N-Heterocyclic Carbene to Actinide d-Based π-bonding Correlates with Observed Metal-Carbene Bond Length Shortening Versus Lanthanide Congeners.

Comparison of bonding and electronic structural features between trivalent lanthanide (Ln) and actinide (An) complexes across homologous series' of molecules can provide insights into subtle and overt periodic trends. Of keen interest and debate is the extent to which the valence f- and d-orbitals of trivalent Ln/An ions engage in covalent interactions with different ligand donor functionalities and, crucially, how bonding differences change as both the Ln and An series are traversed. Synthesis and characterization (SC-XRD, NMR, UV-vis-NIR, and computational modeling) of the homologous lanthanide and actinide N-heterocyclic carbene (NHC) complexes [M(C5Me5)2(X)(IMe4)] {X = I, M = La, Ce, Pr, Nd, U, Np, Pu; X = Cl, M = Nd; X = I/Cl, M = Nd, Am; and IMe4 = [C(NMeCMe)2]} reveals consistently shorter An-C vs Ln-C distances that do not substantially converge upon reaching Am3+/Nd3+ comparison. Specifically, the difference of 0.064(6) Å observed in the La/U pair is comparable to the 0.062(4) Å difference observed in the Nd/Am pair. Computational analyses suggest that the cause of this unusual observation is rooted in the presence of π-bonding with the valence d-orbital manifold in actinide complexes that is not present in the lanthanide congeners. This is in contrast to other documented cases of shorter An-ligand vs Ln-ligand distances, which are often attributed to increased 5f vs 4f radial diffusivity leading to differences in 4f and 5f orbital bonding involvement. Moreover, in these traditional observations, as the 5f series is traversed, the 5f manifold contracts such that by americium structural studies often find no statistically significant Am3+vs Nd3+ metal-ligand bond length differences.

Trace Actinide Signatures of a Bulk Neptunium Sample.

In nuclear forensic analyses, measurements of actinide elements in a sample can assist with identifying interdicted or unknown materials. While these radiochemical signatures have been extensively investigated in uranium materials, less is known about bulk neptunium samples. This paper describes the measurement of trace actinide concentrations and isotopic profiles in a 237Np oxide sample. Uranium, plutonium, americium, and curium concentrations and isotopic profiles in the sample were determined and deemed potentially useful for distinguishing different sources of 237Np. Several different potential radiochronometry systems were also investigated; discordant results indicate that the Np sample was never completely purified of other actinide elements, or that subsequent contamination of the sample occurred. Few prior studies of neptunium materials have been reported, and these data suggest that trace actinide constituents could provide unique signatures to identify material out of regulatory control.

Nuclear Sample Provenance and Age Determination Using Ruthenium Isotopes.

Measurements of the ruthenium isotopic composition of nuclear samples could provide information about the method of sample production, sample irradiation history, and age. To investigate the feasibility and applicability of this idea, this study focuses on measurements of the ruthenium isotope composition of a nominally single-isotope 106Ru radioactivity standard, where the complications of environmental mixing are eliminated. The measurements of the 106Ru standards reveal unusual stable ruthenium isotopic compositions consistent with fissiogenic ruthenium. Three different lots of the material have been investigated, and the isotopic composition is found to be different for lot 1 as compared to lots 2 and 3, indicating a longer irradiation duration incurred during the production of lot 1. Through measurements of 106Ru and its 106Pd daughter, radiochronometry can be used to infer the ages of the samples. Lot 1 is older than lots 2 and 3 and was produced 4.91(5) years before the reference date of 1/1/21, approximately 2.7 years before lots 2 and 3. In an effort to better understand the sample production pathway, the isotopic measurements are compared with nuclear reactor simulations, which suggest that the material was generated by irradiation of a low-enriched uranium target material in a light water reactor. These findings have significant implications for nuclear treaty monitoring, providing an example of the power of ruthenium isotope measurements to discern details of sample origin and history.

Measurements of extinct fission products in nuclear bomb debris: Determination of the yield of the Trinity nuclear test 70 y later.

This paper describes an approach to measuring extinct fission products that would allow for the characterization of a nuclear test at any time. The isotopic composition of molybdenum in five samples of glassy debris from the 1945 Trinity nuclear test has been measured. Nonnatural molybdenum isotopic compositions were observed, reflecting an input from the decay of the short-lived fission products (95)Zr and (97)Zr. By measuring both the perturbation of the (95)Mo/(96)Mo and (97)Mo/(96)Mo isotopic ratios and the total amount of molybdenum in the Trinity nuclear debris samples, it is possible to calculate the original concentrations of the (95)Zr and (97)Zr isotopes formed in the nuclear detonation. Together with a determination of the amount of plutonium in the debris, these measurements of extinct fission products allow for new estimates of the efficiency and yield of the historic Trinity test.

