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An efficient and step-economical approach to access functionalized pyrrolizidine derivatives by a one-pot tandem sequence, including an aldol condensation and subsequent 1,3-dipolar cycloaddition process, has been developed, starting from acetone, aldehyde, and proline. A number of substituted aromatic aldehydes were amenable to this transformation, and the desired products, racemic 7a-7w and chiral 9a-9m, were obtained with excellent regioselectivities and outstanding diastereoselectivities. Moreover, in situ NMR studies revealed MgSO4 could effectively promote the aldol condensation pathway in this tandem process. [ABSTRACT FROM AUTHOR]

The present work investigates the capability of single-stranded DNA (ssDNA) in enhancing the intrinsic peroxidase-like activity of the g-C3N4 nanosheets (NSs). We found that ssDNA adsorbed on g-C3N4 NSs could improve the catalytic activity of the nanosheets. The maximum reaction rate of the H2O2-mediated TMB oxidation catalyzed by the ssDNA-NSs hybrid was at least 4 times faster than that obtained with unmodified NSs. The activity enhancement could be attributed to the strong interaction between TMB and ssDNA mediated by electrostatic attraction and aromatic stacking and by both the length and base composition of the ssDNA The high catalytic activity of the ssDNA-NSs hybrid permitted sensitive colorimetric detection of exosomes if the aptamer against CD63, a surface marker of exosome, was employed in hybrid construction. The sensor recognized the differential expression of CD63 between the exosomes produced by a breast cancer cell line (MCF-7) and a control cell line (MCF-10A). Moreover, a similar trend was detected in the circulating exosomes isolated from the sera samples collected from breast cancer patients and healthy controls. Our work sheds lights on the possibility of using ssDNA to enhance the peroxidase like activity of nanomaterials and demonstrates the high potential of the ssDNA-NSs hybrid in clinical diagnosis using liquid biopsy. [ABSTRACT FROM AUTHOR]

Two new polar polyselenides Rb4Ge4Se12 (1) and Cs4Ge4Se12 (2) with rarely reported dimeric [Ge2Se4(μ-Se2)]4- units were synthesized. They present large second-harmonic generation (SHG) intensities of 7.5 and 6.5 times that of the benchmark AgGaS2 with type I phase-matching behavior, high laser-induced damaged thresholds, a wide transmission region and congruently melting behavior, making them excellent candidates for IR nonlinear optical (NLO) applications. The SHG functional motifs of both compounds are determined to be [Ge2Se4(μ-Se2)]4- unit by time-dependent density functional theory calculation, which further reveals that charge transfers from the lone pairs of terminal Se atoms to the five σ* orbitals of five-membered ring Ge2Se3 have a predominant contribution to the total SHG effect. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum aminopeptidase 1 (ERAP1), a metallopeptidase belonging to the M1 peptidase family, plays an important role in antigen processing in vivo. Additionally, many diseases are caused by ERAP1 perturbation. Thus, an efficient method for monitoring its content is extremely important for disease diagnosis and treatment. However, few fluorescent probes have been reported for efficiently monitoring ERAP1 in living cells and tissues. In this work, a two-photon fluorescent probe (SNCL) containing 1,8-naphthalimide (two-photon fluorophore), l-leucine (trigger moiety), and a methyl sulfonamide moiety (endoplasmic reticulum-targeting group) for imaging ERAP1 activity in living cells is reported for the first time. The optimized probe exhibited high sensitivity toward ERAP1, with about a 95-fold fluorescence enhancement at 550 nm. Herein, we monitored ERAP1 with SNCL by introducing interferon-? to induce ERAP1 activity in living cells. The content of ERAP1 was dependent on the redox state of the endoplasmic reticulum, which was demonstrated by using SNCL to monitor the enzymatic activity of ERAP1 under different redox conditions. Excitingly, SNCL was also successfully applied for monitoring ERAP1 in tumor tissue with an imaging depth of 50-120 µm. In conclusion, SNCL not only can be used for the sensitive detection of endogenous ERAP1 in living cells and tumor tissues but also can serve as a potentially useful tool to reveal ERAP1-related diseases. [ABSTRACT FROM AUTHOR]

There is a great demand to measure protein-ligand interactions in rapid and low cost way. Here, we developed a microfluidic droplet-based thermal shift assay (dTSA) system for high-throughput screening of small-molecule protein ligands. The system is composed of a nanoliter droplet array chip, a microfluidic droplet robot, and a real-time fluorescence detection system. Total 324 assays could be performed in parallel in a single chip with an 18 x 18 droplet array. The consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole scale), which is significantly reduced by over 3 orders of magnitude compared with those in 96- or 384-well plate-based systems. We also observed the implementation of TSA in nanoliter droplet format could substantially improve assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which can be ascribed to the enhanced thermal conduction in small volume reactors. The dTSA system was optimized by studying the effect of droplet volumes, as well as protein and fluorescent dye (SYPRO Orange) concentrations. To demonstrate its potential in drug discovery, we applied the dTSA system in screening inhibitors of human thrombin with a commercial library containing 100 different small molecule compounds, and two inhibitors were successfully identified and confirmed. [ABSTRACT FROM AUTHOR]

Microbial constructions of secondary metabolites are generally biosynthetic gene cluster (BGC)-based, and the forging of different BGC-sourced intermediates tends to be overlooked. Here, we show that the dalesconol bioassembly lines in Daldinia eschscholzii can sequester guest intermediates (i.e., building blocks produced outside the dalesconol biosynthetic gene cluster) to form arrays of skeletally undescribed molecules such as (+)-dalescone A, a potent inhibitor against the NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Rational design of multicomponent material structures with strong interfacial interactions enabling enhanced electrocatalysis represents an attractive but underdeveloped paradigm for creating better catalysts for important electrochemical energy conversion reactions. In this work, we report metal-phosphide core-shell nanostructures as a new model electrocatalyst material system where the surface electronic states of the shell phosphide and its interactions with reaction intermediates can be effectively influenced by the core metal to achieve higher catalytic activity. The strategy is demonstrated by the design and synthesis of iron-iron phosphide (Fe@FeP) core-shell nanoparticles on carbon nanotubes (CNTs) where we find that the electronic interactions between the metal and the phosphide components increase the binding strength of hydrogen adatoms toward the optimum. As a consequence, the Fe@FeP/CNT material exhibits exceptional catalytic activity for the hydrogen evolution reaction, only requiring overpotentials of 53-110 mV to reach catalytic current densities of 10-100 mA cm-2. [ABSTRACT FROM AUTHOR]

