Three-in-One Strategy to Improve Both Catalytic Activity and Selectivity: Nonconcentric Pd-Au Nanoparticles.

In direct H2O2 synthesis, the Pd-Au alloy was considered as a potential catalyst because of its much better performance compared to the prototype Pd; unfortunately, achieving both high activity and selectivity remains a challenge. Here, we synthesized nonconcentric Pd-Au NPs in which Au domain shells are formed only partially on Pd domain cores and tested them for direct H2O2 synthesis. It has three exposed regions of Pd, Au domains, and Pd-Au interfaces in a single NP (hence, a 3-in-1 strategy). Creating nonconcentric forms was demonstrated convincingly by density functional theory calculations. The nonconcentric Pd-Au particles exhibit high and well-balanced performances that are hard to achieve with traditional alloyed Pd-Au. The number of Pd/Au interfaces was found to be the key factor and thus was optimized by controlling the Au precursor concentrations. The hitherto underutilized structure of nonconcentric bimetallic alloys can be useful and thus should be more actively investigated for catalyst development.

Atomistic Insights into H2O2 Direct Synthesis of Ni-Pt Nanoparticle Catalysts under Water Solvents by Reactive Molecular Dynamics Simulations.

In computational catalysis, density-functional theory (DFT) calculations are usually utilized, although they suffer from high computational costs. Thus, it would be challenging to explicitly predict the catalytic properties of nanoparticles (NPs) at the nanoscale under solvents. Using molecular dynamics (MD) simulations with a reactive force field (ReaxFF), we investigated the catalytic performance of Ni-Pt NPs for the direct synthesis of hydrogen peroxide (H2O2), in which water solvents were explicitly considered along with the effects of the sizes (1.5, 2.0, 3.0, and 3.5 nm) and compositions (Ni90Pt10, Ni80Pt20, and Ni50Pt50) of the NPs. Among the Ni-Pt NPs, 3.0 nm NPs show the highest activity and selectivity for the direct synthesis of H2O2, revealing that the catalytic performance is not well correlated with the surface areas of NPs. The superior catalytic performance results from the high H2 dissociation and low O2 dissociation properties, which are correlated with the numbers of NiNiPt-fcc and NiNi-bridge sites on the surface of Ni-Pt NPs, respectively. The ReaxFF-MD simulations propose the optimum composition (Ni80Pt20) of 3.0 nm Ni-Pt NPs, which is also explained by the numbers of NiNiPt-fcc and NiNi-bridge sites. Furthermore, from the ReaxFF-MD simulations, the direct synthesis of H2O2 for the Ni-Pt NPs can be achieved not only with the Langmuir-Hinshelwood mechanism, which has been conventionally considered, but also with the water-induced mechanism, which is unlikely to occur on pure Pd and Pd-based alloy catalysts; these results are supported by DFT calculations. These results reveal that the ReaxFF-MD method provides significant information for predicting the catalytic properties of NPs, which could be difficult to provide with DFT calculations; thus, it can be a useful framework for the design of nanocatalysts through complementation with a DFT method.

Improved Description of a Coordinate Bond in the ReaxFF Reactive Force Field.

To improve the description of a coordinate bond of the reactive force field (ReaxFF), we have developed ReaxFFcoord by explicitly incorporating the coordinate bond contribution, Ecoord, into the original ReaxFF ( Chenoweth et al. J. Phys. Chem. A 2008 , 112 , 1040 - 1053 ), in which the auxiliary functions are newly suggested to describe the plug-in behavior of lone-pair electrons from a donor atom to a vacant orbital of an acceptor atom. To validate the developed ReaxFFcoord, we tested it in various systems, including a representative coordinate bond-containing molecule, namely, carbon monoxide or ammonia borane. Although the fitting abilities of the ReaxFFcoord and original ReaxFF are similar, their molecular dynamics (MD) simulations are significantly different, where MD simulations employing ReaxFFcoord provide more realistic dynamic behaviors of atoms. It is expected that the ReaxFFcoord will significantly help ReaxFF to successfully extend its applicability to the material and biological systems, including coordinate bonds in organometallic systems.

