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With the aid of a class of newly discovered Trost-type bisphosphine ligands bearing a chiral cycloalkane framework, the Pd-catalyzed decarboxylative dearomative asymmetric allylic alkylation (AAA) of benzofurans was achieved with high efficiency [0.2-1.0 mol% Pd2(dba)3/L], good generality, and high enantioselectivity (>30 examples, 82-99% yield and 90-96% ee). Moreover, a diversity-oriented synthesis (DOS) of previously unreachable flavaglines is disclosed. It features a reliable and scalable sequence of the freshly developed Tsuji-Trost-Stoltz AAA, a Wacker-Grubbs-Stoltz oxidation, an intra-benzoin condensation, and a conjugate addition, which allows the efficient construction of the challenging and compact cyclopenta[b]benzofuran scaffold with contiguous stereocenters. This strategy offers a new avenue for developing flavagline-based drugs.

Medium-ring lactones are synthetically challenging due to unfavorable energetics involved in cyclization. We have discovered a thioesterase enzyme DcsB, from the decarestrictine C1 (1) biosynthetic pathway, that efficiently performs medium-ring lactonizations. DcsB shows broad substrate promiscuity towards linear substrates that vary in lengths and substituents, and is a potential biocatalyst for lactonization. X-ray crystal structure and computational analyses provide insights into the molecular basis of catalysis.

Removable tridentate directing groups inspired by pincer ligands have been designed to stabilize otherwise kinetically and thermodynamically disfavored 6-membered alkyl palladacycle intermediates. This family of directing groups enables regioselective remote hydrocarbofunctionalization of several synthetically useful alkene-containing substrate classes, including 4-pentenoic acids, allylic alcohols, homoallyl amines, and bis-homoallylamines, under Pd(II) catalysis. In conjunction with previous findings, we demonstrate regiodivergent hydrofunctionalization of 3-butenoic acid derivatives to afford either Markovnikov or anti-Markovnikov addition products depending on directing group choice. Preliminary mechanistic and computational data are presented to support the proposed catalytic cycle.

Light-driven synthetic micro-/nanomotors have attracted considerable attention due to their potential applications and unique performances such as remote motion control and adjustable velocity. Utilizing harmless and renewable visible light to supply energy for micro-/nanomotors in water represents a great challenge. In view of the outstanding photocatalytic performance of bismuth oxyiodide (BiOI), visible-light-driven BiOI-based Janus micromotors have been developed, which can be activated by a broad spectrum of light, including blue and green light. Such BiOI-based Janus micromotors can be propelled by photocatalytic reactions in pure water under environmentally friendly visible light without the addition of any other chemical fuels. The remote control of photocatalytic propulsion by modulating the power of visible light is characterized by velocity and mean-square displacement analysis of optical video recordings. In addition, the self-electrophoresis mechanism has been confirmed for such visible-light-driven BiOI-based Janus micromotors by demonstrating the effects of various coated layers (e.g., Al_2O_3, Pt, and Au) on the velocity of motors. The successful demonstration of visible-light-driven Janus micromotors holds a great promise for future biomedical and environmental applications.

A Pd-catalyzed, asymmetric oxidative cross-coupling reaction between ferrocenes and heteroarenes is described. The process, which takes place via a twofold C-H bond activation pathway, proceeds with modest to high efficiencies (36-86%) and high levels of regio- and enantioselectivity (95-99% ee). In the reaction, air oxygen serves as a green oxidant and excess amounts of the coupling partners are not required. The process is the first example of a catalytic asymmetric biaryl coupling reaction that occurs via double C-H bond activation. Finally, the generated coupling products can be readily transformed into chiral ligands and catalysts.

© 2015 American Chemical Society. The collective behavior of biological systems has inspired efforts toward the controlled assembly of synthetic nanomotors. Here we demonstrate the use of acoustic fields to induce reversible assembly of catalytic nanomotors, controlled swarm movement, and separation of different nanomotors. The swarming mechanism relies on the interaction between individual nanomotors and the acoustic field, which triggers rapid migration and assembly around the nearest pressure node. Such on-demand assembly of catalytic nanomotors is extremely fast and reversible. Controlled movement of the resulting swarm is illustrated by changing the frequency of the acoustic field. Efficient separation of different types of nanomotors, which assemble in distinct swarming regions, is illustrated. The ability of acoustic fields to regulate the collective behavior of catalytic nanomotors holds considerable promise for a wide range of practical applications.

