Cooperative chemistry between two or more metal centres can show enhanced reactivity compared to the monometallic fragments. Given the paucity of actinide–metal bonds, especially those with group 13, we targeted uranium(iii)–aluminum(i) and –gallium(i) complexes as we envisioned the low-valent oxidation state of both metals would lead to novel, cooperative reactivity. Herein, we report the molecular structure of [(C5Me5)2(MesO)U-E(C5Me5)], E = Al, Ga, Mes = 2,4,6-Me3C6H2, and their reactivity with dihydrogen. The reaction of H2 with the U(iii)–Al(i) complex affords a trihydroaluminate complex, [(C5Me5)2(MesO)U(μ2-(H)3)–Al(C5Me5)] through a formal three-electron metal-based reduction, with concomitant formation of a terminal U(iv) hydride, [(C5Me5)2(MesO)U(H)]. Noteworthy is that neither U(iii) complexes nor [(C5Me5)Al]4 are capable of reducing dihydrogen on their own. To make the terminal hydride in higher yields, the reaction of [(C5Me5)2(MesO)U(THF)] with half an equivalent of diethylzinc generates [(C5Me5)2(MesO)U(CH2CH3)] or treatment of [(C5Me5)2U(i)(Me)] with KOMes forms [(C5Me5)2(MesO)U(CH3)], which followed by hydrogenation with either complex cleanly affords [(C5Me5)2(MesO)U(H)]. All complexes have been characterized by spectroscopic and structural methods and are rare examples of cooperative chemistry in f element chemistry, dihydrogen activation, and stable, terminal ethyl and hydride compounds with an f element.

Most nuclear waste disposal options include compacted bentonite, consisting of montmorillonite clay, as part of a barrier system to minimize contaminant mobility. Uranium (U) is the primary element in spent nuclear fuel, and from an environmental perspective, a potential contaminant of water resources. Furthermore, uranium may control nuclear fuel degradation rates and the consequent release of other radioactive contaminants based on its diffusive transport away from waste canisters. Uranium sorption onto clay and other mineral surfaces is expected to limit U(VI) mobility in these systems. However, at this point a prediction of U(VI) sorption and transport behavior in performance assessment (PA) models is complicated by a series of factors, such as: (1) the presence of various U(VI) solution species with different charges and sorption characteristics; (2) the complex microstructure of montmorillonite clay resulting in two types of clay porosities and multiple sorption sites; (3) the largely unknown effects of bentonite mineral impurities on pore water chemistry, U(VI) sorption and diffusion behavior; and (4) the potential impacts of heat, generated by the decay of spent fuel, on mineralogical and microstructural transformations, and any subsequent effects on radionuclide sorption and mobility. In this project, we will investigate the effects of calcite impurities on U(VI) sorption and diffusion onto montmorillonite before and after mineral exposure to heat. Based on a combination of data from U(VI) batch sorption experiments and extended X-ray absorption fine structure (EXAFS) spectroscopy, we will develop a new U(VI)-montmorillonite surface complexation model to determine under which conditions impurity effects are relevant for U(VI) sorption processes, and how they can be incorporated into PA models. In diffusion experiments, we will further test the relevance of changes in U(VI) sorption behavior for the diffusive transport of U(VI). Molecular dynamics (MD) calculations will support the simulation of diffusion results by evaluating steric effects associated with the size of U(VI) solution complexes (relative to the sub-nanometer width of montmorillonite nanopores). This project will provide a comprehensive experimental data set of U(VI) sorption distribution coefficients (Kd values) for Na-montmorillonite/bentonite systems, in the presence of calcite impurities, over a wide range of chemical solution conditions, and before and after mineral exposure to heat. Our new U(VI) sorption model will allow us to (1) predict U(VI) sorption behavior under these complex system conditions, (2) determine the conditions under which calcite impurities are relevant, and (3) elucidate the most-likely, underlying mechanism(s) for these effects. At last, the integration of our surface complexation model into a state-of-the-art reactive diffusion model will allow us to characterize the impact of U(VI) speciation on U(VI) diffusion in bentonite barriers. All of these results will have direct implications for the development of PA models, since they can either help to justify a decrease in PA model complexity, or provide a scientific basis for the incorporation of these complex system behaviors.

