression analysis was 0.9542. The stability and prediction capacity of the QSSR model have been tested using the leave-one-out cross-validation and test sets methodology. The correlation coefficients R obtained were 0.9540 and 0.9556, respectively, which showed that the predictive potential of the proposed models has good modeling stability and prediction ability.

  6. (13)C-(13)c homonuclear recoupling in solid-state nuclear magnetic resonance at a moderately high magic-angle-spinning frequency.

    PubMed

    Mithu, Venus Singh; Bakthavatsalam, Subha; Madhu, Perunthiruthy K

    2013-01-01

    Two-dimensional (13)C-(13)C correlation experiments are widely employed in structure determination of protein assemblies using solid-state nuclear magnetic resonance. Here, we investigate the process of (13)C-(13)C magnetisation transfer at a moderate magic-angle-spinning frequency of 30 kHz using some of the prominent second-order dipolar recoupling schemes. The effect of isotropic chemical-shift difference and spatial distance between two carbons and amplitude of radio frequency on (1)H channel on the magnetisation transfer efficiency of these schemes is discussed in detail.

  7. Exchange facilitated indirect detection of hyperpolarized 15ND 2-amido-glutamine

    NASA Astrophysics Data System (ADS)

    Barb, A. W.; Hekmatyar, S. K.; Glushka, J. N.; Prestegard, J. H.

    2011-10-01

    Hyperpolarization greatly enhances opportunities to observe in vivo metabolic processes in real time. Accessible timescales are, however, limited by nuclear spin relaxation times, and sensitivity is limited by magnetogyric ratios of observed nuclei. The majority of applications to date have involved direct 13C observation of metabolites with non-protonated carbons at sites of interest ( 13C enriched carbonyls, for example), a choice that extends relaxation times and yields moderate sensitivity. Interest in 15N containing metabolites is equally high but non-protonated sites are rare and direct 15N observation insensitive. Here an approach is demonstrated that extends applications to protonated 15N sites with high sensitivity. The normally short relaxation times are lengthened by initially replacing protons (H) with deuterons (D) and low sensitivity detection of 15N is avoided by indirect detection through protons reintroduced by H/D exchange. A pulse sequence is presented that periodically samples 15N polarization at newly protonated sites by INEPT transfer to protons while returning 15N magnetization of deuterated sites to the + Z axis to preserve polarization for subsequent samplings. Applications to 15ND 2-amido-glutamine are chosen for illustration. Glutamine is an important regulator and a direct donor of nitrogen in cellular metabolism. Potential application to in vivo observation is discussed.

  8. A Bloch-McConnell simulator with pharmacokinetic modeling to explore accuracy and reproducibility in the measurement of hyperpolarized pyruvate

    NASA Astrophysics Data System (ADS)

    Walker, Christopher M.; Bankson, James A.

    2015-03-01

    Magnetic resonance imaging (MRI) of hyperpolarized (HP) agents has the potential to probe in-vivo metabolism with sensitivity and specificity that was not previously possible. Biological conversion of HP agents specifically for cancer has been shown to correlate to presence of disease, stage and response to therapy. For such metabolic biomarkers derived from MRI of hyperpolarized agents to be clinically impactful, they need to be validated and well characterized. However, imaging of HP substrates is distinct from conventional MRI, due to the non-renewable nature of transient HP magnetization. Moreover, due to current practical limitations in generation and evolution of hyperpolarized agents, it is not feasible to fully experimentally characterize measurement and processing strategies. In this work we use a custom Bloch-McConnell simulator with pharmacokinetic modeling to characterize the performance of specific magnetic resonance spectroscopy sequences over a range of biological conditions. We performed numerical simulations to evaluate the effect of sequence parameters over a range of chemical conversion rates. Each simulation was analyzed repeatedly with the addition of noise in order to determine the accuracy and reproducibility of measurements. Results indicate that under both closed and perfused conditions, acquisition parameters can affect measurements in a tissue dependent manner, suggesting that great care needs to be taken when designing studies involving hyperpolarized agents. More modeling studies will be needed to determine what effect sequence parameters have on more advanced acquisitions and processing methods.

  9. Labeling strategies for 13C-detected aligned-sample solid-state NMR of proteins

    NASA Astrophysics Data System (ADS)

    Filipp, Fabian V.; Sinha, Neeraj; Jairam, Lena; Bradley, Joel; Opella, Stanley J.

    2009-12-01

    13C-detected solid-state NMR experiments have substantially higher sensitivity than the corresponding 15N-detected experiments on stationary, aligned samples of isotopically labeled proteins. Several methods for tailoring the isotopic labeling are described that result in spatially isolated 13C sites so that dipole-dipole couplings among the 13C are minimized, thus eliminating the need for homonuclear 13C- 13C decoupling in either indirect or direct dimensions of one- or multi-dimensional NMR experiments that employ 13C detection. The optimal percentage for random fractional 13C labeling is between 25% and 35%. Specifically labeled glycerol and glucose can be used at the carbon sources to tailor the isotopic labeling, and the choice depends on the resonances of interest for a particular study. For investigations of the protein backbone, growth of the bacteria on [2- 13C]-glucose-containing media was found to be most effective.

  10. Synthesis of 13C and 15N labeled 2,4-dinitroanisole.

    PubMed

    Jagadish, Bhumasamudram; Field, Jim A; Chorover, Jon; Sierra-Alvarez, Reyes; Abrell, Leif; Mash, Eugene A

    2014-05-30

    Syntheses of [(13)C6]-2,4-dinitroanisole (ring-(13)C6) from [(13)C6]-anisole (ring-(13)C6) and [(15)N2]-2,4-dinitroanisole from anisole using in situ generated acetyl nitrate and [(15)N]-acetyl nitrate, respectively, are described. Treatment of [(13)C6]-anisole (ring-(13)C6) with acetyl nitrate generated in 100% HNO3 gave [(13)C6]-2,4-dinitroanisole (ring-(13)C6) in 83% yield. Treatment of anisole with [(15)N]-acetyl nitrate generated in 10 N [(15)N]-HNO3 gave [(15)N2 ]-2,4-dinitroanisole in 44% yield after two cycles of nitration. Byproducts in the latter reaction included [(15)N]-2-nitroanisole and [(15)N]-4-nitroanisole.

  11. Model of decision system for 13C Isotope Separation column

    NASA Astrophysics Data System (ADS)

    Boca, M. L.

    2015-11-01

    This paper presents the model of a decisional system for 13C Isotope Separation column, which is used to detect mission critical situation. The start model was a model of one distributed control system of critical situations that may arise in the operation of the distillation column. The research work it is proposed a model of decision system which implement a temperature sensor inside of liquid nitrogen level in the condenser. The condenser is a part of column where take place the cryogenic process using nitrogen liquid. The work temperature is very low about -192oC, and because the temperature can grow or go down more than 2 degrees is a very critical location inside the column. In this way the column has a deeply monitor and supervised and it take a decision in a proper time when the temperature is grow up or getting down and became a critical situation. For monitor and supervised it was used MatLAB SimuLink. The model, the decision system gives a signal to one sensor when something is wrong in the condenser which is the most critical place of the isotopic column. In this way it creates an alarm that something is getting wrong in the isotopic column.

  12. Inelastic pion scattering by /sup 13/C at low energies

    SciTech Connect

    Mitchell, J.H.

