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The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signaling and inhibit the proliferation of RTK-driven cancer cell lines. Here, we describe the first reported fragment-to-lead campaign against SHP2, where X-ray crystallography and biophysical techniques were used to identify fragments binding to multiple sites on SHP2. Structure-guided optimization, including several computational methods, led to the discovery of two structurally distinct series of SHP2 inhibitors binding to the previously reported allosteric tunnel binding site (Tunnel Site). One of these series was advanced to a low-nanomolar lead that inhibited tumor growth when dosed orally to mice bearing HCC827 xenografts. Furthermore, a third series of SHP2 inhibitors was discovered binding to a previously unreported site, lying at the interface of the C-terminal SH2 and catalytic domains.

In the development of single-molecule spectroscopy, the simultaneous detection of the excitation and emission spectra has been limited. The fluorescence excitation spectrum based on background-free signals is compatible with the fluorescence-emission-based detection of single molecules and can provide insight into the variations in the input energy of the different terminal emitters. Here, we implement single-molecule excitation-emission spectroscopy (SMEES) for photosystem I (PSI) via a cryogenic optical microscope. To this end, we extended our line-focus-based excitation-spectral microscope system to the cryogenic temperature-compatible version. PSI is one of the two photosystems embedded in the thylakoid membrane in oxygen-free photosynthetic organisms. PSI plays an essential role in electron transfer in the photosynthesis reaction. PSIs of many organisms contain a few red-shifted chlorophylls (Chls) with much lower excitation energies than ordinary antenna Chls. The fluorescence emission spectrum originates primarily from the red-shifted Chls, whereas the excitation spectrum is sensitive to the antenna Chls that are upstream of red-shifted Chls. Using SMEES, we obtained the inclining two-dimensional excitation-emission matrix (2D-EEM) of PSI particles isolated from a cyanobacterium, Thermosynechococcus vestitus (equivalent to elongatus ), at about 80 K. Interestingly, by decomposing the inclining 2D-EEMs within time course observation, we found prominent variations in the excitation spectra of the red-shifted Chl pools with different emission wavelengths, strongly indicating the variable excitation energy transfer (EET) pathway from the antenna to the terminal emitting pools. SMEES helps us to directly gain information about the antenna system, which is fundamental to depicting the EET within pigment-protein complexes.

We experimentally demonstrated electrical plasmonic color modulation by combining a nematic-phase liquid crystal (LC) layer and a silver nanocube (AgNC) monolayer. The color modulation LC/AgNC device was fabricated by filling LCs with negative dielectric anisotropy onto a densely assembled AgNC monolayer. The transmitted light color through the LC/AgNC device was modulated between green and magenta by applying voltages of 0-15 V. The peaks and dips in the transmission spectrum of the LC/AgNC device at wavelengths of 500-600 nm were switched with voltage. The switching effect of light transmission in the green region was achieved by overlapping the plasmon resonance of the AgNC monolayer and multiple transmittance peaks caused by the birefringence of the LC layer. In addition, the color inversion appeared at cross-Nicole and parallel-Nicole because the LC layer functioned like a half-wave plate due to birefringence. The electrical modulation of the plasmonic color with LCs has a high implementation capability in microdevices and is anticipated to be applied in display devices or color filters., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

MA026, a cyclic lipodepsipeptide, opens the tight junction (TJ) probably via binding to claudin-1. We reported that (1) TJ-opening activity is dependent on the amino acid sequence order at Glu10-Leu11; (2) an epimer at the C3 position of the N -terminal acyl tail decreased the TJ-opening activity; and (3) the epimers D-Leu1/L-Gln6 and L-Leu1/D-Gln6 showed more potent TJ-opening activity than natural MA026, although no systematic structure-activity relationship (SAR) study was conducted. Here, we report the three-dimensional structure and systematic SAR study of MA026. X-Ray crystallography and circular dichroism analysis of MA026 revealed that MA026 forms a left-handed α-helical structure, and hydrophobic amino acids are clustered on one side. Furthermore, the SAR results clearly showed that the hydrophobic region of MA026 is important for TJ-opening activity. These results suggest that MA026 interacts with claudin-1 via the hydrophobic cluster region and provide novel structural insights toward the development of a TJ opener targeting claudin-1.

Deregulating fibroblast growth factor receptor (FGFR) signaling is a promising strategy for cancer therapy. Herein, we report the discovery of compound 5 (TAS-120, futibatinib), a potent and selective covalent inhibitor of FGFR1-4, starting from a unique dual inhibitor of mutant epidermal growth factor receptor and FGFR (compound 1 ). Compound 5 inhibited all four families of FGFRs in the single-digit nanomolar range and showed high selectivity for over 387 kinases. Binding site analysis revealed that compound 5 covalently bound to the cysteine 491 highly flexible glycine-rich loop region of the FGFR2 adenosine triphosphate pocket. Futibatinib is currently in Phase I-III trials for patients with oncogenically driven FGFR genomic aberrations. In September 2022, the U.S. Food & Drug Administration granted accelerated approval for futibatinib in the treatment of previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement., Competing Interests: The authors declare the following competing financial interest(s): All authors are employees of Taiho Pharmaceutical Co. Ltd., (© 2023 American Chemical Society.)

