Exploring Catalytic Intermediates in Pd-Catalyzed Aerobic Oxidative Amination of 1,3-Dienes: Multiple Metal Interactions of the Palladium Nanoclusters.

Metal nanoclusters (NCs) have unique properties because of their small size, which makes them useful as catalysts in reactions like cross-coupling. Pd-catalyzed oxidative amination, which involves dehydrogenative C-N bond formation, uses Pd complexes as the active species. It is known that the catalytic conditions involve the formation of Pd(0) species from Pd NCs, but the precise role of Pd NCs in the transformations has not been established. In this study, we investigated the characteristic properties of Pd NCs in oxidative amination of 1,3-dienes. The reaction achieved direct amination of commercially accessible 1,3-dienes with secondary aromatic amines, providing a variety of nitrogen containing 1,3-dienes. The compound was applicable to radical polymerization to provide the nitrogen-fabricated 1,3-diene-based polymer, which exhibited a different thermal stability compared to aliphatic nitrogen-fabricated diene polymers. In addition to the synthetic utility, by combining X-ray absorption fine structure and small-angle X-ray scattering analysis, we revealed amines and 1,3-dienes affected metal leaching from the Pd nanoparticles and stabilization of Pd NCs in the catalytic reaction. Additionally, DFT calculation suggested that the catalytic intermediate contained multiple adjacent Pd atoms and was responsible for formation of an σ-allylic intermediate that is difficult to form with the use of Pd complexes. These results could be used to understand the underlying phenomenon in the oxidative coupling reaction and develop Pd NCs-based dehydrogenation.

Photoinduced Enantioselective Triplet Radical Reaction on Metal: Copper-Catalyzed Conjugate Addition of Acylsilanes to α,ß-Unsaturated Ketones and Aldehydes.

A photoinduced copper-catalyzed enantioselective conjugate addition of acylsilanes has been developed. The conjugate acylation of α,ß-unsaturated ketones and aldehydes was promoted by a copper(I)/chiral NHC catalyst under visible-light irradiation for synthesizing various 2-substituted 1,4-dicarbonyl compounds in enantioenriched forms. Mechanistic studies combining experiments and quantum chemical calculations indicated a reaction mechanism involving copper-to-acyl charge transfer (i.e., metal-to-ligand charge transfer (MLCT)) excitation of an alkene-bound acylcopper complex. The MLCT excitation is followed by an electronical and geometrical change to generate a ß-radical-C-enolate-Cu(II)-acyl complex with an acyl radical character, which undergoes facile C-C bond formation in the copper coordination sphere, affording the 1,4-conjugate addition product.

A DFT Mechanistic Study on the Aza-Aldol Reaction of Boron Aza-Enolates: Relative Stability of Six-Membered Transition State and Its Relevance to the Coordination Mode of the Leaving Group.

The mechanism of the aza-aldol reaction between boron aza-enolate and benzaldehyde is investigated by using density functional theory calculations. The result shows that the syn-E isomer is preferentially formed, consistent with experimental observations. The six-membered ring transition state (TS) with the boat form leads to the E isomer, while the more unstable chair TS does to the Z isomer. The preference of the syn isomer is determined by the interactions between the substituents of aza-enolate and benzaldehyde. Structural distortion and intrinsic reaction coordinate analyses of simplified model systems provide insights into the origin of the relative stability of the rate-determining TS with boat and chair forms. The boat TS is an early TS; thus, minimal structural distortions of the reactant are required to reach this TS. The Lewis pair interactions between the boron and imine groups during B-N elimination also influenced the relative stability of the TSs. This interaction involves the nitrogen lone pair in the boat TS, while the π(N═C) orbital is involved in the chair TS. The Lewis pair with the lone pair stabilizes the TS more than that with the π orbital. The boron aza-enolate with 9-BBN generates an ate complex and forms C-C bonds sequentially, whereas that with Bpin does not generate an ate complex and exhibits the concerted formation of B-O and C-C bonds. Thus, the higher electrophilicity of boron such as 9-BBN enhances the reactivity by facilitating the formation of the ate complex. A reaction design is proposed to reverse the syn/anti selectivity. Proof-of-concept DFT calculations suggested that the modification of the imine group would change the relative stability of the boat/chair TSs and give the anti-product.