To synthesize complexes with thorium-phosphorus multiple-bond character, reactions of (C5Me5)2Th[P(H)Mes]2 with monovalent alkali-metal bases, MN(SiMe3)2, as well as CuMes, have been investigated. The results with MN(SiMe3)2 are phosphinidiide complexes of the form {(C5Me5)2Th[μ2-P(Mes)][μ2-P(H)Mes]M(L)n}2 (M = Na, n = 0; M = K, L = THF, n = 1; M = Rb, L = THF, n = 1; M = Cs, L = Et2O, n = 1). With CuMes, the product is a Th2Cu3P5 heterometallic structure, {(C5Me5)2Th[(μ2-P(H)Mes)P(Mes)]Cu}2Cu[μ2-P(H)Mes]. All complexes have been characterized using heteronuclear NMR and IR spectroscopy, density functional theory calculations, and their solid-state structure identified by X-ray crystallography. We also report the structure of {(C5Me5)2Th[(μ2-As(H)Mes)As(Mes)]Cu}2Cu[μ2-As(H)Mes] obtained from (C5Me5)2Th[As(H)Mes]2 with CuMes.

While no alkylidene complexes of the f elements are known, the use of phosphorano-stabilized carbene complexes to produce short actinide-carbon bonds has been previously demonstrated. Complexes of the form, (C5Me5)(2)An(X)(CHPPh3), with short thorium(IV)- and uranium(IV)-carbon(carbene) bonds have been synthesized from the reaction of (C5Me5)(2)An(X)(CH3) (An = Th, U; X = Cl, Br, or I) with the ylide, CH2 =PPh3. The resulting uranium complexes feature the shortest uranium(IV)-carbon bonds reported to date. The molecular and electronic structure of the thorium phosphorano-stabilized carbene complexes is detailed using X-ray crystallography, C-13 NMR spectroscopy, and density functional theory calculations, and compared to thorium methandiide complexes.

The complexes (C5 Me5 )2 Th(EHTipp)2 , (E=P or As; Tipp=2,4,6-triisopropylphenyl), provide a ligand framework that results in facile access to rare Th-E multiple bonds. The reaction of (C5 Me5 )2 Th(EHTipp)2 with KN(SiMe3 )2 , proceeds cleanly to the desired bridging phosphinidiide or arsinidiide complex, [{(C5 Me5 )2 Th(μ2 -ETipp)(μ2 -EHTipp)}K]2 under ambient conditions. In the absence of a chelating agent, the potassium cation of one monomeric unit interacts with the aryl ring of a second monomer to form a bridged dimer. In the presence of 2,2,2-cryptand, the terminal phosphinidene complex, [(C5 Me5 )2 Th=PTipp(PHTipp)][K(2,2,2-cryptand)] is isolated. Using X-ray crystallographic analysis, we have determined these complexes display the shortest Th-P and Th-As bond lengths reported.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The cell of origin for prostate cancer remains a subject of debate. Genetically engineered mouse models have demonstrated that both basal and luminal cells can serve as cells of origin for prostate cancer. Using a human prostate regeneration and transformation assay, our group previously demonstrated that basal cells can serve as efficient targets for transformation. Recently, a subpopulation of multipotent human luminal cells defined by CD26 expression that retains progenitor activity in a defined organoid culture was identified. We transduced primary human prostate basal and luminal cells with lentiviruses expressing c-Myc and activated AKT1 (myristoylated AKT1 or myrAKT1) to mimic the MYC amplification and PTEN loss commonly detected in human prostate cancer. These cells were propagated in organoid culture before being transplanted into immunodeficient mice. We found that c-Myc/myrAKT1-transduced luminal xenografts exhibited histological features of well-differentiated acinar adenocarcinoma, with strong androgen receptor (AR) and prostate-specific antigen (PSA) expression. In contrast, c-Myc/myrAKT1-transduced basal xenografts were histologically more aggressive, with a loss of acinar structures and low/absent AR and PSA expression. Our findings imply that distinct subtypes of prostate cancer may arise from luminal and basal epithelial cell types subjected to the same oncogenic insults. This study provides a platform for the functional evaluation of oncogenes in basal and luminal epithelial populations of the human prostate. Tumors derived in this fashion with defined genetics can be used in the preclinical development of targeted therapeutics.