Autoimmune and inflammatory diseases are associated with inappropriate activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, but suitable inhibitors against such improper activations remain scarce. Here, spirodalesol (1) from Daldinia eschscholzii was structurally characterized and is biosynthetically proposed as an NLRP3 inflammasome activation inhibitor with an unprecedented carbon skeleton. [ABSTRACT FROM AUTHOR]

A novel mathematical programming method was applied to acquire the optimal heat exchanger network (HEN) retrofit in the crude oil distillation unit. The mathematical model was based on the stagewise superstructure model with splits of streams from the work of Yee et al. [Chin. J. Chem. Eng. 2007, 15 (2), 296-301]. The objective function was developed into the minimum of the sum of the cost of modifications and the cost of utilities in one year, focusing on the changing heat transfer coefficients arising in the reused existing heat exchangers from stream splits. The HEN modifications included buying new heat exchangers, adding or reducing areas of the existing heat exchangers, moving the existing heat exchangers, and laying pipes. It was a mixed integer nonlinear program (MINLP) problem. A hybrid genetic algorithm was used to optimize the MINLP problem. In order to reduce the total cost of modifications, the heat exchangers and the corresponding matching structures between the hot and cold streams in the existing HENs were designed as elites introduced into the hybrid genetic algorithm. The Dittus-Boelter and Kern correlations were used to estimate the convective heat transfer coefficients of the corresponding streams. One example was given to show the effect of the novel retrofit strategy. [ABSTRACT FROM AUTHOR]

We report a novel composite material, referred to as activated charcoal supported titanate nanotubes (TNTs@AC), for highly efficient adsorption and photodegradation of a representative polycyclic aromatic hydrocarbon (PAH), phenanthrene. TNTs@AC was prepared through a one-step hydrothermal method, and is composed of an activated charcoal core and a shell of carbon-coated titanate nanotubes. TNTs@AC offered a maximum Langmuir adsorption capacity of 12.1 mg/g for phenanthrene (a model PAH), which is -11 times higher than the parent activated charcoal. Phenanthrene was rapidly concentrated onto TNTs@AC, and subsequently completely photodegraded under UV light within 2 h. The photoregenerated TNTs@AC can then be reused for another adsorption-photodegradation cycle without significant capacity or activity loss. TNTs@AC performed well over a wide range of pH, ionic strength, and dissolved organic matter. Mechanistically, the enhanced adsorption capacity is attributed to the formation of carbon-coated ink-bottle pores of the titanate nanotubes, which are conducive to capillary condensation; in addition, the modified microcarbon facilitates transfer of excited electrons, thereby inhibiting recombination of the electron-hole pairs, resulting in high photocatalytic activity. The combined high adsorption capacity, photocatalytic activity, and regenerability/reusability merit TNTs@AC a very attractive material for concentrating and degrading a host of micropollutants in the environment. [ABSTRACT FROM AUTHOR]

Graphitic C3N4 (g-CjN4) nanosheets are a type of emerging graphene-like carbon-based nanomaterials with high fluorescence and large specific surface areas that hold great potential for biosensor applications. However, current g-C3N4 based biosensors have prevailingly been limited to coordination with metal ions, and it is of great significance to develop new designs for g-C3N4 nanosheets based biosensors toward biomarkers of general interest. We report the development of a novel g-C3N4 nanosheetbased nanosensor strategy for highly sensitive, single-step and label-free detection of tyrosinase (TYR) activity and its inhibitor. This strategy relies on the catalytic oxidation of tyrosine by TYR into melanin-like polymers, which form a nanoassembly on the g-C3N4 nanosheets and quench their fluorescence. This strategy was demonstrated to provide excellent selectivity and superior sensitivity and to enable rapid screening for TYR inhibitors. Therefore, the developed approach might create a useful platform for diagnostics and drugs screening for TYR-based diseases including melanoma cancer. [ABSTRACT FROM AUTHOR]

The first two new Na-containing sulfides Na2In2MS6 (M = Si (1), Ge (2)) in the Na2Q-B2Q3-CQ2 (B = Ga, In; C = Si, Ge, Sn; Q = S, Se) system were prepared for the first time through conventional high-temperature solid-state reaction. They are isostructural with space group Cc (No. 9) in monoclinic phases and feature three-dimensional frameworks built by the ∞¹[In2MS6]2- (M = Si, Ge) chains through corner-sharing InS4 tetrahedra and MS4 (M = Si, Ge) tetrahedra, with Na+ cation located in the cavities. They display moderate second harmonic generation (SHG) conversion efficiencies compared with commercial AgGaS2, with phase-matching behavior at 1800 nm and laser-induced damage thresholds 6.9 and 4.0 times higher than that of AgGaS2, respectively. Therefore, the output SHG intensities of 1 and 2 will be ∼4.3 and 4.0 times larger than that of AgGaS2, when the intensity of incident laser increased to close the damage energy of 1 and 2, indicating their potential for high-power nonlinear optical application. [ABSTRACT FROM AUTHOR]

Heme nitric oxide/oxygen binding protein isolated from the obligate anaerobe Clostridium botulinum (Cb H-NOX) was previously reported to bind NO with a femtomolar KD (Nioche, P. et al. Science 2004, 306, 1550-1553). On the other hand, no oxyferrous Cb H-NOX was observed despite full conservation of the key residues that stabilize the oxyferrous complex in the H-NOX from Thermoanaerobacter tengcongensis (Tt H-NOX) (the same study). In this study, we re-measured the kinetics/affinities of Cb H-NOX for CO, NO, and O2. KD(CO) for the simple one-step equilibrium binding was 1.6 × 10-7 M. The KD(NO) of Cb H-NOX was 8.0 × 10-11 M for the first six-coordinate NO complex, and the previous femtomolar KD(NO) was actually an apparent KD for its multiple-step NO binding. An oxyferrous Cb H-NOX was clearly observed with a KD(O2) of 5.3 × 10-5 M, which is significantly higher than Tt H-NOX's KD(O2) = 4.4 × 10-8 M. The gaseous ligand binding of Cb H-NOX provides another supportive example for the "sliding scale rule" hypothesis (Tsai, A.-L. et al. Antioxid. Redox Signal. 2012, 17, 1246-1263), and the presence of hydrogen bond donor Tyr139 in Cb H-NOX selectively enhanced its affinity for oxygen. [ABSTRACT FROM AUTHOR]