Electrochemical reactions in practical batteries occur in confined environments where anode and cathode electrodes are separated only by a thin separator. Therefore, their electrochemical behaviors may differ from those obtained in the conventional experimental cells, where the two electrodes (working and counter electrodes) are largely separated compared to the batteries. The spatial and temporal distributions of the chemical species in the vicinity of each electrode are highly expected to be determined for quantitatively understanding the phenomena in confined environments. In the present study, we developed a line-detected UV-vis absorption microscope that simultaneously measures space-resolved UV-vis absorption spectra. This novel technique has been successfully applied to evaluate the reactivities of the highly reactive lithium (Li) surfaces in organic electrolyte solutions under in situ conditions. The quantitative evaluations of the dissolution rate of Li and the diffusion constant of the product were successfully realized by analyzing the space- and time-resolved absorption spectra based on Fick's law of diffusion. The microscopic technique is expected to open the door to understanding the fundamental electrochemistry in batteries.

Chitin is a biopolymer, which has been proven to be a biomedical material candidate, yet the weak mechanical properties seriously limit their potentials. In this work, a chitin-based double-network (DN) hydrogel has been designed as a potential superficial repairing material. The hydrogel was synthesized through a double-network (DN) strategy composing hybrid regenerated chitin nanofiber (RCN)-poly (ethylene glycol diglycidyl ether) (PEGDE) as the first network and polyacrylamide (PAAm) as the second network. The hybrid RCN-PEGDE/PAAm DN hydrogel was strong and tough, possessing Young's modulus (elasticity) E 0.097 ± 0.020 MPa, fracture stress σ f 0.449 ± 0.025 MPa, and work of fracture W f 5.75 ± 0.35 MJ·m -3 . The obtained DN hydrogel was strong enough for surgical requirements in the usage of soft tissue scaffolds. In addition, chitin endowed the DN hydrogel with good bacterial resistance and accelerated fibroblast proliferation, which increased the NIH3T3 cell number by nearly five times within 3 days. Subcutaneous implantation studies showed that the DN hydrogel did not induce inflammation after 4 weeks, suggesting a good biosafety in vivo. These results indicated that the hybrid RCN-PEGDE/PAAm DN hydrogel had great prospect as a rapid soft-tissue-repairing material.

It has been established that an electron-deficient CpRh III complex, bearing two ester moieties on the Cp ring, [Cp E Rh III ], catalyzes the aerobic oxidative cross coupling of substituted acrylamides with both activated and unactivated alkenes, leading to (2 Z ,4 E )-dienamides, at relatively low temperature (80 °C). Importantly, tertiary, secondary, and primary amide directing groups could equally be used in this catalysis. The mechanistic studies revealed that the electron-deficient nature of the Cp E Rh III complex facilitates the turnover-limiting vinylic C-H bond cleavage of the acrylamides.

A belt-shaped [8]cycloparaphenylene (CPP) and an enantioenriched Möbius-shaped [10]CPP have been synthesized by high-yielding rhodium-catalyzed intramolecular cyclotrimerizations of a cyclic dodecayne and a pentadecayne, respectively. This Möbius-shaped [10]CPP possesses stable chirality and isolated with high enantiomeric purity. It is evident from the reaction Gibbs energy calculation that the above irreversible cyclotrimerizations are highly exothermic; therefore establishing that the intramolecular alkyne cyclotrimerization is a powerful route to strained cyclic molecular strips.

The synthesis of C 2 -symmetrical [6]cycloparaphenylene (CPP) tetracarboxylates has been achieved via macrocyclization by the rhodium-catalyzed intermolecular stepwise cross-alkyne cyclotrimerization and subsequent reductive aromatization. The 1 H NMR spectra of the thus-obtained C 2 -symmetrical [6]CPP-tetracarboxylates revealed that the rotation of unsubstituted benzene rings is slow at room temperature. These [6]CPPs formed columnar packing structures, and their absorption maxima were significantly blue-shifted compared to that of nonsubstituted [6]CPP due to the presence of four electron-withdrawing ester moieties.

To obtain a new anticancer drug, we focused on FER tyrosine kinase. Starting with high-throughput screening with our in-house chemical library, compound 1 , which has a pyridine moiety, was found. Referring to their X-ray crystal structure with FES proto-oncogene tyrosine kinase, as a surrogate of FER followed by chemical modification including scaffold hopping of the pyridine template, we discovered pyrido-pyridazinone derivatives with potent FER kinase inhibitory activity. Here, we disclose the structure-activity relationship on the scaffold and representative compound 21 ( DS21360717 ), which showed in vivo antitumor efficacy in a subcutaneous tumor model., Competing Interests: The authors declare no competing financial interest.