Energetic Chromophores: Low-Energy Laser Initiation in Explosive Fe(II) Tetrazine Complexes.

The synthesis and characterization of air stable Fe(II) coordination complexes with tetrazine and triazolo-tetrazine ligands and perchlorate counteranions have been achieved. Time-dependent density functional theory (TD-DFT) was used to model the structural, electrochemical, and optical properties of these materials. These compounds are secondary explosives that can be initiated with Nd:YAG laser light at lower energy thresholds than those of PETN. Furthermore, these Fe(II) tetrazine complexes have significantly lower sensitivity than PETN toward mechanical stimuli such as impact and friction. The lower threshold for laser initiation was achieved by altering the electronic properties of the ligand scaffold to tune the metal ligand charge transfer (MLCT) bands of these materials from the visible into the near-infrared region of the electromagnetic spectrum. Unprecedented decrease in both the laser initiation threshold and the mechanical sensitivity makes these materials the first explosives that are both safer to handle and easier to initiate than PETN with NIR lasers.

Knocking on wood: base metal complexes as catalysts for selective oxidation of lignin models and extracts.

This work began as part of a biomass conversion catalysis project with UC Santa Barbara funded by the first NSF Chemical Bonding Center, CATSB. Recognizing that catalytic aerobic oxidation of diol C-C bonds could potentially be used to break down lignocellulose, we began to synthesize oxovanadium complexes and explore their fundamental reactivity. Of course there were theories regarding the oxidation mechanism, but our mechanistic studies soon revealed a number of surprises of the type that keep all chemists coming back to the bench! We realized that these reactions were also exciting in that they actually used the oxygen-on-every-carbon property of biomass-derived molecules to control the selectivity of the oxidation. When we found that these oxovanadium complexes tended to convert sugars predominantly to formic acid and carbon dioxide, we replaced one of the OH groups with an ether and entered the dark world of lignin chemistry. In this Account, we summarize results from our collaboration and from our individual labs. In particular, we show that oxidation selectivity (C-C vs C-O bond cleavage) of lignin models using air and vanadium complexes depends on the ancillary ligands, the reaction solvent, and the substrate structure (i.e., phenolic vs non-phenolic). Selected vanadium complexes in the presence of added base serve as effective alcohol oxidation catalysts via a novel base-assisted dehydrogenation pathway. In contrast, copper catalysts effect direct C-C bond cleavage of these lignin models, presumably through a radical pathway. The most active vanadium catalyst exhibits unique activity for the depolymerization of organosolv lignin. After Weckhuysen's excellent 2010 review on lignin valorization, the number of catalysis studies and approaches on both lignin models and extracts has expanded rapidly. Today we are seeing new start-ups and lignin production facilities sprouting up across the globe as we all work to prove wrong the old pulp and paper chemist's adage: you can make anything from lignin except money!

Site-directed spin labeling reveals pentameric ligand-gated ion channel gating motions.

Pentameric ligand-gated ion channels (pLGICs) are neurotransmitter-activated receptors that mediate fast synaptic transmission. In pLGICs, binding of agonist to the extracellular domain triggers a structural rearrangement that leads to the opening of an ion-conducting pore in the transmembrane domain and, in the continued presence of neurotransmitter, the channels desensitize (close). The flexible loops in each subunit that connect the extracellular binding domain (loops 2, 7, and 9) to the transmembrane channel domain (M2-M3 loop) are essential for coupling ligand binding to channel gating. Comparing the crystal structures of two bacterial pLGIC homologues, ELIC and the proton-activated GLIC, suggests channel gating is associated with rearrangements in these loops, but whether these motions accurately predict the motions in functional lipid-embedded pLGICs is unknown. Here, using site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and functional GLIC channels reconstituted into liposomes, we examined if, and how far, the loops at the ECD/TMD gating interface move during proton-dependent gating transitions from the resting to desensitized state. Loop 9 moves ∼9 Šinward toward the channel lumen in response to proton-induced desensitization. Loop 9 motions were not observed when GLIC was in detergent micelles, suggesting detergent solubilization traps the protein in a nonactivatable state and lipids are required for functional gating transitions. Proton-induced desensitization immobilizes loop 2 with little change in position. Proton-induced motion of the M2-M3 loop was not observed, suggesting its conformation is nearly identical in closed and desensitized states. Our experimentally derived distance measurements of spin-labeled GLIC suggest ELIC is not a good model for the functional resting state of GLIC, and that the crystal structure of GLIC does not correspond to a desensitized state. These findings advance our understanding of the molecular mechanisms underlying pLGIC gating.

