Synthesis and Application of Robust Spiro [Fluorene­9] CAAC Ruthenium Alkylidene Complexes for the "One-Pot" Conversion of Allyl Acetate to Butane-1,4-diol.

A series of a novel CAAC ligands featuring a spiro-fluorene group have been synthesized and complexed with ruthenium alkylidenes, yielding the corresponding Hoveyda-type derivatives as a new family of olefin metathesis catalysts. The novel complexes have been characterized by XRD, HRMS and NMR measurements. The synthetized complexes were tested in catalysis and showed good activity in olefin metathesis, as demonstrated on diethyl diallylmalonate and allyl acetate substrates. The unique backbone in the ligand system with the large, yet inflexible condensed system renders interesting properties to the catalyst, exemplified by the good catalytic performance and improved Z­selectivity. In addition, the complex can also serve as a hydrogenation catalyst in a consecutive (one-pot) reaction. The latter reaction can convert allyl acetate to butane­1,4­diol, a valuable chemical intermediate for biodegradable polybutylene succinate (PBS).

Interdisciplinary development of an overall process concept from glucose to 4,5-dimethyl-1,3-dioxolane via 2,3-butanediol.

To reduce carbon dioxide emissions, carbon-neutral fuels have recently gained renewed attention. Here we show the development and evaluation of process routes for the production of such a fuel, the cyclic acetal 4,5-dimethyl-1,3-dioxolane, from glucose via 2,3-butanediol. The selected process routes are based on the sequential use of microbes, enzymes and chemo-catalysts in order to exploit the full potential of the different catalyst systems through a tailor-made combination. The catalysts (microbes, enzymes, chemo-catalysts) and the reaction medium selected for each conversion step are key factors in the development of the respective production methods. The production of the intermediate 2,3-butanediol by combined microbial and enzyme catalysis is compared to the conventional microbial route from glucose in terms of specific energy demand and overall yield, with the conventional route remaining more efficient. In order to be competitive with current 2,3-butanediol production, the key performance indicator, enzyme stability to high aldehyde concentrations, needs to be increased. The target value for the enzyme stability is an acetaldehyde concentration of 600 mM, which is higher than the current maximum concentration (200 mM) by a factor of three.

Making Persistent Plastics Degradable.

The vastness of the scale of the plastic waste problem will require a variety of strategies and technologies to move toward sustainable and circular materials. One of these strategies to address the challenge of persistent fossil-based plastics is new catalytic processes that are being developed to convert recalcitrant waste such as polyethylene to produce propylene, which can be an important precursor of high-performance polymers that can be designed to biodegrade or to degrade on demand. Remarkably, this process also enables the production of biodegradable polymers using renewable raw materials. In this Perspective, current catalyst systems and strategies that enable the catalytic degradation of polyethylene to propylene are presented. In addition, concepts for using "green" propylene as a raw material to produce compostable polymers is also discussed.

Parahydrogen-Induced Polarization of a Labeled, Cancer-Targeting DNA Aptamer.

Enhancing NMR signals of biomacromolecules by hyperpolarization offers exciting opportunities for diagnostic applications. However, their hyperpolarization via parahydrogen remains challenging as specific catalytic interactions are required, which are difficult to tune due to the large size of the biomolecule and its insolubility in organic solvents. Herein, we show the unprecedented hyperpolarization of the cancer-targeting DNA aptamer AS1411. By screening different molecular motifs for an unsaturated label in nucleosides and in DNA oligomers, we were able to identify structural prerequisites for the hyperpolarization of AS1411. Finally, adjusting the polarity of AS1411 by complexing the DNA backbone with amino polyethylene glycol chains allowed the hydrogenation of the label with parahydrogen while the DNA structure remains stable to maintain its biological function. Our results are expected to advance hyperpolarized molecular imaging technology for disease detection in the future.

Effective Production of Selected Dioxolanes by Sequential Bio- and Chemocatalysis Enabled by Adapted Solvent Switching.