It has been established that a newly developed moderately electron-deficient cyclopentadienyl (Cp)-Rh(III) complex, bearing ester and pendant amide moieties on the Cp ring [Cp A Rh(III)], is able to catalyze the aerobic oxidative olefination of benzamides, bearing nonspecial carbamoyl groups, with styrenes including disubstituted ones at relatively low temperature (60-80 °C). The presence of both the ester and pendant acidic N-phenylcarbamoyl moieties on the Cp A ligand play important roles in facilitation of the catalysis without sacrificing thermal stability of the complex.

It has been established that a cationic rhodium(I)/( R)-tol-BINAP or ( R)-BINAP complex catalyzes the enantioselective [2 + 2 + 1] cycloaddition of 1,6-enynes, possessing monosubstituted alkene units, with cyclopropylideneacetamides at room temperature through the elimination of ethylene to give bicyclic (cyclopent-2-en-1-ylidene)acetamides with high enantioselectivity.

It has been established that a cationic rhodium(I)/(R)-BINAP complex catalyzes the asymmetric [2 + 2 + 2] cycloaddition of unsymmetrical α,ω-diynes with acenaphthylene at room temperature to give the corresponding chiral multicyclic compounds with high yields and ee values. Interestingly, enantioselectivity highly depended on the structures of α,ω-diynes used. The structural requirements of α,ω-diynes for high enantioselectivity were opposite to those in our previously reported cationic rhodium(I)/(R)-Difluorphos complex-catalyzed asymmetric [2 + 2 + 2] cycloaddition of α,ω-diynes with indene.

It has been established that a cationic rhodium(I)/BIPHEP complex is able to catalyze the unprecedented intermolecular cross-cyclotrimerization of nonactivated terminal and internal alkynes at room temperature. In this transformation, the use of arylacetylenes as terminal alkynes and 1,4-butynediol derivatives as internal alkynes afforded the cross-cyclotrimerization products with good chemo- and regioselectivity. The present study clearly demonstrated that an electronically biased combination of nonactivated and electron-deficient alkynes is not necessary to realize good chemo- and regioselectivity in the cationic rhodium(I) complex-catalyzed intermolecular cross-cyclotrimerization.

It has been established that a cationic rhodium(I)/(R)-MeO-BIPHEP complex catalyzes the asymmetric [2 + 2 + 2] cyclization of 1,6-enynes with aliphatic and aromatic alkenes to produce chiral cyclic dienes through β-hydride elimination from rhodacycle intermediates. Thus, obtained chiral cyclic dienes could be converted to chiral spirocompounds without racemization.

The synthesis of C 4 - and C 2 -symmetrical [8]cycloparaphenylene (CPP)-octacarboxylates has been achieved via macrocyclization by the rhodium-catalyzed intermolecular stepwise cross-cyclotrimerization and subsequent reductive aromatization. The C 4 -symmetrical octa-tert-butyl [8]CPP-octacarboxylate forms a dimer in which eight ester moieties face each other. The dimers are aligned so as to make a one-dimensional column with a channel structure inside. Both absorption and fluorescence maxima of [8]CPP-octacarboxylates in CHCl 3 were significantly blue-shifted compared to those of [8]CPP due to the presence of eight electron-withdrawing ester moieties.

Organic contaminants, in particular persistent organic pollutants (POPs), adversely affect water quality and aquatic food webs across the globe. As of now, there is no globally consistent information available on concentrations of dissolved POPs in water bodies. The advance of passive sampling techniques has made it possible to establish a global monitoring program for these compounds in the waters of the world, which we call the Aquatic Global Passive Sampling (AQUA-GAPS) network. A recent expert meeting discussed the background, motivations, and strategic approaches of AQUA-GAPS, and its implementation as a network of networks for monitoring organic contaminants (e.g., POPs and others contaminants of concern). Initially, AQUA-GAPS will demonstrate its operating principle via two proof-of-concept studies focused on the detection of legacy and emerging POPs in freshwater and coastal marine sites using both polyethylene and silicone passive samplers. AQUA-GAPS is set up as a decentralized network, which is open to other participants from around the world to participate in deployments and to initiate new studies. In particular, participants are sought to initiate deployments and studies investigating the presence of legacy and emerging POPs in Africa, Central, and South America.

