Dynamic signature of electronically nonadiabatic coupling in sodium hydride: a rigorous test for the symmetric quasi-classical model applied to realistic, ab initio electronic states.

Sodium hydride (NaH) in the gas phase presents a seemingly simple electronic structure making it a potentially tractable system for the detailed investigation of nonadiabatic molecular dynamics from both computational and experimental standpoints. The single vibrational degree of freedom, as well as the strong nonadiabatic coupling that arises from the excited electronic states taking on considerable ionic character, provides a realistic chemical system to test the accuracy of quasi-classical methods to model population dynamics where the results are directly comparable against quantum mechanical benchmarks. Using a simulated pump-probe experiment, this work presents computational predictions of population transfer through the avoided crossings of NaH via symmetric quasi-classical Meyer-Miller (SQC/MM), Ehrenfest, and exact quantum dynamics on realistic, ab initio potential energy surfaces. The main driving force for population transfer arises from a sharply localized avoided crossing between the C and D singlet sigma potential energy surfaces which causes most of the population to transfer between t=15 and t=30 fs depending on the initially excited vibronic wavepacket. While quantum mechanical effects are expected due to the reduced mass of NaH, predictions of the population dynamics from both the SQC/MM and Ehrenfest models perform remarkably well against the quantum dynamics benchmark. Additionally, an analysis of the vibronic structure in the nonadiabatically coupled regime and predicted transient absorption signatures are presented using a variational eigensolver methodology. The prospects for complementary experimental measurements are also assessed.

Synthesis and antiprotozoal activity of pyridine thioaryl ethers

By reaction of pyridine nitro derivatives containing a mobile halogen atom with thiols of the benzene series, twelve thioaryl ethers of nitropyridine were obtained. However, 2-chloro-3-nitropyridine and 2-chloro-5-nitropyridine were used as reactive pyridine compounds. The reaction was carried out in dimethylformamide (DMFA) or dimethyl sulfoxide (DMSO) in the presence of bases: sodium ethylate, potash, sodium hydride. Generally, the yields exceeded 90%. The sulfur containing derivatives of aromatic series were 2-mercaptobenzoic acid (compound 1 of Table 1), methyl ester of 2-mercaptobenzoic acid (compounds 2 and 3 of Table 1), compound 3 being obtained by reduction of nitro group of compound 2. Also the amides of 2-mercaptobenzoic acid were used: 3-dimethylaminopropylamide of 2-mercaptobenzoic acid (compound 4 of Table 1), and also the reduction product of compound 4 to 3-aminopyridine derivative (compound 5 of Table 1) and morfolide of 2-mercaptobenzoic acid (compound 6 of Table 1). To make the water-soluble a sodium salt of 2-mercaptobenzoic acid was obtained (compound 7 of Table 1). A number of compounds with the pyridine ring nitrogroup reduced to amine (compounds 8, 10 of Table 1), as well as a number of derivatives containing both free (compounds 9, 10 of Table 1) and acylated amino group (compound 11 of Table 1) were also obtained. We also prepared compound 12 representing a product of interaction of 2-chloro-3-nitropyridine with 2-mercapto-3-acetylpyridine. We should note that the best nitrogroup reductant for the synthesis of compounds 3, 5, 7, and 10 is powdered iron in alcohol medium containing both inorganic and organic acids (hydrochloric or acetic acid). The application of other reducing agents (sodium sulfide and ammonium sulfide) led to strong resinification of the reaction mixture. The compounds were recrystallized from organic solvents (ethyl acetate, benzene, ethanol) for purification. Significant antiprotozoic activity was found in 7 of 12 compounds (58%), with 3-nitro-2-chloropyridine being the most active (7.8 and 3.9 ?g/ml). To enhance the activity, the synthesis of compounds with an amino group in the benzene ring as well as the introduction of both donor and acceptor substituents into the benzene ring is recommended.

A Sodium-Cooled Thermal-Spectrum Fission Battery

We propose a low-enriched-uranium, thermal-neutron-spectrum sodium-cooled reactor with a peak sodium temperature of 700°C coupled to an air-Brayton power cycle for electricity and heat. Three low-enriched-uranium, thermal spectrum sodium-cooled reactors were built in the 1960s and 1970s; but there has been no examination of such systems for many decades. We develop a pre-conceptual design based on “new” enabling technologies since the 1970s including yttrium hydride as the high-temperature neutron moderator, commercial gas turbines and secure decay heat removal systems. We define the reactor as a sodium hydride reactor (SHR). The initial application is as a fission battery. The concept of the fission battery (FB) is a “plug and play” nuclear reactor defined by multiple characteristics: economics enabled by factory fabrication of large numbers of identical units, easy installation and removal, unattended operation and highly reliable operations. FBs are designed to be a low-carbon replacement for fossil fuels by industrial and commercial companies that require energy to produce some product (manufactured goods, chemicals, education, data centers, ship transportation, etc.). The reactors may be owned or leased by the company. The SHR is at an early stage of development.

