Iridium-catalysed ortho-H/D and -H/T exchange under basic conditions : C-H activation of unprotected tetrazoles

The first examples of selective ortho-directed C-H activation with unprotected 2-aryltetrazoles are described. A new base-assisted protocol for iridium (I) hydrogen isotope exchange catalysis allows access to ortho-deuterated and tritiated tetrazoles, including the tetrazole-containing pharmaceutical, Valsartan. Preliminary mechanistic studies are also presented

Applications of hydrogen isotopes in the life sciences

Hydrogen isotopes are unique tools for identifying and understanding biological or chemical processes. Hydrogen isotope labeling allows for a traceless and direct incorporation of an additional mass or radioactive tag into an organic molecule with almost no change in its chemical structure, physical properties or biological activity. Using deuterium labeled isotopologues to study the unique mass spectrometric (MS)-pattern generated from mixtures of biological relevant molecules drastically simplifies analysis. Such methods are now providing unprecedented levels of insight in a wide and continuously growing range of applications in the life sciences and beyond. Tritium (3H), in particular, has seen an increased utilization, especially in pharmaceutical drug discovery. The efforts and costs required for the synthesis of labeled compounds are more than compensated for by the enhanced molecular sensitivity for analysis and high reliability of the data obtained. In this review, advances in the applications of hydrogen isotopes in the life sciences are described

Iridium-catalyzed Csp3-H activation for mild and selective hydrogen isotope exchange

The increasing demand for isotopically labeled compounds has provided appreciable impetus for the development of improved methods for the late stage introduction of isotopes of hydrogen (deuterium or tritium). Moreover, sp3-rich molecules are becoming increasingly common in the exploration of chemical space for drug design. Herein, we report an efficient iridium(I) catalysed C-H activation method for the hydrogen isotope exchange of sp3 C-H bonds. A wide range of substrates have been labeled, including active pharmaceutical ingredients, delivering excellent levels of isotope incorporation and predictable regiocontrol, with low catalyst loadings, in short reaction times, and under mild reaction conditions

Brain responses to musical feature changes in adolescent cochlear implant users

Cochlear implants (CIs) are primarily designed to assist deaf individuals in perception of speech, although possibilities for music fruition have also been documented. Previous studies have indicated the existence of neural correlates of residual music skills in postlingually deaf adults and children. However, little is known about the behavioral and neural correlates of music perception in the new generation of prelingually deaf adolescents who grew up with CIs. With electroencephalography (EEG), we recorded the mismatch negativity (MMN) of the auditory event-related potential to changes in musical features in adolescent CI users and in normal-hearing (NH) age mates. EEG recordings and behavioral testing were carried out before (T1) and after (T2) a 2-week music training program for the CI users and in two sessions equally separated in time for NH controls. We found significant MMNs in adolescent CI users for deviations in timbre, intensity, and rhythm, indicating residual neural prerequisites for musical feature processing. By contrast, only one of the two pitch deviants elicited an MMN in CI users. This pitch discrimination deficit was supported by behavioral measures, in which CI users scored significantly below the NH level. Overall, MMN amplitudes were significantly smaller in CI users than in NH controls, suggesting poorer music discrimination ability. Despite compliance from the CI participants, we found no effect of the music training, likely resulting from the brevity of the program. This is the first study showing significant brain responses to musical feature changes in prelingually deaf adolescent CI users and their associations with behavioral measures, implying neural predispositions for at least some aspects of music processing. Future studies should test any beneficial effects of a longer lasting music intervention in adolescent CI users.Peer reviewe

Electronic neutron personal dosemeters: their performance in mixed radiation fields in nuclear power plants

This work describes spectral distributions of neutrons obtained as function of energy and direction at four workplace fields at the Krümmel reactor in Germany. Values of personal dose equivalent Hp(10) and effective dose E are determined for different directions of a person's orientation in these fields and readings of personal neutron dosemeters—especially electronic dosemeters—are discussed with respect to Hp(10) and

Summary of personal neutron dosemeter results obtained within the EVIDOS project

Within the EC project EVIDOS (‘Evaluation of Individual Dosimetry in Mixed Neutron and Photon Radiation Fields'), different types of active neutron personal dosemeters (and some passive ones) were tested in workplace fields at nuclear installations in Europe. The results of the measurements which have been performed up to now are summarised and compared to our currently best estimates of the personal dose equivalent Hp(10). Under- and over-readings by more than a factor of two for the same dosemeter in different workplace fields indicate that in most cases the use of field-specific correction factors is require

Individual neutron monitoring in workplaces with mixed neutron/photon radiation

EVIDOS (‘evaluation of individual dosimetry in mixed neutron and photon radiation fields') is an European Commission (EC)-sponsored project that aims at a significant improvement of radiation protection dosimetry in mixed neutron/photon fields via spectrometric and dosimetric investigations in representative workplaces of the nuclear industry. In particular, new spectrometry methods are developed that provide the energy and direction distribution of the neutron fluence from which the reference dosimetric quantities are derived and compared to the readings of dosemeters. The final results of the project will be a comprehensive set of spectrometric and dosimetric data for the workplaces and an analysis of the performance of dosemeters, including novel electronic dosemeters. This paper gives an overview of the project and focuses on the results from measurements performed in calibration fields with broad energy distributions (simulated workplace fields) and on the first results from workplaces in the nuclear industry, inside a boiling water reactor and around a spent fuel transport cas