Iron‐Catalysed Radical Polymerisation by Living Bacteria

The ability to harness cellular redox processes for abiotic synthesis might allow the preparation of engineered hybrid living systems. Towards this goal we describe a new bacteria‐mediated iron‐catalysed reversible deactivation radical polymerisation (RDRP), with a range of metal‐chelating agents and monomers that can be used under ambient conditions with a bacterial redox initiation step to generate polymers. Cupriavidus metallidurans, Escherichia coli, and Clostridium sporogenes species were chosen for their redox enzyme systems and evaluated for their ability to induce polymer formation. Parameters including cell and catalyst concentration, initiator species, and monomer type were investigated. Water‐soluble synthetic polymers were produced in the presence of the bacteria with full preservation of cell viability. This method provides a means by which bacterial redox systems can be exploited to generate “unnatural” polymers in the presence of “host” cells, thus setting up the possibility of making natural–synthetic hybrid structures and conjugates.     

Towards Self‐Assembled Hybrid Artificial Cells: Novel Bottom‐Up Approaches to Functional Synthetic Membranes

There has been increasing interest in utilizing bottom‐up approaches to develop synthetic cells. A popular methodology is the integration of functionalized synthetic membranes with biological systems, producing “hybrid” artificial cells. This Concept article covers recent advances and the current state‐of‐the‐art of such hybrid systems. Specifically, we describe minimal supramolecular constructs that faithfully mimic the structure and/or function of living cells, often by controlling the assembly of highly ordered membrane architectures with defined functionality. These studies give us a deeper understanding of the nature of living systems, bring new insights into the origin of cellular life, and provide novel synthetic chassis for advancing synthetic biology.     

Autonomous Growth of a Spatially Localized Supramolecular Hydrogel with Autocatalytic Ability

Autocatalysis and self‐assembly are key processes in developmental biology and are involved in the emergence of life. In the last decade both of these features were extensively investigated by chemists with the final goal to design synthetic living systems. Herein, we describe the autonomous growth of a self‐assembled soft material, that is, a supramolecular hydrogel, able to sustain its own formation through an autocatalytic mechanism that is not based on any template effect and emerges from a peptide (hydrogelator) self‐assembly. A domino sequence of events starts from an enzymatically triggered peptide generation followed by self‐assembly into catalytic nanofibers that induce and amplify their production over time, resulting in a 3D hydrogel network. A cascade is initiated by traces (10^?18 m ) of a trigger enzyme, which can be localized allowing for a spatial resolution of this autocatalytic buildup of hydrogel growth, an essential condition on the route towards further cell‐mimic designs.     

Controlling supramolecular polymerization through multicomponent self‐assembly

The self‐assembly into supramolecular polymers is a process driven by reversible non‐covalent interactions between monomers, and gives access to materials applications incorporating mechanical, biological, optical or electronic functionalities. Compared to the achievements in precision polymer synthesis via living and controlled covalent polymerization processes, supramolecular chemists have only just learned how to developed strategies that allow similar control over polymer length, (co)monomer sequence and morphology (random, alternating or blocked ordering). This highlight article discusses the unique opportunities that arise when coassembling multicomponent supramolecular polymers, and focusses on four strategies in order to control the polymer architecture, size, stability and its stimuli‐responsive properties: (1) end‐capping of supramolecular polymers, (2) biomimetic templated polymerization, (3) controlled selectivity and reactivity in supramolecular copolymerization, and (4) living supramolecular polymerization. In contrast to the traditional focus on equilibrium systems, our emphasis is also on the manipulation of self‐assembly kinetics of synthetic supramolecular systems. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 34–78     

Copper‐mediated controlled radical polymerization in continuous flow processes: Synergy between polymer reaction engineering and innovative chemistry

Copper(0)‐mediated controlled radical polymerization (CRP), or single‐electron transfer‐living radical polymerization (SET‐LRP) is a robust and dynamic technique that has attracted considerable academic and industrial interest as a synthetic tool for novel value‐added materials. Although SET‐LRP possesses many advantages over other forms of CRP, this novel chemistry still requires concurrent engineering solutions for successful commercial application. In this highlight, the evolution of atom‐transfer radical polymerization chemistry and development in continuous processes is presented, leading to recent research on the use of SET‐LRP in continuous flow tubular reactors. The proofs of concept are reviewed, and remaining challenges and unexplored potential on the use of continuous flow processes with SET‐LRP as a powerful platform for the synthesis of novel polymeric materials are discussed. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3081–3096     