Characterization of changes in the electronic structure of platinum sub-nanoclusters supported on graphene induced by oxygen adsorption.

As the sizes of noble metal catalysts, such as platinum, have been successfully minimized, fundamental insights into the electronic properties of metal sub-nanoclusters are increasingly sought for optimizing their catalytic performance. However, it is difficult to rationalize the catalytic activities of metal sub-nanoclusters owing to their more complex electronic structure compared with those of small molecules and bulky solids. In this study, the adsorption of molecular oxygen on a Pt13 sub-nanocluster supported on a graphene layer was analyzed using density functional theory. Unlike bulk Pt, the Pt13 sub-nanocluster has multiple adsorption sites, and the adsorption energy depends strongly on the type of adsorption site. The O2 adsorption energy does not correlate with the transferred charge between O2 and the Pt13 moiety; therefore, to elucidate the differences in the adsorption sites, we propose an original approach for analyzing the electronic structure change in metal sub-nanoclusters caused by molecular adsorption. Our analysis of the integrated local density of state (LDOS) revealed that O2 adsorption on the Pt13 sub-nanocluster has a distinct feature, different from that on a smaller Pt2 cluster or rather a larger Pt slab. The change in the electronic structure of the Pt13 moiety was primarily observed near the Fermi level, different from that of the Pt slab whose DOS was distributed over a wide energy range. Furthermore, the change in the integrated LDOS correlated well with the O2 adsorption energy on the Pt13 sub-nanocluster.

A Multiconfigurational Wave Function Theoretical Study on Electronic Structure and Magnetic Susceptibility of Dilanthanide Single Molecule Magnet.

Single molecule magnets (SMMs) have been a promising material for next-generation high-density information storage and molecular spintronics. N23--bridged dilanthanide complexes, {[(Me3Si)2N]2Ln(THF)(µ-η2:η2-N2)(THF)Ln[(Me3Si)2N]2}1-, exhibit high blocking temperatures and have been one of the promising candidates for future application. Rational understanding should be established between the magnetic properties and electronic structure. However, the theoretical study is still challenging due to the complexities in their electronic structures. Here, we theoretically studied the magnetic susceptibility of dilanthanide SMMs based on the state-of-the-art multistate-complete active space self-consistent field and perturbation theory at the second order and restricted active space state interaction with spin-orbit coupling calculations. Temperature dependence of the magnetic susceptibility (χmT-T curve) was quantitatively reproduced by the theoretical calculations. The complexities in the electronic states of these dilanthanide complexes originate from significantly strong static electron correlations in the lanthanide 4f and N2 π* orbitals and the SOC effect. The temperature dependence of the magnetic susceptibility results from the energy levels and magnetic properties of the low-lying excited state. The χmT values below 50 K are dominated by the ground state, while thermal distribution in the low-lying excited state affects the χmT values over 50 K. Saturation magnetization at low temperatures was also evaluated, and the result agrees with the experimental observation.

Highly Enantioselective Radical Cation [2 + 2] and [4 + 2] Cycloadditions by Chiral Iron(III) Photoredox Catalysis.

Radical cations show a unique reactivity that is fundamentally different from that of conventional cations and have thus attracted considerable attention as alternative cationic intermediates for novel types of organic reactions. However, asymmetric catalysis to promote enantioselective radical cation reactions remains a major challenge in contemporary organic synthesis. Here, we report that the judicious design of an ion pair consisting of a radical cation and a chiral counteranion induces an excellent level of enantioselectivity. This strategy was applied to enantio-, diastereo-, and regioselective [2 + 2] cycloadditions, as well as enantio-, diastereo-, and regioselective [4 + 2] cycloadditions, by using chiral iron(III) photoredox catalysis. We anticipate that this strategy has the potential to expand the use of several mature chiral anions to develop numerous unprecedented enantioselective radical cation reactions.

Dynamic Behavior of Intermediate Adsorbates to Control Activity and Product Selectivity in Heterogeneous Catalysis: Methanol Decomposition on Pt/TiO2(110).