    1987-03-01

    Angular distributions for inelastically scattered pions were obtained for several states in /sup 13/C at an incident energy of 65 MeV. The data include results from both ..pi../sup +/ and ..pi../sup -/ measurements. In addition, ..pi../sup -/ measurements were made at T/sub ..pi../ = 50 MeV at one angle to give a two point fixed-q excitation function. The data are compared to theory and the data of others. As might be expected, medium corrections are shown to be considerably more important at low energies than at resonance. This is true for inelastic transitions of multipolarity 0,2 and 3. Parameters derived from an analysis of elastic pion scattering and SCX data also provide an adequate description of the inelastic transitions. The charge asymmetry in the cross sections for the 9/2/sup +/ state that was seen at resonance persists at these energies. This result is consistent with an impulse approximation treatment of the spin-flip amplitude. This is true even though the incoming energy of the pions is far below the range where the validity of an impulse treatment is expected. 65 refs., 45 figs.

  13. LIGHT-SABRE enables efficient in-magnet catalytic hyperpolarization

    NASA Astrophysics Data System (ADS)

    Theis, Thomas; Truong, Milton; Coffey, Aaron M.; Chekmenev, Eduard Y.; Warren, Warren S.

    2014-11-01

    Nuclear spin hyperpolarization overcomes the sensitivity limitations of traditional NMR and MRI, but the most general method demonstrated to date (dynamic nuclear polarization) has significant limitations in scalability, cost, and complex apparatus design. As an alternative, signal amplification by reversible exchange (SABRE) of parahydrogen on transition metal catalysts can hyperpolarize a variety of substrates, but to date this scheme has required transfer of the sample to low magnetic field or very strong RF irradiation. Here we demonstrate "Low-Irradiation Generation of High Tesla-SABRE" (LIGHT-SABRE) which works with simple pulse sequences and low power deposition; it should be usable at any magnetic field and for hyperpolarization of many different nuclei. This approach could drastically reduce the cost and complexity of producing hyperpolarized molecules.

  14. Hyperpolarized lithium-6 as a sensor of nanomolar contrast agents.

    PubMed

    van Heeswijk, Ruud B; Uffmann, Kai; Comment, Arnaud; Kurdzesau, Fiodar; Perazzolo, Chiara; Cudalbu, Cristina; Jannin, Sami; Konter, Jacobus A; Hautle, Patrick; van den Brandt, Ben; Navon, Gil; van der Klink, Jacques J; Gruetter, Rolf

    2009-06-01

    Lithium is widely used in psychotherapy. The (6)Li isotope has a long intrinsic longitudinal relaxation time T(1) on the order of minutes, making it an ideal candidate for hyperpolarization experiments. In the present study we demonstrated that lithium-6 can be readily hyperpolarized within 30 min, while retaining a long polarization decay time on the order of a minute. We used the intrinsically long relaxation time for the detection of 500 nM contrast agent in vitro. Hyperpolarized lithium-6 was administered to the rat and its signal retained a decay time on the order of 70 sec in vivo. Localization experiments imply that the lithium signal originated from within the brain and that it was detectable up to 5 min after administration. We conclude that the detection of submicromolar contrast agents using hyperpolarized NMR nuclei such as (6)Li may provide a novel avenue for molecular imaging.

  15. Two Categories of 13C/12C Ratios for Higher Plants 1

    PubMed Central

    Smith, Bruce N.; Epstein, Samuel

    1971-01-01

    13C/12C ratios have been determined for plant tissue from 104 species representing 60 families. Higher plants fall into two categories, those with low δPDBI13C values (—24 to —34‰) and those with high δ 13C values (—6 to —19‰). Algae have δ 13C values of —12 to —23‰. Photosynthetic fractionation leading to such values is discussed. PMID:16657626

  16. 40 CFR 721.6505 - Polymers of C13C15 oxoalcohol ethoxolates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymers of C13C15 oxoalcohol... Specific Chemical Substances § 721.6505 Polymers of C13C15 oxoalcohol ethoxolates. (a) Chemical substance... polymers of C13C15 oxoalcohol ethoxolates (PMNs P-96-950/951) are subject to reporting under this...

  17. 40 CFR 721.6505 - Polymers of C13C15 oxoalcohol ethoxolates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymers of C13C15 oxoalcohol... Specific Chemical Substances § 721.6505 Polymers of C13C15 oxoalcohol ethoxolates. (a) Chemical substance... polymers of C13C15 oxoalcohol ethoxolates (PMNs P-96-950/951) are subject to reporting under this...

  18. 40 CFR 721.6505 - Polymers of C13C15 oxoalcohol ethoxolates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymers of C13C15 oxoalcohol... Specific Chemical Substances § 721.6505 Polymers of C13C15 oxoalcohol ethoxolates. (a) Chemical substance... polymers of C13C15 oxoalcohol ethoxolates (PMNs P-96-950/951) are subject to reporting under this...

  19. 40 CFR 721.6505 - Polymers of C13C15 oxoalcohol ethoxolates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymers of C13C15 oxoalcohol... Specific Chemical Substances § 721.6505 Polymers of C13C15 oxoalcohol ethoxolates. (a) Chemical substance... polymers of C13C15 oxoalcohol ethoxolates (PMNs P-96-950/951) are subject to reporting under this...

  20. 40 CFR 721.6505 - Polymers of C13C15 oxoalcohol ethoxolates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymers of C13C15 oxoalcohol... Specific Chemical Substances § 721.6505 Polymers of C13C15 oxoalcohol ethoxolates. (a) Chemical substance... polymers of C13C15 oxoalcohol ethoxolates (PMNs P-96-950/951) are subject to reporting under this...

  1. Calibration of δ13C and δ18O measurements in CO2 using Off-axis Integrated Cavity Output Spectrometer (ICOS)

    NASA Astrophysics Data System (ADS)

    Joseph, Jobin; Külls, Christoph

    2014-05-01

    The δ13C and δ18O of CO2 has enormous potential as tracers to study and quantify the interaction between the water and carbon cycles. Isotope ratio mass spectrometry (IRMS) being the conventional method for stable isotopic measurements, has many limitations making it impossible for deploying them in remote areas for online or in-situ sampling. New laser based absorption spectroscopy approaches like Cavity Ring Down Spectroscopy (CRDS) and Integrated Cavity Output Spectroscopy (ICOS) have been developed for online measurements of stable isotopes at an expense of considerably less power requirement but with precision comparable to IRMS. In this research project, we introduce a new calibration system for an Off- Axis ICOS (Los Gatos Research CCIA-36d) for a wide range of varying concentrations of CO2 (800ppm - 25,000ppm), a typical CO2 flux range at the plant-soil continuum. The calibration compensates for the concentration dependency of δ13C and δ18O measurements, and was performed using various CO2 standards with known CO2 concentration and δC13 and δO18 values. A mathematical model was developed after the calibration procedure as a correction factor for the concentration dependency of δ13C and δ18O measurements. Temperature dependency of δ13C and δ18O measurements were investigated and no significant influence was found. Simultaneous calibration of δ13C and δ18O is achieved using this calibration system with an overall accuracy of (~ 0.75±0.24 ‰ for δ13C, ~ 0.81 ±0.26‰ for δ18O). This calibration procedure is found to be appropriate for making Off-Axis ICOS suitable for measuring CO2 concentration and δ13C and δ18O measurements at atmosphere-plant-soil continuum.

  2. Geochemical Approach to Archaeal Ecology: δ13C of GDGTs

    NASA Astrophysics Data System (ADS)

    Lichtin, S.; Warren, C.; Pearson, A.; Pagani, M.