We describe catalytic micromotors powered by remarkably low concentrations of chemical fuel, down to the 0.0000001% level. These Janus micromotors rely on an iridium hemispheric layer for the catalytic decomposition of hydrazine in connection to SiO_2 spherical particles. The micromotors are self-propelled at a very high speed (of ∼20 body lengths s^(–1)) in a 0.001% hydrazine solution due to osmotic effects. Such a low fuel concentration represents a 10 000-fold decrease in the level required for common catalytic nanomotors. The attractive propulsion performance, efficient catalytic energy-harvesting, environmentally triggered swarming behavior, and magnetic control of the new Janus micromotors hold considerable promise for diverse practical applications.

A new nanomotor-based target isolation strategy, based on a “built-in” recognition capability, is presented. The concept relies on a poly(3-aminophenylboronic acid) (PAPBA)/Ni/Pt microtube engine coupling the selective monosaccharide recognition of the boronic acid-based outer polymeric layer with the catalytic function of the inner platinum layer. The PAPBA-based microrocket is prepared by membrane-templated electropolymerization of 3-aminophenylboronic acid monomer. The resulting boronic acid-based microengine itself provides the target recognition without the need for additional external functionalization. “On-the-fly” binding and transport of yeast cells (containing sugar residues on their wall) and glucose are illustrated. The use of the recognition polymeric layer does not hinder the efficient propulsion of the microengine in aqueous and physiological media. Release of the captured yeast cells is triggered via a competitive sugar binding involving addition of fructose. No such capture and transport are observed in control experiments involving other cells or microengines. Selective isolation of monosaccharides is illustrated using polystyrene particles loaded with different sugars. Such self-propelled nanomachines with a built-in recognition capability hold considerable promise for diverse applications.

The use of an ultrasound (US) field for rapid and reversible control of the movement of bubble-propelled chemically powered PEDOT/Ni/Pt microengines is demonstrated. Such operation reflects the US-induced disruption of normal bubble evolution and ejection, essential for efficient propulsion of catalytic microtubular engines. It offers precise speed control, with sharp increases and decreases of the speed at low and high US powers, respectively. A wide range of speeds can thus be generated by tuning the US power. Extremely fast changes in the motor speed (

A highly efficient synthesis of planar chiral ferrocenes by enantioselective Pd(0)-catalyzed direct C–H arylation from readily available starting materials under mild reaction conditions was developed (up to 99% yield, 99% ee). The products can be easily transformed to the highly efficient planar ferrocene ligands, which have demonstrated high efficiency in Pd-catalyzed asymmetric allylic alkylation and amination reactions.

We demonstrate an attractive nanomachine “capture and transport” target isolation strategy based on molecularly imprinted polymers (MIPs). MIP-based catalytic microtubular engines are prepared by electropolymerization of the outer polymeric layer in the presence of the target analyte (template). Tailor-made selective artificial recognition sites are thus introduced into the tubular microtransporters through complementary nanocavities in the outer polymeric layer. The new microtransporter concept is illustrated using bilayer poly(3,4-ethylenedioxythiophene) (PEDOT)/Pt–Ni microengines and fluorescein isothiocyanate (FITC)-labeled avidin (Av-FITC) as the template. The avidin-imprinted polymeric layer selectively concentrates the fluorescent-tagged protein target onto the moving microengine without the need for additional external functionalization, allowing “on-the-fly” extraction and isolation of Av-FITC from raw serum and saliva samples along with real-time visualization of the protein loading and transport. The new micromachine–MIP-based target isolation strategy can be extended to the capture and transport of other important target molecules, leading toward diverse biomedical and environmental applications.

Organized self-assemblies of Janus catalytic motors, induced by hydrophobic surface interactions involving multiple motor/motor and motor/nonmotor particles, display controlled coordinated self-propulsion. The influence of the self-assembled structures upon the motion behavior is investigated. A dynamic ‘on-the-fly’ assembly is observed during the continuous movement of the individual components, along with changes in the motion behavior. Organized assemblies of multiple motor/nonmotor particles are also illustrated toward optimal cargo transport and delivery. Such controlled structures and motion of chemically powered Janus micromotor assemblies hold considerable promise for the creation of intelligent nanomachines that perform collective tasks.

Enantioselective Pd(II)-catalyzed direct coupling of aminomethylferrocene derivatives with boronic acids was realized. With commercially available Boc-l-Val-OH as a ligand, planar-chiral ferrocenes could be synthesized in yields of 14–81% with up to 99% ee under mild conditions.