Independent Control of Optical and Explosive Properties: Pyrazole-Tetrazine Complexes of First Row Transition Metals.

Complexes of 3-amino-6-(3,5-dimethylpyrazole)tetrazine) (NH2TzDMP, 1) and 3-(3,3'-dinitroazetidine)-6-(3,5-dimethylpyrazole)tetrazine) (DNAZTzDMP, 2) with first row transition metal centers were synthesized. Reactions of Fe(II)(H2O)6(BF4)2 and Fe(NO3)3·9H2O with 1 and 2 both led to complexes of the form [(RTzDMP)3Fe]X2 (X = BF4, R = NH2 (3), DNAZ (4); X = NO3, R = NH2 (5), DNAZ (6)), which showed intense MLCT bands in the visible region of the spectrum. Ligands 1 and 2 also reacted with Cu(II)(NO3)2·5/2H2O to form [(RTzDMP)2Cu(NO3)][NO3] (R = NH2 (7), DNAZ (8)) in addition to reacting with Cu(I)(CH3CN)4(PF6) to form [(RTzDMP)2Cu][PF6] (R = NH2 (9), DNAZ (10)). Lastly reactions of 1 and 2 with Co(NO3)2·6H2O and Ni(NO3)2·6H2O led to [(NH2TzDMP)2Co(H2O) (NO3)][NO3] (11), [(DNAZTzDMP)2Co(H2O)2][NO3]2 (12), [(NH2TzDMP)3Ni][NO3]2 (13), and [(DNAZTzDMP)2Ni(H2O)2][NO3]2 (14). The complexes display rich electrochemical and photophysical properties that are unaffected by derivation with explosive groups.

Conformation of receptor-bound visual arrestin.

Arrestin-1 (visual arrestin) binds to light-activated phosphorylated rhodopsin (P-Rh*) to terminate G-protein signaling. To map conformational changes upon binding to the receptor, pairs of spin labels were introduced in arrestin-1 and double electron-electron resonance was used to monitor interspin distance changes upon P-Rh* binding. The results indicate that the relative position of the N and C domains remains largely unchanged, contrary to expectations of a "clam-shell" model. A loop implicated in P-Rh* binding that connects ß-strands V and VI (the "finger loop," residues 67-79) moves toward the expected location of P-Rh* in the complex, but does not assume a fully extended conformation. A striking and unexpected movement of a loop containing residue 139 away from the adjacent finger loop is observed, which appears to facilitate P-Rh* binding. This change is accompanied by smaller movements of distal loops containing residues 157 and 344 at the tips of the N and C domains, which correspond to "plastic" regions of arrestin-1 that have distinct conformations in monomers of the crystal tetramer. Remarkably, the loops containing residues 139, 157, and 344 appear to have high flexibility in both free arrestin-1 and the P-Rh*complex.

Kläui ligand thin films for rapid plutonium analysis by alpha spectrometry.

As part of a nuclear forensics capability, rapid and effective methods to analyze for plutonium and other actinide metals are needed. A key requirement of these methods is that they afford a high chemical yield while still providing isotopic information necessary for forensic evaluation. Toward this objective, a new method for binding plutonium for analysis by alpha spectrometry has been developed. Thin films of Kläui-type tripodal oxygen donor ligands were prepared by spin-casting solutions onto glass substrates. Three different ligands were evaluated for plutonium binding, and the best results were obtained using the ethyl-substituted complex Na[Cp*Co(P(O)(OEt)2)3], which bound 80-88% of the dissolved Pu under equilibrium conditions. The thin films are simple and inexpensive to prepare and exhibit excellent alpha spectral resolution, having line widths of ~33 keV. The method has been successfully applied to analyze for plutonium in both an archived nuclear debris sample and a certified environmental soil sample. The results obtained from the soil analysis are in good agreement with the certified values, demonstrating the effectiveness of the method for rapid plutonium analysis.

Self-association of arrestin family members.