Hypoxia plays an important role in tumor progression, and the development of efficient methods for monitoring hypoxic degree in living systems is of great biomedical importance. In the solid tumors, the nitroreductase level is directly corresponded with the hypoxic status. Many one-photon excited fluorescent probes have been developed for hypoxia imaging in tumor cells via the detection of nitroreductase level. However, two-photon excited probes are more suitable for bioimaging. In this work, a two-photon probe I for nitroreductase detection and hypoxic status monitoring in living tumor cells and tissues was reported for the first time. The detection is based on the fact that the nitro-group of probe 1 could be selectively reduced to an amino-group by nitroreductase in the presence of reduced NADH, following by a 1,6- rearrangement-elimination to release the fluorophore, resulting in the enhancement of fluorescence. The probe exhibited both one-photon and two-photon excited remarkable fluorescence enhancement (~70-fold) for nitroreductase, which afforded a high sensitivity for nitroreductase, with a detection limit of 20 ng/mL observed. Moreover, the applications of the probe for fluorescent bioimaging of hypoxia in living cells and two-photon bioimaging in tissues were carried out, with tissue-imaging depths of 70-160 µm observed, which demonstrates its practical application in complex biosystems. [ABSTRACT FROM AUTHOR]

Strong metal/oxide interactions havebeen acknowledged to play prominent roles in chemical catalysis inthe gas phase, but remain as an unexplored area in electrocatalysisin the liquid phase. Utilization of metal/oxide interface structurescould generate high performance electrocatalysts for clean energystorage and conversion. However, building highly dispersed nanoscalemetal/oxide interfaces on conductive scaffolds remains a significantchallenge. Here, we report a novel strategy to create metal/oxideinterface nanostructures by growing mixed metal oxide nanoparticleson carbon nanotubes (CNTs) and then selectively promoting migrationof one of the metal ions to the surface of the oxide nanoparticlesand simultaneous reduction to metal. Employing this strategy, we havesynthesized Ni/CeO2nanointerfaces coupled with CNTs. TheNi/CeO2interface promotes hydrogen evolution catalysisby facilitating water dissociation and modifying the hydrogen bindingenergy. The Ni/CeO2–CNT hybrid material exhibitssuperior activity for hydrogen evolution as a result of synergisticeffects including strong metal/oxide interactions, inorganic/carboncoupling, and particle size control. [ABSTRACT FROM AUTHOR]

The rechargeable lithium-sulfur battery is a promising option for energy storage applications because of its low cost and high energy density. The electrochemical performance of the sulfur cathode, however, is substantially compromised because of fast capacity decay caused by polysulfide dissolution/shuttling and low specific capacity caused by the poor electrical conductivities of the active materials. Herein we demonstrate a novel strategy to address these two problems by designing and synthesizing a carbon nanotube (CNT)/NiFe2O4-S ternary hybrid material structure. In this unique material architecture, each component synergistically serves a specific purpose: The porous CNT network provides fast electron conduction paths and structural stability. The NiFe2O4 nanosheets afford strong binding sites for trapping polysulfide intermediates. The fine S nanoparticles well-distributed on the CNT/NiFe2O4 scaffold facilitate fast Li+ storage and release for energy delivery. The hybrid material exhibits balanced high performance with respect to specific capacity, rate capability, and cycling stability with outstandingly high Coulombic efficiency. Reversible specific capacities of 1350 and 900 mAh g-1 are achieved at rates of 0.1 and 1 C respectively, together with an unprecedented cycling stability of ~0.009% capacity decay per cycle over more than 500 cycles. [ABSTRACT FROM AUTHOR]

Thiophenols, a dass of highly toxic and pollutant compounds, are widely used in industrial production. Some aliphatic thiols play important roles in living organisms. Therefore, the development of efEdent methods to discriminate thiophenols from aliphatic thiols is of great importance. Although several onephoton fluorescent probes have been reported for thiophenols, two-photon fluorescent probes are more favorable for biological imaging due to its low background fluorescence, deep penetration depth, and so on In this work, a twophoton fluorescent probe for thiophenols, termed NpRbl, has been developed for the first time by employing 2,4-dinitrobenzene-sulfonate (DNBS) as a recognition unit (also a fluorescence quencher) and a naphthalene-BODIPY-based throughbond energy transfer (TBET) cassette as a fluorescent reporter. The TBET system consists of a D-π-A structured two-photon naphthalene fluorophore and a redemitting BODIPY. It displayed highly energy transfer efficiency (93.5%), large pseudo-Stokes shifts upon one-photon excitation, and red fluorescence emission (λem = 586 nm), which is highly desirable for bioimaging applications. The probe exhibited a 163- fold thiophenol-triggered two-photon excited fluorescence enhancement at 586 nm. It showed a high selectivity and excellent sensitivity to thiophenols, with a detection limit of 4.9 nM. Moreover, it was successfully applied for practical detection of thiophenol in water samples with a good recovery, two-photon imaging of thiophenol in living cells, and tissues with tissueimaging depths of 90-220 pm, demonstrating its practical application in environmental samples and biological systems. [ABSTRACT FROM AUTHOR]

Conspectus: Despite great advances in molecular dynamics simulations, there remain large gaps between the simulations and experimental observations in terms of the time and length scales that can be approached. Developing fast and accurate algorithms and methods is of ultimate importance to bridge these gaps. In this Account, we briefly summarize recent efforts in such directions. In particular, we focus on integrated tempering sampling. The efficiency of this sampling method has been demonstrated by applications to a range of chemical and biological problems: protein folding, molecular cluster structure searches, and chemical reactions. The combination of integrated tempering sampling and a trajectory sampling method allows the calculation of rate constants and reaction pathways without predefined collective coordinates. [ABSTRACT FROM AUTHOR]

