Showing papers in "Nature Chemistry in 2017"

Activating lattice oxygen redox reactions in metal oxides to catalyse oxygen evolution

Abstract: Understanding how materials that catalyse the oxygen evolution reaction (OER) function is essential for the development of efficient energy-storage technologies. The traditional understanding of the OER mechanism on metal oxides involves four concerted proton-electron transfer steps on metal-ion centres at their surface and product oxygen molecules derived from water. Here, using in situ 18O isotope labelling mass spectrometry, we provide direct experimental evidence that the O2 generated during the OER on some highly active oxides can come from lattice oxygen. The oxides capable of lattice-oxygen oxidation also exhibit pH-dependent OER activity on the reversible hydrogen electrode scale, indicating non-concerted proton-electron transfers in the OER mechanism. Based on our experimental data and density functional theory calculations, we discuss mechanisms that are fundamentally different from the conventional scheme and show that increasing the covalency of metal-oxygen bonds is critical to trigger lattice-oxygen oxidation and enable non-concerted proton-electron transfers during OER.

Hypersensitive dual-function luminescence switching of a silver-chalcogenolate cluster-based metal–organic framework

Abstract: Silver(i) chalcogenide/chalcogenolate clusters are promising photofunctional materials for sensing, optoelectronics and solar energy harvesting applications. However, their instability and poor room-temperature luminescent quantum yields have hampered more extensive study. Here, we graft such clusters to adaptable bridging ligands, enabling their interconnection and the formation of rigid metal–organic frameworks. By controlling the spatial separation and orientation of the clusters, they then exhibit enhanced stability (over one year) and quantum yield (12.1%). Ultrafast dual-function fluorescence switching (<1 s) is also achieved, with turn-off triggered by O2 and multicoloured turn-on by volatile organic compounds. Single-crystal X-ray diffraction of the inclusion materials, obtained by single-crystal-to-single-crystal transformation, enables precise determination of the position of the small molecules within the framework, elucidating the switching mechanism. The work enriches the cluster-based metal–organic framework portfolio, bridges the gap between silver chalcogenide/chalcogenolate clusters and metal–organic frameworks, and provides a foundation for further development of functional silver-cluster-based materials. The properties of discrete species can sometimes be improved by fixing them into extended materials. This strategy has now been applied to silver(I) chalcogenide/chalcogenolate clusters, resulting in a metal–organic framework with enhanced stability and fluorescent sensing capabilities. Crystallographic analysis allows precise structural determination of guest binding, which is responsible for both emission turn-off and multicoloured turn-on.

Direct conversion of CO2 into liquid fuels with high selectivity over a bifunctional catalyst.

Abstract: Although considerable progress has been made in carbon dioxide (CO2) hydrogenation to various C1 chemicals, it is still a great challenge to synthesize value-added products with two or more carbons, such as gasoline, directly from CO2 because of the extreme inertness of CO2 and a high C-C coupling barrier. Here we present a bifunctional catalyst composed of reducible indium oxides (In2O3) and zeolites that yields a high selectivity to gasoline-range hydrocarbons (78.6%) with a very low methane selectivity (1%). The oxygen vacancies on the In2O3 surfaces activate CO2 and hydrogen to form methanol, and C-C coupling subsequently occurs inside zeolite pores to produce gasoline-range hydrocarbons with a high octane number. The proximity of these two components plays a crucial role in suppressing the undesired reverse water gas shift reaction and giving a high selectivity for gasoline-range hydrocarbons. Moreover, the pellet catalyst exhibits a much better performance during an industry-relevant test, which suggests promising prospects for industrial applications.