Most combinations of chemo- and biocatalysis take place in aqueous media or require a solvent change with complex intermediate processing. Using enzymes in the same organic solvent as the chemocatalyst eliminates this need. Here, it was shown that a complete chemoenzymatic cascade to form dioxolanes could be carried out in a purely organic environment. The result, including downstream processing, was compared with a classical mode, shifting solvent. First, a two-step enzyme cascade starting from aliphatic aldehydes to chiral diols (3,4-hexanediol and 4,5-octanediol) was run either in an aqueous buffer or in the potentially biobased solvent cyclopentyl methyl ether. Subsequently, a ruthenium molecular catalyst enabled the conversion to dioxolanes [e. g., (4S,5S)-dipropyl-1,3-dioxolane]. Importantly, the total synthesis of this product was not only highly stereoselective but also based on the combination of biomass, CO2 , and hydrogen, thus providing an important example of a bio-hybrid chemical.

MIXed plastics biodegradation and UPcycling using microbial communities: EU Horizon 2020 project MIX-UP started January 2020.

This article introduces the EU Horizon 2020 research project MIX-UP, "Mixed plastics biodegradation and upcycling using microbial communities". The project focuses on changing the traditional linear value chain of plastics to a sustainable, biodegradable based one. Plastic mixtures contain five of the top six fossil-based recalcitrant plastics [polyethylene (PE), polyurethane (PUR), polypropylene (PP), polyethylene terephthalate (PET), polystyrene (PS)], along with upcoming bioplastics polyhydroxyalkanoate (PHA) and polylactate (PLA) will be used as feedstock for microbial transformations. Consecutive controlled enzymatic and microbial degradation of mechanically pre-treated plastics wastes combined with subsequent microbial conversion to polymers and value-added chemicals by mixed cultures. Known plastic-degrading enzymes will be optimised by integrated protein engineering to achieve high specific binding capacities, stability, and catalytic efficacy towards a broad spectrum of plastic polymers under high salt and temperature conditions. Another focus lies in the search and isolation of novel enzymes active on recalcitrant polymers. MIX-UP will formulate enzyme cocktails tailored to specific waste streams and strives to enhance enzyme production significantly. In vivo and in vitro application of these cocktails enable stable, self-sustaining microbiomes to convert the released plastic monomers selectively into value-added products, key building blocks, and biomass. Any remaining material recalcitrant to the enzymatic activities will be recirculated into the process by physicochemical treatment. The Chinese-European MIX-UP consortium is multidisciplinary and industry-participating to address the market need for novel sustainable routes to valorise plastic waste streams. The project's new workflow realises a circular (bio)plastic economy and adds value to present poorly recycled plastic wastes where mechanical and chemical plastic recycling show limits.

Mapping Cell Viability Quantitatively and Independently From Cell Density in 3D Gels Noninvasively.

OBJECTIVE: In biomanufacturing there is a need for quantitative methods to map cell viability and density inside 3D bioreactors to assess health and proliferation over time. Recently, noninvasive MRI readouts of cell density have been achieved. However, the ratio of live to dead cells was not varied. Herein we present an approach for measuring the viability of cells embedded in a hydrogel independently from cell density to map cell number and health. METHODS: Independent quantification of cell viability and density was achieved by calibrating the 1H magnetization transfer- (MT) and diffusion-weighted NMR signals to samples of known cell density and viability using a multivariate approach. Maps of cell viability and density were generated by weighting NMR images by these parameters post-calibration. RESULTS: Using this method, the limits of detection (LODs) of total cell density and viable cell density were found to be 3.88 ×108 cells · mL -1· Hz -1/2 and 2.36 ×109 viable cells · mL -1· Hz -1/2 respectively. CONCLUSION: This mapping technique provides a noninvasive means of visualizing cell viability and number density within optically opaque bioreactors. SIGNIFICANCE: We anticipate that such nondestructive readouts will provide valuable feedback for monitoring and controlling cell populations in bioreactors.

Efficient Plastic Waste Recycling to Value-Added Products by Integrated Biomass Processing.

The industrial production of polymeric materials is continuously increasing, but sustainable concepts directing towards a circular economy remain rather elusive. The present investigation focuses on the recycling of polyoxymethylene polymers, facilitated through combined catalytic processing of polymer waste and biomass-derived diols. The integrated concept enables the production of value-added cyclic acetals, which can flexibly function as solvents, fuel additives, pharmaceutical intermediates, and even monomeric materials for polymerization reactions. Based on this approach, an open-loop recycling of these waste materials can be envisaged in which the carbon content of the polymer waste is efficiently utilized as a C1 building block, paving the way to unprecedented possibilities within a circular economy of polyoxymethylene polymers.

