High Isotopic Purity Research Articles

A facile synthesis of 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one as a deuterium labeled synthon for (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide.

Deuterium-labeled biologically active compounds are gaining importance because they can be utilized as tracers or surrogate compounds to understand the mechanism of action, absorption, distribution, metabolism, and excretion. Deuterated drug molecules (heavy drugs) become novel as well as popular because of better stability and bioavailability compared with their hydrogen analogs. Labeling of organic molecules with deuterium at specific positions is thus gaining popularity. In this work, we have exploited a highly regioselective and enantioselective direct Michael addition of methyl-d3 alkyl ketones to dimethyl(phenyl)silylmethylene malonate that was catalyzed by (S)-N-(2-pyrrolidinylmethyl)pyrrolidine/trifluoroacetic acid/ D2 O combination with high yield and isotopic purity. The 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one was obtained from the adduct of methyl-d3 undecanyl ketone and dimethyl(phenyl)silylmethylene malonate by a silicon controlled diastereoselective ketone reduction, lactonization, and deethoxycarbonylation. The dideuterated silylated tetrahydropyran-2-one is the precursor for geminal (2) H2 -labeled (+)-4-hydroxy-6-undecyl-tetrahydropyran-2-one, an advanced intermediate for gem-dideutero (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide syntheses.

Monoisotopic varieties of silicon and germanium with a high chemical and isotopic purity

We presented the results on the preparation of high-purity monoisotopic varieties of silicon and germanium. The process involves the separation of isotopes in the form of SiF4 and GeH4 by centrifugation, ultrapurification of volatile compounds, and preparation of poly and single crystals. The attained degree of isotopic and chemical purities of single crystals obtained was shown. The content of the main isotope in the single crystals of 28Si is >99.99% and those in the single crystals of 29Si and 30Si are >99.9%. The specific resistivity of the 28Si single crystals is ∼1 kOhm cm and those of 29Si and 30Si are about 100–150 Ohm cm. The samples of the 76Ge single crystals have the main isotope content of >88 at.% and the difference concentration of electrochemically active impurities of 5·1010 cm−3. The main isotope content in the 74Ge polycrystal is 99.93 at.%. The optical and thermophysical properties of the isotope-enriched silicon and germanium single crystals were measured, which suggest a significant effect of the isopotic composition on thermal capacity, thermal conductivity, luminiscence, and light absorption.

Simultaneous Measurements of the Torsional Oscillator Anomaly and Thermal Conductivity in SolidHe4

In these torsional oscillator experiments, the samples of solid (4)He were characterized by measuring their thermal conductivity. Polycrystalline samples of helium of either high isotopic purity or natural concentration of (3)He were grown in an annular container by the blocked-capillary method and investigated before and after annealing. No correlation has been found between the magnitude of the low-temperature shift of the torsional oscillator frequency and the amount of crystalline defects as measured by the thermal conductivity. In samples with the natural (3)He concentration, a substantial excess thermal conductivity over the usual T(3) dependence was observed below 120 mK.

Synthesis of deuterium‐labeled (24R)‐methyl brassinosteroids

AbstractSynthesis of labeled brassinosteroids (24‐epibrassinolide and its biosynthetic precursors) containing three deuterium atoms in the terminal part of the side chain is reported. Labeling was achieved by three‐step reductive transformation of carbethoxy group into methyl using lithium aluminium deuteride. The proposed method ensured high isotopic purity of (24R)‐methyl brassinosteroids containing a label in a position which is not subjected to its loss. Copyright © 2011 John Wiley & Sons, Ltd.