MoS2 monolayer catalyst doped with isolated Co atoms for the hydrodeoxygenation reaction

Abstract: The conversion of oxygen-rich biomass into hydrocarbon fuels requires efficient hydrodeoxygenation catalysts during the upgrading process. However, traditionally prepared CoMoS2 catalysts, although efficient for hydrodesulfurization, are not appropriate due to their poor activity, sulfur loss and rapid deactivation at elevated temperature. Here, we report the synthesis of MoS2 monolayer sheets decorated with isolated Co atoms that bond covalently to sulfur vacancies on the basal planes that, when compared with conventionally prepared samples, exhibit superior activity, selectivity and stability for the hydrodeoxygenation of 4-methylphenol to toluene. This higher activity allows the reaction temperature to be reduced from the typically used 300 °C to 180 °C and thus allows the catalysis to proceed without sulfur loss and deactivation. Experimental analysis and density functional theory calculations reveal a large number of sites at the interface between the Co and Mo atoms on the MoS2 basal surface and we ascribe the higher activity to the presence of sulfur vacancies that are created local to the observed Co–S–Mo interfacial sites. Converting oxygen-rich biomass into fuels requires the removal of oxygen groups through hydrodeoxygenation. MoS2 monolayer sheets decorated with isolated Co atoms bound to sulfur vacancies in the basal plane have now been synthesized that exhibit superior catalytic activity, selectivity and stability for the hydrodeoxygenation of 4-methylphenol to toluene when compared to conventionally prepared materials.

Adsorbate-mediated strong metal–support interactions in oxide-supported Rh catalysts

Abstract: The optimization of supported metal catalysts predominantly focuses on engineering the metal site, for which physical insights based on extensive theoretical and experimental contributions have enabled the rational design of active sites. Although it is well known that supports can influence the catalytic properties of metals, insights into how metal-support interactions can be exploited to optimize metal active-site properties are lacking. Here we utilize in situ spectroscopy and microscopy to identify and characterize a support effect in oxide-supported heterogeneous Rh catalysts. This effect is characterized by strongly bound adsorbates (HCOx) on reducible oxide supports (TiO2 and Nb2O5) that induce oxygen-vacancy formation in the support and cause HCOx-functionalized encapsulation of Rh nanoparticles by the support. The encapsulation layer is permeable to reactants, stable under the reaction conditions and strongly influences the catalytic properties of Rh, which enables rational and dynamic tuning of CO2-reduction selectivity.

Photoswitching of glass transition temperatures of azobenzene-containing polymers induces reversible solid-to-liquid transitions

Abstract: The development of polymers with switchable glass transition temperatures (Tg) can address scientific challenges such as the healing of cracks in high-Tg polymers and the processing of hard polymers at room temperature without using plasticizing solvents. Here, we demonstrate that light can switch the Tg of azobenzene-containing polymers (azopolymers) and induce reversible solid-to-liquid transitions of the polymers. The azobenzene groups in the polymers exhibit reversible cis-trans photoisomerization abilities. Trans azopolymers are solids with Tg above room temperature, whereas cis azopolymers are liquids with Tg below room temperature. Because of the photoinduced solid-to-liquid transitions of these polymers, light can reduce the surface roughness of azopolymer films by almost 600%, repeatedly heal cracks in azopolymers, and control the adhesion of azopolymers for transfer printing. The photoswitching of Tg provides a new strategy for designing healable polymers with high Tg and allows for control over the mechanical properties of polymers with high spatiotemporal resolution.

Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles.

Abstract: Many intracellular membraneless organelles form via phase separation of intrinsically disordered proteins (IDPs) or regions (IDRs). These include the Caenorhabditis elegans protein LAF-1, which forms P granule-like droplets in vitro. However, the role of protein disorder in phase separation and the macromolecular organization within droplets remain elusive. Here, we utilize a novel technique, ultrafast-scanning fluorescence correlation spectroscopy, to measure the molecular interactions and full coexistence curves (binodals), which quantify the protein concentration within LAF-1 droplets. The binodals of LAF-1 and its IDR display a number of unusual features, including ‘high concentration’ binodal arms that correspond to remarkably dilute droplets. We find that LAF-1 and other in vitro and intracellular droplets are characterized by an effective mesh size of ∼3–8 nm, which determines the size scale at which droplet properties impact molecular diffusion and permeability. These findings reveal how specific IDPs can phase separate to form permeable, low-density (semi-dilute) liquids, whose structural features are likely to strongly impact biological function. Ultrafast-scanning fluorescence correlation spectroscopy has now been used to measure the molecular interactions underlying the phase behaviour of disordered proteins. Sequence-encoded conformational fluctuations of these proteins are shown to give rise to phase-separated droplets of surprisingly low concentrations. These results provide insight into how the structural features of the droplets affect the properties of liquid-phase intracellular organelles.