Two new metal sulfides, Ba2Ga8MS16 (M = Si, Ge), have been synthesized by high-temperature solid-state reactions. They are isostructural and crystallize in the noncentrosymmetric space group P63mc (No. 186) with a = 10.866(5) Å, c = 11.919(8) Å, and z = 2 for Ba2Ga8SiS16 (1) and a = 10.886(8) Å, c = 11.915(3) Å, and z = 2 for Ba2Ga8GeS16 (2). Their three-dimensional frameworks are constructed by corner-sharing mixed (Ga/M)S4 (M = Si, Ge) and pure GaS4 tetrahedra, with Ba2+ cations filling in the tunnels. Compounds 1 and 2 are transparent over 0.42-20 μm and have wide band gaps of around 3.4 and 3.0 eV, respectively. Polycrystalline 2 displays strong nonlinear second-harmonic-generation (SHG) intensities that are comparable to that of the benchmark AgGaS2 (AGS) with phase-matching behavior at a laser irradiation of 1950 nm. Of particular interest, compound 2 also possesses a high powder laser-induced damage threshold of ~22 times that of AGS. The alternate stacking of the mixed (Ga/M)S4 (M = Si, Ge) tetrahedral layer with the pure GaS4 tetrahedral layer along the c axis and the alignment of these two types of tetrahedra in the same direction may be responsible for the large SHG signals observed. [ABSTRACT FROM AUTHOR]

Vc H-NOX (or VCA0720) is an H-NOX (heme-nitric oxide and oxygen binding) protein from facultative aerobic bacterium Vibrio chokrac. It share significant sequence homology with soluble guanylyl cyclase (sGC), a NO sensor protein commonly found in animals. Similar to sGC, Vc H-NOX binds strongly to NO and CO with affinities of 0.27 nM and 0.77 μM, respectively, but weakly to O2. When positioned on a "sliding scale" plot [Tsai, A.-1., et al. (2012) Biochemistry S1, 172-186], the line connecting log KD(NO) and log KD(CO) of Vc H-NOX car almost be superimposed with that of Ns H-NOX. Therefore, the measured affinities and kinetic parameters of gaseous ligands to Vc H-NOX provide more evidence to validate the "sliding scale rule" hypothesis. Like sGC, Vc H-NOX binds NO in multiple steps, forming first a six-coordinate heme-NO complex at a rate of 1.1 × 109 M-1 s-1, and then converts to a five-coordinate heme-NO complex at a rate that is also dependent on NO concentration. Although the formation of oxyferrous Vc H-NOX cannot be detected at a normal atmospheric oxygen level, ferrous Vc H-NOX is oxidized to the ferric form at a rate of 0.06 s-1 when mixed with O2. Ferric Vc H-NOX exists as a mixture of high- and low-spin states and is influenced by binding to different ligands. Characterization of both ferric and ferrous Vc H-NOX and their complexes with various ligands lays the foundation for understanding the possible dual roles in gas and redox sensing of Vc H-NOX. [ABSTRACT FROM AUTHOR]

High quality graphene materials that readily disperse in water or organic solvents are needed to achieve some of the most ambitious applications. However, current synthetic approaches are typically limited by irreversible structural damages, little solubility, or low scalability. Here, we describe a fundamental study of graphene chemistry and covalent functionalization patterns on sp2 carbon lattices, from which a facile, scalable synthesis of high quality graphene sheets was developed. Graphite materials were efficiently exfoliated by reductive, propagative alkylation. The exfoliated, propagatively alkylated graphene sheets (PAGenes) not only exhibited high solubility in common solvents such as chloroform, water, and N-methyl-pyrrolidone, but also showed electrical conductivity as high as 4.1 × 10³ S/m, which is 5 orders of magnitude greater than those of graphene oxides. Bright blue photoluminescence, unattainable in graphene, was also observed. We attribute the rise of blue photoluminescence in PAGenes to small on-graphene sp² domains created by the propagative covalent chemistry, which may expand from graphene edges or existing defect sites leaving sp²-hybridized patches interlaced with sp³-hybridized regions. The intact sp² domains enable effective electrical percolation among different graphene layers affording the observed high electrical conductivity in PAGene films. [ABSTRACT FROM AUTHOR]

In order to understand the microsolvation of LiI and CsI in water and provide information about the dependence of solvation processes on different ions, we investigated the LiI(H2O)n- and CsI(H2O)n- (n = 0-6) clusters using photoelectron spectroscopy. The structures of these clusters and their corresponding neutrals were investigated with ab initio calculations and confirmed by comparing with the photoelectron spectroscopy experiments. Our studies show that the structural evolutions of LiI(H2O)n and CsI(H2O)n clusters are very different. The Li–I distance in LiI(H2O)n- increases abruptly at n = 3, whereas the abrupt elongation of the Li–I distance in neutral LiI(H2O)n occurs at n = 5. In contrast to the LiI(H2O)n- clusters, the Cs–I distance in CsI(H2O)n- increases significantly at n = 3, reaches a maximum at n = 4, and decreases again as n increases further. There is no abrupt change of the Cs–I distance in neutral CsI(H2O)n as n increases from 0 to 6. Water molecules interact strongly with the Li ion; consequently, water molecule(s) can insert within the Li+-I- ion pair. In contrast, five or six water molecules are not enough to induce obvious separation of the Cs+-I- ion pair since the Cs–water interaction is relatively weak compared to the Li–water interaction. Our work has shown that the structural variation and microsolvation in MI(H2O)n clusters are determined by the delicate balance between ion–ion, ion–water, and water–water interactions, which may have significant implications for the general understanding of salt effects in water solution. [ABSTRACT FROM AUTHOR]

Spinosyns A and D (spinosad), like many other complex polyketides, are tailored near the end of their biosyntheses through the addition of sugars. SpnG, which catalyzes their 9-OH rhamnosylation, is also capable of adding other monosaccharides to the spinosyn aglycone (AGL) from TDP-sugars; however, the substitution of UDP-D-glucose for TDP-D-glucose as the donor substrate is known to result in a >60000-fold reduction in kcat. Here, we report the structure of SpnG at 1.65 Å resolution, SpnG bound to TDP at 1.86 Å resolution, and SpnG bound to AGL at 1.70 Å resolution. The SpnG-TDP complex reveals how SpnG employs N202 to discriminate between TDP- and UDP-sugars. A conformational change of several residues in the active site is promoted by the binding of TDP. The SpnG-AGL complex shows that the binding of AGL is mediated via hydrophobic interactions and that H13, the potential catalytic base, is within 3 Å of the nucleophilic 9-OH group of AGL. A model for the Michaelis complex was constructed to reveal the features that allow SpnG to transfer diverse sugars; it also revealed that the rhamnosyl moiety is in a skew-boat conformation during the transfer reaction. [ABSTRACT FROM AUTHOR]