The convenient synthesis of substituted benzopicenes and azabenzopicenes has been achieved by the cationic rhodium(I)/H 8 -BINAP or BINAP complex-catalyzed [2+2+2] cycloaddition under mild conditions. This method was applied to the synthesis of benzopicene-based long ladder and helical molecules. The X-ray crystal structure analysis revealed that the benzopicene-based helical molecule is highly distorted and the average distance of overlapped rings is markedly shorter than that in the triphenylene-based helical molecule. Photophysical and chiroptical properties of these benzopicene and azabenzopicene derivatives have also been examined. With respect to photophysical properties, substituted benzopicenes and azabenzopicenes showed red shifts of absorption and emission maxima compared with the corresponding triphenylenes and azatriphenylenes. With respect to chiroptical properties, the CPL spectra of the benzopicene-based helical molecule showed two opposite peaks, and thus the value of the CPL was smaller than that of the triphenylene-based helical molecule presumably due to the presence of two chiral fluorophores.

The enantioselective synthesis of phenanthrenol-based [9]helicene-like molecules has been achieved via the rhodium-mediated intramolecular [2 + 2 + 2] cycloadditions of 3-phenanthrenol-linked triynes. Crystal structures and photophysical/chiroptical properties of these [9]helicene-like molecules were compared with the corresponding [7]helicene-like molecules.

It has been established that the oxidative sp(2) C-H bond allylation with aliphatic alkenes proceeds under mild conditions by using heteroarenes as directing groups and an (electron-deficient η(5)-cyclopentadienyl)rhodium(III) complex, [Cp(E)RhCl2]2, as a precatalyst. In sharp contrast, the use of [Cp*RhCl2]2 instead of [Cp(E)RhCl2]2 led to a complex mixture of products under the same reaction conditions.

It has been established that a cationic rhodium(I)/axially chiral biaryl bisphosphine complex catalyzes the asymmetric [2 + 2 + 2] cycloaddition of α,ω-diynes with electron-rich and unstrained unsymmetrical 1,2-disubstituted alkenes to give chiral multicyclic compounds with good yields and ee values. Interestingly, enantioselectivity highly depends on the structures of α,ω-diynes used presumably due to the presence of two distinct reaction pathways.

Axially chiral 3-(2-halophenyl)pyridines were successfully synthesized in high yields with excellent enantioselectivity by the cationic rhodium(I)/(S)-H8-BINAP complex-catalyzed atroposelective [2 + 2 + 2] cycloaddition of (o-halophenyl)diynes with nitriles. Interestingly, regio- and enantioselectivity highly depend on ortho substituents on the phenyl group of diynes. When the ortho substituents were methoxy and methoxycarbonyl groups, axially chiral 3-arylpyridines were obtained as a major product, while enantioselectivity was lowered significantly. On the other hand, when the ortho substituents were alkyl groups, regioselectivity was switched to give achiral 6-arylpyridines in high yields.

It has been established that a cationic rhodium(I)/BINAP complex catalyzes the cycloisomerization of 2-silylethynylphenols, leading to 3-silylbenzofurans, via 1,2-silicon migration. Similarly, the cycloisomerization of 2-silylethynylanilines, leading to 3-silylindoles, via 1,2-silicon migration was catalyzed by a cationic rhodium(I)/H8-BINAP complex.

It has been established that a cationic rhodium(I)/H8-BINAP complex catalyzes the asymmetric [2 + 2 + 2] cycloaddition of 1,6-enynes with cyclopropylideneacetamides to produce spirocyclohexenes in excellent enantioselectivity with retaining cyclopropane rings.

A photosystem II-enriched membrane (PSII-em) consists of the PSII core complex (PSII-cc) which is surrounded by peripheral antenna complexes. PSII-cc consists of two core antenna (CP43 and CP47) and the reaction center (RC) complex. Time-resolved fluorescence spectra of a PSII-em were measured at 77 K. The data were globally analyzed with a new compartment model, which has a minimum number of compartments and is consistent with the structure of PSII-cc. The reliability of the model was investigated by fitting the data of different experimental conditions. From the analysis, the energy-transfer time constants from the peripheral antenna to CP47 and CP43 were estimated to be 20 and 35 ps, respectively. With an exponential time constant of 320 ps, the excitation energy was estimated to accumulate in the reddest chlorophyll (Red Chl), giving a 692 nm fluorescence peak. The excited state on the Red Chl was confirmed to be quenched upon the addition of an oxidant, as reported previously. The calculations based on the Förster theory predicted that the excitation energy on Chl29 is quenched by ChlZD1(+), which is a redox active but not involved in the electron-transfer chain, located in the D1 subunit of RC, in the other monomer with an exponential time constant of 75 ps. This quenching pathway is consistent with our structure-based simulation of PSII-cc, which assigned Chl29 as the Red Chl. On the other hand, the alternative interpretation assigning Chl26 as the Red Chl was not excluded. The excited Chl26 was predicted to be quenched by another redox active ChlZD2(+) in the D2 subunit of RC in the same monomer unit with an exponential time constant of 88 ps.