Breaking scaling relations to achieve low-temperature ammonia synthesis through LiH-mediated nitrogen transfer and hydrogenation

Abstract: Ammonia synthesis under mild conditions is a goal that has been long sought after. Previous investigations have shown that adsorption and transition-state energies of intermediates in this process on transition metals (TMs) scale with each other. This prevents the independent optimization of these energies that would result in the ideal catalyst: one that activates reactants well, but binds intermediates relatively weakly. Here we demonstrate that these scaling relations can be broken by intervening in the TM-mediated catalysis with a second catalytic site, LiH. The negatively charged hydrogen atoms of LiH act as strong reducing agents, which remove activated nitrogen atoms from the TM or its nitride (TMN), and as an immediate source of hydrogen, which binds nitrogen atoms to form LiNH2. LiNH2 further splits H2 heterolytically to give off NH3 and regenerate LiH. This synergy between TM (or TMN) and LiH creates a favourable pathway that allows both early and late 3d TM–LiH composites to exhibit unprecedented lower-temperature catalytic activities. The existence of linear scaling relations between the adsorption energies of reaction intermediates on transition-metal surfaces prevents their independent optimization and limits catalytic activity. It has now been shown that using a catalytic LiH site alongside a transition-metal catalyst can break these intrinsic scaling relations, leading to unprecedented lower-temperature ammonia-synthesis activity.

Salinomycin kills cancer stem cells by sequestering iron in lysosomes

Abstract: Cancer stem cells (CSCs) represent a subset of cells within tumours that exhibit self-renewal properties and the capacity to seed tumours. CSCs are typically refractory to conventional treatments and have been associated to metastasis and relapse. Salinomycin operates as a selective agent against CSCs through mechanisms that remain elusive. Here, we provide evidence that a synthetic derivative of salinomycin, which we named ironomycin (AM5), exhibits a more potent and selective activity against breast CSCs in vitro and in vivo, by accumulating and sequestering iron in lysosomes. In response to the ensuing cytoplasmic depletion of iron, cells triggered the degradation of ferritin in lysosomes, leading to further iron loading in this organelle. Iron-mediated production of reactive oxygen species promoted lysosomal membrane permeabilization, activating a cell death pathway consistent with ferroptosis. These findings reveal the prevalence of iron homeostasis in breast CSCs, pointing towards iron and iron-mediated processes as potential targets against these cells.

Rational design of reversible fluorescent probes for live-cell imaging and quantification of fast glutathione dynamics

Abstract: Reversible fluorescent probes for intracellular glutathione (GSH) imaging have now been designed and synthesized based on Si-rhodamine fluorophores. These probes are shown to be capable of quantifying the GSH concentration in various living cell types and also for monitoring real-time live-cell imaging of GSH dynamics with a temporal resolution of seconds.

Control over differentiation of a metastable supramolecular assembly in one and two dimensions.

Abstract: Molecular self-assembly under kinetic control is expected to yield nanostructures that are inaccessible through the spontaneous thermodynamic process. Moreover, time-dependent evolution, which is reminiscent of biomolecular systems, may occur under such out-of-equilibrium conditions, allowing the synthesis of supramolecular assemblies with enhanced complexities. Here we report on the capacity of a metastable porphyrin supramolecular assembly to differentiate into nanofibre and nanosheet structures. Mechanistic studies of the relationship between the molecular design and pathway complexity in the self-assembly unveiled the energy landscape that governs the unique kinetic behaviour. Based on this understanding, we could control the differentiation phenomena and achieve both one- and two-dimensional living supramolecular polymerization using an identical monomer. Furthermore, we found that the obtained nanostructures are electronically distinct, which illustrates the pathway-dependent material properties.