Microbial production can be advantageous over the extraction of phytoterpenoids from natural plant sources, but it remains challenging to rationally and rapidly access efficient pathway variants. Previous engineering attempts mainly focused on the mevalonic acid (MVA) or methyl-d-erythritol phosphate (MEP) pathways responsible for the generation of precursors for terpenoids biosynthesis, and potential interactions between diterpenoids synthases were unexplored. Miltiradiene, the product of the stepwise conversion of (E,E,E)-geranylgeranyl diphosphate (GGPP) catalyzed by diterpene synthases SmCPS and SmKSL, has recently been identified as the precursor to tanshionones, a group of abietane-type norditerpenoids rich in the Chinese medicinal herb Salvia miltiorrhiza . Here, we present the modular pathway engineering (MOPE) strategy and its application for rapid assembling synthetic miltiradiene pathways in the yeast Saccharomyces cerevisiae . We predicted and analyzed the molecular interactions between SmCPS and SmKSL, and engineered their active sites into close proximity for enhanced metabolic flux channeling to miltiradiene biosynthesis by constructing protein fusions. We show that the fusion of SmCPS and SmKSL, as well as the fusion of BTS1 (GGPP synthase) and ERG20 (farnesyl diphosphate synthase), led to significantly improved miltiradiene production and reduced byproduct accumulation. The MOPE strategy facilitated a comprehensive evaluation of pathway variants involving multiple genes, and, as a result, our best pathway with the diploid strain YJ2X reached miltiradiene titer of 365 mg/L in a 15-L bioreactor culture. These results suggest that terpenoids synthases and the precursor supplying enzymes should be engineered systematically to enable an efficient microbial production of phytoterpenoids.

Tubular polyaniline (PANI)/Zn microrockets are described that display effective autonomous motion in extreme acidic environments, without any additional chemical fuel. These acid-driven hydrogen-bubble-propelled microrockets have been electrosynthesized using the conical polycarbonate template. The effective propulsion in acidic media reflects the continuous thrust of hydrogen bubbles generated by the spontaneous redox reaction occurring at the inner Zn surface. The propulsion characteristics of PANI/Zn microrockets in different acids and in human serum are described. The observed speed–pH dependence holds promise for sensitive pH measurements in extreme acidic environments. The new microrockets display an ultrafast propulsion (as high as 100 body lengths/s) along with attractive capabilities including guided movement and directed cargo transport. Such acid-driven microtubular rockets offer considerable potential for diverse biomedical and industrial applications.

Highly efficient catalytic microtubular engines are synthesized rapidly and inexpensively using an electrochemical growth of bilayer polyaniline/platinum microtubes within the conically shaped pores of a polycarbonate template membrane. These mass-produced microtubular engines are only 8 μm long, are self-propelled at an ultrafast speed (of over 350 body lengths s^(–1)), and can operate in very low levels of the hydrogen peroxide fuel (down to 0.2%). The propulsion characteristics and optimization of these microtubular engines are described, along with their efficient operation in different biological environments which holds great promise for biomedical applications.

Fuel-free magnetically driven propulsion of flexible Au/Ag/Ni nanowires, with a gold ‘head’ and nickel ‘tail’, linked by a partially dissolved and weakened silver bridge, is described. The flexible bridge facilitates the cyclic mechanical deformations under an external rotating magnetic field. Under such a field the nickel segment starts to rotate, facilitating the rotation of the gold segment at a different amplitude, hence breaking the system symmetry and inducing the movement. Forward (‘pushing’) and backward (‘pulling’) magnetically powered locomotion and a precise On/Off motion control are achieved by tailoring the length of the nickel and gold segments and modulating the magnetic field, respectively. Efficient locomotion in urine samples and in high-salt media is illustrated. The new magnetic nanowire swimmers can be prepared in large scale using a simple template electrodeposition protocol and offer considerable promise for diverse practical applications.

The formation of titania nanotubes through CeO2 colloids seeded deposition process in solution has been demonstrated. The interactions among colloidal particles play important roles for the solution “VLS”-type growth of nanotubes. The observation has significance for understanding solution nucleation and for developing new methods for nanomaterials preparation via the disclosed colloids seeded deposition (CSD) mechanism.

A successful structure-based design of a class of non-peptide small-molecule MDM2 inhibitors targeting the p53-MDM2 protein-protein interaction is reported. The most potent compound 1d binds to MDM2 protein with a Ki value of 86 nM and is 18 times more potent than a natural p53 peptide (residues 16-27). Compound 1d is potent in inhibition of cell growth in LNCaP prostate cancer cells with wild-type p53 and shows only a weak activity in PC-3 prostate cancer cells with a deleted p53. Importantly, 1d has a minimal toxicity to normal prostate epithelial cells. Our studies provide a convincing example that structure-based strategy can be employed to design highly potent, non-peptide, cell-permeable, small-molecule inhibitors to target protein-protein interaction, which remains a very challenging area in chemical biology and drug design.