Nucleophile Promiscuity of Natural and Engineered Aldolases

The asymmetric aldol addition reaction mediated by aldolases is recognized as a green and sustainable method for carbon–carbon bond formation. Research in this area has unveiled their unprecedented synthetic potential toward diverse, new chemical structures; novel product families; and even as a technology for industrial manufacturing processes. Despite these advances, aldolases have long been regarded as strictly selective catalysts, particularly for nucleophilic substrates, which limits their broad applicability. In recent years, advances in screening technologies and metagenomics have uncovered novel C?C biocatalysts from superfamilies of widely known lyases. Moreover, protein engineering has revealed the extraordinary malleability of different carboligases to offer a toolbox of biocatalysts active towards a large structural diversity of nucleophile substrates. Herein, the nucleophile ambiguity of native and engineered aldolases is discussed with recent examples to prove this novel concept.     

Synthesis of well-defined star-branched polymers by stepwise iterative methodology using living anionic polymerization

This article reviews the synthesis of regular and asymmetric star-branched polymers with well-defined structures by methodologies using living anionic polymerization, especially focusing on the synthetic approaches accessible for precisely controlled architectures of star-branched polymers concerning molecular weight, molecular weight distribution, arm number, and composition. The reason for selecting living anionic polymerization from many living/controlled polymerization systems so far developed is that this living polymerization system is still the best to meet the strict requirements for the precise structures of star-branched polymers. Furthermore, we herein mainly introduce a novel and quite versatile stepwise iterative methodology recently developed by our group for the successive synthesis of many-armed and multi-compositional asymmetric star-branched polymers. The methodology basically involves only two sets of the reaction conditions for the entire iterative synthetic sequence. The reaction sequence can be, in principle, limitlessly iterated to introduce a definite number of the same or different polymer segments at each stage of the iteration. As a result, a wide variety of many-armed and multi-compositional asymmetric star-branched polymers can be synthesized.     

Synthesis of a novel organosoluble,biocompatible, and antibacterial chitosan derivative for biomedical applications

Electrospun materials have a number of applications in the tissue engineering field. However, the limited solubility of chitosan (CS), especially in organic solvents, makes its electrospinning with other synthetic organosoluble polymers impossible. In this article, we report the synthesis of a novel organosoluble derivative of CS through the application of a simple synthetic methodology. CS was reacted with 1,3‐diethyl‐2‐thiobarbituric acid (DETBA) with triethylorthoformate in the presence of methanol and acetic acid (4:1). The functional groups in the synthesized materials were confirmed by Fourier transform infrared and solid‐state NMR spectroscopy, whereas X‐ray diffraction revealed the level of crystallinity. The CS derivative (CS–DETBA) was tested for its cytotoxic effects on human gastric adenocarcinoma AGS cells and was found to be nontoxic. The prepared derivative showed a much enhanced inhibitory effect on the growth of three bacterial strains, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, over that of CS itself. Overall, CS–DETBA showed good solubility in a range of organic solvents, such as dimethyl sulfoxide and N,N‐dimethylformamide, and was blended with polycaprolactone (PCL) to form films and electrospun nanofibers. The morphologies of the synthesized materials were analyzed by field emission scanning electron microscopy, and the fiber diameter was 360 nm under optimum conditions. This study demonstrated that the CS–DETBA–PCL blend could be a potential material for tissue engineering and biomedical applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45905.     

Cell-free synthetic biology in the new era of enzyme engineering

With the gradual rise of enzyme engineering, it has played an essential role in synthetic biology, medicine, and biomanufacturing. However, due to the limitation of the cell membrane, the complexity of cellular metabolism, the difficulty of controlling the reaction environment, and the toxicity of some metabolic products in traditional in vivo enzyme engineering, it is usually problematic to express functional enzymes and produce a high yield of synthesized compounds. Recently, cell-free synthetic biology methods for enzyme engineering have been proposed as alternative strategies. This cell-free method has no limitation of the cell membrane and no need to maintain cell viability, and each biosynthetic pathway is highly flexible. This property makes cell-free approaches suitable for the production of valuable products such as functional enzymes and chemicals that are difficult to synthesize. This article aims to discuss the latest advances in cell-free enzyme engineering, assess the trend of this developing topical filed, and analyze its prospects.     