The location of the triple line as a function of time has been recorded for a series of organic liquids, with various surface tension to viscosity ratios, wicking upward a rough Cu6Sn5/Cu intermetallic (IMC) substrate. The complex topographical features of such an IMC rough surface are characterized by surface porosity and surface roughness. A theoretical model for wicking upward a rough surface has been established by treating the rough IMC surface as a two-dimensional porous medium featuring a network of open microtriangular grooves. The model is verified against experimental data. The study confirms that the kinetics of capillary rise of organic liquids in a nonreactive flow regime over a porous surface having arbitrary but uniformly distributed topographical features involves (i) surface topography metrics (i.e., permeability, tortuosity/porosity, and geometry of the microchannel cross section); (ii) wicking features (i.e., contact angle and filling factor); and (iii) physical properties of liquids (i.e., surface tension and viscosity). An excellent agreement between theoretical predictions and experimentally obtained data proves, for a selected filling factor η, validity of the analytically established model. Scaled data sets show that, for a given rough surface topography, (i) wicking kinetics of considered liquids depend on properties of liquids, that is, surface tension to viscosity ratios and contact angles; (ii) the filling factor for all tested liquids is an invariant, offering good prediction within the range of ∼0.9–1.0. The distance of the wicking front versus square root of time relationship was well established throughout the whole considered wicking evolution time. [ABSTRACT FROM AUTHOR]

A theoretical model of a capillary driven flow of liquid metal through topography features of rough surfaces has been verified by a study of molten solder (Sn–Pb) spreading over Cu6Sn5/Cu3Sn/Cu intermetallic (IMC) substrates. Flow through microgrooves over a rough IMC substrate is considered as spreading through an isotropic porous medium featuring a network of open microgrooves having predefined free-flow area cross sections. The relative margin of deviation between theoretically predicted and empirically determined locus of points of triple line locations is within the range of 5–15%. This margin supports the validity of the developed, analytically formulated square root power law model for a whole spreading domain in terms of (i) geometry of topographical features of the rough surface (i.e., effective intrinsic permeability, porosity/tortuosity, and microchannel cross section geometry), (ii) wetting/spreading features (equilibrium contact angle and filling factor), and (iii) molten metal/substrate properties (viscosity and surface tension). Experimental data involving triple line kinetics represent the data set of locations of the triple line versus time obtained by in situ monitoring of the spreading of molten metal systems over IMC substrates by using the controlled atmosphere hot stage microscopy. [ABSTRACT FROM AUTHOR]

Several residues in the third extramembrane segment (EM3) of adrenal cytochrome b561 have been proposed to be involved in this cytochrome's interaction with ascorbate, but there has been no systematic evaluation of residues in the segment. We used alanine scanning mutagenesis to assess the functional and structural roles of the EM3 residues and several adjacent residues (residues 70-85) in the bovine cytochrome. Each alanine mutant was expressed in a bacterial system, solubilized with detergent, and affinity-purified. The recombinant proteins contained approximately two hemes per monomer and, except for R74A, retained basic functionality (=94% reduced by 20 mM ascorbate). Equilibrium spectrophotometric titrations with ascorbate were used to analyze the a-band line shape and amplitude during reduction of the high- and low-potential heme centers (bH and bL, respectively) and the midpoint ascorbate concentrations for the bH and bL transitions (CH and CL, respectively). Y73A and K85A markedly narrowed the bH a-band peak; other mutants had weaker effects or no effect on bH or bL spectra. Relative changes in CH for the mutants were larger than changes in CL, with 1.5-2.9-fold increases in CH for L70A, L71A, Y73A, R74A, N78A, and K85A. The amounts of functional bH and bL centers in additional Arg74 mutants, assessed by ascorbate titration and EPR spectroscopy, declined in concert in the following order: wild type > R74K > R74Q > R74T and R74Y > R74E. The results of this first comprehensive experimental test of the proposed roles of EM3 residues have identified residues with a direct or indirect impact on ascorbate interactions, on the environment of the bH heme center, and on formation of the native bH-bL unit. Surprisingly, no individual EM3 residue was by itself indispensable for the interaction with ascorbate, and the role of the segment appears to be more subtle than previously thought. These results also support our topological model of the adrenal cytochrome, which positions bH near the cytoplasmic side of the membrane. [ABSTRACT FROM AUTHOR]

I -Aminocyclopropane- I -carboxylic acid (ACC) deaminase (ACCD) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that cleaves the cyclopropane ring of ACC, to give α-ketobutyric acid and ammonia as products. The cleavage of the Cα–Cβ bond of an amino acid substrate is a rare event in PLP-dependent enzyme catalysis. Potential chemical mechanisms involving nucleophile- or acid-catalyzed cyclopropane ring opening have been proposed for the unusual transformation catalyzed by ACCD. but the actual mode of cyclopropane ring cleavage remains obscure. In this report, we aim to elucidate the mechanistic features of ACCD catalysis by investigating the kinetic properties ofACCD from Pseudomona.s sp. ACP and several of its mutant enzymes. Our studies suggest that the pKa of the conserved active site residue, Tyr294, is lowered by a hydrogen bonding interaction with a second conserved residue, Tyr268. This allows Tyr294 to deprotonate the incoming amino group of ACC to initiate the aldimine exchange reaction between ACC and the PLP coenzyme and also likely helps to activate Tyr294 for a role as a nucleophile to attack and cleave the cyclopropane ring of the substrate. In addition, solvent kinetic isotope effect (KIE), proton inventory, and 13C KIE studies of the wild type enzyme suggest that the Cα–Cβ bond cleavage step in the chemical mechanism is at least partially rate-limiting under kcat/Km conditions and is likely preceded in the mechanism by a partially rate-limiting step involving the conversion of a stable gens-diamine intermediate into a reactive external aldimine intermediate that is poised for cyclopropane ring cleavage. When viewed within the context of previous mechanistic and structural studies of ACCD enzymes, our studies are most consistent with a mode of cyclopropane ring cleavage involving nucleophilic catalysis by Tyr294. [ABSTRACT FROM AUTHOR]

