Chemoenzymatic Asymmetric Synthesis of Pyridine-Based α-Fluorinated Secondary Alcohols

Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield.     

Blends of Bio-Based Poly(Limonene Carbonate) with Commodity Polymers

In this study, blends of the bio-based poly(limonene carbonate) (PLimC) with different commodity polymers are investigated in order to explore the potential of PLimC toward generating more sustainable polymer materials by reducing the amount of petro- or food-based polymers. PLimC is employed as minority component in the blends. Next to the morphology and thermal properties of the blends the impact of PLimC on the mechanical properties of the matrix polymers is studied. The interplay of incompatibility and zero-shear melt viscosity contrast determines the blend morphology, leading for all blends to a dispersed droplet morphology for PLimC. Blends with polymers of similar structure to PLimC (i.e., aliphatic/aromatic polyester) show the best performance with respect to mechanical properties, whereas blends with polystyrene or poly(methyl methacrylate) are too brittle and polyamide 12 blends show very low elongations at break. In blends with Ecoflex (poly(butylene adipate-co-terephthalate)) and Arnitel EM400 (copoly(ether ester)) with poly(butylene terephthalate) hard and polytetrahydrofuran soft segments) a threefold increase in E-modulus can be achieved, while keeping the elongation at break at reasonable high values of ≈200%, making these blends highly interesting for applications.     

What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.     

Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

Multi-objective particle swarm optimisation based integrated production inventory routing planning for efficient perishable food logistics operations

Sustainable and efficient food supply chain has become an essential component of one’s life. The model proposed in this paper is deeply linked to people's quality of life as a result of which there is a large incentive to fulfil customer demands through it. This proposed model can enhance food quality by making the best possible food quality accessible to customers, construct a sustainable logistics system considering its environmental impact and ensure the customer demand to be fulfilled as fast as possible. In this paper, an extended model is examined that builds a unified planning problem for efficient food logistics operations where four important objectives are viewed: minimising the total expense of the system, maximising the average food quality along with the minimisation of the amount of CO₂ emissions in transportation along with production and total weighted delivery lead time minimisation. A four objective mixed integer linear programming model for intelligent food logistics system is developed in the paper. The optimisation of the formulated mathematical model is proposed using a modified multi-objective particle swarm optimisation algorithm with multiple social structures: MO-GLNPSO (Multi-Objective Global Local Near-Neighbour Particle Swarm Optimisation). Computational results of a case study on a given dataset as well as on multiple small, medium and large-scale datasets followed by sensitivity analysis show the potency and effectiveness of the introduced method. Lastly, there has been a scope for future study displayed which would lead to the further progress of these types of models.     

Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Makespan minimization with OR-precedence constraints

We consider a variant of the NP-hard problem of assigning jobs to machines to minimize the completion time of the last job. Usually, precedence constraints are given by a partial order on the set of jobs, and each job requires all its predecessors to be completed before it can start. In this paper, we consider a different type of precedence relation that has not been discussed as extensively and is called OR-precedence. In order for a job to start, we require that at least one of its predecessors is completed—in contrast to all its predecessors. Additionally, we assume that each job has a release date before which it must not start. We prove that a simple List Scheduling algorithm due to Graham (Bell Syst Tech J 45(9):1563–1581, 1966) has an approximation guarantee of 2 and show that obtaining an approximation factor of \(4/3 - \varepsilon \) is NP-hard. Further, we present a polynomial-time algorithm that solves the problem to optimality if preemptions are allowed. The latter result is in contrast to classical precedence constraints where the preemptive variant is already NP-hard. Our algorithm generalizes previous results for unit processing time jobs subject to OR-precedence constraints, but without release dates. The running time of our algorithm is \(O(n^2)\) for arbitrary processing times and it can be reduced to O(n) for unit processing times, where n is the number of jobs. The performance guarantees presented here match the best-known ones for special cases where classical precedence constraints and OR-precedence constraints coincide.