We analyzed the crystallization process of the CH3NH3PbI3 perovskite by observing real-time X-ray diffraction immediately after combining a PbI2 thin film with a CH3NH3I solution. A detailed analysis of the transformation kinetics demonstrated the fractal diffusion of the CH3NH3I solution into the PbI2 film. Moreover, the perovskite crystal was found to be initially oriented based on the PbI2 crystal orientation but to gradually transition to a random orientation. The fluctuating characteristics of the crystallization process of perovskites, such as fractal penetration and orientational transformation, should be controlled to allow the fabrication of high-quality perovskite crystals. The characteristic reaction dynamics observed in this study should assist in establishing reproducible fabrication processes for perovskite solar cells.

We have successfully developed a circularly polarized near-field scanning optical microscope (NSOM) that enables us to irradiate circularly polarized light with spatial resolution below the diffraction limit. As a demonstration, we perform real-space mapping of the quantum Hall chiral edge states near the edge of a Hall-bar structure by injecting spin polarized electrons optically at low temperature. The obtained real-space mappings show that spin-polarized electrons are injected optically to the two-dimensional electron layer. Our general method to locally inject spins using a circularly polarized NSOM should be broadly applicable to characterize a variety of nanomaterials and nanostructures.

Tris[N,N-bis(trimethylsilyl)amido] complexes of group 3 metals, especially yttrium and gadolinium, served as catalysts for ortho-C-H bond addition of pyridine derivatives and N-heteroaromatics into the C═N double bond of nonactivated imines to afford the corresponding aminomethylated products. Addition of catalytic amounts of secondary amines, such as dibenzylamine, dramatically improved the catalytic activity through the formation of a mixed ligated complex such as [(Me3Si)2N]2Y(NBn2)(THF) (4). Furthermore, kinetic studies using the isolated complex 4 provided a plausible reaction mechanism by which coordination of two pyridine derivatives afforded a penta-coordinated species as a key step.

Aerosol samples were collected from Tsukuba, Japan, soon after the 2011 Fukushima nuclear accident and analyzed for speciation of radiocesium and radioiodine to explore their chemical behavior and isotopic ratios after the release. Most (134)Cs and (137)Cs were bound in organic matter (53–91%) and some in water-soluble fractions (5–15%), whereas a negligible proportion of radiocesium remained in minerals. This pattern suggests that sulfate salts and organic matter may be the main carrier of Cs-bearing particles. The (129)I in aerosol samples is contained in various proportions as soluble inorganic iodine (I(–) and IO3(–)), soluble organic iodine, and unextractable iodine. The measured mean (129)I/(131)I atomic ratio of 16.0 ± 2.2 is in good agreement with that measured from rainwater and consistent with ratios measured in surface soil samples. Together with other aerosols and seawater samples, an initial (129)I/(137)Cs activity ratio of ∼4 × 10(–7) was obtained. In contrast to the effectively constant (134)Cs/(137)Cs activity ratios (1.04 ± 0.04) and (129)I/(131)I atomic ratios (16.0 ± 2.2), the (129)I/(137)Cs activity ratios scattered from 3.5 × 10(–7) to 5 × 10(–6) and showed temporally and spatially different dispersion and deposition patterns between radiocesium and radioiodine. These findings confirm that (129)I, instead of (137)Cs, should be considered as a proxy for (131)I reconstruction.

We report the development of a new trifluoromethyltriazolobenzoxazepine series of squalene synthase inhibitors. Structure-activity studies and pharmacokinetics optimization on this series led to the identification of compound 23 (DF-461), which exhibited potent squalene synthase inhibitory activity, high hepatic selectivity, excellent rat hepatic cholesterol synthesis inhibitory activity, and plasma lipid lowering efficacy in nonrodent repeated dose studies.

The oxidative kinetic resolution of 2-substituted indoline derivatives was achieved by hydrogen transfer to imines by means of a chiral phosphoric acid catalyst. The oxidative kinetic resolution was applicable to racemic alkyl- or aryl-substituted indolines, and the remaining indolines were obtained in good yields with excellent enantioselectivities.