Synthetic Biology—The Synthesis of Biology

Synthetic biology concerns the engineering of man-made living biomachines from standardized components that can perform predefined functions in a (self-)controlled manner. Different research strategies and interdisciplinary efforts are pursued to implement engineering principles to biology. The “top-down” strategy exploits nature's incredible diversity of existing, natural parts to construct synthetic compositions of genetic, metabolic, or signaling networks with predictable and controllable properties. This mainly application-driven approach results in living factories that produce drugs, biofuels, biomaterials, and fine chemicals, and results in living pills that are based on engineered cells with the capacity to autonomously detect and treat disease states in vivo. In contrast, the “bottom-up” strategy seeks to be independent of existing living systems by designing biological systems from scratch and synthesizing artificial biological entities not found in nature. This more knowledge-driven approach investigates the reconstruction of minimal biological systems that are capable of performing basic biological phenomena, such as self-organization, self-replication, and self-sustainability. Moreover, the syntheses of artificial biological units, such as synthetic nucleotides or amino acids, and their implementation into polymers inside living cells currently set the boundaries between natural and artificial biological systems. In particular, the in vitro design, synthesis, and transfer of complete genomes into host cells point to the future of synthetic biology: the creation of designer cells with tailored desirable properties for biomedicine and biotechnology.     

Temperature‐Sensitive Artificial Channels through Pillar[5]arene‐based Host–Guest Interactions

In living systems, temperature‐sensitive ion channels play a vital role in numerous cellular processes and can be controlled by biological ion channels in response to specific temperature stimuli. Facile pillar[5]arene‐based host–guest interactions are introduced into a nanochannel pattern for constructing a temperature‐sensitive artificial channel. Ion transport was switched from cations to anions by controlling the extent of the host bound to the guest with temperature stimuli. This efect is mainly due to the changing of the inner surface charge and wettability of the nanochannel during the process. This study paves a new way for better understanding the mechanism of temperature‐sensitive properties and shows great promise for biomedical research.     

Photoswitchable Phase Separation and Oligonucleotide Trafficking in DNA Coacervate Microdroplets

Coacervate microdroplets produced by liquid–liquid phase separation have been used as synthetic protocells that mimic the dynamical organization of membrane‐free organelles in living systems. Achieving spatiotemporal control over droplet condensation and disassembly remains challenging. Herein, we describe the formation and photoswitchable behavior of light‐responsive coacervate droplets prepared from mixtures of double‐stranded DNA and an azobenzene cation. The droplets disassemble and reassemble under UV and blue light, respectively, due to azobenzene trans/cis photoisomerisation. Sequestration and release of captured oligonucleotides follow the dynamics of phase separation such that light‐activated transfer, mixing, hybridization, and trafficking of the oligonucleotides can be controlled in binary populations of the droplets. Our results open perspectives for the spatiotemporal control of DNA coacervates and provide a step towards the dynamic regulation of synthetic protocells.     

Thiomaleimide Functionalization for Selective Biological Fluorescence Detection of Peroxynitrite as Tested in HeLa and RAW 264.7 Cells

The role of fluorescent molecules in diagnosis, treatment as well as in biomedical research has great current medicinal significance and is the focus of concentrated effort across the scientific research spectrum. Related research continues to reveal new practical sensing systems that bear enhanced features for interfacing of substituted molecules with biological systems. As part of an effort to better understand chalcogenide systems, a new dithiomaleimide BODIPY ( BDP‐NGM ) probe has been designed, synthesized and characterized. The fluorescence of BDP‐NGM was quenched by the incorporation of [3,4‐bis (phenylthio)] on the maleimide‐4‐phenyl moiety which is, in turn, placed at the meso ‐position of the BODIPY system. The probe shows a turn‐on fluorescence response upon reaction with ONOO⁻; mass spectral evidence reveals peaks in agreement with products involving oxidation of the sulfur groups to sulfone groups. An about 18.0‐fold emission intensity enhancement was found. By comparison, the emission signal from another ROS/RNS, superoxide, gave a modest turn on signal (≈5.0‐fold). The reaction is complete within 10 min, judging from the monitoring of the turn‐on fluorescence process; the detection limit was found to be 0.4 μm . BDP‐NGM can be used for the detection of ONOO⁻ under both acidic and basic conditions. Live cell imaging showed that the current probe can be used for the selective detection of ONOO⁻ in living systems.     