    2015-12-01

    Over the last decade and a half, glycerol dialkyl glycerol tetraethers (GDGTs) have increasingly been used to reconstruct environmental temperatures; proxies like TEX86 that correlate the relative abundance of these archaeal cell membrane lipids to sea surface temperature are omnipresent in paleoclimatology literature. While it has become common to make claims about past temperatures using GDGTs, our present understanding of the organisms that synthesize the compounds is still quite limited. The generally accepted theory states that microorganisms like the Thaumarchaeota modify the structure of membrane lipids to increase intermolecular interactions, strengthening the membrane at higher temperatures. Yet to date, culture experiments have been largely restricted to a single species, Nitrosopumilus maritimes, and recent studies on oceanic archaeal rRNA have revealed that these biomarkers are produced in diverse, heterogeneous, and site-specific communities. This brings up questions as to whether different subclasses of GDGTs, and all subsequent proxies, represent adaptation within a single organismal group or a shift in community composition. To investigate whether GDGTs with different chain structures, from the simple isoprenoidal GDGT-0 to Crenarchaeol with its many cyclopentane groups, are sourced from archaea with similar or disparate metabolic pathways—and if that information is inherited in GDGTs trapped in marine sediments—this study examines the stable carbon isotope values (δ13C) of GDGTs extracted from the uppermost meters of sediment in the Orca Basin, Gulf of Mexico, using spooling-wire microcombustion isotope-ratio mass spectrometer (SWiM-IRMS), tackling a fundamental assumption of the TEX86 proxy that influences the way we perceive the veracity of existing temperature records.

  3. Topological Constraints on Chain-Folding Structure of Semicrystalline Polymer as Studied by 13C-13C Double Quantum NMR

    NASA Astrophysics Data System (ADS)

    Hong, Youlee; Miyoshi, Toshikazu

    Chain-folding process is a prominent feature of long polymer chains during crystallization. Over the last half century, much effort has been paid to reveal the chain trajectory. Even though various chain-folding models as well as theories of crystallization at molecule levels have been proposed, they could be not reconciled due to the limited experimental evidences. Recent development of double quantum NMR with selective isotope labeling identified the chain-trajectory of 13C labeled isotactic poly(1-butene). The systematic experiments covered a wide range of parameters, i.e. kinetics, concentration, and molecular weight (Mw) . It was demonstrated that i) adjacent re-entry site was invariant as a function of crystallization temperature (Tc) , concentration, andMw, ii) long-range order of adjacent re-entry sequence is independence of kinetics at a given concentration while it decreased with increasing the polymer concentration at a given Tc due to the increased interruption between the chains, and iii) high Mw chains led to the multilayer folded structures in single crystals, but the melt state induced the identical short adjacent sequences of long and short polymer over a wide range of Tc due to the entanglements. The behaviors indicated that the topological restriction plays significant roles in the chain-folding process rather than the kinetics. The proposed framework to control the chain-folding structure presents a new perspective into the chain organization by either the intra- or inter-chain interaction. National Science Foundation Grants DMR-1105829 and 1408855.

  4. Determination of fructose metabolic pathways in normal and fructose-intolerant children: A sup 13 C NMR study using (U- sup 13 C)fructose

    SciTech Connect

    Gopher, A.; Lapidot, A. ); Vaisman, N. ); Mandel, H. )

    1990-07-01

    An inborn deficiency in the ability of aldolase B to split fructose 1-phosphate is found in humans with hereditary fructose intolerance (HFI). A stable isotope procedure to elucidate the mechanism of conversion of fructose to glucose in normal children and in HFI children has been developed. A constant infusion of D-(U-{sup 13}C)fructose was given nasogastrically to control and to HFI children. Hepatic fructose conversion to glucose was estimated by examination of {sup 13}C NMR spectra of plasma glucose. Significantly lower values ({approx}3-fold) for fructose conversion to glucose were obtained for the HFI patients as compared to the controls. A quantitative determination of the metabolic pathways of fructose conversion to glucose was derived from {sup 13}C NMR measurement of plasma ({sup 13}C)glucose isotopomer populations. The finding of isotopomer populations of three adjacent {sup 13}C atoms at glucose C-4 ({sup 13}C{sub 3}-{sup 13}C{sub 4}-{sup 13}C{sub 5}) suggests that there is a direct pathway from fructose, by-passing fructose-1-phosphate aldolase, to fructose 1,6-bisphosphate. The metabolism of fructose by fructose-1-phosphate aldolase activity accounts for only {approx}50% of the total amount of hepatic fructose conversion to glucose. In view of the marked decline by 67% in synthesis of glucose from fructose in HFI subjects found in this study, the extent of ({sup 13}C)glucose formation from a trace amount of (U-{sup 13}C)fructose infused into the patient can be used as a safe and noninvasive diagnostic test for inherent faulty fructose metabolism.

  5. 13C NMR Metabolomic Evaluation of Immediate and Delayed Mild Hypothermia in Cerebrocortical Slices After Oxygen-Glucose Deprivation

    PubMed Central

    Liu, Jia; Segal, Mark; Kelly, Mark J.S.; Pelton, Jeffrey G.; Kim, Myungwon; James, Thomas L.; Litt, Lawrence

    2013-01-01

    Background Mild brain hypothermia (32°C–34°C) after human neonatal asphyxia improves neurodevelopmental outcomes. Astrocytes but not neurons have pyruvate carboxylase (PC) and an acetate uptake transporter. 13C NMR spectroscopy of rodent brain extracts after administering [1-13C]glucose and [1,2-13C]acetate can distinguish metabolic differences between glia and neurons, and tricarboxylic acid cycle (TCA cycle) entry via pyruvate dehydrogenase (PDH) and PC. Methods Neonatal rat cerebrocortical slices receiving a 13C-acetate/glucose mixture underwent a 45-min asphyxia simulation via oxygen-glucose-deprivation (OGD) followed by 6 h of recovery. Protocols in three groups of N = 3 experiments were identical except for temperature management. The three temperature groups were: normothermia (37°C), hypothermia (32°C for 3.75 h beginning at OGD start), and delayed hypothermia (32°C for 3.75 h, beginning 15 min after OGD start). Multivariate analysis of nuclear magnetic resonance metabolite quantifications included principal component analyses and the L1-Penalized Regularized Regression algorithm known as the Least Absolute Shrinkage and Selection Operator (LASSO). Results The most significant metabolite difference (p < 0.0056) was [2-13C]glutamine’s higher final/control ratio for the Hypothermia group (1.75 ± 0.12) compared to ratios for the Delayed (1.12 ± 0.12) and Normothermia group (0.94 ± 0.06), implying a higher PC/PDH ratio for glutamine formation. LASSO found the most important metabolites associated with adenosine triphosphate preservation: [3,4-13C]glutamate—produced via PDH entry, [2-13C]taurine--an important osmolyte, and phosphocreatine. Final principal component analyses scores plots suggested separate cluster formation for the hypothermia group, but with insufficient data for statistical significance. Conclusions Starting mild hypothermia simultaneously with OGD, compared with delayed starting or no hypothermia, has higher PC throughput

  6. The Late Pleistocene history of surface water δ13C in the Sulu Sea: Possible relationship to Pacific Deepwater δ13C changes

    NASA Astrophysics Data System (ADS)

    Linsley, Braddock K.; Dunbar, Robert B.