Dynamic behavior of intermediate adsorbates, such as diffusion, spillover, and reverse spillover, has a strong influence on the catalytic performance in oxide-supported metal catalysts. However, it is challenging to elucidate how the intermediate adsorbates move on the catalyst surface and find active sites to give the corresponding products. In this study, the effect of the dynamic behavior of methoxy intermediate on methanol decomposition on a Pt/TiO2(110) surface has been clarified by combination of scanning tunneling microscopy (STM), temperature-programmed desorption (TPD), and density functional theory (DFT) calculations. The methoxy intermediates were formed by the dissociative adsorption of methanol molecules on Pt nanoparticles at room temperature followed by spillover to the TiO2(110) support surface. TPD results showed that the methoxy intermediates were thermally decomposed at >350 K on the Pt sites to produce CO (dehydrogenation) and CH4 (C-O bond scission). A decrease of the Pt nanoparticle density lowered the activity for the decomposition reaction and increased the selectivity toward CH4, which indicates that the reaction is controlled by diffusion and reverse spillover of the methoxy intermediates. Time-lapse STM imaging and DFT calculations revealed that the methoxy intermediates migrate on the five-fold coordinated Ti (Ti5c) sites along the [001] or [11¯0] direction with the aid of hydrogen adatoms bonded to the bridging oxygens (Obr) and can move over the entire surface to seek and find active Pt sites. This work offers an in-depth understanding of the important role of intermediate adsorbate migration in the control of the catalytic performance in oxide-supported metal catalysts.

First-principles study on unidirectional proton transfer on anatase TiO2 (101) surface induced by external electric fields.

The electric field (EF) effect on hydrogen or proton transfer (PT) via hydroxyl groups on an anatase TiO2 (101) surface is examined using first-principles density functional theory and the modern theory of polarization. This study focuses on unidirectional surface PT caused by external EFs at various orientations toward the surface. The preferred PT pathway can change depending on the magnitude and direction of the EF. Detailed analysis reveals that the variation in the energy profile with the EF is significantly different from that determined by the classical electric work of an EF carrying a point charge. The EF effect on the energy profile of the PT is governed by the rearrangement of the chemical bond network at the interface between the water molecules and the surface.

Optimization of General Molecular Properties in the Equilibrium Geometry Using Quantum Alchemy: An Inverse Molecular Design Approach.

Inverse molecular design allows the optimization of molecules in chemical space and is promising for accelerating the development of functional molecules and materials. To design realistic molecules, it is necessary to consider geometric stability during optimization. In this work, we introduce an inverse design method that optimizes molecular properties by changing the chemical composition in the equilibrium geometry. The optimization algorithm of our recently developed molecular design method has been modified to allow molecular design for general properties at a low computational cost. The proposed method is based on quantum alchemy and does not require empirical data. We demonstrate the applicability and limitations of the present method in the optimization of the electric dipole moment and atomization energy in small chemical spaces for (BF, CO), (N2, CO), BN-doped benzene derivatives, and BN-doped butane derivatives. It was found that the optimality criteria scheme adopted for updating the molecular species yields faster convergence of the optimization and requires a less computational cost. Moreover, we also investigate and discuss the applicability of quantum alchemy to the electric dipole moment.

Efficacy and safety of twice-daily tramadol hydrochloride bilayer sustained-release tablets with an immediate release component for postherpetic neuralgia: Results of a Phase III, randomized, double-blind, placebo-controlled, treatment-withdrawal study.