Complete protein–protein association kinetics in atomic detail revealed by molecular dynamics simulations and Markov modelling

Abstract: Protein-protein association is fundamental to many life processes. However, a microscopic model describing the structures and kinetics during association and dissociation is lacking on account of the long lifetimes of associated states, which have prevented efficient sampling by direct molecular dynamics (MD) simulations. Here we demonstrate protein-protein association and dissociation in atomistic resolution for the ribonuclease barnase and its inhibitor barstar by combining adaptive high-throughput MD simulations and hidden Markov modelling. The model reveals experimentally consistent intermediate structures, energetics and kinetics on timescales from microseconds to hours. A variety of flexibly attached intermediates and misbound states funnel down to a transition state and a native basin consisting of the loosely bound near-native state and the tightly bound crystallographic state. These results offer a deeper level of insight into macromolecular recognition and our approach opens the door for understanding and manipulating a wide range of macromolecular association processes.

Engineering live cell surfaces with functional polymers via cytocompatible controlled radical polymerization

Abstract: A cytocompatible controlled radical polymerization method has now been developed that initiates polymer synthesis directly on the surface of living cells. This method achieves significantly enhanced polymer grafting and enables active manipulation of cellular phenotypes.

Interplay between defects, disorder and flexibility in metal-organic frameworks

Abstract: Metal-organic frameworks are a novel family of chemically diverse materials, which are of interest across engineering, physics, chemistry, biology and medicine-based disciplines. Since the development of the field in its current form more than two decades ago, priority has been placed on the synthesis of new structures. However, more recently, a clear trend has emerged in shifting the emphasis from material design to exploring the chemical and physical properties of structures already known. In particular, although such nanoporous materials were traditionally seen as rigid crystalline structures, there is growing evidence that large-scale flexibility, the presence of defects and long-range disorder are not the exception in metal-organic frameworks, but the rule. Here we offer some perspective into how these concepts are perhaps inescapably intertwined, highlight recent advances in our understanding and discuss how a consideration of the interfaces between them may lead to enhancements of the materials' functionalities.

A two-dimensional conjugated aromatic polymer via C–C coupling reaction

Abstract: The synthesis of well-defined planar polymers presents a significant challenge for chemists seeking to investigate their potential for use in emerging technologies. Now, a two-dimensional conjugated aromatic polymer has been synthesized via endogenous solid-state polymerization of pre-arranged monomers, and its performance as an organic anode in an ambient temperature sodium cell tested.

Multistep nucleation of nanocrystals in aqueous solution

Abstract: The nucleation and growth of solids from solutions impacts many natural processes and is fundamental to applications in materials engineering and medicine. For a crystalline solid, the nucleus is a nanoscale cluster of ordered atoms that forms through mechanisms still poorly understood. In particular, it is unclear whether a nucleus forms spontaneously from solution via a single- or multiple-step process. Here, using in situ electron microscopy, we show how gold and silver nanocrystals nucleate from supersaturated aqueous solutions in three distinct steps: spinodal decomposition into solute-rich and solute-poor liquid phases, nucleation of amorphous nanoclusters within the metal-rich liquid phase, followed by crystallization of these amorphous clusters. Our ab initio calculations on gold nucleation suggest that these steps might be associated with strong gold-gold atom coupling and water-mediated metastable gold complexes. The understanding of intermediate steps in nuclei formation has important implications for the formation and growth of both crystalline and amorphous materials.

Enantioselective, intermolecular benzylic C-H amination catalysed by an engineered iron-haem enzyme.