Mammals express four arrestin subtypes, three of which have been shown to self-associate. Cone photoreceptor-specific arrestin-4 is the only one that is a constitutive monomer. Visual arrestin-1 forms tetramers both in crystal and in solution, but the shape of its physiologically relevant solution tetramer is very different from that in the crystal. The biological role of the self-association of arrestin-1, expressed at very high levels in rod and cone photoreceptors, appears to be protective, reducing the concentration of cytotoxic monomers. The two nonvisual arrestin subtypes are highly homologous, and self-association of both is facilitated by IP6, yet they form dramatically different oligomers. Arrestin-2 apparently self-associates into "infinite" chains, very similar to those observed in IP6-soaked crystals, where IP6 connects the concave sides of the N- and C-domains of adjacent protomers. In contrast, arrestin-3 only forms dimers, in which IP6 likely connects the C-domains of two arrestin-3 molecules. Thus, each of the three self-associating arrestins does it in its own way, forming three different types of oligomers. The physiological role of the oligomerization of arrestin-1 and both nonvisual arrestins might be quite different, and in each case it remains to be definitively elucidated.

Scaling high-speed counter-current chromatography for preparative neodymium purification: Insights and challenges.

Efficient rare earth element (REE) separations are becoming increasingly important to technologies ranging from renewable energy and high-performance magnets to applied radioisotope separations. These separations are made challenging by the extremely similar chemical and physical characteristics of the individual elements, which almost always occupy the 3+ oxidation state under ambient conditions. Herein, we discuss the development of a novel REE separation aimed at obtaining purified samples of neodymium (Nd) on a multi-milligram scale using high-speed counter-current chromatography (HSCCC). The method takes advantage of the subtle differences in ionic radii between neighboring REEs to tune elution rates in dilute acid through implementation of the di-(2-ethylhexyl)phosphoric acid (HDEHP)-infused stationary phase (SP) of the column. A La/Ce/Nd/Sm separation was demonstrated at a significantly higher metal loading than previously accomplished by HSCCC (15 mg, RNd/REE > 0.85), while the Pr/Nd separation was achieved at lower metal loadings (0.3 mg, RNd/Pr = 0.75 - 0.83). The challenges associated with scaling REE separations via HSCCC are presented and discussed within.

A new method for quantifying 64Cu in nuclear debris samples.

Quantifying 64Cu in post-detonation nuclear debris samples can provide important diagnostic information regarding the structural materials used within a nuclear device. However, this task is challenging due to the weak gamma emissions associated with the decay of 64Cu, its short half-life (12.701 h), and the presence of interfering fission product radioisotopes. Large quantities of debris sample are generally needed to accurately quantify 64Cu, which can be problematic in sample-limited scenarios where other radiometric analyses are required. Herein, we present a new method for the separation of 64Cu from solutions of mixed fission products and demonstrate the quantification of its activity through use of gas-flow proportional beta counting. The new method was validated through a series of rigorous tests and was shown to improve the detection limit of 64Cu by over two orders of magnitude, from 2.5 × 106 to 1.3 × 104 atoms/sample for 100 min measurements.

Understanding the mechanisms of cobalt-catalyzed hydrogenation and dehydrogenation reactions.

Cobalt(II) alkyl complexes of aliphatic PNP pincer ligands have been synthesized and characterized. The cationic cobalt(II) alkyl complex [(PNHP(Cy))Co(CH2SiMe3)]BAr(F)4 (4) (PNHP(Cy) = bis[(2-dicyclohexylphosphino)ethyl]amine) is an active precatalyst for the hydrogenation of olefins and ketones and the acceptorless dehydrogenation of alcohols. To elucidate the possible involvement of the N-H group on the pincer ligand in the catalysis via a metal-ligand cooperative interaction, the reactivities of 4 and [(PNMeP(Cy))Co(CH2SiMe3)]BAr(F)4 (7) were compared. Complex 7 was found to be an active precatalyst for the hydrogenation of olefins. In contrast, no catalytic activity was observed using 7 as a precatalyst for the hydrogenation of acetophenone under mild conditions. For the acceptorless dehydrogenation of 1-phenylethanol, complex 7 displayed similar activity to complex 4, affording acetophenone in high yield. When the acceptorless dehydrogenation of 1-phenylethanol with precatalyst 4 was monitored by NMR spectroscopy, the formation of the cobalt(III) acetylphenyl hydride complex [(PNHP(Cy))Co(III)(κ(2)-O,C-C6H4C(O)CH3)(H)]BAr(F)4 (13) was detected. Isolated complex 13 was found to be an effective catalyst for the acceptorless dehydrogenation of alcohols, implicating 13 as a catalyst resting state during the alcohol dehydrogenation reaction. Complex 13 catalyzed the hydrogenation of styrene but showed no catalytic activity for the room temperature hydrogenation of acetophenone. These results support the involvement of metal-ligand cooperativity in the room temperature hydrogenation of ketones but not the hydrogenation of olefins or the acceptorless dehydrogenation of alcohols. Mechanisms consistent with these observations are presented for the cobalt-catalyzed hydrogenation of olefins and ketones and the acceptorless dehydrogenation of alcohols.