    1994-04-01

    A reconstruction of late Pleistocene surface water carbon isotopic (δ13C) variability is presented from Ocean Drilling Program (ODP) site 769 in the Sulu Sea in the western tropical Pacific. The Sulu Sea is a shallowly silled back arc basin with a maximum sill depth of 420 m. Site 769 was drilled on a bathymetric high in 3643 m of water and has average late Pleistocene sedimentation rates of 8.5 cm/kyr. The oxygen isotope record (δ18O) of Globigerinoides ruber at site 769 shows a strong correlation with the SPECMAP stacked δ18O record, attesting to the continuity of sediment archive at the site. Surface δ13C displays consistent glacial-interglacial variability which averages ˜0.9‰ and has varied from 0.75 to 1.1‰ over the last 800 kyr. Comparison to surface water δ13C records in the South China Sea and western tropical Pacific suggests that the glacial-interglacial surface δ13C variability is regional in scale. Planktonic δ13C data from ODP site 677 in the eastern Pacific is also coherent with the site 769. Additionally, we have found that the site 769 surface δ13C record is coherent at periods of 100 and 41 kyr with deepwater δ13C records from the Pacific. The highest correlation occurs with the deep eastern Pacific, where benthic δ13C data from cores RC13-110 and ODP site 677 closely match the Sulu Sea surface water record. We evaluate several possible controls of surface water δ13C in the Sulu Sea that may explain the coherent timing with Pacific deepwater δ13C records. These include variations in terrestrial organic matter flux to the basin, the upwelling of subsurface water and productivity changes, and the influx of western Pacific intermediate water to the Sulu Sea. Our preferred explanation involves a region of upper intermediate water upwelling in the far western Pacific which has been shown to outgas CO2 from subsurface waters into surface waters. Upwelling also occurs in the area of Panama Basin site 677. These equatorial upwelling zones

  7. Hyperpolar multichromophoric nanoassembly for molecular nonlinear optics

    NASA Astrophysics Data System (ADS)

    Blanchard-Desce, Mireille H.; Ait Amer Meziane, M.; Rekai, El Djouhar; Baudin, Jean-Bernard; Jullien, Ludovic; Ledoux, Isabelle N.; Zyss, Joseph

    2002-12-01

    A multichromophoric nanoassembly was designed by gathering seven push-pull chromophores on a β-cyclodextrin assembling unit via covalent linkers. Such supermolecule provides a valuable model for the investigation of confinement effects on the linear and nonlinear optical properties of push-pull chromophores in the condensed phase. Push-pull chromophores display a significant ground-state dipole, thus promoting dipolar interactions that are expected to influence both the conformation and the optical properties of the multichromophoric assembly. In this perspective, the photophysical and nonlinear optical properties of the mutichromophoric bundle were investigated and compared to those of the monomeric chromophore. The absorption, circular dichroism and fluorescence investigations provide evidence that the push-pull chromophores do not behave as isolated independent chromophores within the multichromophoric assembly. The nanoscale supermolecule is hypsochromically and significantly hypochromically shifted with respect to its monomeric analogue. In addition, the close proximity promotes excitonic coupling, as well as excimer formation phenomena. The nanoscopic assembly also shows a very large dipolar moment (μ = 38 D), and a significant molecular first-order hyperpolarisability, which reveal a spontaneous sheaf-type self-arrangement of the dipolar chromophores within the supermolecule. Such chiral hyperpolar nanoassemblies are promising candidates as model systems for nanophotonics.

  8. Determination of 13C/ 12C ratios with (d, p) nuclear reactions

    NASA Astrophysics Data System (ADS)

    Wang, Y. Q.; Zhang, J.; Tesmer, J. R.; Li, Y. H.; Greco, R.; Grim, G. P.; Obst, A. W.; Rundberg, R. S.; Wilhelmy, J. B.

    2010-06-01

    Stable isotope ratios such as 13C/ 12C play an important role in many applications including environment and energy research. Since many surface analysis techniques are plagued with unavoidable hydrocarbon contamination issues during analysis, it is highly desirable that 13C and 12C isotopes be measured simultaneously especially in specimens with a minute amount of 13C, in order to reliably determine 13C/ 12C ratios. In this paper, we report that deuterium induced proton particle reactions, 13C(d, p) 14C and 12C(d, p) 13C, provide a convenient and reliable approach for 13C/ 12C ratio determination. Optimizations on experimental considerations and potential interferences from other common light isotopes are discussed as well as results from the application of this technique to diagnose the performance of a target debris collection in an inertial confinement fusion (ICF) experiment.

  9. Sc3CH@C80: selective (13)C enrichment of the central carbon atom.

    PubMed

    Junghans, Katrin; Rosenkranz, Marco; Popov, Alexey A

    2016-05-01

    Sc3CH@C80 is synthesized and characterized by (1)H, (13)C, and (45)Sc NMR. A large negative chemical shift of the proton, -11.73 ppm in the Ih and -8.79 ppm in the D5h C80 cage isomers, is found. (13)C satellites in the (1)H NMR spectrum enabled indirect determination of the (13)C chemical shift for the central carbon at 173 ± 1 ppm. Intensity of the satellites allowed determination of the (13)C content for the central carbon atom. This unique possibility is applied to analyze the cluster/cage (13)C distribution in mechanistic studies employing either (13)CH4 or (13)C powder to enrich Sc3CH@C80 with (13)C. PMID:27109443

  10. Sc3CH@C80: selective 13C enrichment of the central carbon atom†

    PubMed Central

    Junghans, Katrin; Rosenkranz, Marco; Popov, Alexey A.

    2016-01-01

    Sc3CH@C80 is synthesized and characterized by 1H, 13C, and 45Sc NMR. A large negative chemical shift of the proton, −11.73 ppm in the Ih and −8.79 ppm in the D5h C80 cage isomers, is found. 13C satellites in the 1H NMR spectrum enabled indirect determination of the 13C chemical shift for the central carbon at 173 ± 1 ppm. Intensity of the satellites allowed determination of the 13C content for the central carbon atom. This unique possibility is applied to analyze the cluster/cage 13C distribution in mechanistic studies employing either 13CH4 or 13C powder to enrich Sc3CH@C80 with 13C. PMID:27109443

  11. Thermal Degradation studies of nitroplasticized estane 5703 utilizing [sup 13] C enriched model polymers.

    SciTech Connect

    Wrobleski, Debra A.; Langlois, D. A.; Orler, E. B.; Schoonover, J. R.; Osborn, J. C.; Small, J. H.

    2002-01-01

    Predicting the lifetime of PBX 9501 is critical to assurance of the reliability of the nuclear weapons stockpile. Ln support of the Lifetime Prediction Model, we have been investigating the physical and chemical aging processes that can potentially affect the lifetime of PBX 9501. Surveillance data of stockpile PBX 9501 binder have shown a decrease in Estane molecular weight as a fiinction of age. Estane is a poly(ester urethane) consisting of poly(buly1ene adipate) as the flexible soft segment and 4,4{prime}-methylenediphenyl-1,1{prime}-diisocyanate (MDI) chain extended with 1,4-butanediol (BDO) as the rigid hard segment efforts have focused on chemical reactions that may cause chain scission of Estane through hydrolytic degradation of the polyester soft segments. Thermal aging of Estane in the absence of water shows no signs of hydrolytic degradation, whereas, appearance of high molecular weight species has been observed for Estane aged at elevated temperatures in the presence of nitroplasticizer. These high molecular weight species are most likely due to branching reactions that eventually leads to formation of an insoluble, cross-linked gel. While the mechanisms of hydrolytic degradation of polyesters has been addressed, the degradations reactions of poly(ester urethane) (PESU) in the presence of NP are not well understood. We have prepared a series of isotopically enriched PESU model compounds chemically similar to Estane for aging experiments in order to understand possible cross-linking mechanisms. Changes in physical properties are observed with less than 1% chemical cross-linking. Isotopic enrichment of 13C from 1.1 % natural abundance to 100% improves the sensitivity of spectroscopic techniques so that small quantities of degradation products can be observed. Because degradation reaction mechanisms of importance may occur at the hard segment portion of the polymer, we have prepared 13C PESU with 13C labeled at the methylene carbon. These model polymers

  12. The 3 A Band System in the Spectrum of the 13C 16O Molecule

    NASA Astrophysics Data System (ADS)

    Hakalla, R.; Kępa, R.; Rytel, M.; Zachwieja, M.