Abstract: C–H bonds are ubiquitous structural units of organic molecules Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C–H functionalization promises to transform the way synthetic chemistry is performed The intermolecular amination of C–H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist Here we report the directed evolution of an iron-containing enzymatic catalyst—based on a cytochrome P450 monooxygenase—for the highly enantioselective intermolecular amination of benzylic C–H bonds The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines Iron complexes are generally poor catalysts for C–H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor

Global profiling of lysine reactivity and ligandability in the human proteome

Abstract: Nucleophilic amino acids make important contributions to protein function, including performing key roles in catalysis and serving as sites for post-translational modification. Electrophilic groups that target amino-acid nucleophiles have been used to create covalent ligands and drugs, but have, so far, been mainly limited to cysteine and serine. Here, we report a chemical proteomic platform for the global and quantitative analysis of lysine residues in native biological systems. We have quantified, in total, more than 9,000 lysines in human cell proteomes and have identified several hundred residues with heightened reactivity that are enriched at protein functional sites and can frequently be targeted by electrophilic small molecules. We have also discovered lysine-reactive fragment electrophiles that inhibit enzymes by active site and allosteric mechanisms, as well as disrupt protein-protein interactions in transcriptional regulatory complexes, emphasizing the broad potential and diverse functional consequences of liganding lysine residues throughout the human proteome.

Suppression of Kasha's rule as a mechanism for fluorescent molecular rotors and aggregation-induced emission

Abstract: Although there are some proposed explanations for aggregation-induced emission, a phenomenon with applications that range from biosensors to organic light-emitting diodes, current understanding of the quantum-mechanical origin of this photophysical behaviour is limited. To address this issue, we assessed the emission properties of a series of BF2-hydrazone-based dyes as a function of solvent viscosity. These molecules turned out to be highly efficient fluorescent molecular rotors. This property, in addition to them being aggregation-induced emission luminogens, enabled us to probe deeper into their emission mechanism. Time-dependent density functional theory calculations and experimental results showed that the emission is not from the S1 state, as predicted from Kasha's rule, but from a higher energy (>S1) state. Furthermore, we found that suppression of internal conversion to the dark S1 state by restricting the rotor rotation enhances fluorescence, which leads to the proposal that suppression of Kasha's rule is the photophysical mechanism responsible for emission in both viscous solution and the solid state.

Solvent-switchable continuous-breathing behaviour in a diamondoid metal-organic framework and its influence on CO2 versus CH4 selectivity.

Abstract: Understanding the behaviour of flexible metal-organic frameworks (MOFs)-porous crystalline materials that undergo a structural change upon exposure to an external stimulus-underpins their design as responsive materials for specific applications, such as gas separation, molecular sensing, catalysis and drug delivery. Reversible transformations of a MOF between open- and closed-pore forms-a behaviour known as 'breathing'-typically occur through well-defined crystallographic transitions. By contrast, continuous breathing is rare, and detailed characterization has remained very limited. Here we report a continuous-breathing mechanism that was studied by single-crystal diffraction in a MOF with a diamondoid network, (Me2NH2)[In(ABDC)2] (ABDC, 2-aminobenzene-1,4-dicarboxylate). Desolvation of the MOF in two different solvents leads to two polymorphic activated forms with very different pore openings, markedly different gas-adsorption capacities and different CO2 versus CH4 selectivities. Partial desolvation introduces a gating pressure associated with CO2 adsorption, which shows that the framework can also undergo a combination of stepped and continuous breathing.

Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow

Abstract: Although carbon dioxide (CO2) is highly abundant, its low reactivity has limited its use in chemical synthesis. In particular, methods for carbon-carbon bond formation generally rely on two-electron mechanisms for CO2 activation and require highly activated reaction partners. Alternatively, radical pathways accessed via photoredox catalysis could provide new reactivity under milder conditions. Here we demonstrate the direct coupling of CO2 and amines via the single-electron reduction of CO2 for the photoredox-catalysed continuous flow synthesis of α-amino acids. By leveraging the advantages of utilizing gases and photochemistry in flow, a commercially available organic photoredox catalyst effects the selective α-carboxylation of amines that bear various functional groups and heterocycles. The preliminary mechanistic studies support CO2 activation and carbon-carbon bond formation via single-electron pathways, and we expect that this strategy will inspire new perspectives on using this feedstock chemical in organic synthesis.