A single-nucleotide polymorphism in CYP2B6 leads to >3-fold increases in efavirenz concentrations in plasma and hair among HIV-infected women.

BACKGROUND: Efavirenz exhibits marked interindividual variability in plasma levels and toxicities. Prior pharmacogenetic studies usually measure exposure via single plasma levels, examine limited numbers of polymorphisms, and rarely model multiple contributors. We analyzed numerous genetic and nongenetic factors impacting short-term and long-term exposure in a large heterogeneous population of human immunodeficiency virus (HIV)-infected women. METHODS: We performed 24-hour intensive pharmacokinetic studies in 111 women receiving efavirenz under actual-use conditions and calculated the area-under-the-concentration-time curve (AUC) to assess short-term exposure; the efavirenz concentration in hair was measured to estimate long-term exposure. A total of 182 single-nucleotide polymorphisms (SNPs) and 45 haplotypes in 9 genes were analyzed in relationship to exposure by use of multivariate models that included a number of nongenetic factors. RESULTS: Efavirenz AUCs increased 1.26-fold per doubling of the alanine aminotransferase level and 1.23-fold with orange and/or orange juice consumption. Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AUCs and 3.2-fold increases in hair concentrations, compared with individuals with the TG/GG genotype. Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected AUCs without substantially altering long-term exposure. CONCLUSIONS: This comprehensive pharmacogenomics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in both short-term and long-term efavirenz exposure, signifying durable effects. Pharmacogenetic testing combined with monitoring of hair levels may improve efavirenz outcomes and reduce toxicities.

Chemical separation and measurement of platinum activation products.

A method has been developed to purify and measure platinum radioisotopes in the presence of fission products and environmental constituents. The method uses a combination of cation exchange and anion exchange chromatography and selective precipitation steps to remove other radioisotopes from the sample. The addition of stable platinum carrier allows for a gravimetric determination of the chemical yield of the procedure. Overall, the method is fast, simple, and potentially applicable for rapid turnaround of unknown samples. Using this method, multiple platinum radioisotopes were measured in two different irradiation experiments. The measured ratios of the platinum radioisotopes clearly reflect the neutron spectrum of the irradiation, suggesting that platinum radioisotopes could be valuable signatures in nuclear forensic analyses.

Global survey shows planners use widely varying sea-level rise projections for coastal adaptation.

Including sea-level rise (SLR) projections in planning and implementing coastal adaptation is crucial. Here we analyze the first global survey on the use of SLR projections for 2050 and 2100. Two-hundred and fifty-three coastal practitioners engaged in adaptation/planning from 49 countries provided complete answers to the survey which was distributed in nine languages - Arabic, Chinese, English, French, Hebrew, Japanese, Korean, Portuguese and Spanish. While recognition of the threat of SLR is almost universal, only 72% of respondents currently utilize SLR projections. Generally, developing countries have lower levels of utilization. There is no global standard in the use of SLR projections: for locations using a standard data structure, 53% are planning using a single projection, while the remainder are using multiple projections, with 13% considering a low-probability high-end scenario. Countries with histories of adaptation and consistent national support show greater assimilation of SLR projections into adaptation decisions. This research provides new insights about current planning practices and can inform important ongoing efforts on the application of the science that is essential to the promotion of effective adaptation.

Few residues within an extensive binding interface drive receptor interaction and determine the specificity of arrestin proteins.

Arrestins bind active phosphorylated forms of G protein-coupled receptors, terminating G protein activation, orchestrating receptor trafficking, and redirecting signaling to alternative pathways. Visual arrestin-1 preferentially binds rhodopsin, whereas the two non-visual arrestins interact with hundreds of G protein-coupled receptor subtypes. Here we show that an extensive surface on the concave side of both arrestin-2 domains is involved in receptor binding. We also identified a small number of residues on the receptor binding surface of the N- and C-domains that largely determine the receptor specificity of arrestins. We show that alanine substitution of these residues blocks the binding of arrestin-1 to rhodopsin in vitro and of arrestin-2 and -3 to ß2-adrenergic, M2 muscarinic cholinergic, and D2 dopamine receptors in intact cells, suggesting that these elements critically contribute to the energy of the interaction. Thus, in contrast to arrestin-1, where direct phosphate binding is crucial, the interaction of non-visual arrestins with their cognate receptors depends to a lesser extent on phosphate binding and more on the binding to non-phosphorylated receptor elements.