AZEOTROPE PREDICTION BY MONTE CARLO MOLECULAR SIMULATION

This article presents a methodology for checking the existence of the azeotrope and computing its composition, density, and pressure at a given temperature by integrating chemical engineering insights with molecular simulation principles. Liquid-vapor equilibrium points are computed by molecular simulations using the Gibbs ensemble Monte Carlo (GEMC) method at constant volume. The appearance of the azeotropic point is marked by a shift of the equilibrium constant from one side of the unity to the other. After each GEMC simulation, an identity change move is derived in the grand canonical ensemble to progress towards the azeotrope along the equilibrium curve. The effectiveness of the proposed methodology is successfully tested for several binary Lennard-Jones mixtures reported in the literature.     

Cell-free synthetic biology in the new era of enzyme engineering

With the gradual rise of enzyme engineering, it has played an essential role in synthetic biology, medicine, and biomanufacturing. However, due to the limitation of the cell membrane, the complexity of cellular metabolism, the difficulty of controlling the reaction environment, and the toxicity of some metabolic products in traditional in vivo enzyme engineering, it is usually problematic to express functional enzymes and produce a high yield of synthesized compounds. Recently, cell-free synthetic biology methods for enzyme engineering have been proposed as alternative strategies. This cell-free method has no limitation of the cell membrane and no need to maintain cell viability, and each biosynthetic pathway is highly flexible. This property makes cell-free approaches suitable for the production of valuable products such as functional enzymes and chemicals that are difficult to synthesize. This article aims to discuss the latest advances in cell-free enzyme engineering, assess the trend of this developing topical filed, and analyze its prospects.     

分子化学工程学——一门新兴的学科

分子化学工程学是利用分子科学、分子工程的成就和研究方法、手段来探求化学工程中的规律,逐步形成的一门新兴的工程技术类学科。它利用超高速电子计算机技术,从分子·原子尺度进行材料的分子设计和合成及工艺设计。以更有效地指导工业生产和发展化学工程学。     

Helical tubuland diols: a synthetic and crystal engineering quest

Despite many advances in recent years, crystal engineering remains a risky venture. A successful outcome requires manipulation of the noncovalent bonding and properties such as size, shape, repulsion, attraction, polarity, and chirality. In this Account, we describe the interplay of crystal engineering and synthetic organic chemistry required to develop the family of helical tubuland diol hosts, the members of which exhibit a wide range of tube dimensions and inclusion properties. Certain alicyclic dialcohols crystallize with a hydrogen-bonded network structure, termed the helical tubuland lattice, in space group P3(1)21 (or its enantiomorph P3(2)21). Double helices of diol molecules surround parallel tubes that contain guest molecules, which are included on the basis of size and shape rather than functional group. The crystal structure of (diol)(3).(chloroacetic acid)(1.2) is illustrative. These chiral helical tubulate lattice inclusion compounds are formed when the racemic host diol is allowed to crystallize from solution. Complete enantiomer separation occurs during this process, producing a 1:1 mixture of pure (+)- and pure (-)-crystals (a conglomerate). The challenge of creating this family of compounds required the development of much synthetic chemistry, in particular new pathways to alicyclic ring systems with specific substitution patterns. It was also necessary to understand and control the supramolecular properties of the diol molecules. What makes the original compound tick, and why did it behave in this remarkable manner, when most of its structural neighbors crystallize totally differently? The synthesis of new helical tubuland diols requires not just preparation of a new molecular structure but also a transplant of the original unchanged hydrogen-bonding supramolecular synthon. Synthesis of the specific crystal space group is necessary. This was achieved by defining structural characteristics, termed molecular determinants, which are essential for the helical tubuland structure to occur. If these requirements were met, then the target molecule had a high probability of success. This investigation has close conceptual parallels with the search for pharmacophore properties of bioactive molecules. In both situations, parts of a molecule with little or no chemical reactivity may actually play vital supramolecular roles. The review illustrates how crystal engineering is based on specific supramolecular properties that can be uncovered and then exploited by synthetic chemists.     