A stable compound of helium and sodium at high pressure

Abstract: Helium is generally understood to be chemically inert and this is due to its extremely stable closed-shell electronic configuration, zero electron affinity and an unsurpassed ionization potential. It is not known to form thermodynamically stable compounds, except a few inclusion compounds. Here, using the ab initio evolutionary algorithm USPEX and subsequent high-pressure synthesis in a diamond anvil cell, we report the discovery of a thermodynamically stable compound of helium and sodium, Na2He, which has a fluorite-type structure and is stable at pressures >113 GPa. We show that the presence of He atoms causes strong electron localization and makes this material insulating. This phase is an electride, with electron pairs localized in interstices, forming eight-centre two-electron bonds within empty Na8 cubes. We also predict the existence of Na2HeO with a similar structure at pressures above 15 GPa.

Engineering genetic circuit interactions within and between synthetic minimal cells

Abstract: Genetic circuits and reaction cascades are of great importance for synthetic biology, biochemistry and bioengineering. An open question is how to maximize the modularity of their design to enable the integration of different reaction networks and to optimize their scalability and flexibility. One option is encapsulation within liposomes, which enables chemical reactions to proceed in well-isolated environments. Here we adapt liposome encapsulation to enable the modular, controlled compartmentalization of genetic circuits and cascades. We demonstrate that it is possible to engineer genetic circuit-containing synthetic minimal cells (synells) to contain multiple-part genetic cascades, and that these cascades can be controlled by external signals as well as inter-liposomal communication without crosstalk. We also show that liposomes that contain different cascades can be fused in a controlled way so that the products of incompatible reactions can be brought together. Synells thus enable a more modular creation of synthetic biology cascades, an essential step towards their ultimate programmability. Genetic circuits are important for synthetic biology, biochemistry and bioengineering. Now, the encapsulation of genetic circuits into liposomes has been shown to enable a more modular design, the selective isolation of reactions from the environment and from each other, and the hierarchical assembly of reaction products.

Sequence-controlled methacrylic multiblock copolymers via sulfur-free RAFT emulsion polymerization.

Abstract: Translating the precise monomer sequence control achieved in nature over macromolecular structure (for example, DNA) to whole synthetic systems has been limited due to the lack of efficient synthetic methodologies. So far, chemists have only been able to synthesize monomer sequence-controlled macromolecules by means of complex, time-consuming and iterative chemical strategies such as solid-state Merrifield-type approaches or molecularly dissolved solution-phase systems. Here, we report a rapid and quantitative synthesis of sequence-controlled multiblock polymers in discrete stable nanoscale compartments via an emulsion polymerization approach in which a vinyl-terminated macromolecule is used as an efficient chain-transfer agent. This approach is environmentally friendly, fully translatable to industry and thus represents a significant advance in the development of complex macromolecule synthesis, where a high level of molecular precision or monomer sequence control confers potential for molecular targeting, recognition and biocatalysis, as well as molecular information storage.

A reductive aminase from Aspergillus oryzae

Abstract: Reductive amination is one of the most important methods for the synthesis of chiral amines Here we report the discovery of an NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm, Uniprot code Q2TW47) that can catalyse the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines with up to >98% conversion and with up to >98% enantiomeric excess In cases where both carbonyl and amine show high reactivity, it is possible to employ a 1:1 ratio of the substrates, forming amine products with up to 94% conversion Steady-state kinetic studies establish that the enzyme is capable of catalysing imine formation as well as reduction Crystal structures of AspRedAm in complex with NADP(H) and also with both NADP(H) and the pharmaceutical ingredient (R)-rasagiline are reported We also demonstrate preparative scale reductive aminations with wild-type and Q240A variant biocatalysts displaying total turnover numbers of up to 32,000 and space time yields up to 373 g l−1 d−1 An enzyme (AspRedAm) capable of coupling carbonyls with a variety of amines in a reductive amination has now been discovered Kinetic studies revealed that the enzyme catalysed both the imine formation step, as well as the reduction step Structure and mutagenesis studies have highlighted essential catalytic residues and preparative scale examples have demonstrated total turnover numbers of up to 32,000