    1999-10-01

    In the emission spectrum of the carbon monoxide 13C16O isotopic molecule three bands comprising about 1820 lines of the 3A band system (c3Π-a3Π) were recorded and analyzed. The 0-0 and 0-1 bands of this system were photographed for the first time and the 0-2 band was rephotographed by using methods of conventional high-resolution spectroscopy. The result of the rotational band analysis includes expanding of the spectrum interpretation up to J = 25 as well as the identification of four previously unobserved branches P13, R13, P31, and R31. Because of strong perturbations in the c3Π (v = 0) state, the calculation of the rovibronic structure constants was performed only for the lower a3Π state. By using a calculation based on a nonlinear least-squares method, an effective Hamiltonian of Brown [J. M. Brown, E. A. Colbourn, J. K. G. Watson, and F. D. Wayne, J. Mol. Spectrosc. 74, 294-318 (1979)] and a separative procedure proposed by Curl-Dane-Watson [R. F. Curl and C. B. Dane, J. Mol. Spectrosc. 128, 406-412 (1988); J. K. G. Watson, J. Mol. Spectrosc. 138, 302-308 (1989)], it was possible to derive the rotational structure constants for the v = 0, 1, and 2 levels for the a3Π state in the 13C16O isotopic molecule. Term values for the c3Π (v = 0) level and the equilibrium molecular constants for the a3Π state also are reported.

  13. BEBEtr and BUBI: J-compensated concurrent shaped pulses for 1H-13C experiments

    NASA Astrophysics Data System (ADS)

    Ehni, Sebastian; Luy, Burkhard

    2013-07-01

    Shaped pulses designed for broadband excitation, inversion and refocusing are important tools in modern NMR spectroscopy to achieve robust pulse sequences especially in heteronuclear correlation experiments. A large variety of mostly computer-optimized pulse shapes exist for different desired bandwidths, available rf-field strengths, and tolerance to B1-inhomogeneity. They are usually derived for a single spin 1/2, neglecting evolution due to J-couplings. While pulses with constant resulting phase are selfcompensated for heteronuclear coupling evolution as long as they are applied exclusively on a single nucleus, the situation changes for concurrently applied pulse shapes. Using the example of a 1H,13C two spin system, two J-compensated pulse pairs for the application in INEPT-type transfer elements were optimized: a point-to-point pulse sandwich called BEBEtr, consisting of a broadband excitation and time-reversed excitation pulse, and a combined universal rotation and point-to-point pulse pair called BUBI, which acts as a refocusing pulse on 1H and a corresponding inversion pulse on 13C. After a derivation of quality factors and optimization protocols, a theoretical and experimental comparison with conventionally derived BEBOP, BIBOP, and BURBOP-180° pulses is given. While the overall transfer efficiency of a single pulse pair is only reduced by approximately 0.1%, resulting transfer to undesired coherences is reduced by several percent. In experiments this can lead to undesired phase distortions for pairs of uncompensated pulse shapes and even differences in signal intensities of 5-10% in HSQC and up to 68% in more complex COB-HSQC experiments.

  14. The 3A Band System in the Spectrum of the (13)C(16)O Molecule.

    PubMed

    Hakalla; Kepa; Rytel; Zachwieja

    1999-10-01

    In the emission spectrum of the carbon monoxide (13)C(16)O isotopic molecule three bands comprising about 1820 lines of the 3A band system (c(3)Pi-a(3)Pi) were recorded and analyzed. The 0-0 and 0-1 bands of this system were photographed for the first time and the 0-2 band was rephotographed by using methods of conventional high-resolution spectroscopy. The result of the rotational band analysis includes expanding of the spectrum interpretation up to J = 25 as well as the identification of four previously unobserved branches P(13), R(13), P(31), and R(31). Because of strong perturbations in the c(3)Pi (v = 0) state, the calculation of the rovibronic structure constants was performed only for the lower a(3)Pi state. By using a calculation based on a nonlinear least-squares method, an effective Hamiltonian of Brown [J. M. Brown, E. A. Colbourn, J. K. G. Watson, and F. D. Wayne, J. Mol. Spectrosc. 74, 294-318 (1979)] and a separative procedure proposed by Curl-Dane-Watson [R. F. Curl and C. B. Dane, J. Mol. Spectrosc. 128, 406-412 (1988); J. K. G. Watson, J. Mol. Spectrosc. 138, 302-308 (1989)], it was possible to derive the rotational structure constants for the v = 0, 1, and 2 levels for the a(3)Pi state in the (13)C(16)O isotopic molecule. Term values for the c(3)Pi (v = 0) level and the equilibrium molecular constants for the a(3)Pi state also are reported. Copyright 1999 Academic Press.

  15. Cigarette butt decomposition and associated chemical changes assessed by 13C CPMAS NMR.

    PubMed

    Bonanomi, Giuliano; Incerti, Guido; Cesarano, Gaspare; Gaglione, Salvatore A; Lanzotti, Virginia

    2015-01-01

    Cigarette butts (CBs) are the most common type of litter on earth, with an estimated 4.5 trillion discarded annually. Apart from being unsightly, CBs pose a serious threat to living organisms and ecosystem health when discarded in the environment because they are toxic to microbes, insects, fish and mammals. In spite of the CB toxic hazard, no studies have addressed the effects of environmental conditions on CB decomposition rate. In this study we investigate the interactive effects of substrate fertility and N transfer dynamics on CB decomposition rate and carbon quality changes. We carried out an experiment using smoked CBs and wood sticks, used as a slow decomposing standard organic substrate, incubated in both laboratory and field conditions for two years. CB carbon quality changes during decomposition was assessed by 13C CPMAS NMR. Our experiment confirmed the low degradation rate of CBs which, on average, lost only 37.8% of their initial mass after two years of decomposition. Although a net N transfer occurred from soil to CBs, contrary to our hypothesis, mass loss in the medium-term (two years) was unaffected by N availability in the surrounding substrate. The opposite held for wood sticks, in agreement with the model that N-rich substrates promote the decomposition of other N-poor natural organic materials with a high C/N ratio. As regards CB chemical quality, after two years of decomposition 13C NMR spectroscopy highlighted very small changes in C quality that are likely to reflect a limited microbial attack.

  16. Cigarette Butt Decomposition and Associated Chemical Changes Assessed by 13C CPMAS NMR

    PubMed Central

    Bonanomi, Giuliano; Incerti, Guido; Cesarano, Gaspare; Gaglione, Salvatore A.; Lanzotti, Virginia

    2015-01-01

    Cigarette butts (CBs) are the most common type of litter on earth, with an estimated 4.5 trillion discarded annually. Apart from being unsightly, CBs pose a serious threat to living organisms and ecosystem health when discarded in the environment because they are toxic to microbes, insects, fish and mammals. In spite of the CB toxic hazard, no studies have addressed the effects of environmental conditions on CB decomposition rate. In this study we investigate the interactive effects of substrate fertility and N transfer dynamics on CB decomposition rate and carbon quality changes. We carried out an experiment using smoked CBs and wood sticks, used as a slow decomposing standard organic substrate, incubated in both laboratory and field conditions for two years. CB carbon quality changes during decomposition was assessed by 13C CPMAS NMR. Our experiment confirmed the low degradation rate of CBs which, on average, lost only 37.8% of their initial mass after two years of decomposition. Although a net N transfer occurred from soil to CBs, contrary to our hypothesis, mass loss in the medium-term (two years) was unaffected by N availability in the surrounding substrate. The opposite held for wood sticks, in agreement with the model that N-rich substrates promote the decomposition of other N-poor natural organic materials with a high C/N ratio. As regards CB chemical quality, after two years of decomposition 13C NMR spectroscopy highlighted very small changes in C quality that are likely to reflect a limited microbial attack. PMID:25625643

  17. Solid state 13C NMR studies of methane dehydroaromatization reaction on Mo/HZSM-5 and W/HZSM-5 catalysts.

    PubMed

    Yang, Jun; Ma, Ding; Deng, Feng; Luo, Qing; Zhang, Mingjin; Bao, Xinhe; Ye, Chaohui

    2002-12-21

    Methane dehydroaromatization on Mo/HZSM-5 and W/HZSM-5 catalysts was studied by solid state 13C NMR spectroscopy, both variation of the state of transition metal component and products such as ethane, benzene, ethene adsorbed on or in zeolite were observed after high temperature (900-1000 K) reaction.