BACKGROUND: We investigated the efficacy and safety of twice-daily bilayer sustained-release tramadol hydrochloride tablets (35% immediate-release; 65% sustained-release) in patients with postherpetic neuralgia. METHODS: This was a Phase III treatment-withdrawal study with 1-4-week dose-escalation, 1-week fixed-dose, and 4-week randomized, double-blind, placebo-controlled withdrawal periods performed at 43 medical institutions in Japan. Patients aged ≥20 years, ≥3 months after the onset of herpes zoster with localized, persistent pain despite fixed-dose analgesics for ≥2 weeks before enrollment were eligible. Patients started tramadol at 100 mg/day and its dose escalated to a maximum of 400 mg/day to achieve a reduction in their Numeric Rating Scale (NRS) for pain of ≥2 points. Eligible patients were randomized to continue tramadol or switched to placebo for 4 weeks (double-blind period). Patients were withdrawn due to inadequate analgesia (NRS deteriorated on ≥2 consecutive days) or their request. RESULTS: Overall, 252 patients started tramadol and 173 were randomized (tramadol: 85; placebo: 88). Tramadol was superior to placebo for the primary endpoint (time from randomization to an inadequate analgesic effect) with log-rank test p = 0.0005. The hazard ratio was 0.353 (95% confidence interval 0.190-0.657) in favor of tramadol and fewer patients in the tramadol group experienced inadequate analgesic effects (16.9% vs. 39.8%). Adverse events in ≥10% of patients in the open-label period were constipation (43.8%), nausea (34.9%), somnolence (18.5%), and dizziness (11.6%). The frequencies of adverse events in the double-blind period were similar in both groups. CONCLUSION: Sustained-release tramadol tablets with an immediate-release component are effective and well tolerated for managing postherpetic neuralgia.

Iron/Photosensitizer Hybrid System Enables the Synthesis of Polyaryl-Substituted Azafluoranthenes.

Photosensitization of organometallics is a privileged strategy that enables challenging transformations in transition-metal catalysis. However, the usefulness of such photocatalyst-induced energy transfer has remained opaque in iron-catalyzed reactions despite the intriguing prospects of iron catalysis in synthetic chemistry. Herein, we demonstrate the use of iron/photosensitizer-cocatalyzed cycloaddition to synthesize polyarylpyridines and azafluoranthenes, which have been scarcely accessible using the established iron-catalyzed protocols. Mechanistic studies indicate that triplet energy transfer from the photocatalyst to a ferracyclic intermediate facilitates the thermally demanding nitrile insertion and accounts for the distinct reactivity of the hybrid system. This study thus provides the first demonstration of the role of photosensitization in overcoming the limitations of iron catalysis.

Photoinduced Copper-Catalyzed Asymmetric Acylation of Allylic Phosphates with Acylsilanes.

We report a visible-light-induced copper-catalyzed highly enantioselective umpolung allylic acylation reaction with acylsilanes as acyl anion equivalents. Triplet-quenching experiments and DFT calculations supported our reaction design, which is based on copper-to-acyl metal-to-ligand charge transfer (MLCT) photoexcitation that generates a charge-separated triplet state as a highly reactive intermediate. According to the calculations, the allylic phosphate substrate in the excited state undergoes novel molecular activation into an allylic radical weakly bound to the copper complex. The allyl radical fragment undergoes copper-mediated regio- and stereocontrolled coupling with the acyl group under the influence of the chiral N-heterocyclic carbene ligand.

Mechanism of BPh3 -Catalyzed N-Methylation of Amines with CO2 and Phenylsilane: Cooperative Activation of Hydrosilane.

BPh3 catalyzes the N-methylation of secondary amines and the C-methylenation (methylene-bridge formation between aromatic rings) of N,N-dimethylanilines or 1-methylindoles in the presence of CO2 and PhSiH3 ; these reactions proceed at 30-40 °C under solvent-free conditions. In contrast, B(C6 F5 )3 shows little or no activity. 11 B NMR spectra suggested the generation of [HBPh3 ]- . The detailed mechanism of the BPh3 -catalyzed N-methylation of N-methylaniline (1) with CO2 and PhSiH3 was studied by using DFT calculations. BPh3 promotes the conversion of two substrates (N-methylaniline and CO2 ) into a zwitterionic carbamate to give three-component species [Ph(Me)(H)N+ CO2 - ⋅⋅⋅BPh3 ]. The carbamate and BPh3 act as the nucleophile and Lewis acid, respectively, for the activation of PhSiH3 to generate [HBPh3 ]- , which is used to produce key CO2 -derived species, such as silyl formate and bis(silyl)acetal, essential for the N-methylation of 1. DFT calculations also suggested other mechanisms involving water for the generation of [HBPh3 ]- species.

Asymmetric Dehydrative Cyclization of Allyl Alcohol to Cyclic Ether Using Chiral Brønsted Acid/CpRu(II) Hybrid Catalysts: A DFT Study of the Origin of Enantioselectivity.