Efficient 16O–18O isotope exchange reactions of carbonyl compounds in aqueous organic solvents catalyzed by acidic resin

A facile preparative method for stable isotope labeled molecules is widely demanded in analytical standard chemicals, biochemical science and medical applications. A rapid 16O–18O isotope exchange reaction of carbonyl group to attain a high isotopic purity has been demonstrated using a capillary column reactor packed with Dowex 50WX4 resin as a solid acid catalyst. Thus, carbonyl-18O compounds such as benzaldehyde-18O, 3-/4-nitrobenzaldehydes-18O, 1-naphthaldehyde-18O and acetophenone-18O were produced with more than 95at.% purity under the stable flow operation at a moderate temperature within a residence time of 51s, when the acetonitrile solutions of carbonyl-16O compounds were injected to the reactor with 100eq.mol of H218O. The maximal product isotopic ratio, zmax, has been formularized as zmax=(x0y+z0)/(y+1), where x0 and z0 are isotopic ratio of H2O and carbonyl group as reactants, respectively, and y is the molar ratio [H2O]/[carbonyl group]. The achievement ratio of the actual isotopic ratio (z) to theoretical zmax has reached 0.98 or higher.

Production of silanes 29SiH4 and 30SiH4 of high chemical and isotopic purity

Production of silanes 29SiH4 and 30SiH4 of high chemical and isotopic purity

Low frequency shear modulus of bcc 3He below 1 K

Recent measurements on hcp 4He crystals showed an anomalous stiffening of the shear modulus below 200 mK. This is the temperature range in which torsional oscillator experiments saw evidence of supersolidity. The temperature, frequency, strain amplitude and 3He impurity dependence of the shear modulus mirrored that of the torsional oscillator period, indicating that they are closely connected, although the exact relationship is not clear. The elastic behavior appears to be related to the mobility and impurity pinning of dislocations. Since the behavior of dislocations depends on crystal structure, while supersolidity is not expected in solid 3He, we have extended our shear modulus measurements to the bcc phase of high isotopic purity 3He (1 ppm 4He). We do not see a modulus anomaly like that in hcp 4He, nor is there significant amplitude dependence. We compare the behavior of hcp 4He to that of bcc 3He. Measurements on high purity hcp 3He will provide the most valuable comparison to the supersolid 4He system.

Expedient Deuterolabeling of Polyphenols in Ionic LiquidsDCl/D2O under Microwave Irradiation

Postsynthetic regioselective aromatic ring H/D exchanges in polyphenolic compounds are rapidly performed in high yields and isotopic purities in ionic liquid-DCl/D2O under microwave irradiation. Other C-H bonds, including benzylic and lactone alpha-carbonyl sites, are not affected.

Synthesis of deuterated isoflavone disulfates

AbstractEfficient synthesis of polydeuterated di‐O‐sulfates of three isoflavones, daidzein (1), genistein (2), glycitein (3), is described. The isoflavones were first deuterated with CF3COOD under microwave irradiation to yield daidzein‐d6 (4), genistein‐d4 (5) and glycitein‐d6 (6) in 90% yield and in a high isotopic purity. The deuterated isoflavones were then sulfated with chlorosulfonic acid and pyridine to give the title compounds, again in high yield and isotopic purity (>90%). The compounds are useful as internal standards in LC‐MS quantitation of isoflavones. Copyright © 2006 John Wiley & Sons, Ltd.

Continuous H/D exchange of aromatic hydrocarbons using near-critical deuterium oxide

Near- and supercritical D 2O is both a relatively cheap deuterium source and an environmentally benign solvent for batch-wise H/D exchange reactions. In this work, a new continuous flow reactor online-coupled with liquid–liquid extraction was constructed for the selective deuteration of aromatic hydrocarbons in pressurized hot D 2O at short contact times. Exchange positions were identified by GC–MS, 1H NMR, and FTIR analysis. Four aromatic hydrocarbons (eugenol, 9-fluorenone, 4-hydroxyacetophenone, and xanthone) were screened for H/D exchange in conventional batch reactors with use of near- and supercritical D 2O ( p = 300 bar, t = 2 h, T = 250–450 °C) alone and with basic or metal catalyst (Na 2CO 3, Pd/C). Highest isotopic purities were obtained for deuteration of eugenol ( d 1 = 59%) and 4-hydroxyacetophenone ( d 5 = 91%) in the absence of catalyst. 2H-labelling of these two compounds was then investigated in continuous flow experiments ( p = 300 bar, T = 250–350 °C, τ = 1–4 min). Under optimized conditions, high isotopic purities were obtained for eugenol ( d 1 = 61%) and 4-hydroxyacetophenone ( d 5 = 82%), as before in batch runs, but the contact time, and the probability of decomposition, were significantly reduced. The continuous process developed offers good potential for the deuteration of thermally sensitive substrates.