Thiopeptides are a class of clinically interesting and highly modified peptide antibiotics. Their biosyntheses share a common paradigm for characteristic core formation but differ in tailoring to afford individual members. Herein we report an unusual deesterification-amidation process in thiostrepton maturation to furnish the terminal amide moiety. TsrB, serving as a carboxylesterase, catalyzes the hydrolysis of the methyl ester intermediate to provide the carboxylate intermediate, which can be converted to the amide product by an amidotransferase, TsrC. These findings revealed a C-terminal methylation of the precursor peptide, which is cryptic in thiostrepton biosynthesis but potentially common in the formation of its homologous series of thiopeptides that vary in the C-terminal form as methyl ester, carboxylate, or amide. [ABSTRACT FROM AUTHOR]

The solid solution series CexZr1-xO2(x= 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1.0) with a bimodal pore structure was prepared by the citric acid sol−gel method. Results from X-ray diffraction, Raman spectroscopy, scanning electron microscopy, mercury porosimetry, and N2adsorption/desorption measurements indicated that the physical properties of the solid solutions were significantly affected by the Ce/Zr molar ratio and the calcination temperatures. These solid solutions can be used in the synthesis of dimethyl carbonate (DMC) from methanol and carbon dioxide. Results indicated that the structure of the solid solutions and the Ce/Zr molar ratio in CexZr1-xO2were the key factor in determining the catalytic activity for the synthesis of DMC. Higher catalytic performance was observed with a 1:1 Ce/Zr molar ratio at a calcination temperature of 1273 K. 1,1,1-Trimethoxymethane (TMM) was used to remove residual H2O in situ, and was found to increase the methanol conversion from 1.8 to 7.9% at 373 K under a pressure of 20 MPa after 24 h. The combination of the bimodal porous catalyst with an effective H2O removal agent gave a methanol conversion of 10.4% at 373 K, under 12 MPa after 34 h. The catalytic activity was almost doubled when the ionic liquid 1-ethyl-3-methylimidazolium bromide was loaded on Ce0.5Zr0.5O2, which may be a promising means for selective production of DMC from CO2and CH3OH. [ABSTRACT FROM AUTHOR]

Unique spindle-shaped nanoporous anatase Ti02 mesocrystals with a sngle-crystal-like structure and tunable sizes were successfully fabricated on a large scale through mesoscale assembly in the tetrabutyl titanate-acetic acid system without any additives under solvothermal conditions. A complex mesoscale assembly process involving slow release of soluble species from metastable solid precursors for the continuous formation of nascent anatase nanocrystals, oriented aggregation of tiny anatase nanocrystals, and entrapment of in situ produced butyl acetate as a porogen was put forward for the formation of the anatase mesocrystals. It was revealed that the acetic acid molecules played multiple key roles during the nonhydrolytic processing of the [OO1]-oriented, singlecrystal-like anatase mesocrystals. The obtained nanoporous anatase mesocrystals exhibited remarkable crystalline-phase stability (i.e., the pure phase of anatase can be retained after leing annealed at 900 °C) and improved performance as anode materials for lithium ion batteries, which could be largely attributed to the intrinsic single-crystal-like nature as well as high porosity of the nanoporous mesocrystals. [ABSTRACT FROM AUTHOR]

The in vitro characterization of the catalytic activity of DesVII, the glycosyltransferase involved in the biosynthesis of the macrolide antibiotics methymycin, neomethymycin, narbomycin, and pikromycin in Streptomyces venezuelae, is described. DesVII is unique among glycosyltransferases in that it requires an additional protein component, DesVIII, for activity. Characterization of the metabolites produced by a S. venezuelae mutant lacking the desVIII gene confirmed that desVIII is important for the biosynthesis of glycosylated macrolides but can be replaced by at least one of the homologous genes from other pathways. The addition of recombinant DesVIII protein significantly improves the glycosylation efficiency of DesVII in the in vitro assay. When affinity-tagged DesVII and DesVIII proteins were coproduced in Escherichia coli, they formed a tight (αβ)3 complex that is at least 10³-fold more active than DesVII alone. The formation of the DesVII/DesVIII complex requires coexpression of both genes in vivo and cannot be fully achieved by mixing the individual protein components in vitro. The ability of the DesVII/DesVIII system to catalyze the reverse reaction with the formation of TDP-desosamine was also demonstrated in a transglycosylation experiment. Taken together, our data suggest that DesVIII assists the folding of DesVII during protein production and remains tightly bound during catalysis. This requirement must be taken into consideration in the design of combinatorial biosynthetic experiments with new glycosylated macrolides. [ABSTRACT FROM AUTHOR]

The mechanism of the copolymerization of CO2 and epoxides to afford the corresponding polycarbonates catalyzed by a highly active and thermally stable cobalt(III) complex with 1,5,7-triabicyclo[4,4,0] dec-5-ene (designated as TBD, a sterically hindered organic base) anchored on the ligand framework has been studied by means of electrospray ionization mass spectrometry (ESI-MS) and Fourier transform infrared spectroscopy (FTIR). The single-site, cobalt-based catalyst exhibited excellent activity and selectivity for polymer formation during CO2/propylene oxide (PO) copolymerization even at temperatures up to 100 °C and high [epoxide]/[catalyst] ratios, and/or low CO2 pressures. The anchored TBD on the ligand framework plays an important role in maintaining thermal stability and high activity of the catalyst. ESI-MS and FTIR studies, in combination with some control experiments, confirmed the formation of the carboxylate intermediate with regard to the anchored TBD on the catalyst ligand framework. This analysis demonstrated that the formed carboxylate intermediate helped to stabilize the active Co(III) species against decomposition to inactive Co(II) by reversibly intramolecular Co-O bond formation and dissociation. Previous studies of binary catalyst systems based on Co(III)-Salen complexes did not address the role of these nucleophilic cocatalysts in stabilizing active Co(III) species during the copolymerization. The present study provides a new mechanistic understanding of these binary catalyst systems in which alternating chain-growth and dissociation of propagating carboxylate species derived from the nucleophilic axial anion and the nucleophilic cocatalyst take turns at both sides of the Co(III)-Salen center. This significantly increases the reaction rate and also helps to stabilize the active SalenCo(III) against decomposition to inactive SalenCo(II) even at low CO2 pressures and/or relatively high temperatures. [ABSTRACT FROM AUTHOR]