To elucidate the reaction mechanism and the origin of the enantioselectivity of the asymmetric dehydrative cyclization of allyl alcohol to cyclic ether catalyzed by a Cp-ruthenium complex and a chiral pyridinecarboxylic acid, (R)-X-Naph-PyCOOH, density functional theory (DFT) calculations were performed. According to the DFT calculations, the rate-determining step is the dehydrative σ-allyl formation step with ΔG‡ = 18.1 kcal mol-1 at 80 °C. This agrees well with the experimental data (ΔG‡ = 19.01 kcal mol-1 at 80 °C). The DFT result showed that both hydrogen and halogen bonds play a key role in the high enantioselectivity by facilitating the major R,SRu-catalyzed reaction pathway via a σ-allyl Ru intermediate to generate the major (S)-product. In contrast, the reaction is sluggish in the presence of the diastereomeric R,RRu catalyst with an apparent activation energy of 33.1 kcal mol-1; the minor (R)-product is formed via a typical π-allyl Ru intermediate and via a minor pathway for the cyclization step. In addition, the calculated activation Gibbs free energies, 14.4 kcal mol-1 for I < 16.8 kcal mol-1 for Br < 18.1 kcal mol-1 for Cl, reproduced the observed halogen-dependent reactivity with the (R)-X-Naph-PyCOOH ligands. The origin of the halogen trend was clarified by a structural decomposition analysis.

Neutron imaging with an inertial electrostatic confinement fusion neutron source.

A compact inertial electrostatic confinement (IEC) fusion neutron source was developed. Imaging tests using the cylindrical IEC neutron source were conducted with the indirect imaging plate (IP) method using dysprosium foil and an imaging plate. An array of B4C powder contained in a stainless-steel blade and Cd pins was successfully imaged. To calculate thermal neutron flux of the device, we tested multiple types of IP and IP scanners with the indirect IP method to create a calibration curve, and it was confirmed that dental IP scanners, which are more widely used than industrial ones, can be applied to the indirect IP method.

Selective Catalytic Reduction of NOx with NH3 by Using Novel Catalysts: State of the Art and Future Prospects.

Selective catalytic reduction with NH3 (NH3-SCR) is the most efficient technology to reduce the emission of nitrogen oxides (NOx) from coal-fired industries, diesel engines, etc. Although V2O5-WO3(MoO3)/TiO2 and CHA structured zeolite catalysts have been utilized in commercial applications, the increasing requirements for broad working temperature window, strong SO2/alkali/heavy metal-resistance, and high hydrothermal stability have stimulated the development of new-type NH3-SCR catalysts. This review summarizes the latest SCR reaction mechanisms and emerging poison-resistant mechanisms in the beginning and subsequently gives a comprehensive overview of newly developed SCR catalysts, including metal oxide catalysts ranging from VOx, MnOx, CeO2, and Fe2O3 to CuO based catalysts; acidic compound catalysts containing vanadate, phosphate and sulfate catalysts; ion exchanged zeolite catalysts such as Fe, Cu, Mn, etc. exchanged zeolite catalysts; monolith catalysts including extruded, washcoated, and metal-mesh/foam-based monolith catalysts. The challenges and opportunities for each type of catalysts are proposed while the effective strategies are summarized for enhancing the acidity/redox circle and poison-resistance through modification, creating novel nanostructures, exposing specific crystalline planes, constructing protective/sacrificial sites, etc. Some suggestions are given about future research directions that efforts should be made in. Hopefully, this review can bridge the gap between newly developed catalysts and practical requirements to realize their commercial applications in the near future.

Impact of tensile and compressive forces on the hydrolysis of cellulose and chitin.