The closed tritium cycle of KATRIN

The objective of the KArlsruhe TRItium Neutrino experiment (KATRIN) is a direct measurement of the absolute mass of the electron (anti)neutrino by means of a precise spectroscopy of the tritium β -spectrum near its endpoint. KATRIN combines an ultra-luminous molecular windowless tritium source (WGTS) with a high resolution electrostatic retarding spectrometer. It is planned to inject ultra-cold molecular tritium gas of high isotopic purity (>95%) through a set of capillaries at the middle of the 10 m long WGTS tube. For a gas injection pressure of 3.4×10 −3 mbar and a source temperature of 27 K, the column density of the WGTS is fixed to the reference value of 5×10 17 molecules/cm 2. Since the main systematic uncertainty of the WGTS is associated with the column density, it has to be known to a precision of 0.1%. This stability is the most challenging requirement for the KATRIN WGTS and has essentially influenced its design and the design of the connected tritium cycles. Technical solutions to meet these demands are the proposed WGTS tube cooling system by means of two-phase neon to a stability of ±30 mK and the setup of a so-called Inner Loop to achieve a tritium injection rate of 4.7 Ci/s=1.7×10 11 Bq/s (=40 g tritium throughput per day) with a stability on the level of 0.1%. The Tritium Laboratory Karlsruhe is worldwide the only scientific laboratory which can provide the infrastructure necessary to accomplish such a challenging task.

Effects of spectral shifting in an inertial confinement fusion system

Abstract The main objective is to study the effects of spectral shifting in an inertial confinement system for kT/shot energy regime on the breeding performance for tritium and for high quality fissile fuel. A protective liquid droplet jet zone of 2 m thickness is used as coolant, energy carrier, and breeder. Flibe as the main constituent is mixed with increased mole-fractions of heavy metal salt (ThF4 or UF4) starting by 2 moles% up to 12 moles%. Spectrum softening within the inertial confinement system reduces the tritium production ratio (TBR) in the protective coolant to a lower level than unity. However, additional tritium production in the 6Li2DT zone of the system increases TBR to values above unity and allows a continuous operation of the power plant with a self-sustained fusion fuel supply. By modest fusion fuel burn efficiencies (40 to 60 %) and with a few mol.% of heavy metal salt in the coolant in form of ThF4 or % UF4, a satisfactory TBR of > 1.05 can be realized. In addition to that, excess fissile fuel of extremely high isotopic purity with a rate of ∼ 1000 kg/year of 233U or 239Pu can be produced. Radiation damage through atomic displacements and helium gas production after a plant operation period of 30 years is very low, namely dpa < 1 and He < 2 ppm, respectively.

Preparation of deuterated abscisic acid metabolites for use in mass spectrometry and feeding studies

Four deuterium-labelled ABA catabolites of high isotopic purity were prepared for hormone profiling studies using HPLC-ESI-MS-MS. The catabolites, namely [7′,7′,7′-d3]-PA, [7′,7′,7′-d3]-DPA, [5,8′,8′,8′-d4]-7′-hydroxyABA and [4,5,8′,8′,8′-d5]-ABA glucose ester were prepared either by biotransformation or chemical synthesis starting with labelled ABA. The labelled compounds are employed as internal standards for plant hormone profiling by liquid chromatography–electrospray–tandem mass spectrometry. Copyright © 2005 John Wiley & Sons, Ltd.