Borate as a Phosphate Ester Mimic in Aldolase‐Catalyzed Reactions: Practical Synthesis of L‐Fructose and L‐Iminocyclitols

Dihydroxyacetone phosphate (DHAP)‐dependent aldolases have been widely used for the organic synthesis of unnatural sugars or derivatives. The practicality of using DHAP‐dependent aldolases is limited by their strict substrate specificity and the high cost and instability of DHAP. Here we report that the DHAP‐dependent aldolase L ‐rhamnulose 1‐phosphate aldolase (RhaD) accepts dihydroxyacetone (DHA) as a donor substrate in the presence of borate buffer, presumably by reversible in situ formation of DHA borate ester. The reaction appears to be irreversible, with the products thermodynamically trapped as borate complexes. We have applied this discovery to develop a practical one‐step synthesis of the non‐caloric sweetener L ‐fructose. L ‐Fructose was synthesized from racemic glyceraldehyde and DHA in the presence of RhaD and borate in 92 % yield on a gram scale. We also synthesized a series of L ‐iminocyclitols, which are potential glycosidase inhibitors, in only two steps.     

Methodology of developing optimal nanotechnologies

The knowledge accumulated by chemical engineering makes it possible to create a methodology of the rational development of new science intensive technologies. One of the versions of such a methodology implies the formulation of principles and the revelation of methods for study, which shortens the way from the technological idea formation to its industrial implementation. This version implies passing from an a priori physicochemical model of phenomena which led to a technological idea to an a posteriori model of processes in industrial apparatuses where these phenomena should occur. In doing this, it seems expedient to combine numerical and real experiments with an iterative extension of the range of implementation conditions of phenomena from laboratory to industrial ones. The efficiency of such a methodological approach is evidenced by the experience of the development of the technology of an Ostim medicinal preparation.     

A network theory for the structured modelling of chemical processes

A structuring methodology for dynamic models of chemical engineering processes is presented. The main ideas of the methodology were outlined in a previous publication for the class of well-mixed systems. In this contribution, the methodology is extended to spatially distributed systems and to particulate processes. Furthermore, the structuring principle is used to make a conceptual link between the macroscopic world of process simulation and the microscopic world of molecular simulation. It is shown that a uniform structuring principle can be applied to the modularisation of most classes of chemical engineering models. The structuring principle can be used as a theoretical framework for the implementation of modular families of chemical engineering models in modern computer aided modelling tools.     

基于绿色化工的化学反应路径选择

In the preliminary stage of chemical process design, the choice of chemical reaction route is the key design decision, and the concepts of atom utilization and environmental quotient have become extremely useful tools. However, the waste quality such as chemical toxicity and other engineering factors have not been taken into account. Therefore, a synthetic route selection index, /Route, is proposed to determine the suitability of a chemical route in this paper. /Route considers the effects of “extended atom economy”, material renewability, chemical characteristics and some engineering factors. The extended atom economy concept regards not only the value of the desired product but also the value of byproducts. The methodology by using IRoute to compare different routes is illustrated in case study of cyclohexanone oxime and acrylonitrile manufacture.     

Chemical Reaction Route Selection Based on Green Chemical Engineering

In the preliminary stage of chemical process design, the choice of chemical reaction route is the key design decision, and the concepts of atom utilization and environmental quotient have become extremely useful tools. However, the waste quality such as chemical toxicity and other engineering factors have not been taken into account. Therefore, a synthetic route selection index, IRoute is proposed to determine the suitability of a chemical route in this paper. IRoute considers the effects of "extended atom economy", material renewability, chemical characteristics and some engineering factors. The extended atom economy concept regards not only the value of the desired product but also the value of byproducts. The methodology by using IRoute to compare different routes is illustrated in case study of cyclohexanone oxime and acrylonitrile manufacture.     

DNA及基因组改组在代谢工程中的应用

代谢工程是应用分子生物学与反应工程的结合,已发展成为菌种改进的平台技术.后基因组学时代的基因组学、转录组学、蛋白质组学及代谢物组学等为代谢工程的发展提供了极好的机遇.DNA改组及基因组改组可以构建新的代谢途径、对已知或未知的代谢途径进行快速优化,极大地促进了代谢工程的进一步发展和应用.DNA改组及基因组改组技术可以加深对代谢网络及其分子调节机制的理解,是对合理代谢设计策略的完善和补充.本文首先分别介绍了DNA改组、基因组改组在代谢工程中的应用,进而展望了基于基因组改组的代谢工程方法步骤及发展方向.     