Nanoarchitectonics from Atom to Life

Functional materials with rational organization cannot be directly created only by nanotechnology‐related top‐down approaches. For this purpose, a novel research paradigm next to nanotechnology has to be established to create functional materials on the basis of deep nanotechnology knowledge. This task can be assigned to an emerging concept, nanoarchitectonics. In the nanoarchitectonics approaches, functional materials are architected through combination of atom/molecular manipulation, organic chemical synthesis, self‐assembly and related spontaneous processes, field‐applied assembly, micro/nano fabrications, and bio‐related processes. In this short review article, nanoarchitectonics‐related approaches on materials fabrications and functions are exemplified from atom‐scale to living creature level. Based on their features, unsolved problems for future developments of the nanoarchitectonics concept are finally discussed.     

Evaporation‐induced Self‐assembly Process Controlled for Obtaining Highly Ordered Mesoporous Materials with Demanded Morphologies

A large number of periodic mesoporous materials have been reported using amphiphilic organic molecules with increasing development of synthetic methods for mesostructural, morphological, and compositional designs. The evaporation‐induced self‐assembly (ESIA) process to fabricate ordered mesoporous films is one of the most essential synthetic methods, which has extensively been applied for obtaining a wide variety of samples (e.g., films and monoliths, including powders). It contains complicated physical variations and chemical reactions, but has been simply explained by several research groups. However, a current, exact understanding of such complicated systems should be given with respect to all the variations and reactions. In this article, I have mainly surveyed the exact EISA process by considering the difference between simple and controlled EISA processes on the basis of my own experiments. I believe that the insights are consequently helpful for obtaining highly ordered mesoporous materials with demanded morphologies.     

Protein Organic Chemistry and Applications for Labeling and Engineering in Live‐Cell Systems

The modification of proteins with synthetic probes is a powerful means of elucidating and engineering the functions of proteins both in vitro and in live cells or in vivo. Herein we review recent progress in chemistry‐based protein modification methods and their application in protein engineering, with particular emphasis on the following four strategies: 1) the bioconjugation reactions of amino acids on the surfaces of natural proteins, mainly applied in test‐tube settings; 2) the bioorthogonal reactions of proteins with non‐natural functional groups; 3) the coupling of recognition and reactive sites using an enzyme or short peptide tag–probe pair for labeling natural amino acids; and 4) ligand‐directed labeling chemistries for the selective labeling of endogenous proteins in living systems. Overall, these techniques represent a useful set of tools for application in chemical biology, with the methods 2–4 in particular being applicable to crude (living) habitats. Although still in its infancy, the use of organic chemistry for the manipulation of endogenous proteins, with subsequent applications in living systems, represents a worthy challenge for many chemists.     

Biomimetic Assembly Lines Producing Natural Product Analogs: Strategies from a Versatile Manifold to Skeletally Diverse Scaffolds

Biosynthetic assembly lines have evolved in nature, adopting divergent processes to produce a vast number of secondary metabolites. Inspired by these biogenetic processes, this account introduces recent investigations by my research group to formulate a synthetic strategy for establishing a biomimetic assembly line. With the aim not only to construct natural product‐relevant scaffolds within 5–7 steps, but also to systematically diversify skeletal and stereochemical properties and functional groups, divergent synthetic processes exploiting a versatile manifold have been developed. This approach allows for cost‐effective production of skeletally diverse and biologically active natural product analogs inaccessible by other means. Discovery of several lead candidates for a neglected tropical disease is a proof‐of‐concept of this synthetic approach.     

Mussel‐Directed Synthesis of Nitrogen‐Doped Anatase TiO2

Structure‐forming processes leading to biominerals are well worth learning in pursuit of new synthetic techniques. Strategies that attempt to mimic nature in vitro cannot replace an entire complex natural organism, requiring ingenuity beyond chemists′ hands. A “bioprocess‐inspired synthesis” is demonstrated for fabrication of N‐doped TiO₂ materials at ambient temperature by direct implantation of precursor into living mussels. The amorphous precursor transforms into N‐doped anatase TiO₂ with a hierarchical nanostructure. Synthetic TiO₂ exhibits high phase stability and enhanced visible‐light photocatalytic activity as a result of modifications to its band gap during in vivo mineralization. Intracellular proteins were found to be involved in TiO₂ mineralization. Our findings may inspire material production by new synthetic techniques, especially under environmentally benign conditions.     

Bis‐thiourea Derivatives and Their Utility in Synthesis of Mono‐heterocyclic,Bis‐heterocyclic,and Fused Heterocyclic Systems

Bis‐thiourea derivatives have distinguished synthetic potentialities. They are interesting substrates for construction of various classes of heterocycles, such as thiazoles, thiadiazoles, imidazoles, bis‐thiazoles, bis‐thiadiazoles, and fused heterocyclic systems. The current review is concerned on disclosing the synthetic and research applications of bis‐thioureas that were reported in the literature during the last decade.     