The experimentally obtained time-resolved fluorescence spectra of photosystem II (PS II) core complexes, purified from a thermophilic cyanobacterium Thermosynechococcus vulcanus, at 5-180 K are compared with simulations. Dynamic localization effects of excitons are treated implicitly by introducing exciton domains of strongly coupled pigments. Exciton relaxations within a domain and exciton transfers between domains are treated on the basis of Redfield theory and generalized Förster theory, respectively. The excitonic couplings between the pigments are calculated by a quantum chemical/electrostatic method (Poisson-TrEsp). Starting with previously published values, a refined set of site energies of the pigments is obtained through optimization cycles of the fits of stationary optical spectra of PS II. Satisfactorily agreement between the experimental and simulated spectra is obtained for the absorption spectrum including its temperature dependence and the linear dichroism spectrum of PS II core complexes (PS II-CC). Furthermore, the refined site energies well reproduce the temperature dependence of the time-resolved fluorescence spectrum of PS II-CC, which is characterized by the emergence of a 695 nm fluorescence peak upon cooling down to 77 K and the decrease of its relative intensity upon further cooling below 77 K. The blue shift of the fluorescence band upon cooling below 77 K is explained by the existence of two red-shifted chlorophyll pools emitting at around 685 and 695 nm. The former pool is assigned to Chl45 or Chl43 in CP43 (Chl numbering according to the nomenclature of Loll et al. Nature2005, 438, 1040) while the latter is assigned to Chl29 in CP47. The 695 nm emitting chlorophyll is suggested to attract excitations from the peripheral light-harvesting complexes and might also be involved in photoprotection.

Benzothiazoline is an efficient reducing agent for the chiral BINOL-phosphoric acid catalyzed enantioselective transfer hydrogenation of ketimines and α-imino esters to afford the corresponding amines with high enantioselectivities. DFT studies (M05-2X/6-31G*//ONIOM(B3LYP/6-31G*:HF/3-21G)) revealed the reaction mechanism and the origin of the high enantioselectivity in the present BINOL-phosphoric acid catalyzed transfer hydrogenation of ketimines and α-imino esters using benzothiazoline. The reaction mechanism is similar to that reported in the asymmetric transfer hydrogenation of ketimines using Hantzsch ester. Phosphoric acid simultaneously activates ketimine (α-imino ester) and benzothiazoline to form cyclic transition structures. The high enantioselectivity is attributed to the steric interaction between the substituents at the 3,3'-positions of BINOL-phosphoric acid and substrates. In contrast to the C2-symmetrical Hantzsch ester, the readily tunable 2-aryl substituent of unsymmetrical benzothiazoline plays a significant role in the steric interaction, influencing the asymmetric induction. This feature is responsible for the advantage of benzothiazoline over Hantzsch ester.

Described herein is the enantioselective synthesis of multisubstituted biaryl derivatives by chiral phosphoric acid catalyzed asymmetric bromination. Two asymmetric reactions (desymmetrization and kinetic resolution) proceeded successively to afford chiral biaryls in excellent enantioselectivities (up to 99% ee). Both experimental and computational studies suggested that this excellent selectivity could be achieved via a highly organized hydrogen bond network among a substrate, a catalyst (chiral phosphoric acid), and a brominating reagent (N-bromophthalimide).

The rhodium-catalyzed cyclization of a series of 2,2-diarylalkanoic acids in the presence of copper acetate as an oxidant smoothly proceeded through double C-H bond cleavages and subsequent decarboxylation to produce the corresponding fluorene derivatives. The direct cyclization of triarylmethanols also took place efficiently by using an iridium catalyst in place of the rhodium, while the hydroxy function was still intact.

π-Conjugated trinuclear iridium and cobalt dithiolenes undergo multiple metal-metal bond formation with Co(2)(CO)(8) and Fe(CO)(5), giving rise to Ir(3)Co(6) nonanuclear and Co(3)Fe(3) hexanuclear cluster complexes 5 and 6, respectively. 5 retains a planar framework and intense π conjugation across the three iridadithiolenes and the phenylene bridge, which results in intense electronic communication among the three Co(2)(CO)(5) units in reduced mixed-valent states.

The radiocarbon ((14)C) of total carbon (TC) in atmospheric fine particles was measured at 6 h or 12 h intervals at two sites, 50 and 100 km downwind from Tokyo, Japan (Kisai and Maebashi) in summer 2007. The percent modern carbon (pMC) showed clear diurnal variations with minimums in the daytime. The mean pMC values at Maebashi were 28 ± 7 in the daytime and 45 ± 16 at night (37 ± 15 for the overall period). Those at Kisai were 26 ± 9 in the daytime and 44 ± 8 at night (37 ± 12 for the overall period). This data indicates that fossil sources were major contributors to the daytime TC, while fossil and modern sources had comparable contributions to nighttime TC in the suburban areas. At both sites, the concentration of fossil carbon as well as O(3) and the estimated secondary organic carbon increased in the daytime. These results suggest that fossil sources around Tokyo contributed significantly to the high daytime concentration of secondary organic aerosols (SOA) at the two suburban sites. A comparison of pMC and the ratio of elemental carbon/TC from our particulate samples with those from three end-member sources corroborates the dominant role of fossil SOA in the daytime.

Axially chiral hydroxy carboxylic acid derivatives were successfully synthesized with high yields and ee values by the cationic rhodium(I)/axially chiral biaryl bisphosphine complex-catalyzed enantioselective [2 + 2 + 2] cycloaddition. Axially chiral hydroxy and dihydroxy carboxylic acid derivatives, bearing the aryl group at the ortho-position of the alkoxycarbonyl group, were also synthesized with high regio- and enantioselectivity.