A highly active non-precious transition metal catalyst for the hydrogenation of carbon dioxide to formates.

Herein a highly active non-precious transition metal catalyst system for homogeneous hydrogenation of carbon dioxide to formate is presented. The application of selected nickel(ii) salts in combination with tailored multidentate ligands enabled the effective transformation of carbon dioxide with an exceptional TON of up to 4.65 × 106. This unprecedented productivity based on the novel nickel catalyst not only outmatches that of existing systems containing first row transition metals, but also established catalysts based on precious transition metals.

Ruthenium-Catalyzed Synthesis of Cyclic and Linear Acetals by the Combined Utilization of CO2 , H2 , and Biomass Derived Diols.

Herein a transition-metal catalyst system for the selective synthesis of cyclic and linear acetals from the combined utilization of carbon dioxide, molecular hydrogen, and biomass derived diols is presented. Detailed investigations on the substrate scope enabled the selectivity of the reaction to be largely guided and demonstrated the possibility of integrating a broad variety of substrate molecules. This approach allowed a change between the favored formation of cyclic acetals and linear acetals, originating from the bridging of two diols with a carbon-dioxide based methylene unit. This new synthesis option paves the way to novel fuels, solvents, or polymer building blocks, by the recently established "bio-hybrid" approach of integrating renewable energy, carbon dioxide, and biomass in a direct catalytic transformation.

Molecular catalyst systems as key enablers for tailored polyesters and polycarbonate recycling concepts.

A transition metal catalyst system for the selective catalytic depolymerization of various polyester- and polycarbonate-based materials is presented. The use of a molecular ruthenium catalyst with selected triphos ligands enabled a selective hydrogenolysis of a large diversity of polymeric consumer products, paving the way to innovative and sustainable recycling strategies within a circular economy.

Non-Pairwise Interactions in Parahydrogen Experiments: Nuclear Exchange of Single Protons Enables Bulk Water Hyperpolarization.

Hyperpolarization with parahydrogen (p-H2 ) is a fast developing field in NMR, which enables overcoming the inherent low sensitivity of this important technique. The hyperpolarization of solvents, particularly of water, offers a wide range of applications for structural investigations of macromolecules and biomedical imaging. Until lately, only organic solvents could be polarized by means of parahydrogen via coherent redistribution of polarization (SABRE mechanism). In this study, we investigate in detail the mechanism of the recently reported bulk water hyperpolarization with a combination of theoretical and experimental methods, finally showing a chemical exchange pathway of single protons as basis for the enhancement. The prerequisites for preserving hyperpolarization upon separation of the two hydrogen atoms of p-H2 are demonstrated by theoretical examinations of the boundary conditions for the hyperpolarization experiments in accordance with the OneH-PHIP theory. These findings yielded the proposal of the novel NEPTUN mechanism (Nuclear Exchange Polarization by Transposing Unattached Nuclei) as the non-hydrogenative equivalent to the established OneH-PHIP and thus the missing link in parahydrogen hyperpolarization theory.

Hyperpolarizing Water with Parahydrogen.

Studies of water-based systems are of fundamental interest for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) as water is the most abundant and important medium for global living. Hence, increasing the polarization of water and dissolved compounds is particularly attractive for biomedical applications such as investigations of intermolecular interactions and metabolite structures as well as for imaging purposes. In this work, we show a new approach based on para enriched hydrogen (p-H2 ) that enables the hyperpolarization of bulk water if a suitable catalytic system is employed. The results indicate that the polarization is transferred by a new exchange mechanism.

Tailor-made Molecular Cobalt Catalyst System for the Selective Transformation of Carbon Dioxide to Dialkoxymethane Ethers.

Herein a non-precious transition-metal catalyst system for the selective synthesis of dialkoxymethane ethers from carbon dioxide and molecular hydrogen is presented. The development of a tailored catalyst system based on cobalt salts in combination with selected Triphos ligands and acidic co-catalysts enabled a synthetic pathway, avoiding the oxidation of methanol to attain the formaldehyde level of the central CH2 unit. This unprecedented productivity based on the molecular cobalt catalyst is the first example of a non-precious transition-metal system for this transformation utilizing renewable carbon dioxide sources.

