Delft Conference Proceedings Editorial 2008: safety and efficacy for new techniques and imaging using new equipment to support European Legislation

Radiation Protection Dosimetry, 129 (1-3): 1–2     

Oxidation of suspected N-nitrosodimethylamine (NDMA) precursors by ferrate (VI): kinetics and effect on the NDMA formation potential of natural waters

The potential of ferrate (Fe(VI)) oxidation to remove N-nitrosodimethylamine (NDMA) precursors during water treatment was assessed. Apparent second-order rate constants (k(app)) for the reactions of NDMA and its suspected precursors (dimethylamine (DMA) and 7 tertiary amines with DMA functional group) with Fe(VI) were determined in the range of pH 6-12. Four model NDMA precursors (dimethyldithiocarbamate, dimethylaminobenzene, 3-(dimethylaminomethyl)indole and 4-dimethylaminoantipyrine) showed high reactivity toward Fe(VI) with k(app) values at pH 7 between 2.6 x 10(2) and 3.2 x 10(5)M(-1)s(-1). The other NDMA precursors (DMA, trimethylamine, dimethylethanolamine, dimethylformamide) and NDMA had k(app) values ranging from 0.55 to 9.1M(-1)s(-1) at pH 7. In the second part of the study, the NDMA formation potentials (NDMA-FP) of the model NDMA precursors and natural waters were measured with and without pre-oxidation by Fe(VI). For most of the NDMA precursors with the exception of DMA, a significant reduction of the NDMA-FP (>95%) was observed after complete transformation of the NDMA precursor. This result was supported by low yields of DMA from the Fe(VI) oxidation of tertiary amine NDMA precursors. Pre-oxidation of several natural waters (rivers Rhine, Neckar and Pfinz) with a high dose of Fe(VI) (0.38 mM = 21 mg L(-1) as Fe) led to removals of the NDMA-FP of 46-84%. This indicates that the NDMA precursors in these waters have a low reactivity toward Fe(VI) because it has been shown that for fast-reacting NDMA precursors Fe(VI) doses of 20 microM (1.1 mg L(-1) as Fe) are sufficient to completely oxidize the precursors.     

18F-Labeled FAUC 346 and BP 897 derivatives as subtype-selective potential PET radioligands for the dopamine D3 receptor

Disturbances of neutrotransmission at the dopamine D3 receptor are related to several neuropsychiatric diseases and in particular to drug addiction. Herein, we report the computer-assisted prediction of D3 selectivities of new fluoroalkoxy-substituted receptor ligands by means of 3D-QSAR analysis. As close analogues of the D3-selective lead compound FAUC 346 and BP 879, the (19)F-substituted test compounds 4 a-d were synthesized and evaluated. In vitro investigation of their binding characteristics in transfected Chinese Hamster Ovary (CHO) cells led to excellent K(i) values between 0.12 and 0.69 nM at the dopamine D3 subtype. The benzothiophene-substituted carboxamide 4 a (K(i)=0.12 nM) displayed 133 and 283-fold selectivity over the structurally related D2(Long) and D4 subtypes, respectively. Mitogenesis assays showed the behavior of partial agonists. Based on these data, we synthesized the [(18)F]fluoroethoxy-substituted radioligands [(18)F]4 a-d. The N-[4-[4-(2-hydroxyphenyl)piperazin-1-yl]butyl]-2-carboxamides 3 a-d were prepared and labeled with 2-[(18)F]fluoroethyltosylate in a two-step procedure. Optimization of the (18)F-labeling conditions led to radiochemical yields between 24 and 65 %.     

Dipeptide derivatives of AZT: synthesis, chemical stability, activation in human plasma, hPEPT1 affinity, and antiviral activity