Enzymes are complicated solvated systems that typically require many atoms to simulate their function with any degree of accuracy. We have recently developed numerical techniques for large scale first-principles molecular dynamics simulations and applied them to the study of the enzymatic reaction catalyzed by acetylcholinesterase. We carried out density functional theory calculations for a quantum-mechanical (QM) subsystem consisting of 612 atoms with an O(N) complexity finite-difference approach. The QM subsystem is embedded inside an external potential field representing the electrostatic effect due to the environment. We obtained finite-temperature sampling by first-principles molecular dynamics for the acylation reaction of acetylcholine catalyzed by acetylcholinesterase. Our calculations show two energy barriers along the reaction coordinate for the enzyme-catalyzed acylation of acetylcholine. The second barrier (8.5 kcal/mol) is rate-limiting for the acylation reaction and in good agreement with experiment.

We investigated the atomic structure and infrared spectra of the alumina(0001)/water interface, using first-principles molecular dynamics simulations based on density functional theory within the generalized gradient approximation. The computed structural properties of the interface are in good agreement with the results of synchrotron X-ray experiments. Detailed analyses of the computed infrared spectra revealed two types of water molecules at the hydrophilic oxide/water interface: molecules participating in strong "ice-like" hydrogen bonding with the oxide surface and molecules involved in weaker "liquid-like" hydrogen bonding. Our results provide a molecular interpretation of the "ice-like" and "liquid-like" bands observed in sum-frequency vibrational spectroscopy experiments and underscore the significance of strong hydrogen-bonding interactions in determining the orientation of interfacial water molecules.

Nanostructured optical components, such as nanolenses, direct light at subwavelength scales to enable, among others, high-resolution lithography, miniaturization of photonic circuits, and nanoscopic imaging of biostructures. A major challenge in fabricating nanolenses is the appropriate positioning of the lens with respect to the sample while simultaneously ensuring it adopts the optimal size and shape for the intended use. One application of particular interest is the enhancement of contrast and signal-to-noise ratio in the imaging of nanoscale objects, especially over wide fields-of-view (FOVs), which typically come with limited resolution and sensitivity for imaging nano-objects. Here we present a self-assembly method for fabricating time- and temperature-tunable nanolenses based on the condensation of a polymeric liquid around a nanoparticle, which we apply to the high-throughput on-chip detection of spheroids smaller than 40 nm, rod-shaped particles with diameter smaller than 20 nm, and biofunctionalized nanoparticles, all across an ultralarge FOV of >20 mm2. Previous nanoparticle imaging efforts across similar FOVs have detected spheroids no smaller than 100 nm, and therefore our results demonstrate the detection of particles >15-fold smaller in volume, which in free space have >240 times weaker Rayleigh scattering compared to the particle sizes detected in earlier wide-field imaging work. This entire platform, with its tunable nanolens condensation and wide-field imaging functions, is also miniaturized into a cost-effective and portable device, which might be especially important for field use, mobile sensing, and diagnostics applications, including, for example, the measurement of viral load in bodily fluids.

Traditional chemical weapon agents (CWAs) are known to bind acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).Their lethality is known to be different for different mammalian species.We have modeled the binding affinity of CWAs to AChE and BuChE in human, rabbit, rat and mouse using molecular docking and free energy calculations.Through molecular docking we are able to correctly bind the CWAs at the active site.Using molecular mechanics generalized Born surface area (MMGBSA) calculations, we determined the binding free energy in the active site.Through these calculations, we observe that correct orientation at the active site is critical to binding.

The electronic and geometric structure of the Pu(OH)4 molecule and Pu(OH)4(H2O)n (n=1-19) clusters are compared using a range of single- and multi-reference theories. We find that single-reference methods such as unrestricted, second-order Møller–Plesset perturbation theory provide a reasonable description, and explicit inclusion of multi-configurational effects involving Pu 5f-electrons is not essential. However, density functional theory (DFT) with standard approximations for exchange–correlation performs poorly for Pu(OH)4 and Pu(OH)4(H2O)n clusters. We propose the use of DFT+U as a simple improvement over standard DFT, and determine an ab initio parameterization of DFT+U suitable for atomistic simulations of Pu(OH)4 in aqueous environments.

We present a study of the infrared (IR) spectra of the (0001) deuterated ice surface based on first-principles molecular dynamics simulations. The computed spectra show a good agreement with available experimental IR measurements. We identified the bonding configurations associated with specific features in the spectra, allowing us to provide a detailed interpretation of IR signals. We computed the spectra of several proton ordered and disordered models of the (0001) surface of ice, and we found that IR spectra do not appear to be a sensitive probe of the microscopic arrangement of protons at ice surfaces.