Effector‐Triggered Self‐Replication in Coupled Subsystems

In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self‐replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector‐mediated control over self‐replication. The subsystem based on the first building block shows only self‐replication, whereas that based on the second one is solely responsive toward a specific external effector molecule. Mixing the subsystems arrests replication until the effector molecule is added, resulting in the formation of a host–effector complex and the liberation of the building block that subsequently engages in self‐replication. The onset, rate and extent of self‐replication is controlled by the amount of effector present.     

Precise Design of Phosphorescent Molecular Butterflies with Tunable Photoinduced Structural Change and Dual Emission

Photoinduced structural change (PSC) is a fundamental excited‐state dynamic process in chemical and biological systems. However, precise control of PSC processes is very challenging, owing to the lack of guidelines for designing excited‐state potential energy surfaces (PESs). A series of rationally designed butterfly‐like phosphorescent binuclear platinum complexes that undergo controlled PSC by Pt–Pt distance shortening and exhibit tunable dual (greenish‐blue and red) emission are herein reported. Based on the Bell–Evans–Polanyi principle, it is demonstrated how the energy barrier of the PSC, which can be described as a chemical‐reaction‐like process between the two energy minima on the first triplet excited‐state PES, can be controlled by synthetic means. These results reveal a simple method to engineer the dual emission of molecular systems by manipulating PES to control PSC.     

Enzymatic functionalization of carbon-hydrogen bonds

The development of new catalytic methods to functionalize carbon-hydrogen (C-H) bonds continues to progress at a rapid pace due to the significant economic and environmental benefits of these transformations over traditional synthetic methods. In nature, enzymes catalyze regio- and stereoselective C-H bond functionalization using transformations ranging from hydroxylation to hydroalkylation under ambient reaction conditions. The efficiency of these enzymes relative to analogous chemical processes has led to their increased use as biocatalysts in preparative and industrial applications. Furthermore, unlike small molecule catalysts, enzymes can be systematically optimized via directed evolution for a particular application and can be expressed in vivo to augment the biosynthetic capability of living organisms. While a variety of technical challenges must still be overcome for practical application of many enzymes for C-H bond functionalization, continued research on natural enzymes and on novel artificial metalloenzymes will lead to improved synthetic processes for efficient synthesis of complex molecules. In this critical review, we discuss the most prevalent mechanistic strategies used by enzymes to functionalize non-acidic C-H bonds, the application and evolution of these enzymes for chemical synthesis, and a number of potential biosynthetic capabilities uniquely enabled by these powerful catalysts (110 references).     

Luciferase‐Induced Photouncaging: Bioluminolysis

Bioluminescence resonance energy transfer (BRET) has been widely used for studying dynamic processes in biological systems such as protein–protein interactions and other signaling events. Aside from acting as a reporter, BRET can also turn on functions in living systems. Herein, we report the application of BRET to performing a biorthogonal reaction in living cells; namely, releasing functional molecules through energy transfer to a coumarin molecule, a process termed bioluminolysis. An efficient BRET from Nanoluc‐Halotag chimera protein (H‐Luc) to a coumarin substrate yields the excited state of coumarin, which in turn triggers hydrolysis to uncage a target molecule. Compared to the conventional methods, this novel uncaging system requires no external light source and shows fast kinetics (t_1/2<2 min). We applied this BRET uncaging system to release a potent kinase inhibitor, ibrutinib, in living cells, highlighting its broad utility in controlling the supply of bioactive small molecules in vivo.     

Time‐dependent density functional theory study on direction‐dependent electron and hole transfer processes in molecular systems

We report on real‐time time‐dependent density functional theory calculations on direction‐dependent electron and hole transfer processes in molecular systems. As a model system, we focus on α‐sulfur. It is shown that time scale of the electron transfer process from a negatively charged S₈ molecule to a neighboring neutral monomer is comparable to that of a strong infrared‐active molecular vibrations of the dimer with one negatively charged monomer. This results in a strong coupling between the electrons and the nuclei motion which eventually leads to S₈ ring opening before the electron transfer process is completed. The open‐ring structure is found to be stable. The similar infrared‐active peak in the case of hole transfer, however, is shown to be very weak and hence no significant scattering by the nuclei is possible. The presented approach to study the charge transfer processes in sulfur has direct applications in the increasingly growing research field of charge transport in molecular systems. © 2017 Wiley Periodicals, Inc.