A new route for the preparation of cellulose triacetate (CTA) optical films from the biomass of ramie fiber has been found with environmental benefits. CTA with a degree of substitution (DS) of 2.81−2.92 was prepared by the reaction of acetic anhydride with ramie fiber catalyzed by sulfuric acid in acetic acid solution at 55 °C. The CTA film was prepared by casting the solution of CTA dissolving in dichloromethane on the culture disk via spreading the solution through a syringe. The structure and properties of CTA and its film were investigated by Fourier transform infrared (FT-IR), ultraviolet (UV), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and titration. It was found that the CTA films prepared from ramie fiber shows a high transparency of 89% and excellent mechanical properties with stress measurements of 31.04−47.80 MPa and strain of 3.99−5.22%. The CTA films prepared from ramie fiber are suitable as protective films for the liquid crystal displays (LCD). [ABSTRACT FROM AUTHOR]

Fucosylated glycoconjugates have critical roles in biological processes, but a limited availability of α-L-fucosidase has hampered research on this human enzyme (h-Fuc) at a molecular level. After overexpressing h-Fuc in Escherichia coli as an active form, we investigated the catalytic function of this recombinant enzyme. Based on sequence alignment and structural analysis of close homologues of h-Fuc, nine residues of glutamate and aspartate in h-Fuc were selected for mutagenic tests to determine the essential residues. Among the mutants, D225N, E289Q, and E289G lost catalytic activity significantly; their kcat values are 1/5700, 1/430, and 1/340, respectively, of that of the wild-type enzyme. The Br∅nsted plot for kcat/Km for the E289G mutant is linear with 131g = -0.93, but that for kcat is biphasic, with j3,~ for poor substrates being -0.88 and for activated substrates being -0.11. The small magnitude of β1g for the activated substrates may indicate that the rate-limiting step of the reaction is defucosylation, whereas the large magnitude of the latter β1g value for the poor substrates indicates that the rate-limiting step of the reaction becomes fucosylation. The kinetic outcomes support an argument that Asp225 functions as a nucleophile and Glu289 as a general acid/base catalyst. As further evidence, azide significantly reactivated D225G and E289G, and 1H NMR spectral analysis confirmed the formation of β-fucosyl azide and α-fucosyl azide in the azide rescues of D225G and E289G catalyses, respectively. As direct evidence to prove the function of Glu289, an accumulation of fucosyl-enzyme intermediate was detected directly through ES!] MS analysis. [ABSTRACT FROM AUTHOR]

A simple one-step template method for the fabrication of crystalline titania (TiO 2) hollow microspheres, based on template-directed deposition and in situ template-sacrificial dissolution, is developed in pure water by using SiO 2microspheres as templates and TiF 4as the precursor at 60 °C. The wall thickness and size of the TiO 2hollow spheres can be controlled by adjusting the concentration of the precursor TiF 4and the size of the SiO 2spheres, respectively. The prepared TiO 2hollow spheres exhibit hierarchically nanoporous structures and a high photocatalytic activity. This hierarchically micromeso-macrostructured TiO 2hollow microspheres should find various potential applications in photocatalysis, catalysis, solar cells, and separation and purification processes. [ABSTRACT FROM AUTHOR]

Cytochrome (cyt) b561 transports electrons across the membrane of chromaffin granules (CG) present in the adrenal medulla, supporting the biosynthesis of norepinephrine in the CG matrix. We have conducted a detailed characterization of cyt b561 using electron paramagnetic resonance (EPR) and optical spectroscopy on the wild-type and mutant forms of the cytochrome expressed in insect cells. The gz = 3.7 (low-potential heme) and gz = 3.1 (high-potential heme) signals were found to represent the only two authentic hemes of cyt b561 models that propose smaller or greater amounts of heme can be ruled out. We identified the axial ligands to hemes in cyt b561 by mutating four conserved histidines (His54 and His 122 at the matrix-side heme center and His88 and His161 at the cytoplasmic-side heme center), thus confirming earlier structural models. Single mutations of any of these histidines produced a constellation of spectroscopic changes that involve not one but both heme centers. We hypothesize that the two hemes and their axial ligands in cyt b561 are integral parts of a structural unit that we term the "kernel". Histidine to glutamine substitutions in the cytoplasmic-side heme center but not in the matrix-side heme center led to the retention of a small fraction of the low-potential heme with gz = 3.7. We provisionally assign the low-potential heme to the matrix side of the membrane; this arrangement suggests that the membrane potential modulates electron transport across the CG membrane. [ABSTRACT FROM AUTHOR]

Hydroperoxides induce formation of a tyrosyl radical on Tyr385 in prostaglandin H synthase (PGHS). The Tyr385 radical initiates hydrogen abstraction from arachidonic acid, thereby mechanistically connecting the peroxidase and cyclooxygenase activities. In both PGHS isoforms the tyrosyl radical undergoes a time-dependent transition from a wide doublet to a wide singlet species; pretreatment with cyclooxygenase inhibitors results in a third type of signal, a narrow singlet [Tsai, A.-L.; Kulmacz, R. J. (2000) Prost Lipid Med. 62, 231-254]. These transitions have been interpreted as resulting from Tyr385 ring rotation, but could also be due to radical migration from Tyr385 to another tyrosine residue. PATHWAYS analysis of PGHS crystal structures identified four tyrosine residues with favorable predicted electronic coupling: residues 148, 348, 404, and 504 (ovine PGHS-1 numbering). We expressed recombinant PGHS-2 proteins containing single Tyr→ Phe mutations at the target residues, a quadruple mutant with all four tyrosines mutated, and a quintuple mutant, which also contains a Y385F mutation. All mutants bind heme and display appreciable peroxidase activity, and with the exception of the quintuple mutant, all retain cyclooxygenase activity, indicating that neither of the active sites is significantly perturbed. Reaction of the Y148F, Y348F, and Y404F mutants with EtOOH generates a wide singlet EPR signal similar to that of native PGHS-2. However, reaction of the Y504F and the quadruple mutants with peroxide yields persistent wide doublets, and the quintuple mutant is EPR silent. Nimesulide pretreatment of Y504F and the quadruple mutant results in an abnormally small amount of wide doublet signal, with no narrow singlet being formed. [ABSTRACT FROM AUTHOR]

Examines the synthesis of 1-aminocyclopropanecarboxylic acid (ACC). Description of ACC; Identification of the amino acid residue; Characterization of the mononuclear non-heme iron enzyme.