Mechanochemistry enables unique reaction pathways in comparison to conventional thermal reactions. Notably, it can achieve selective hydrolysis of cellulose and chitin, a set of abundant and recalcitrant biomass, by solvent-free ball-milling in the presence of acid catalysts. Although the merits of mechanochemistry for this reaction are known, the reaction mechanism is still unclear. Here, we show how the mechanical forces produced by ball-milling activate the glycosidic bonds of carbohydrate molecules towards hydrolysis. This work uses experimental and theoretical evaluations to clarify the mechanism. The experimental results reveal that the ball-mill accelerates the hydrolysis by mechanical forces rather than local heat. Meanwhile, the classical and quantum mechanics calculations indicate the subnano to nano Newton order of tensile and compressive forces that activate polysaccharide molecules in the ball-milling process. Although previous studies have taken into account only the stretching of the molecules, our results show that compressive forces are stronger and effective for the activation of glycosidic bonds. Accordingly, in addition to stretching, compression is crucial for the mechanocatalytic reaction. Our work connects the classical physics of ball-milling on a macro scale with molecular activation at a quantum level, which would help to understand and control mechanochemical reactions.

On the Electronic Structure Origin of Mechanochemically Induced Selectivity in Acid-Catalyzed Chitin Hydrolysis.

Recently, mechanical ball milling was applied to chitin depolymerization. The mechanical activation afforded higher selectivity toward glycosidic bond cleavage over amide bond breakage. Hence, the bioactive N-acetylglucosamine (GlcNAc) monomer was preferentially produced over glucosamine. In this regard, the force-dependent mechanochemical activation-deactivation process in the relaxed and pulled GlcNAc dimer undergoing deacetylation and depolymerization reactions was studied. For the relaxed case, the activation energies of the rate-determining steps (RDS) proved that the two reactions could occur simultaneously. Mechanical forces associated with ball milling were approximated with linear pulling and were introduced explicitly in the RDS of both reactions through force-modified potential energy surface (FMPES) formalism. In general, as the applied pulling force increases, the activation energy of the RDS of deacetylation shows no meaningful change, while that of depolymerization decreases. This result is consistent with the selectivity exhibited in the experiment. Energy and structural analyses for the depolymerization showed that the activation can be attributed to a significant change in the glycosidic dihedral at the reactant state. A lone pair of the neighboring pyranose ring O adopts a syn-periplanar conformation relative to the glycosidic bond. This promotes electron donation to the σ*-orbital of the glycosidic bond, leading to activation. Consequently, the Brønsted-Lowry basicity of the glycosidic oxygen also increases, which can facilitate acid catalysis.

Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy.

The Keap1-Nrf2 system and autophagy are both involved in the oxidative-stress response, metabolic pathways, and innate immunity, and dysregulation of these processes is associated with pathogenic processes. However, the interplay between these two pathways remains largely unknown. Here, we show that phosphorylation of the autophagy-adaptor protein p62 markedly increases p62's binding affinity for Keap1, an adaptor of the Cul3-ubiquitin E3 ligase complex responsible for degrading Nrf2. Thus, p62 phosphorylation induces expression of cytoprotective Nrf2 targets. p62 is assembled on selective autophagic cargos such as ubiquitinated organelles and subsequently phosphorylated in an mTORC1-dependent manner, implying coupling of the Keap1-Nrf2 system to autophagy. Furthermore, persistent activation of Nrf2 through accumulation of phosphorylated p62 contributes to the growth of human hepatocellular carcinomas (HCCs). These results demonstrate that selective autophagy and the Keap1-Nrf2 pathway are interdependent, and that inhibitors of the interaction between phosphorylated p62 and Keap1 have potential as therapeutic agents against human HCC.

Spin-inversion mechanisms in O2 binding to a model heme complex revisited by density function theory calculations.

Spin-inversion mechanisms in O2 binding to a model heme complex, consisting of Fe(II)-porphyrin and imidazole, were investigated using density-functional theory calculations. First, we applied the recently proposed mixed-spin Hamiltonian method to locate spin-inversion structures between different total spin multiplicities. Nine spin-inversion structures were successfully optimized for the singlet-triplet, singlet-quintet, triplet-quintet, and quintet-septet spin-inversion processes. We found that the singlet-triplet spin-inversion points are located around the potential energy surface region at short Fe-O distances, whereas the singlet-quintet and quintet-septet spin-inversion points are located at longer Fe-O distances. This suggests that both narrow and broad crossing models play roles in O2 binding to the Fe-porphyrin complex. To further understand spin-inversion mechanisms, we performed on-the-fly Born-Oppenheimer molecular dynamics calculations. The reaction coordinates, which are correlated to the spin-inversion dynamics between different spin multiplicities, are also discussed.