Stereocontrolled synthesis of (7E,9Z)‐[9,10‐2H]‐conjugated linoleic acid

AbstractTo study the metabolism of minor conjugated linoleic acid isomers (CLAs), (7E,9Z)‐[9,10‐2H] CLA was prepared in three steps from a conjugated enyne precursor. In the labelling step, deuterium atoms were introduced by partial reduction of the triple bond using deuterated disiamylborane and acetic acid‐d4. Deuterated (7E,9Z) CLA was obtained with high isotopic enrichment (>99%) and purity greater than 95%. Copyright © 2004 John Wiley & Sons, Ltd.

Status report on high-pressure TPC

HELLAZ experiment intends to measure with high precision the low-energy solar neutrino (p–p and 7Be) spectrum. The method uses the neutrino elastic scattering over the 2×10 30 electrons contained in a 2000 m 3 TPC filled with helium (for its high radio isotopic purity, its low transverse diffusion and its low drift velocity), at a pressure of 20 bar at 300 K. Reconstructing the neutrino energy requires a precise measurement over the angle and energy (between 100 keV and 1 MeV) of the scattered electron. 1% electron energy accuracy is easy to get through an integral charge measurement. An angular accuracy ≈±2° yields a neutrino energy resolution better than 10%, not only enough to separate the p-p and 7Be spectrum, but which also possibly allows to show the shape variation of p–p spectrum in certain cases of neutrino oscillations. In a TPC the only way to obtain an angular resolution better than 5° is to detect every single ionization electrons of the diffused electron cloud. Hence, we need a very fast detector (collection time ⩽10 ns) and a gain of around 10 6 with a signal over noise ratio near 2 for the single electron detection. The only gas detector that meets the criterion is the MICROMEGAS detector which has a very good separation between electron and ion signal. These conditions are easy to obtain with a gas mixture like He and isoC 4H 10 at atmospheric pressure. But in the real condition at 20 bar, where we currently use CH 4 as a quencher, we are limited to a gain ⩽4–5×10 4. We have studied the dependence of the gain with the gas mixture. Several improvements have been done with a new mixing gas He, isoC 4H 10 and CH 4. After a simulation with IMONTE45 we did obtain the right mixing gas and high gain up to 5×10 5 with near 50% efficiency for the single electron detection. Recently, a new improvement has been done with a double stage MICROMEGAS. With this set-up we obtained 1.6×10 6 and an efficiency greater than 90% for the single electron detection.

Preparation and mass spectrometry of 14 pure and 18O 2-labeled oxidation products from the phytosterols β-sitosterol and stigmasterol

To lower cholesterol, phytosterols are currently introduced as food additives, where they may become oxidized. In addition, specific biological effects of oxyphytosterols are suggested by the recent molecular clarification of the phytosterol storage disease as a dysfunctional mutation of an active sterol reexporter potentially regulated by oxidized phytosterols. We therefore studied the hydroxybenzotriazole-mediated PbO 2-driven oxidation of phytosterols and compared it to the oxidation of cholesterol. We prepared, identified, and purified standards of 14 oxidation products of two major phytosterols. The gas chromatographic mass spectrometric characteristics of the 7α- and 7β-hydroxy-, 5α,6α-epoxy, 5β,6β-epoxy, 7keto-, 3β,5α,6β-trihydroxy-, 3keto-, and 7-dehydro-derivatives of β-sitosterol and stigmasterol are presented. The method also provided a convenient access to prepare 18O-labeled oxyphytosterols of high chemical and isotopic purity and can easily be extended to further phytosterols and -stanols. This enables the gas chromatography–mass spectrometry analysis of oxyphytosterols and the study of their biological effects.