5'-O-Dipeptide ester prodrugs of antiviral zidovudine (AZT) were designed to target the human intestinal oligopeptide transporter, hPEPT1, and were evaluated for their stability at pH 7.4 in buffer and in human plasma, affinity toward hPEPT1, cytotoxicity, and antiretroviral activity. The dipeptide esters of AZT undergo cyclization in buffer at pH 7.4 to release the parent drug at a rate that depends on the size of the side chains of the peptide carrier; the prodrug is considerably more stable if bulky beta-branched amino acids such as Ile and Val are present, particularly as C-terminal residues. Incubation in human plasma showed that most of the dipeptide esters of AZT release the parent drug through two aminopeptidase-mediated pathways: 1) stepwise cleavage of each of the amino acids and 2) direct cleavage of the dipeptide-drug ester bond. However, the plasma hydrolysis of Gly-Gly-AZT and Phe-Gly-AZT showed only direct cleavage of the dipeptide-drug ester bond. Substrate half-lives in plasma were again remarkably high when hydrophobic beta-branched amino acids (Val, Ile) were present. The esters were also good substrates for the intestinal oligopeptide transporter hPEPT1 in vitro, with Val-Gly-AZT and Val-Ala-AZT presenting the highest affinity toward the transporter (IC(50): 0.20 and 0.15 mM, respectively). The AZT dipeptide esters were assayed against the IIIB and ROD strains of HIV, and their cytotoxicity was evaluated in MT-4 cells. The selectivity index of the prodrugs was two- to threefold higher than that of AZT for all compounds analyzed. These results point to the potential of dipeptide-based carriers for the development of effective antiviral drug-delivery systems. Val-Ala-AZT appears to combine chemical stability with good affinity for the hPEPT1 transporter and an improved cytotoxicity/antiretroviral index relative to AZT.     

Control of spatiotemporal chaos in catalytic CO oxidation by laser-induced pacemakers

Control of spatiotemporal chaos is achieved in the catalytic oxidation of CO on Pt(110) by localized modification of the kinetic properties of the surface chemical reaction. In the experiment, a small temperature heterogeneity is created on the surface by a focused laser beam. This heterogeneity constitutes a pacemaker and starts to emit target waves. These waves slowly entrain the medium and suppress the spatiotemporal chaos that is present in the absence of control. We compare this experimental result with a numerical study of the Krischer-Eiswirth-Ertl model for CO oxidation on Pt(110). We confirm the experimental findings and identify regimes where complete and partial controls are possible.     

Structural coherency of graphene on Ir(111)

Low-pressure chemical vapor deposition allows one to grow high structural quality monolayer graphene on Ir(111). Using scanning tunneling microscopy, we show that graphene prepared this way exhibits remarkably large-scale continuity of its carbon rows over terraces and step edges. The graphene layer contains only a very low density of defects. These are zero-dimensional defects, edge dislocation cores consisting of heptagon-pentagon pairs of carbon atom rings, which we relate to small-angle in-plane tilt boundaries in the graphene. We quantitatively examined the bending of graphene across Ir step edges. The corresponding radius of curvature compares to typical radii of thin single-wall carbon nanotubes.     

Calculation of the torque on dielectric elliptical cylinders

We present our investigation of the torque exerted on dielectric elliptical cylinders by highly focused laser beams. The calculations are performed with rigorous diffraction theory, and the size-dependent torque is analyzed as a function of the axis ratio. It is found that highly elongated particles will experience a reversal of the torque for a radius that is approximately one third of the wavelength. This effect is attributed to interference effects inside the structure due to multiple reflections of the incoming wave. The evolution from a perfectly sinusoidal angular dependence of the torque to a more complicated pattern for increasing particle size is presented in detail.     

Gold nanorods as novel nonbleaching plasmon-based orientation sensors for polarized single-particle microscopy

By monitoring the polarized light scattering from individual gold nanorods in a darkfield microscope, we are able to determine their orientation as a function of time. We demonstrate time resolution of milliseconds and observation times of hours by observing the two-dimensional rotational diffusion of gold rods attached to a glass surface. The observed orientational diffusion shows a fast component of about 60 ms and "sticky times" of seconds. The large signal-to-noise ratio, chemical and photochemical stability, fast time response, and small size of these gold nanorods make them an ideal probe for orientation sensing in material science and molecular biology.     

Single-crystal neutron diffraction: a valuable tool for probing bond activation in transition metal σ complexes

Transition metal complexes are ubiquitous intermediates in metal-catalyzed reactions, including hydrogenations, activation and functionalization reactions of hydrocarbons, and hydroborations. For over 20years, single-crystal neutron diffraction has been exploited to investigate bond activation in these systems. Topics investigated include H–H activation in H2 complexes, C–H activation in agostic systems and, most recently, B–H activation in a catecholborane metal complex. These results are illustrated here drawing upon studies carried out at both pulsed neutron sources and steady-state reactors. Despite notable successes such as those that we highlight, however, single-crystal neutron diffraction has seen somewhat limited application here to date primarily due to the need for large crystals. Revolutionary improvements are anticipated with the advent of a new generation of sources including the Spallation Neutron Source (SNS) that is scheduled to become operational at Oak Ridge, TN in 2006. At the SNS, it will be possible to work with crystals approaching the size commonly used in X-ray studies employing laboratory sources and to greatly expand the range of materials that are open to investigation.*To whom correspondence should be addressed.