Activity, Selectivity, and Durability of Ruthenium Nanoparticle Catalysts for Ammonia Synthesis by Reactive Molecular Dynamics Simulation: The Size Effect.

We report a molecular dynamics (MD) simulation employing the reactive force field (ReaxFF), developed from various first-principles calculations in this study, on ammonia (NH3) synthesis from nitrogen (N2) and hydrogen (H2) gases over Ru nanoparticle (NP) catalysts. Using ReaxFF-MD simulations, we predict not only the activities and selectivities but also the durabilities of the nanocatalysts and discuss the size effect and process conditions (temperature and pressure). Among the NPs (diameter = 3, 4, 5, and 10 nm) considered in this study, the 4 nm NPs show the highest activity, in contrast to our intuition that the smallest NP should provide the highest activity, as it has the highest surface area. In addition, the best selectivity is observed with the 10 nm NPs. The activity and selectivity are mainly determined by the hcp, fcc, and top sites on the Ru NP surface, which depend on the NP size. Moreover, the selectivity can be improved more significantly by increasing the H2 pressure than by increasing the N2 pressure. The durability of the NPs can be determined by the mean stress and the stress concentration, and these two factors have a trade-off relationship with the NP size. In other words, as the NP size increases, its mean stress decreases, whereas the stress concentration simultaneously increases. Because of these two effects, the best durability is found with the 5 nm NPs, which is also in contrast to our intuition that larger NPs should show better durability. We expect that ReaxFF-MD simulations, along with first-principles calculations, could be a useful tool in developing novel catalysts and understanding catalytic reactions.

Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury.

In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.

Impact of the cation composition on the electrical performance of solution-processed zinc tin oxide thin-film transistors.

This study examined the structural, chemical, and electrical properties of solution-processed (Zn,Sn)O3 (ZTO) films with various Sn/[Zn+Sn] ratios for potential applications to large-area flat panel displays. ZTO films with a Zn-rich composition had a polycrystalline wurtzite structure. On the other hand, the Sn-rich ZTO films exhibited a rutile structure, where the Zn atom was speculated to replace the Sn site, thereby acting as an acceptor. In the intermediate composition regions (Sn/[Zn+Sn] ratio from 0.28 to 0.48), the ZTO films had an amorphous structure, even after annealing at 450 °C. The electrical transport properties and photobias stability of ZTO thin film transistors (TFTs) were also examined according to the Sn/[Zn+Sn] ratio. The optimal transport property of ZTO TFT was observed for the device with an amorphous structure at a Sn/[Zn+Sn] ratio of 0.48. The mobility, threshold voltage, subthreshold swing, and on/off current ratio were 4.3 cm(2)/(V s), 0 V, 0.4 V/decade, and 4.1 × 10(7), respectively. In contrast, the device performance for the ZTO TFTs with either a higher or lower Sn concentration suffered from low mobility and a high off-state current, respectively. The photoelectrical stress measurements showed that the photobias stability of the ZTO TFTs was improved substantially when the ZTO semiconducting films had a lower oxygen vacancy concentration and an amorphous structure. The relevant rationale is discussed based on the phototransition and subsequent migration mechanism from neutral to positively charged oxygen vacancies.

Photobias instability of high performance solution processed amorphous zinc tin oxide transistors.

The effects of the annealing temperature on the structural and chemical properties of soluble-processed zinc-tin-oxide (ZTO) films were examined by transmission electron microscopy, atomic force microscopy, high resolution X-ray reflectivity, and X-ray photoelectron spectroscopy. The density and purity of the resulting ZTO channel layer increased with increasing annealing temperature, whereas the oxygen vacancy defect density decreased. As a result, the device performance of soluble ZTO thin film transistors (TFTs) was improved at higher annealing temperature. Although the 300 °C-annealed ZTO TFT showed a marginal field-effect mobility (µFE) and high threshold voltage (Vth) of 0.1 cm(2)/(V s) and 7.3 V, respectively, the 500 °C-annealed device exhibited a reasonably high µFE, low subthreshold gate swing (SS), Vth, and Ion/off of 6.0 cm(2)/(V s), 0.28 V/decade, 0.58 V, and 4.0 × 10(7), respectively. The effects of dark negative bias stress (NBS) and negative bias illumination stress (NBIS) on the degradation of transfer characteristics of ZTO TFTs were also investigated. The instability of Vth values of the ZTO TFTs under NBS and NBIS conditions was suppressed with increasing annealing temperature. To better understand the charge trapping mechanism, the dynamics of Vth shift with NBS and NBIS time for all ZTO TFTs was analyzed on the basis of the stretched exponential relaxation. The negative Vth shift for each transistor was accelerated under NBIS conditions compared to NBS, which resulted in a higher dispersion parameter and smaller relaxation time for NBIS degradation. The relaxation time for NBS and NBIS instability increased with increasing annealing temperature, which is discussed on the basis of the transition mechanism of oxygen vacancy defects.