Emergence of a catalytic tetrad during evolution of a highly active artificial aldolase

Abstract: Designing catalysts that achieve the rates and selectivities of natural enzymes is a long-standing goal in protein chemistry. Here, we show that an ultrahigh-throughput droplet-based microfluidic screening platform can be used to improve a previously optimized artificial aldolase by an additional factor of 30 to give a >109 rate enhancement that rivals the efficiency of class I aldolases. The resulting enzyme catalyses a reversible aldol reaction with high stereoselectivity and tolerates a broad range of substrates. Biochemical and structural studies show that catalysis depends on a Lys-Tyr-Asn-Tyr tetrad that emerged adjacent to a computationally designed hydrophobic pocket during directed evolution. This constellation of residues is poised to activate the substrate by Schiff base formation, promote mechanistically important proton transfers and stabilize multiple transition states along a complex reaction coordinate. The emergence of such a sophisticated catalytic centre shows that there is nothing magical about the catalytic activities or mechanisms of naturally occurring enzymes, or the evolutionary process that gave rise to them.

Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation

Abstract: Nucleic acids have attracted widespread attention due to the simplicity with which they can be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of DNA/RNA nanotechnology offer numerous opportunities for in-cell and in-vivo applications, and the technology holds great promise to advance the growing field of synthetic biology. Many elegant examples have revealed the potential in integrating nucleic acid nanostructures in cells and in vivo where they can perform important physiological functions. In this Review, we summarize the current abilities of DNA/RNA nanotechnology to realize applications in live cells and then discuss the key problems that must be solved to fully exploit the useful properties of nanostructures. Finally, we provide viewpoints on how to integrate the tools provided by DNA/RNA nanotechnology and related new technologies to construct nucleic acid nanostructure-based molecular circuitry for synthetic biology.

Enantioselective amine α-functionalization via palladium-catalysed C-H arylation of thioamides.

Abstract: Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, the development of methods to functionalize the α-methylene C-H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (-)-sparteine followed by Pd(0) catalysed cross-coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalysed enantioselective α-C-H coupling of a wide range of amines, which include ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C-H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments.

Activation and discovery of earth-abundant metal catalysts using sodium tert -butoxide

Abstract: First-row, earth-abundant metals offer an inexpensive and sustainable alternative to precious-metal catalysts. As such, iron and cobalt catalysts have garnered interest as replacements for alkene and alkyne hydrofunctionalization reactions. However, these have required the use of air- and moisture-sensitive catalysts and reagents, limiting both adoption by the non-expert as well as applicability, particularly in industrial settings. Here, we report a simple method for the use of earth-abundant metal catalysts by general activation with sodium tert-butoxide. Using only robust air- and moisture-stable reagents and pre-catalysts, both known and, significantly, novel catalytic activities have been successfully achieved, covering hydrosilylation, hydroboration, hydrovinylation, hydrogenation and [2π+2π] alkene cycloaddition. This activation method allows for the easy use of earth-abundant metals, including iron, cobalt, nickel and manganese, and represents a generic platform for the discovery and application of non-precious metal catalysis.

Self-propelled supramolecular nanomotors with temperature-responsive speed regulation

Abstract: Self-propelled catalytic micro- and nanomotors have been the subject of intense study over the past few years, but it remains a continuing challenge to build in an effective speed-regulation mechanism. Movement of these motors is generally fully dependent on the concentration of accessible fuel, with propulsive movement only ceasing when the fuel consumption is complete. Here we report a demonstration of control over the movement of self-assembled stomatocyte nanomotors via a molecularly built, stimulus-responsive regulatory mechanism. A temperature-sensitive polymer brush is chemically grown onto the nanomotor, whereby the opening of the stomatocytes is enlarged or narrowed on temperature change, which thus controls the access of hydrogen peroxide fuel and, in turn, regulates movement. To the best of our knowledge, this represents the first nanosized chemically driven motor for which motion can be reversibly controlled by a thermally responsive valve/brake. We envision that such artificial responsive nanosystems could have potential applications in controllable cargo transportation.