It has been established that a cationic rhodium(I)/cod complex catalyzes the cotrimerization of propargyl esters and arylacetylenes, leading to substituted dihydropentalenes, in the presence of excess cod through elimination of carboxylic acids.

Model calculations of linear dichroism (LD) and circular dichroism (CD) spectra were conducted for the chlorosomes of green sulfur bacteria, Chlorobium phaeobacteroides and Chlorobium tepidum, on the basis of the theory of delocalized exciton. The chlorosomes of Chl. phaeobacteroides and Chl. tepidum contain bacteriochlorophylls (BChls) e and c as the major light-harvesting pigments, respectively. The excitonic couplings among the Soret and Q(y) transitions were considered on the basis of the "rodlike" structural model for the pigment self-aggregates in a chlorosome. Trial simulations were conducted by assuming the B(x) and B(y) transition-dipole vectors to be parallel to the molecular x- and y-axes, respectively. The simulation at this stage could nicely reproduce the larger splitting of the Soret band and more significant enhancement of the Q(y) band upon formation of chlorosome in the BChl e-containing chlorosome than in the BChl c-containing one. Intensity borrowing was indicated to be the key mechanism inducing the enhancement of the Q(y) band in the BChl e-containing chlorosomes. However, the simulated LD and CD spectra in the Soret region showed qualitative disagreement from the observed ones. To resolve the deviations, the directions of the B(x) and B(y) transition-dipole vectors and the orientations of the molecular planes of BChls were adjusted in the next stage. The fine-tuning of these parameters resulted in a striking agreement between the observed and simulated CD and LD spectra over the whole spectral range studied. The best fit was obtained when the B(x) and B(y) transition-dipole vectors were assumed to be rotated 25 degrees clockwise from the molecular x- and y-axes and the molecular planes in the pigment aggregate were tilted 5 degrees from that assumed in the original model without alteration in the direction of the molecular y-axis. The calculated spectral profiles were affected little by the change in the curvatures of the rod surface, showing that the optical spectra of chlorosomes were determined essentially by the local pigment arrangement, but not by the higher-order structure, of the aggregate.

The ultrafast fluorescence dynamics of photosystem I (PS I) purified from a marine centric diatom, Chaetoceros gracilis, at 17 K was studied using fluorescence up-conversion and streak-camera setups. The experiments were done for two kinds of sample preparations containing different amounts of the peripheral antenna proteins, the fucoxanthin-chlorophyll (Chl) binding proteins associated with PS I (FCPI). Upon excitation at 430 nm, which selectively excites Chl a mainly contained in the core complex, the fluorescence dynamics of both samples was roughly expressed by four decay-associated spectra (DASs) with time constants of ca. 5, ca. 22, ca. 100, and ca. 400 ps. These DAS components have corresponding counterparts in the results of a previous study of Thermosynechococcus elongatus PS I (Shibata et al. J. Phys. Chem. B 2010, 114, 2954) except for that with a time constant of ca. 22 ps. The similar distribution of the time constants suggests a shared light-harvesting pathway by PS I of these two organisms. The DAS with a ca. 400 ps time constant has its peak wavelength at around 710 nm, suggesting the presence of antenna pigment states with slightly lower excitation energy than that of P700. This antenna state acts as a shallow sink in the core complex of the diatom PS I and causes a specific temperature dependence of its fluorescence spectrum below 77 K. Excitation energy funneling into the shallow-sink state seems to take place within 0.2 ps, suggesting an extremely efficient energy transfer. Upon the selective excitation of Chl c in FCPI by a 460 nm laser, three DAS components suggesting excitation energy transfers were obtained. The 0.2 ps DAS shows the energy transfer from Chl c to Chl a within FCPI, while the 0.7 and 40 ps DASs suggest the energy transfer from FCPI to the core complex. The excitation energy seems to be effectively transferred from FCPI to the core complex in diatom PS I because the selective excitation of Chl c in FCPI does not induce a severe retardation of the overall light-harvesting kinetics.

A cationic rhodium(I) complex, [Rh(cod)(2)]SbF(6), catalyzes the [3 + 2] cycloaddition of propargyl esters with dialkyl acetylenedicarboxylates in good yields, presumably through carbonyl-stabilized cationic rhodium(I) alkenylcarbene intermediates. The same rhodium(I) complex also catalyzes the [2 + 1] cycloaddition (cyclopropanation) of propargyl esters with N,N-disubstituted acrylamides in good yields with perfect diastereoselectivity.