Discovery of potent, selective, and orally bioavailable PDE5 inhibitor: Methyl-4-(3-chloro-4-methoxybenzylamino)-8-(2-hydroxyethyl)-7-methoxyquinazolin-6-ylmethylcarbamate (CKD 533).

In a continuing effort to discover novel PDE5 inhibitors, we have successfully found quinazolines with 4-benzylamino substitution as potent and selective PDE5 inhibitors. Initial lead compound (1) was found to be easily metabolized when incubated with human liver microsomes mainly through C6 amide hydrolysis. Blocking of this metabolic hot spot led to discovery of 10 (CKD533) which is highly potent, selective and orally efficacious in conscious rabbit model for erectile dysfunction and now is undergoing preclinical toxicology study.

Methano-ldinitrato[N-(2-pyridylmethyl-ene)aniline]copper(II).

The Cu atom in the title compound, [Cu(NO(3))(2)(C(12)H(10)N(2))(CH(3)OH)], adopts a square-pyramidal geometry, being ligated by two N atoms of the bidentate N-(2-pyridylmethyl-ene)-aniline (ppma) ligand, two O atoms of NO(3) ligands and one O atom of a methanol molecule, which occupies the apical position. The phenyl ring on the ppma ligand is twisted out of the pyridine plane, forming a dihedral angle of 42.9 (1)°. In the crystal, inter-molecular O-H⋯O hydrogen bonds between methanol and NO(3) ligands form an extensive one-dimensional network extending parallel to [100].

Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction.

In an effort to minimize side effects associated with low selectivity against PDE isozymes, we have successfully identified a series of 6,7,8-substituted quinzaolines as potent inhibitors of PDE5 with high level of isozyme selectivity, especially against PDE6 and PDE11. PDE5 potency and isozyme selectivity of quinazolines were greatly improved with substitutions both at 6- and 8-position. The synthesis, structure-activity relationships and in vivo efficacy of this novel series of potent PDE5 inhibitors are described.

Design, synthesis, and antiangiogenic effects of a series of potent novel fumagillin analogues.

A series of fumagillin analogues containing the C6-substituted cinnamoyl moiety were designed, synthesized, and evaluated for antiangiogenic activity. Among them, 4-hydroxyethoxy-cinnamoyl fumagillol (4a) and 4-hydroxyethoxy-3,5-dimethoxycinnamoyl fumagillol (4d) exhibited more potent anti-proliferation activity in CPAE and HUVEC cells with low cytotoxicity in vitro. These compounds are presently under further pharmacological evaluation studies.

Enantiomers of higenamine inhibit LPS-induced iNOS in a macrophage cell line and improve the survival of mice with experimental endotoxemia.

The importance of development of single enantiomers (optically pure isomers) of chiral molecules has been recognized and manifested in countless pharmaceutical and biological advancement. (RS)-(+/-)-Higenamine (racemic mixture), an active ingredient of Aconite tuber, has been shown to have antioxidant activity along with inhibitory action of iNOS expression in various cells. In the present study, the effects of each enantiomer of higenamine [(S)-(-)-higenamine and (R)-(+)-higenamine] were investigated in comparison with the effects of racemic mixture [(RS)-(+/-)-higenamine] on iNOS expression and NO production in RAW 264.7 cells activated with LPS. In addition, the effects of higenamine enantiomers on the survival rates were also investigated using mice, in which each test compound was injected (i.p.) 90 min prior to LPS. All three forms of higenamine inhibited iNOS expression and reduced NO production with IC50 of 26.2, 86.3, and 53.4 microM, for (S)-, (R)-, and (RS)-higenamine, respectively. (S)-higenamine also significantly reduced serum NOx level and increased survival rates in LPS-treated mice. In contrast, (R)-isomer only showed tendency to increase the survival rates which was not statistically significant when compared to LPS-treated controls. Taken together, it was concluded that (S)-higenamine may be more beneficial than (R)-enantiomer in diseases associated with iNOS over-expression, such as septic shock.

