State of practice and emerging application of analytical techniques of nuclear forensic analysis: highlights from the 5th Collaborative Materials Exercise of the Nuclear Forensics International Technical Working Group (ITWG)

The Nuclear Forensics International Technical Working Group (ITWG), a community of nuclear forensic practitioners who respond to incidents involving nuclear and other radioactive material out of regulatory control, completed its fifth Collaborative Materials Exercise in 2017 (CMX-5). Forensic laboratories from 19 countries and one multinational organization aimed to advance nuclear forensic science and improve international cooperation in the event of a nuclear material security incident. In all, over 30 analytical techniques were utilized to investigate the samples, many techniques applying novel methods or offering improvements in turnaround time. An objective review of the state of practice and emerging application of analytical techniques of nuclear forensic analysis based upon this exercise is provided.

     

The Effect of Grafting Zirconia and Ceria onto Alumina as a Support for Silicotungstic Acid for the Catalytic Dehydration of Glycerol to Acrolein

The effect of ceria and zirconia grafting onto alumina (α and θ–δ phases) as supports for silicotungstic acid for the dehydration of glycerol to acrolein was studied. 30 % Silicotungstic acid (STA) supported on 5 % zirconia/δ,θ‐alumina was the best catalyst, producing 85 % selectivity to acrolein at 100 % glycerol conversion, and it showed stable activity without using oxygen as a co‐feed. The catalyst produced a STA of 90 g_(acrolein) kg_(cat)^?1 h^?1, which was greater than the STA simply supported on δ,θ‐alumina, which only demonstrated 75 % selectivity towards acrolein. The effect of grafting on the support material was investigated by means of nitrogen adsorption, ammonia temperature‐programmed desorption, thermogravimetric analysis, Raman spectroscopy, and powder X‐ray diffraction. A pulsed‐field gradient (PFG) NMR technique was also used to study diffusion processes associated with the catalysts. Diffusion studies of the grafted catalysts showed that zirconia contributes to the formation of more tortuous pathways within the pore structure, leading to the diminution of acid strength and making the catalyst less susceptible to coke formation.     

An unsymmetrical approach to the synthesis of bismethylene triphosphate analogues

A protected, unsymmetrical bismethylene triphosphate analogue was prepared by sequential Michaelis-Arbuzov reactions on ethyl bis(halomethyl)phosphinates. This species was monodeprotected at one of the terminal phosphonate groups in high yield. The resulting monodeprotected compound was used to achieve the first syntheses of the bismethylene triphosphate analogues of UTP and CTP.     

The total synthesis of moenomycin A

Moenomycin A is the only known natural antibiotic that inhibits bacterial cell wall synthesis by binding to the transglycosylases that catalyze formation of the carbohydrate chains of peptidoglycan. We report here the total synthesis of moenomycin A using the sulfoxide glycosylation method. A newly discovered byproduct of sulfoxide reactions was isolated that resulted in substantial loss of the glycosyl acceptor. A general method to suppress this byproduct was introduced, which enabled the glycosylations to proceed efficiently. The inverse addition protocol for sulfoxide glycosylations also proved essential in constructing some of the glycosidic linkages. The synthetic route is flexible and will allow for derivatives to be constructed to further analyze moenomycin A's mechanism of action.     

Synthesis of methylene- and difluoromethylenephosphonate analogues of uridine-4-phosphate and 3-deazauridine-4-phosphate

Cytidine triphosphate synthetase (CTPS) catalyzes the formation of cytidine triphosphate from glutamine, uridine-5'-triphosphate (UTP), and adenosine-5'-triphosphate. Inhibitors of CTPS are of interest because of their potential as therapeutic agents. One approach to potent enzyme inhibitors is to use analogues of high energy intermediates formed during the reaction. The CTPS reaction proceeds via the high energy intermediate UTP-4-phosphate (UTP-4-P). Four novel analogues of uridine-4-phosphate (U-4-P) and 3-deazauridine-4-phosphate (3-deazaU-4-P) were synthesized in which the labile phosphate ester oxygen was replaced with a methylene and difluoromethylene group. The methylene analogue of U-4-P, compound 1, was prepared by a reaction of the sodium salt of tert-butyl diethylphosphonoacetate with protected, 4-O-activated uridine followed by acetate deprotection and decarboxylation. It was found that this compound undergoes relatively facile dephosphonylation presumably via a metaphosphate intermediate. The difluoromethylene derivative, compound 2, was prepared by electrophilic fluorination of protected 1. This compound was stable and did not undergo dephosphonylation. Synthesis of the methylene analogue of 3-deazaU-4-P, compound 3, was achieved by ribosylation of protected 4-(phosphonomethyl)-2-hydroxypyridine. Electrophilic fluorination was also employed in the preparation of protected 4-(phosphonodifluoromethyl)-2-hydroxypyridine which was used as the key building block in the synthesis of difluoro derivative 4. These compounds represent the first examples of a nucleoside in which the base has been chemically modified with a methylene or difluormethylenephosphonate group.     