Time-resolved fluorescence spectra of photosystem I (PS-I) trimeric complex isolated from a thermophilic cyanobacterium, Thermosynechococcus (T.) elongatus, were observed at 15 K over the time range from 100 fs to a few nanoseconds under P700-oxidized condition and 10 ps to a few nanoseconds under P700-reduced condition. Global-fitting analysis of the data of P700-oxidized condition revealed the existence of three kinetically different red chlorophylls (Chls) having the energy-transfer times to P700(+) of 6.1 ps (C(6.1 ps)), 140 ps (C(140 ps)), and 360 ps (C(360 ps)). According to the spectral shape of DAS, C(6.1 ps), C(140 ps), and C(360 ps) were assigned to the previously reported red Chls with the absorption maxima at 715 nm (C715), 710 nm (C710), and 719 nm (C719), respectively. In PS-I containing P700(+), ca. 60 Chls funnel the excitation energy into C(6.1 ps) in a subpicosecond time region at 15 K. The analysis of the present data together with the conclusions of the previous reports revealed that in PS-I containing a neutral P700 the direct energy transfer from the bulk Chls to P700 seems to dominate the energy-flow process. Simulation of the energy-transfer time to P700(+) based on Forster theory suggested the dimeric Chls A32-B7 and A33-A34 as the most probable candidates for C(140 ps) (C710) and C(360 ps) (C719), respectively. C(6.1 ps) (C715) was tentatively assigned to the dimeric Chl B24-B25 or A26-A27, for which the fastest energy transfer to P700(+) was predicted from the simulation. However, the estimated energy-transfer times to P700(+) for these dimeric Chls were 44-46 ps, which were still much slower than the observed value of 6.1 ps. A theoretical framework beyond the standard Forster theory might be required in order to account for the severe deviation.

We have established that a cationic rhodium(I)/(R,R)-QuinoxP* complex catalyzes the highly enantioselective direct intermolecular hydroacylation of alpha-substituted acrylamides with unfunctionalized aliphatic aldehydes to yield the corresponding gamma-ketoamides in high yields with excellent ee values.

We have established that a cationic rhodium(I)-dppf complex catalyzes isomerizations of allyl propargyl ethers to allenic aldehydes in good yields from room temperature to 40 degrees C. On the other hand, carbonyl migration reactions from allenic aldehydes further proceed to give dienals in good yields at 80 degrees C.

TePixD is a blue light using flavin (BLUF) protein of a thermophilic cyanobacterium, Thermosynechococcus elongatus. The fluorescence dynamics of TePixD was observed for the first time in both its dark-adapted and signaling (red-shifted) forms with a 200-fs time resolution. The fluorescence up-conversion setup was used in the time region up to 60 ps, and the streak-camera setup was used in the time region up to 1 ns. To avoid the accumulation of the red-shifted form by the exciting laser irradiation, the sample solution was circulated using a diaphragm pump. A handmade flow cuvette with a small cross section was used to achieve a fast flow of the solution in the excited region. The fluorescence decay times were unequivocally determined to be 13.6 and 114 ps for the dark-adapted form and 1.37 ps for the red-shifted form. The double-exponential fluorescence decay in the dark-adapted form suggested the coexistence of two conformations that have the 13.6- and 114-ps decay components, respectively. The single-exponential fluorescence decay in the red-shifted form suggested the elimination of heterogeneity in the conformation upon the light-induced conversion. The fast fluorescence-quenching components were almost eliminated in the mutant in which the conserved tyrosine Tyr8 is replaced by phenylalanine. Thus, the fluorescence quench was concluded to arise from the electron transfer from Tyr8, to the excited flavin chromophore. The 10-fold-faster quenching in the red-shifted form suggested the acceleration of the electron transfer. The faster decay time of 13.6 ps for the dark-adapted form was found to be almost temperature independent in the region from 10 to 40 degrees C. This suggested that the energy gap, DeltaG, in Marcus's electron-transfer theory is optimized to give the fastest rate. The acceleration of the electron transfer in the red-shifted form is interpreted to be due to the enhancement of the electronic-coupling factor between the donor and acceptor. A shortening of the Tyr8-flavin distance by 1.0-1.5 A was suggested if we adopt the empirical formula for the donor-acceptor distance dependence of the electron transfer rate.

A cationic palladium(II)/(S)-xyl-Segphos complex catalyzes enantioselective cycloisomerizations of N-alkenyl arylethynylamides leading to axially chiral 4-aryl-2-pyridones in high yields with high ee values. The present catalysis represents the first enantioselective construction of axial chirality by the transition-metal-catalyzed cycloisomerization.

A cationic rhodium(I)/BIPHEP complex catalyzes amide-directed regioselective alkenylations of olefinic or aromatic sp(2) C-H bonds in good yields under mild reaction conditions. The use of a 1-pyrrolidinecarbonyl group as a directing group dramatically accelerates the reaction.

A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5 H-cyclohepta[ b]pyridine-9-ol ( (-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K (+) channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K (+)channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.