Examines the synthesis of a deoxysugar dinucleotide containing an exo-difluoromethylene moiety. Probe for the analysis of enzymes involved in sugar biosynthesis; Potential of fluorine-containing compounds as enzyme inhibitors; Methods of controlling enzymatic transformation.

Investigates UDP-galactopyranose mutase from escherichia coli using 2- and 3-fluorinated UDP-galactofuranose as probes. Determination of kinetic parameters; Inhibition of UDP-galactopyranose mutase by fluorinated analogues; Reductive reactivation of inactivated mutase.

Examines the role of flavin adenine dinucleotide (FAD) in regulating the catalytic efficiency of UDP-galactopyranose mutase from Escherichia coli. Derivation of the galactofuranose moiety; Effect of sodium dithionite on the enzyme; Rate enhancement of the flavin coenzyme during photoreduction.

Monodisperse 3.1 nm Ag2Te NCs show a sharp optical absorption feature at 1154 nm with a large linear temperature dependence and the photoconductive response consistent with semiconducting character in Ag2Te NCs. The wavelength of the resonance is within the window of transparency for biological tissue making it a potential in vivo temperature marker or transducer for in situ heating with deep-penetrating near-infrared radiation. [ABSTRACT FROM AUTHOR]

The first mechanistic insight into 2-thiosugar production in an angucycline-type antibiotic, BE-7585A, is reported. D-Glucose 6-phosphate was identified as the substrate for the putative thiosugar biosynthetic protein, BexX, by trapping the covalently bonded enzyme-substrate intermediate. The site- specific modification at K110 residue was determined by mutagenesis studies and LC-MS/MS analysis. A key intermediate carrying a keto functionality was confirmed to exist in the enzyme-substrate complex. These results suggest that the sulfur insertion mechanism in 2-thiosugar biosynthesis shares similarities with that for thiamin biosynthesis. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the formation of aziridine in azicemicins based on the biosynthesis experiments. The study involves the use of the results of isotope-tracer experiments and cloning of the azicemicin biosynthetic gene. It notes that there is a limitation in the chemical formation particularly the cyclization step which is not apparent.

Examines a silylcopper catalyst for the reductive bromination of Hajos dione. Transformation of diol into epoxy-ketone; Production of synthon from Hajos dione; Stereo- and regioselectivities in Hajos dione reduction.

The article focuses on the biosynthesis of macrolide derivatives which bear the non-natural deoxysugars 4-epi-D-mycaminose and 3-N-monomethylamino-3-deoxy-D-fucose. Macrolide antibiotics, such as methymycin, neomethymycin and pikromycin, produced by Streptomyces venezueiae comprise an important class of compounds, many of which are effective antibacterial agents.

Natural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external. These processes/concerns are often dynamic and thus motivate the diversification, optimization, and selection of small molecules in line with changes in biological function. Consequently, the interactions between living organisms and their environments serve as an engine that drives coevolution of natural products and their biological functions and ultimately programs the constant theme of small-molecule development in nature based on biosynthesis generality and specificity. Following this theme, we herein review the biosynthesis of lincosamide antibiotics and dissect the process through which nature creates an unusual eight-carbon aminosugar (lincosamide) and then functionalizes this common high-carbon chain-containing sugar core with diverse l-proline derivatives and sulfur appendages to form individual members, including the clinically useful anti-infective agent lincomycin A and its naturally occurring analogues celesticetin and Bu-2545. The biosynthesis of lincosamide antibiotics is unique in that it results from an intersection of anabolic and catabolic chemistry. Many reactions that are usually involved in degradation and detoxification play a constructive role in biosynthetic processes. Formation of the trans-4-propyl-l-proline residue in lincomycin A biosynthesis requires an oxidation-associated degradation-like pathway composed of heme peroxidase-catalyzed ortho-hydroxylation and non-heme 2,3-dioxygenase-catalyzed extradiol cleavage for l-tyrosine processing prior to the building-up process. Mycothiol (MSH) and ergothioneine (EGT), two small-molecule thiols that are known for their redox-relevant roles in protection against various endogenous and exogenous stresses, function through two unusual S-glycosylations to mediate an eight-carbon aminosugar transfer, activation, and modification during the molecular assembly and tailoring processes in lincosamide antibiotic biosynthesis. Related intermediates include an MSH S-conjugate, mercapturic acid, and a thiomethyl product, which are reminiscent of intermediates found in thiol-mediated detoxification metabolism. In these biosynthetic pathways, "old" protein folds can result in "new" enzymatic activity, such as the DinB-2 fold protein for thiol exchange between EGT and MSH, the γ-glutamyltranspeptidase homologue for C-C bond cleavage, and the pyridoxal-5'-phosphate-dependent enzyme for diverse S-functionalization, generating interest in how nature develops remarkably diverse biochemical functions using a limited range of protein scaffolds. These findings highlight what we can learn from natural product biosynthesis, the recognition of its generality and specificity, and the natural theme of the development of bioactive small molecules, which enables the diversification process to advance and expand small-molecule functions. [ABSTRACT FROM AUTHOR]

Examines the catalysis of C-1027 biosynthetic gene cluster by SgcC4, a novel tyrosine aminomutase. Alpha-beta elimination of L-tyrosine; Molecular structure of the C-1027 chromophore; Conversion of L-tyrosine into (S)-B-tyrosine during the biosynthesis of C-1027.

In this report, originally proposed apratoxin E (30S-7), revised apratoxin E (30R-7), and (30S)/(30R)-oxoapratoxin E (30S)-38/(30R)-38 were efficiently prepared by two synthetic methods. The chiral lactone 10, recycled from the degradation of saponin glycosides, was utilized to prepare the key nonpeptide fragment 9. Our alternative convergent assembly strategy was applied to the divergent synthesis of revised apratoxin E and its three analogues. Moreover, ring-closing metathesis (RCM) was for the first time found to be an efficient strategy for the macrocyclization of apratoxins. [ABSTRACT FROM AUTHOR]