Application of Strong Porous Polymer Sheets for Superior Oil Spill Recovery

The usage of natural and synthetic sorbents in order to control oil spills is gaining increasing attention due to environmental concerns. In particular, polyolefins including polypropylene and polyethylene are the most commonly used oil sorbent materials because of their low cost but suffer from low oil absorption capacity. Attempts at trying to increase the surface‐to‐thickness ratio for improving uptake capacity makes them vulnerable to breakage and impractical for most oil spill applications. Novel super oil sorbent polymer sheets consisting of porous ultrahigh‐molecular‐weight polyethylene have been prepared. The presented sorbent exhibits extremely high uptake and retention capacities along with a mechanically strong structure. The combination of these factors as well as the cost effectiveness of the material used makes these sheets viable candidates for widespread production and utilization.     

分子催化工程

主要论述了分子催化工程的建立及其3个分支,即:能谱技术与催化体系的表征,催化合成有机化学,催化反应机理研究的现状。并以金属催化剂、金属氧化物催化剂和分子筛催化剂3种典型的多相催化剂给予了分析论证。结合这3种催化剂论述了催化剂的分子模拟和工程控制。     

The triplet “molecular processes–product–process” engineering: the future of chemical engineering ?

Today chemical engineering has to answer to the changing needs of the chemical and related process industries and to meet the market demands. Being a key to survival in globalization of trade and competition, the evolution of chemical engineering is thus necessary. Its ability to cope with the scientific and technological problems encountered will be appraised in this paper. To satisfy both the markets requirements for specific end-use properties of products and the social and environmental constraints of the industrial-scale processes, it is shown that a necessary progress is coming via a multidisciplinary and a time and length multiscale approach. This will be obtained due to breakthroughs in molecular modelling, scientific instrumentation and related signal processing and powerful computational tools. For the future of chemical engineering four main objectives are concerned: (a) to increase productivity and selectivity through intelligent operations via intensification and multiscale control of processes; (b) to design novel equipment based on scientific principles and new methods of production: process intensification; (c) to extend chemical engineering methodology to product focussed engineering, i.e. manufacturing and synthesizing end-use properties required by the customer, which needs a triplet “molecular processes–product–process” engineering; (d) to implement multiscale application of computational chemical engineering modelling and simulation to real-life situations, from the molecular scale to the overall complex production scale.     

A unified polymer reaction engineering methodology for catalytic olefin polymerization: From reaction conditions and catalyst reaction performance to molecular and rheological properties for forward,reverse engineering and deconvolution applications

This work presents a unified polymer reaction engineering methodology for the catalytic olefin polymerization process. The proposed modelling approach offers a modelling pathway from the polymerization recipe to production rate and polymer microstructure, and finally to rheological properties. Furthermore, this work introduces for the first time the constraint of the actual reaction performance of the polymerization catalyst in the inverse rheology and microstructural deconvolution problem, limiting the solution only to the most realistic potential molecular weight distributions (MWDs) that a specific catalyst can produce. This approach can be applied for both single- and multi-site catalysts, providing not a potential MWD but the unique one that the selected catalyst can offer under given polymerization conditions. Depending on the available catalyst reaction performance insight, the constraint can vary and include from the number of active sites in use to the exact kinetic parameters of each site type. The potential of the proposed methodology is highlighted within a series of indicative examples, including forward, reverse engineering and deconvolution applications.     

Molecular dynamics simulations to investigate polymer–polymer and polymer–metal oxide interactions

Polymer–polymer interactions in majority of engineering polymers are difficult to measure experimentally, since many polymers are usually insoluble in solvents, have high glass transition temperatures, and are sometimes poorly characterized. Therefore, applying molecular modeling strategies would be helpful in such situations in order to provide useful information, which would be difficult to obtain by other means. Poly(methyl methacrylate), PMMA, is a widely used engineering polymer that exists in a glassy state at room temperature. Therefore, we have selected PMMA to perform the molecular dynamics simulations to investigate its interfacial interaction with many other important polymers such as PAN, PC, PEO, PES, PMS, PU, PVAc, PVDF, PVME and PVP. Small molecular fragments of repeating units of these polymers were chosen for interaction studies, whose polymers and/or their blends with PMMA are used in many engineering applications. The COMPASS force field methodology was used in the present study for oligomers containing up to 10-mers for simulations to compute solubility parameters that are closely agreeable with the experimental data. Molecular dynamics (MD) simulations have also been performed to explore the adsorption behavior of MMA with several metal oxides (Al₂O₃, Fe₂O₃, SiO₂ and TiO₂), since such studies are important in developing polymer composites. Interfacial interactions between MMA and metal oxides have been calculated using the vibrational absorptions in order to identify the functional groups that might interact quite favorably with the PMMA.