Molecular design, synthesis, and hypoglycemic and hypolipidemic activities of novel pyrimidine derivatives having thiazolidinedione.

We previously reported the synthesis and biological activity of novel substituted pyridines and purines having thiazolidinedione with hypoglycemic and hypolipidemic activities. We now report the synthesis and antidiabetic activity of novel substituted pyrimidines having thiazolidinedione moiety. These compounds (entry No. 5a-i, 10a-d and 16) were evaluated for their glucose and lipid lowering activity in KKA(y) mice. From the results, novel compounds, 5c and 5g, exhibited considerably more potent biological activity than that of the reference compounds, pioglitazone and rosiglitazone, respectively.

Synthesis and biological activity of novel substituted pyridines and purines containing 2,4-thiazolidinedione.

A series of substituted pyridines and purines containing 2,4-thiazolidinedione were designed and synthesized from their corresponding pyridines and purines. These synthesized compounds (entry no. 6a-d, 12a-e, 18a-d, 23a-c) were evaluated for their effect on triglyceride accumulation in 3T3-L1 cells in vitro and their hypoglycemic and hypolipidemic activity in the genetically diabetic KKA(y) mice in vivo. On the basis of their biological activities, 5-(4-[2-[N-methyl-(5-phenyl-pyridin-2-yl)amino]ethoxy]benzyl)thiazolidine-2,4-dione (6d) was selected as a candidate for further pharmacological studies.

5-Demethoxyfumagillol, a potent angiogenesis inhibitor isolated from Aspergillus fumigatus.

A novel angiogenesis inhibitor, 5-demethoxyfumagillol (1), was obtained by isolation, purification and saponification of cultured broth of Aspergillus fumigatus. The structure was assigned as (3R,4R,6R)-4-[(2R,3R)-2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2,5]octan-6-ol (1) by spectroscopic analysis and confirmed by independent synthesis from fumagillol (3). In addition, 6-O-(chloroacetylcarbamoyl)-5-demethoxyfumagillol (7) showed a potential anti-angiogenic activity in CAPE cells in vitro.

Synthesis and antihyperglycemic activity of erythrose, ribose and substituted pyrrolidine containing thiazolidinedione derivatives.

A series of erythrose, ribose, and substituted pyrrolidine containing 2,4-thiazolidinediones were synthesized. Among them, thirteen unsaturated thiazolidinediones, six saturated thiazolidinediones and two unsaturated malonates were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. On the basis of the in vitro activity, 5-[4-[2-(1-benzyl-3,4-bis-benzyloxypyrrolidin-2-yl)ethoxy]benzylidene]thiazolidine-2,4-dione 24b was selected as the candidate for further pharmacological studies.

Palladium-Catalyzed Cross-Coupling of Organoboron Compounds with Iodonium Salts and Iodanes.

The palladium-catalyzed cross-coupling reaction of iodinanes (iodonium salts and iodanes) with organoboron compounds to form carbon-carbon bonds was achieved at ambient temperature under aqueous conditions in the absence of base. Coupling of phenylboronic acid with diphenyliodonium tetrafluoroborate in the presence of Pd(PPh(3))(4) (0.2 mol %) or Pd(OAc)(2) (0.2 mol %) under aqueous conditions gave biphenyl in almost quantitative yield. Under the same conditions, substituted boronic acids, boronates, and trialkylboranes were readily coupled with diaryl-, alkenyl-, and alkynyliodonium salts. Finally, the iodanes ArI(OH)OTs underwent cross-coupling with boronic acids, boronates, and trialkylboranes to afford biphenyls and aryl-substituted alkenes.