  18. Long-lived states to sustain hyperpolarized magnetization

    PubMed Central

    Vasos, P. R.; Comment, A.; Sarkar, R.; Ahuja, P.; Jannin, S.; Ansermet, J.-P.; Konter, J. A.; Hautle, P.; van den Brandt, B.; Bodenhausen, G.

    2009-01-01

    Major breakthroughs have recently been reported that can help overcome two inherent drawbacks of NMR: the lack of sensitivity and the limited memory of longitudinal magnetization. Dynamic nuclear polarization (DNP) couples nuclear spins to the large reservoir of electrons, thus making it possible to detect dilute endogenous substances in magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). We have designed a method to preserve enhanced (“hyperpolarized”) magnetization by conversion into long-lived states (LLS). It is shown that these enhanced long-lived states can be generated for proton spins, which afford sensitive detection. Even in complex molecules such as peptides, long-lived proton states can be sustained effectively over time intervals on the order of tens of seconds, thus allowing hyperpolarized substrates to reach target areas and affording access to slow metabolic pathways. The natural abundance carbon-13 polarization has been enhanced ex situ by almost four orders of magnitude in the dipeptide Ala-Gly. The sample was transferred by the dissolution process to a high-resolution magnet where the carbon-13 polarization was converted into a long-lived state associated with a pair of protons. In Ala-Gly, the lifetime TLLS associated with the two nonequivalent Hα glycine protons, sustained by suitable radio-frequency irradiation, was found to be seven times longer than their spin-lattice relaxation time constant (TLLS/T1 = 7). At desired intervals, small fractions of the populations of long-lived states were converted into observable magnetization. This opens the way to observing slow chemical reactions and slow transport phenomena such as diffusion by enhanced magnetic resonance. PMID:19841270

  19. 13C metabolic flux analysis at a genome-scale.

    PubMed

    Gopalakrishnan, Saratram; Maranas, Costas D

    2015-11-01

    Metabolic models used in 13C metabolic flux analysis generally include a limited number of reactions primarily from central metabolism. They typically omit degradation pathways, complete cofactor balances, and atom transition contributions for reactions outside central metabolism. This study addresses the impact on prediction fidelity of scaling-up mapping models to a genome-scale. The core mapping model employed in this study accounts for (75 reactions and 65 metabolites) primarily from central metabolism. The genome-scale metabolic mapping model (GSMM) (697 reaction and 595 metabolites) is constructed using as a basis the iAF1260 model upon eliminating reactions guaranteed not to carry flux based on growth and fermentation data for a minimal glucose growth medium. Labeling data for 17 amino acid fragments obtained from cells fed with glucose labeled at the second carbon was used to obtain fluxes and ranges. Metabolic fluxes and confidence intervals are estimated, for both core and genome-scale mapping models, by minimizing the sum of square of differences between predicted and experimentally measured labeling patterns using the EMU decomposition algorithm. Overall, we find that both topology and estimated values of the metabolic fluxes remain largely consistent between core and GSM model. Stepping up to a genome-scale mapping model leads to wider flux inference ranges for 20 key reactions present in the core model. The glycolysis flux range doubles due to the possibility of active gluconeogenesis, the TCA flux range expanded by 80% due to the availability of a bypass through arginine consistent with labeling data, and the transhydrogenase reaction flux was essentially unresolved due to the presence of as many as five routes for the inter-conversion of NADPH to NADH afforded by the genome-scale model. By globally accounting for ATP demands in the GSMM model the unused ATP decreased drastically with the lower bound matching the maintenance ATP requirement. A non

  20. Hydrogen Sulfide as Endothelial Derived Hyperpolarizing Factor Sulfhydrates Potassium Channels

    PubMed Central

    Mustafa, Asif K.; Sikka, Gautam; Gazi, Sadia K.; Steppan, Jochen; Jung, Sung M.; Bhunia, Anil K.; Barodka, Viachaslau M.; Gazi, Farah K.; Barrow, Roxanne K.; Wang, Rui; Amzel, L. Mario; Berkowitz, Dan E.; Snyder, Solomon H.

    2011-01-01

    Rationale Nitric oxide, the classic endothelial derived relaxing factor (EDRF), acts via cyclic GMP and calcium without notably affecting membrane potential. A major component of EDRF activity derives from hyperpolarization and is termed endothelial derived hyperpolarizing factor (EDHF). Hydrogen sulfide (H2S) is a prominent EDRF, since mice lacking its biosynthetic enzyme, cystathionine γ-lyase (CSE), display pronounced hypertension with deficient vasorelaxant responses to acetylcholine. Objective The purpose of this study is to determine if H2S is a major physiologic EDHF. Methods and Results We now show that H2S is a major EDHF, as in blood vessels of CSE deleted mice hyperpolarization is virtually abolished. H2S acts by covalently modifying (sulfhydrating) the ATP-sensitive potassium channel, as mutating the site of sulfhydration prevents H2S-elicited hyperpolarization. The endothelial intermediate conductance (IKCa) and small conductance (SKCa) potassium channels mediate in part the effects of H2S, as selective IKCa and SKCa channel inhibitors, charybdotoxin and apamin, inhibit glibenclamide insensitive H2S induced vasorelaxation. Conclusions H2S is a major EDHF that causes vascular endothelial and smooth muscle cell hyperpolarization and vasorelaxation by activating the ATP-sensitive, intermediate conductance and small conductance potassium channels through cysteine S-sulfhydration. As EDHF activity is a principal determinant of vasorelaxation in numerous vascular beds, drugs influencing H2S biosynthesis offer therapeutic potential. PMID:21980127

  1. Complexation of oxygen ligands with dimeric rhodium(II) tetrakistrifluoroacetate in chloroform: 1H, 13C NMR and DFT studies

    NASA Astrophysics Data System (ADS)

    Głaszczka, Rafał; Jaźwiński, Jarosław

    2013-03-01

    The complexation of dimeric rhodium(II) tetrakistrifluoroacetylate with 25 ligands containing oxygen atoms: alcohols, ethers, ketones, aldehydes, carboxylic acids and esters in chloroform solution have been investigated by 1H and 13C NMR spectroscopy and Density Functional Theory (DFT) methods. Investigated ligands form 1:1 adducts in our experimental conditions, with stability constants in the order of several hundred mol-1. The exchange of ligands in solution is fast on the NMR spectroscopic timescale. The decrease of longitudinal relaxation times T1 in ligands in the presence of rhodium salt has been tested as the means of determination of the complexation site in ligands. The influence of complexation on chemical shifts in ligands was evaluated by a parameter complexation shift Δδ (Δδ = δadd - δlig). These parameters were positive (>0 ppm) and did not exceed 1 ppm for 1H NMR; and varied from ca. -5 to +15 ppm in the case of 13C NMR. The calculation by DFT methods using the B3LYP functional (structure optimization, electronic energy) and B3PW91 functional (shielding), and combinations of the (6-31G(2d), 6-311G++(2d,p), and LANL2DZ basis sets, followed by scaling procedures reproduced satisfactorily 1H and 13C chemical shifts and, with some limitations, allowed to estimate Δδ parameters.