Fissile fuel breeding with peaceful nuclear explosives

Neutron physics analysis of a dual purpose modified PACER concept has been conducted. A protective liquid droplet jet zone of 2 m thickness is considered as coolant, energy carrier, and fusile and fissile breeder. Flibe as the main constituent is mixed with increased mole-fractions of heavy metal salt (ThF 4 and UF 4) starting by 2 up to 12 mol.%. The neutronic model assumed a 30 m radius underground spherical geometry cavity with a 1 cm thick SS-304 stainless steel liner attached to the excavated rock wall. By a self-sufficient tritium breeding of 1.05 with 5 mol.% ThF 4, or 9 mol.% UF 4 an excess nuclear fuel breeding rate of 1900 kg/year of 233U or 3000 kg/year 239Pu of extremely high isotopic purity can be realized. This precious fuel can be considered for special applications, such as spacecraft reactors or other compact reactors. The heavy metal constituents in jet zone acts as an energy amplifier, leading to an energy multiplication of M=1.27 or 1.65 for 5 mol.% ThF 4, or 9 mol.% UF 4, respectively. As an immediate result of the strong neutron attenuation in the jet zone, radiation damage with dpa<1.4 and He<7 ppm after a plant operation period of 30 years will be well below the damage limit values. The site could essentially be abandoned, or the cavity could be used as a shallow burial site for other qualified materials upon decommissioning. Finally, the totality of the site with all nuclear peripheral sections must be internationally safeguarded carefully.

Anomalously high excretion of Pu in urine following inhalation of plutomium nitrate?

A study of the biokinetics of inhaled plutonium nitrate in two volunteers has been carried out. Low doses (approximately 80 microSv) were achievable because tracers of high isotopic purity were used: 237Pu (measurable by X ray spectrometry) and 244Pu (measurable by accelerator mass spectrometry). Lung retention, amount in blood, uptake to the liver and skeleton, and urinary and faecal excretion were measured. The measured urinary excretion rates are about a factor of three higher than those predicted from urine excretion data measured following intravenous injection of plutonium to the same volunteers. If similar biokinetic behaviour occurs in workers exposed to plutonium nitrate, intakes by inhalation and corresponding committed doses assessed by urine bioassay could be consistently overestimated by a similar factor.

Separation of the alpha-emitting radioisotopes actinium-225 and bismuth-213 from thorium-229 using alpha recoil methods

An innovative method has been demonstrated for separating alpha-emitting isotopes for medical radiotherapy applications. The method relies on recoil-ion separation rather than on conventional wet chemistry techniques to separate medical isotopes from their precursor sources. The isotopes 225Ac and 213Bi have been separated from electro-deposited sources of 229ThO 2. Separations of 225Ac were carried out by placing nickel recoil collector foils in firm contact with the 229ThO 2 sources. One-stage recoil-ion separations of 225Ac from 229Th have been performed as well as two-stage separations of 213Bi from previously recoil separated 225Ac. In addition, a direct recoil separation of 213Bi from 229Th has been demonstrated. The 213Bi from the one-stage direct separation has a high isotopic purity, but contains small amounts of long-lived 225Ac alpha activity. The two-stage separations of 213Bi produce high isotopic purity material (>99.9999%), but result in lower isotopic yields. Range-energy calculations have been carried out to determine the yields of recoil ions as a function of alpha-particle energy and ThO 2 thickness. The results of the calculations have been benchmarked with recoil separation measurements carried out using ThO 2 electro-deposits over a range of thickness. A computer code based on the generalized Bateman equations has been developed to allow calculations of the amounts of any isotope in the 229Th decay chain as a function of recoil separation exposure time and elapsed time after the separation. An excellent match has been obtained between the predictions of the Bateman calculations and the results of recoil separation measurements. The recoil separation method has proven to be a simple and effective way of separating medically useful isotopes such as 213Bi. In addition, the method has been shown to produce no chemical or radioactive wastes, in contrast to radiochemical separation methods, which generate mixed (chemical and radioactive) waste.

Isotope-pure silicon layers grown by MBE

Molecular-beam epitaxy with a solid source was used to grow silicon layers enriched with 28Si and 30Si isotopes to 99.93 and 99.34%, respectively. Secondary-ion mass spectrometry and Raman scattering spectroscopy were applied to demonstrate the high isotopic purity and crystal perfection of the layers obtained.