The Synthesis of Amino Acid Methyl Ester 5′-Phosphoamidates of Protected Uridine

In this article, we used the Atherton–Todd reaction to synthesize amino acid methyl ester 5′-phosphoamidates of uridine as prodrugs. Their structures were confirmed by ¹H NMR, ³¹P NMR, ¹³C NMR, IR, and mass spectrometry.

Supplemental materials are available for this article. Go to the publisher′s online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

2H Chemical-shift resolution and dipolar2H-1H,2H-15N correlations in solid-state MAS NMR spectroscopy for structure determination and distance measurements in hydrogen-bonded systems

In solid-state NMR, deuteron (²H) spectroscopy can be performed in full analogy to¹H spectroscopy, including²H chemical-shift resolution and²H-X dipolar correlation schemes, when the NMR experiments are conducted in a “rotor-synchronized” fashion under fast magic-angle spinning. Here, 2H-X NMR experiments of this type, including²H-¹⁵N and²H-¹H chemical-shift correlations and distance measurements, are introduced and demonstrated on cytosine monohydrate, whose acidic protons can readily be replaced by deuterons by recrystallization from D₂O. In this way,²H NMR spectroscopy provides information complementary to¹H NMR data, which is particularly useful for studying hydrogen bonds in supra- or biomolecular systems. Electronic supplementary material Supplementary material is available in the online versionof this article atand is accessible for authorized users.     

Development of a fully automated toxicological LC-MS<Superscript>n</Superscript> screening system in urine using online extraction with turbulent flow chromatography

In clinical toxicology, fast and specific methods are necessary for the screening of different classes of drugs. Therefore, an online extraction high-performance liquid chromatography coupled to mass spectrometry (LC-MSⁿ) screening method using a MS² and MS³ spectral library for the identification of xenobiotic substances has been developed and validated. Samples were run twice, once native and once after enzymatic hydrolysis. Internal standards and buffer were added to the urine samples. Following centrifugation, the supernatant was injected into the system. Extraction was performed by online turbulent flow chromatography. The chromatographic separation was achieved using a Phenyl/Hexyl column. For detection, a linear ion trap, equipped with an APCI interface, was used and the different compounds were identified using a MS² and MS³ spectral library containing 356 compounds. The turnaround time to report the results of the screening including hydrolysis was approximately 2 h. About 92% of the 356 substances could be identified with a limit of identification below 100 ng/ml. The recovery and matrix effect experiments showed suitable results, and in six drug-free urine samples of healthy volunteers analyzed for selectivity, no substances have been identified. Carryover could be well controlled, and the method had a good reproducibility. The comparison of the results of 103 real patient urine samples showed a good agreement between the existing GC-MS and LC-MS methods with offline extraction and the new online extraction LC-MSⁿ screening method. The presented method allows a fast and sensitive analysis of a broad range of compounds.     

The effect of high amounts of chlorine and sodium on measurement of aluminum by instrumental neutron activation analysis and decrease of spectrum noises by means of digital low pass filter equations

Aluminum is a pathogenic factor in some diseases, like Alzheimer and aluminum toxicity in dialysis patients. This subject signifies Al measurement in biological samples. Different methods have been proposed for Al determination. One of the known methods for the analysis of this element is instrumental neutron activation analysis (INAA). ³¹P, ²⁸Si, ³²Cl and ²⁴Na interfere the determination of Al in this method. In this study, the effects of high amounts of ³⁸Cl and ²⁴Na on the measurement of ²⁸Al are discussed. The data gathered by the detector is filtered by an equation named digital low pass filter equation with the help of a computer. The net-areas of filtered and non-filtered peaks of ²⁸Al are compared. Finally these areas are compared with the net-area of ²⁸Al peak in the standard reference material, NIST-SRM-1547. This revised version was published online in July 2006 with corrections to the Cover Date.     