  2. Development of a rapid method for the quantification of cellulose in tobacco by (13)C CP/MAS NMR.

    PubMed

    Jiang, Jinhui; Hu, Yonghua; Tian, Zhenfeng; Chen, Kaibo; Ge, Shaolin; Xu, Yingbo; Tian, Dong; Yang, Jun

    2016-01-01

    A method was developed for rapid quantitative determination of cellulose in tobacco by utilizing (13)C cross polarization magic angle spinning NMR spectroscopy ((13)C CP/MAS NMR). Sample powder was loaded into NMR rotor, which was customized rotor containing a matched silicon tube as an intensity reference. (13)C CP/MAS NMR spectra of tobacco samples were processed with spectral deconvolution to obtain the area of the C-1 resonance at 105.5ppm and the internal standard at 0ppm. The ratio between the area of 105.5ppm and 0ppm of a set of standard cellulose samples was used to construct a calibration curve. The cellulose content of a tobacco sample was determined by comparison of the ratio between the area of 105.5ppm and 0ppm to the calibration curve. Results of this developed method showed good agreement with those obtained from chemical analysis. The proposed method has such advantages of accuracy, quickness and efficiency, and could be an alternative to chemical analyses of cellulose.

  3. Catabolism of glucose and lactose in Bifidobacterium animalis subsp. lactis, studied by 13C Nuclear Magnetic Resonance.

    PubMed

    González-Rodríguez, Irene; Gaspar, Paula; Sánchez, Borja; Gueimonde, Miguel; Margolles, Abelardo; Neves, Ana Rute

    2013-12-01

    Bifidobacteria are widely used as probiotics in several commercial products; however, to date there is little knowledge about their carbohydrate metabolic pathways. In this work, we studied the metabolism of glucose and lactose in the widely used probiotic strain Bifidobacterium animalis subsp. lactis BB-12 by in vivo (13)C nuclear magnetic resonance (NMR) spectroscopy. The metabolism of [1-(13)C]glucose was characterized in cells grown in glucose as the sole carbon source. Moreover, the metabolism of lactose specifically labeled with (13)C on carbon 1 of the glucose or the galactose moiety was determined in suspensions of cells grown in lactose. These experiments allowed the quantification of some intermediate and end products of the metabolic pathways, as well as determination of the consumption rate of carbon sources. Additionally, the labeling patterns in metabolites derived from the metabolism of glucose specifically labeled with (13)C on carbon 1, 2, or 3 in cells grown in glucose or lactose specifically labeled in carbon 1 of the glucose moiety ([1-(13)Cglucose]lactose), lactose specifically labeled in carbon 1 of the galactose moiety ([1-(13)Cgalactose]lactose), and [1-(13)C]glucose in lactose-grown cells were determined in cell extracts by (13)C NMR. The NMR analysis showed that the recovery of carbon was fully compatible with the fructose 6-phosphate, or bifid, shunt. The activity of lactate dehydrogenase, acetate kinase, fructose 6-phosphate phosphoketolase, and pyruvate formate lyase differed significantly between glucose and lactose cultures. The transcriptional analysis of several putative glucose and lactose transporters showed a significant induction of Balat_0475 in the presence of lactose, suggesting a role for this protein as a lactose permease. This report provides the first in vivo experimental evidence of the metabolic flux distribution in the catabolic pathway of glucose and lactose in bifidobacteria and shows that the bifid shunt is the only

  4. Catabolism of Glucose and Lactose in Bifidobacterium animalis subsp. lactis, Studied by 13C Nuclear Magnetic Resonance

    PubMed Central

    González-Rodríguez, Irene; Gaspar, Paula; Sánchez, Borja; Gueimonde, Miguel; Neves, Ana Rute

    2013-01-01

    Bifidobacteria are widely used as probiotics in several commercial products; however, to date there is little knowledge about their carbohydrate metabolic pathways. In this work, we studied the metabolism of glucose and lactose in the widely used probiotic strain Bifidobacterium animalis subsp. lactis BB-12 by in vivo 13C nuclear magnetic resonance (NMR) spectroscopy. The metabolism of [1-13C]glucose was characterized in cells grown in glucose as the sole carbon source. Moreover, the metabolism of lactose specifically labeled with 13C on carbon 1 of the glucose or the galactose moiety was determined in suspensions of cells grown in lactose. These experiments allowed the quantification of some intermediate and end products of the metabolic pathways, as well as determination of the consumption rate of carbon sources. Additionally, the labeling patterns in metabolites derived from the metabolism of glucose specifically labeled with 13C on carbon 1, 2, or 3 in cells grown in glucose or lactose specifically labeled in carbon 1 of the glucose moiety ([1-13Cglucose]lactose), lactose specifically labeled in carbon 1 of the galactose moiety ([1-13Cgalactose]lactose), and [1-13C]glucose in lactose-grown cells were determined in cell extracts by 13C NMR. The NMR analysis showed that the recovery of carbon was fully compatible with the fructose 6-phosphate, or bifid, shunt. The activity of lactate dehydrogenase, acetate kinase, fructose 6-phosphate phosphoketolase, and pyruvate formate lyase differed significantly between glucose and lactose cultures. The transcriptional analysis of several putative glucose and lactose transporters showed a significant induction of Balat_0475 in the presence of lactose, suggesting a role for this protein as a lactose permease. This report provides the first in vivo experimental evidence of the metabolic flux distribution in the catabolic pathway of glucose and lactose in bifidobacteria and shows that the bifid shunt is the only pathway

  5. High-field n.m.r. studies of keratan sulphates. 1H and 13C assignments of keratan sulphate from shark cartilage.

    PubMed

    Cockin, G H; Huckerby, T N; Nieduszynski, I A

    1986-06-15

    Keratan sulphate was extracted from a shark/whale cartilage preparation and examined by 400 MHz 1H- and 100 MHz 13C-n.m.r. spectroscopy. Assignment of the majority of the resonances was facilitated by two-dimensional 13C-1H correlation by using a modified COLOC procedure and a COSY-45 experiment. The spectra are consistent with an N-acetyl-lactosamine repeating unit that is predominantly sulphated at C-6 of both galactose and N-acetylglucosamine. Gel chromatography of a keratanase digest of the shark keratan sulphate confirmed the high degree of galactose sulphation.

  6. Synthesis of isotopically labeled R- or S-[.sup.13C, .sup.2H] glycerols

    DOEpatents

    Martinez, Rodolfo A.; Unkefer, Clifford J.; Alvarez, Marc A.

    2008-01-22

    The present invention is directed to asymmetric chiral labeled glycerols including at least one chiral atom, from one to two .sup.13C atoms and from zero to four deuterium atoms bonded directly to a carbon atom, e.g., (2S) [1,2-.sup.13C.sub.2]glycerol and (2R) [1,2-.sup.13C.sub.2]glycerol, and to the use of such chiral glycerols in the preparation of labeled amino acids.