Studies of the Interaction of Platinum Drugs with DNA Using Oligonucleotide Microarrays

Summary: A novel method for the study of the interaction of the platinum drug cis-diamminedichloroplatinum(II) (cis-DDP or cisplatin) with 50-mer oligonucleotides that were printed in high throughput microarray format is introduced. Our aim has been to identify sequence level differences in the interaction of various drug candidates that may serve to enable rational targeting of drugs to specific genes. A microarray of 26 control genes commonly used in oligonucleotide, Affymetrix and c-DNA microarray platforms were microcontact spotted as amine-terminated 50-mer oligonucleotides onto glycidoxypropyltimethoxy silane (GPMS)-modified glass slides. The generalized study format involved hybridization of probes with 10 fluorescently labeled complements as target followed by confocal imaging to reveal original spot intensities. Microarrays were then incubated at 37 °C with hydrolysed cisplatin while in hybridization cassettes, washed in buffer and then scanned again to reveal secondary intensities. We have investigated the influence of cisplatin to stabilize the relative fluorescence intensity via intrastrand crosslinking by studying the impact of varying drug:probe-DNA mole ratio (0:1 (blank), 1:1, 25:1 and 50:1) and annealing temperatures (36, 46, or 56 °C) on retained intensity. ANOVA revealed that 4 of the 10 genes demonstrated (p < 0.0001) the expected result of increased signal retention with decreased temperature and increased drug concentration.     

Vinyl‐triazolium monomers: Versatile and new class of radically polymerizable ionic monomers

A set of eight functional 4‐vinyl‐1,2,3‐triazolium monomers were synthesized using copper catalyzed azide‐alkyne 2 + 3 Hüisgen cycloaddition. These vinyl‐trizolium monomers readily polymerized via free radical polymerization. The physical properties of the vinyl‐triazolium based poly(ionic liquid)s (PILs) are strongly dependent on the pendant functional groups. These polymers were characterized for glass transition temperature (T_g), solubility, and the thermal decomposition. The vinyl‐triazolium based PILs offer an efficient route to highly functional PILs with the advantage of facile synthesis and the ability to incorporate many desirable functional moieties. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 417–423     

Inactivation of Bacteriophage Infecting Bacteroides Strain GB124 Using UV‐B Radiation

Ultraviolet‐B radiation (280–320 nm) has long been associated with the inactivation of microorganisms in the natural environment. Determination of the environmental inactivation kinetics of specific indicator organisms [used as tools in the field of microbial source tracking (MST)] is fundamental to their successful deployment, particularly in geographic regions subject to high levels of solar radiation. Phage infecting Bacteroides fragilis host strain GB124 (B124 phage) have been demonstrated to be highly specific indicators of human fecal contamination, but to date, little is known about their susceptibility to UV‐B radiation. Therefore, B124 phage (n = 7) isolated from municipal wastewater effluent, were irradiated in a controlled laboratory environment using UV‐B collimated beam experiments. All B124 phage suspensions possessed highly similar first order log‐linear inactivation profiles and the mean fluence required to inactivate phage by 4 ? log¹⁰ was 320 mJ cm^?2. These findings suggest that phage infecting GB124 are likely to be inactivated when exposed to the levels of UV‐B solar radiation experienced in a variety of environmental settings. As such, this may limit the utility of such methods for determining more remote inputs of fecal contamination in areas subject to high levels of solar radiation.     

Fluorescence and metastability of N2O2+: theory and experiment

State-selective mass spectrometry has revealed one conclusive and another probable metastable state of the N2O2+ dication, assigned respectively as 1 3Pi at 38.5 eV and 2 3Pi at 42.5 eV. Photon coincidence experiments confirm that dissociation of 1 3Pi is preceded by a fluorescent transition to X 3Sigma- and also indicate that an identical mechanism occurs for 2 3Pi. Highly correlated MRCI calculations are performed at a range of N2O2+ geometries, from which both N-N and N-O bond stretching curves are generated. Substantial barriers along both coordinates are observed for 1 3Pi and 2 3Pi, although the increasing density of states at higher energy may allow spin-orbit or vibronic predissociation for 2 3Pi. Fragment emissions derived from N2O+ and N2O2+ are analyzed with the aid of glass filters, from which NO (X 2Pi<--A 2Sigma+) and vibrationally excited N2+ (X 2Sigmag+<--B 2Sigmau+) transitions are deduced.     

The absolute configuration of (+)-(E)-4-phenylbut-3-ene-2-ol

A derivative of (+)-(E)-4-phenylbut-3-ene-2-ol is shown by X-ray crystallography to be of (R) configuration, confirming the assumption in the literature that the absolute configuration of (+)-(E)-4-phenylbut-3-ene-2-ol is (R).