Measurement and behavior of 14C and 129I in the environment

¹⁴C and ¹²⁹I are known to be the most important radionuclides in the global scale long-term radiological assessment of a reprocessing plant in the UNSCEAR reports. Both nuclides have sufficiently long half-lives, 5,730 years and 1.6^.10⁷ years, respectively, and readily migrate through the ecological environment, achieving widespread distribution. ¹⁴C is also an important radionuclide for regional radiological assessment because it gives a significant fraction of effective dose to the public through atmosphere-rice ingestion pathway. ¹²⁹I is not dominant for the regional radiological effect but its behavior in the environment has been interested to get basic data for long-term worldwide assessment. In this paper, investigations for discharge behaviors of ¹⁴C and ¹²⁹I nuclides, amounts of discharges and environmental concentrations are discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Generation of metabolites by an automated online metabolism method using human liver microsomes with subsequent identification by LC-MS(n), and metabolism of 11 cathinones

Human liver microsomes (HLMs) are used to simulate human xenobiotic metabolism in vitro. In forensic and clinical toxicology, HLMs are popularly used to study the metabolism of new designer drugs for example. In this work, we present an automated online extraction system we developed for HLM experiments, which was compared to a classical offline approach. Furthermore, we present studies on the metabolism of 11 cathinones; for eight of these, the metabolism has not previously been reported. Metabolites were identified based on MS² and MS³ scans. Fifty-three substances encompassing various classes of drugs were employed to compare the established offline and the new online methods. The metabolism of each of the following 11 cathinones was studied using the new method: 3,4-methylenedioxy-N-benzylcathinone, benzedrone, butylone, dimethylcathinone, ethylone, flephedrone, methedrone, methylone, methylethylcathinone, naphyrone, and pentylone. The agreement between the offline and the online methods was good; a total of 158 metabolites were identified. Using only the offline method, 156 (98.7%) metabolites were identified, while 151 (95.6%) were identified using only the online method. The metabolic pathways identified for the 11 cathinones included the reduction of the keto group, desalkylation, hydroxylation, and desmethylenation in cathinones containing a methylenedioxy moiety. Our method provides a straightforward approach to identifying metabolites which can then be added to the library utilized by our clinical toxicological screening method. The performance of our method compares well with that of an established offline HLM procedure, but is as automated as possible.     

Application of 129I as an environmental tracer

¹²⁹I is produced naturally by cosmic-ray spallation of Xe and by spontaneous fission of ²³⁸U. In the environment ¹²⁹I is mainly due to nuclear weapon tests and reprocessing plants. The high water solubility of iodine makes ¹²⁹I a good oceanographic tracer. Long residence time and large air releases of ¹²⁹I from reprocessing plants allow ¹²⁹I to be used as a geochemical and metrological tracer. The same chemical and physical properties of ¹²⁹I and ¹³¹I enable one to use ¹²⁹I as a tool for the reconstruction of ¹³¹I doses after a nuclear accident. Some studies using ¹²⁹I as a tracer which were carried out in the author's laboratory, are summarized. This revised version was published online in July 2006 with corrections to the Cover Date.     

Photocatalytic destruction of catechol on illuminated titania

First-order kinetics was found for the photocatalytic oxidation of catechol on TiO₂. Kinetic constants calculated from the Langmuir-Hinshelwood equation are: k=2.03x10^-8 mol dm^-3 s^-1; K_ads=1.63x10⁴ dm³ mol^-1. Full catechol mineralization is a multistep reaction, 1,2,4-benzenetriol and glycol are the main intermediates. This revised version was published online in August 2006 with corrections to the Cover Date.     

On electrostatic chiral discrimination

In this paper, the roles of interbond angles, bond lengths, and electric charges in intermolecular electrostatic Chiral Discrimination (ChD) in the regimes of high temperature T and large intermolecular distance D are investigated. When both interacting molecules have asymmetries involving only interbond angles, or bond lengths, or charges, ChD varies as D^-17, D^-21, D^-24, respectively. In addition, ChD due to dispersion forces is studied. Given the popularity of computer calculations, the estimation of ChD between the various types of molecules can be used as a testbed for accuracy. This revised version was published online in July 2006 with corrections to the Cover Date.     

One-Step Synthesis of Unsymmetrical Sulfides Bearing Hexafluorocumyl Moiety

A facile and convenient one-pot synthesis of novel unsymmetrical sulfides, 2′-alkylthio- and 2′-arylthio-1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-oles 1a–k, is presented. Physicochemical characterization; IR infrared; ¹H, ¹³C, and ¹⁹F NMR; and mass spectral analyses of the obtained compounds are discussed as well.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]