  7. Measuring (13)C-(2)D dipolar couplings with a universal REDOR dephasing curve

    PubMed

    Gullion

    2000-09-01

    A (13)C-observe REDOR experiment is described which allows (13)C-(2)D dipolar couplings to be obtained by a universal dipolar dephasing curve. Previous (13)C-observe REDOR experiments on (13)C-(2)D spin pairs generally relied on numerical simulations to obtain the dipolar coupling. The REDOR experiment described in this article is based on a deuterium composite pulse, and the data analysis eliminates the need for numerical simulations and is the same as the traditional REDOR analysis performed on pairs of spin-12 nuclei. Copyright 2000 Academic Press. PMID:10968975

  8. Nuclear hyperpolarization in solids and the prospects for nuclear spintronics.

    PubMed

    Reimer, Jeffrey A

    2010-01-01

    Nuclear hyperpolarization can be achieved in a number of ways. This article focuses on the use of coupling of nuclei to (nearly) pure quantum states, with particular emphasis on those states obtained by optical excitation in bulk semiconductors. I seek an answer to this question: "What is to prevent the design and analysis of nuclear spintronics devices that use the extremely long-lived hyperpolarized nuclear spin states, and their weak couplings to each other, to affect computation, memory, or informational technology schemes?" The answer, I argue, is in part because there remains a lack of fundamental understanding of how to generate and control nuclear polarization with schemes other than with rf coils.

  9. New study of the astrophysical reaction 13C(a,n)16O via the 13C(7Li,t)17O transfer reaction

    NASA Astrophysics Data System (ADS)

    Pellegriti, Maria Grazia; Hammache, F.; Roussel, P.; Audouin, L.; Beaumel, D.; Fortier, S.; Gaudefroy, L.; Kiener, J.; Lefebvre-Schujl, A.; Stanoiu, M.; Tatischeff, V.; Vilmay, M.

    PoS(NIC-IX)161 , , [1] , L. Gaudefroy[2] , J. Kiener[3] , A. Lefebvre-Schuhl[3] , M. Stanoiu[4] , V. The cross section of the 13 C(α,n)16 O reaction is a key ingredient for the comprehension of the s-process (slow neutron captures) in stars. This reaction is considered as the main neutron source for the s-process in low-mass Asymptotic Giant Branch (AGB) stars (1-3 solar mass) [1, 2, 3]. At the α-13 C energies of astrophysical interest (Ecm around 190 keV, corresponding to a tem- perature of 108 K) the contribution of the 17 O α-decay subthreshold resonance at 6.356 MeV to the 13 C(α,n)16 O cross section should be taken into account. The effect of this resonance is controversial after the different analyses of the Kubono et al. measurement [4] of the 6.356 MeV α-spectroscopic factor (Sα ) via the transfer reaction 13 C(6 Li,d)17 O . In order to further investigate the contribution of the 6.356 MeV resonance to the 13 C(α,n)16 O cross section, we performed a new measurement of its Sα factor via a different α-transfer reac- tion, namely the 13 C(7 Li,t)17 O reaction. The experiment was performed at the Orsay Tandem by using a 7 Li beam of 28 and 34 MeV on a 13C target. The angular distribution for the transfer dif- ferential cross section was measured by detecting the tritons at the focal plane of the SPLITPOLE spectrometer. The analysis procedure used in order to extract the yield of the 6.356 MeV level will be described. Preliminary results of the angular distribution will be shown.

  10. Synthesis of aromatic (13)C/(2)H-α-ketoacid precursors to be used in selective phenylalanine and tyrosine protein labelling.

    PubMed

    Lichtenecker, R J

    2014-10-14

    Recent progress in protein NMR spectroscopy revealed aromatic residues to be valuable information sources for performing structure and motion analysis of high molecular weight proteins. However, the applied NMR experiments require tailored isotope labelling patterns in order to regulate spin-relaxation pathways and optimize magnetization transfer. We introduced a methodology to use α-ketoacids as metabolic amino acid precursors in cell-based overexpression of phenylalanine and/or tyrosine labelled proteins in a recent publication, which we have now developed further by providing synthetic routes to access the corresponding side-chain labelled precursors. The target compounds allow for selective introduction of (13)C-(1)H spin systems in a highly deuterated chemical environment and feature alternating (12)C-(13)C-(12)C ring-patterns. The resulting isotope distribution is especially suited to render straightforward (13)C spin relaxation experiments possible, which provide insight into the dynamic properties of the corresponding labelled proteins.

  11. Molecular structure, vibrational and 13C NMR spectra of two ent-kaurenes spirolactone type diterpenoids rabdosinate and rabdosin B: A combined experimental and density functional methods

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Wang, Xueliang

    2015-01-01

    The title compounds, rabdosinate and rabdosin B, were isolated from the leaves of Isodon japonica, and characterized by IR-NMR spectroscopy. The molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO-13C) chemical shift values of the title compounds have been calculated by using DFT/B3LYP method with 6-311++G(d,p) basis set. In addition, obtained results were related to the linear regression of experimental 13C NMR chemical shifts values. The integral equation formalism polarized continuum model (IEFPCM) was used in treating chloroform solvation effects on optimized structural parameters and 13C chemical shifts. Besides, molecular electrostatic potential (MEP), HOMO-LUMO analysis were performed by the B3LYP method.

  12. Molecular structure, vibrational and 13C NMR spectra of two ent-kaurenes spirolactone type diterpenoids rabdosinate and rabdosin B: a combined experimental and density functional methods.

    PubMed

    Wang, Tao; Wang, Xueliang

    2015-01-25

    The title compounds, rabdosinate and rabdosin B, were isolated from the leaves of Isodon japonica, and characterized by IR-NMR spectroscopy. The molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO-13C) chemical shift values of the title compounds have been calculated by using DFT/B3LYP method with 6-311++G(d,p) basis set. In addition, obtained results were related to the linear regression of experimental 13C NMR chemical shifts values. The integral equation formalism polarized continuum model (IEFPCM) was used in treating chloroform solvation effects on optimized structural parameters and 13C chemical shifts. Besides, molecular electrostatic potential (MEP), HOMO-LUMO analysis were performed by the B3LYP method. PMID:25123947

  13. Molecular structure, vibrational and 13C NMR spectra of two ent-kaurenes spirolactone type diterpenoids rabdosinate and rabdosin B: a combined experimental and density functional methods.

    PubMed

    Wang, Tao; Wang, Xueliang

    2015-01-25

    The title compounds, rabdosinate and rabdosin B, were isolated from the leaves of Isodon japonica, and characterized by IR-NMR spectroscopy. The molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO-13C) chemical shift values of the title compounds have been calculated by using DFT/B3LYP method with 6-311++G(d,p) basis set. In addition, obtained results were related to the linear regression of experimental 13C NMR chemical shifts values. The integral equation formalism polarized continuum model (IEFPCM) was used in treating chloroform solvation effects on optimized structural parameters and 13C chemical shifts. Besides, molecular electrostatic potential (MEP), HOMO-LUMO analysis were performed by the B3LYP method.

  14. A Large Metabolic Carbon Ccontribution to the δ13C Record in Marine Aragonitic Bivalve Shells

    NASA Astrophysics Data System (ADS)

    Gillikin, D. P.; Lorrain, A.; Dehairs, F.

    2006-12-01

    The stable carbon isotopic signature archived in bivalve shells was originally thought to record the δ13C of seawater dissolved inorganic carbon (δ13C-DIC). However, more recent studies have shown that the incorporation of isotopically light metabolic carbon (M) significantly affects the δ13C signal recorded in biogenic carbonates. To assess the M contribution to Mercenaria mercenaria shells collected in North Carolina, USA, we sampled seawater δ13C-DIC, tissue, hemolymph and shell δ13C. We found up to a 4‰ decrease through ontogeny in shell δ13C in a 23 year old individual. There was no correlation between shell height or age and tissue δ13C. Thus, the ontogenic decrease observed in the shell δ13C could not be attributed to changes in food sources as the animal ages leading to more negative metabolic CO2, since this would require a negative relationship between tissue δ13C and shell height. Hemolymph δ13C, on the other