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

The indazole scaffold represents a promising pharmacophore, commonly incorporated in a variety of therapeutic drugs. Although indazole-containing drugs are frequently marketed as the corresponding N-alkyl 1H- or 2H-indazole derivative, the efficient synthesis and isolation of the desired N-1 or N-2 alkylindazole regioisomer can often be challenging and adversely affect product yield. Thus, as part of a broader study focusing on the synthesis of bioactive indazole derivatives, we aimed to develop a regioselective protocol for the synthesis of N-1 alkylindazoles. Initial screening of various conditions revealed that the combination of sodium hydride (NaH) in tetrahydrofuran (THF) (in the presence of an alkyl bromide), represented a promising system for N-1 selective indazole alkylation. For example, among fourteen C-3 substituted indazoles examined, we observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric distribution. For example, employing C-7 NO2 or CO2Me substituted indazoles conferred excellent N-2 regioselectivity (≥ 96%). Importantly, we show that this optimized N-alkylation procedure tolerates a wide structural variety of alkylating reagents, including primary alkyl halide and secondary alkyl tosylate electrophiles, while maintaining a high degree of N-1 regioselectivity.

Synthesis and Biological Evaluation of a Radiolabeled PET Probe for Visualization of In Vivo α-Fucosidase Expression

The acidic hydrolase α-fucosidase (AF) is a biomarker for maladies such as cancer and inflammation. The most advanced probes for α-fucosidase are unfortunately constrained to ex vivo or in vitro applications. The in vivo detection and quantification of AF using positron emission tomography would allow for better discovery and diagnosis of disease as well as provide better understanding of disease progression. We synthesized, characterized, and evaluated a radiolabeled small molecule inhibitor of AF based on a known molecule. The radiosynthesis involved the 11C methylation of a phenoxide, which was generated in situ by ultrasonification of the precursor with sodium hydride. The tracer was produced with a decay corrected yield of 41.7 ± 16.5% and had a molar activity of 65.4 ± 30.3 GBq/μmol. The tracer was shown to be stable in mouse serum at 60 min. To test the new tracer, HCT116 colorectal carcinoma cells were engineered to overexpress human AF. In vitro evaluation revealed 3.5-fold higher uptake in HCT116AF cells compared to HCT116 controls (26.4 ± 7.8 vs. 7.5 ± 1.0 kBq/106 cells). Static PET scans 50 min post injection revealed 2.5-fold higher tracer uptake in the HCT116AF tumors (3.0 ± 0.8%ID/cc (n = 6)) compared with the controls (1.2 ± 0.8 (n = 5)). Dynamic scans showed higher uptake in the HCT116AF tumors at all time-points (n = 2). Ex vivo analysis of the tumors, utilizing fluorescent DDK2 antibodies, confirmed the expression of human AF in the HCT116AF xenografts. We have developed a novel PET tracer to image AF in vivo and will now apply this to relevant disease models.

Sustainable Myrcene-Based Elastomers via a Convenient Anionic Polymerization

Soluble heterocomplexes consisting of sodium hydride in combination with trialkylaluminum derivatives have been used as anionic initiating systems at 100 °C in toluene for convenient homo-, co- and ter-polymerization of myrcene with styrene and isoprene. In this way it has been possible to obtain elastomeric materials in a wide range of compositions with interesting thermal profiles and different polymeric architectures by simply modulating the alimentation feed and the (monomers)/(initiator systems) ratio. Especially, a complete study of the myrcene-styrene copolymers (PMS) was carried out, highlighting their tapered microstructures with high molecular weights (up to 159.8 KDa) and a single glass transition temperature. For PMS copolymer reactivity ratios, rmyr = 0.12 ± 0.003 and rsty = 3.18 ± 0.65 and rmyr = 0.10 ± 0.004 and rsty = 3.32 ± 0.68 were determined according to the Kelen–Tudos (KT) and extended Kelen–Tudos (exKT) methods, respectively. Finally, this study showed an easy accessible approach for the production of various elastomers by anionic copolymerization of renewable terpenes, such as myrcene, with commodities.

Crystal structure and spectroscopic properties of (E)-1,3-dimethyl-2-[3-(4-nitrophenyl)triaz-2-enylidene]-2,3-dihydro-1H-imidazole

The title compound (E)-1,3-dimethyl-2-[3-(4-nitrophenyl)triaz-2-enylidene]-2,3-dihydro-1H-imidazole, C11H12N6O2, has monoclinic (C2/c) symmetry at 100 K. This triazene derivative was synthesized by the coupling reaction of 1,3-dimethylimidazolium iodide with 1-azido-4-nitro benzene in the presence of sodium hydride (60% in mineral oil) and characterized by 1H NMR, 13C NMR, IR, mass spectrometry, and single-crystal X-ray diffraction. The molecule consists of six-membered and five-membered rings, which are connected by a triazene moiety (–N=N—N–). In the solid-state, the molecule is found to be planar due to conjugation throughout the molecule. The extended structure shows two layers of molecules, which present weak intermolecular interactions that facilitate the stacked arrangement of the molecules forming the extended structure. Furthermore, there are several weak pseudo-cyclical interactions between the nitro oxygen atoms and symmetry-adjacent H atoms, which help to arrange the molecules.