Multi-step biocatalytic depolymerization of lignin.

Lignin is a biomass-derived aromatic polymer that has been identified as a potential renewable source of aromatic chemicals and other valuable compounds. The valorization of lignin, however, represents a great challenge due to its high inherent functionalization, what compromises the identification of chemical routes for its selective depolymerization. In this work, an in vitro biocatalytic depolymerization process is presented, that was applied to lignin samples obtained from beech wood through OrganoCat pretreatment, resulting in a mixture of lignin-derived aromatic monomers. The reported biocracking route comprises first a laccase-mediator system to specifically oxidize the Cα hydroxyl group in the ß-O-4 structure of lignin. Subsequently, selective ß-O-4 ether cleavage of the oxidized ß-O-4 linkages is achieved with ß-etherases and a glutathione lyase. The combined enzymatic approach yielded an oily fraction of low-molecular-mass aromatic compounds, comprising coniferylaldehyde and other guaiacyl and syringyl units, as well as some larger (soluble) fractions. Upon further optimization, the reported biocatalytic route may open a valuable approach for lignin processing and valorization under mild reaction conditions.

Advanced Biofuels and Beyond: Chemistry Solutions for Propulsion and Production.

Sustainably produced biofuels, especially when they are derived from lignocellulosic biomass, are being discussed intensively for future ground transportation. Traditionally, research activities focus on the synthesis process, while leaving their combustion properties to be evaluated by a different community. This Review adopts an integrative view of engine combustion and fuel synthesis, focusing on chemical aspects as the common denominator. It will be demonstrated that a fundamental understanding of the combustion process can be instrumental to derive design criteria for the molecular structure of fuel candidates, which can then be targets for the analysis of synthetic pathways and the development of catalytic production routes. With such an integrative approach to fuel design, it will be possible to improve systematically the entire system, spanning biomass feedstock, conversion process, fuel, engine, and pollutants with a view to improve the carbon footprint, increase efficiency, and reduce emissions.

Genetic and biochemical insights into the itaconate pathway of Ustilago maydis enable enhanced production.

The Ustilaginaceae family of smut fungi, especially Ustilago maydis, gained biotechnological interest over the last years, amongst others due to its ability to naturally produce the versatile bio-based building block itaconate. Along with itaconate, U. maydis also produces 2-hydroxyparaconate. The latter was proposed to be derived from itaconate, but the underlying biochemistry and associated genes were thus far unknown. Here, we confirm that 2-hydroxyparaconate is a secondary metabolite of U. maydis and propose an extension of U. maydis' itaconate pathway from itaconate to 2-hydroxyparaconate. This conversion is catalyzed by the P450 monooxygenase Cyp3, encoded by cyp3, a gene, which is adjacent to the itaconate gene cluster of U. maydis. By deletion of cyp3 and simultaneous overexpression of the gene cluster regulator ria1, it was possible to generate an itaconate hyper producer strain, which produced up to 4.5-fold more itaconate in comparison to the wildtype without the by-product 2-hydroxyparaconate. By adjusting culture conditions in controlled pulsed fed-batch fermentations, a product to substrate yield of 67% of the theoretical maximum was achieved. In all, the titer, rate and yield of itaconate produced by U. maydis was considerably increased, thus contributing to the industrial application of this unicellular fungus for the biotechnological production of this valuable biomass derived chemical.

Ruthenium-Catalyzed Modular Synthesis of Cyclic Tertiary Amines from Lactams.

Reported is the development of a novel catalytic cascade reaction facilitating the modular synthesis of cyclic tertiary amines from simple lactam substrates and secondary alcohols. Using a single molecular ruthenium-triphos catalyst in the presence of molecular hydrogen enabled the versatile formation of various amines in high yield with excellent selectivity. Extending the reaction system to using an alcohol as the hydrogen transfer reagent allowed the reduction of lactams without the need for molecular hydrogen.

Ruthenium-Catalyzed Synthesis of Dialkoxymethane Ethers Utilizing Carbon Dioxide and Molecular Hydrogen.

The synthesis of dimethoxymethane (DMM) by a multistep reaction of methanol with carbon dioxide and molecular hydrogen is reported. Using the molecular catalyst [Ru(triphos)(tmm)] in combination with the Lewis acid Al(OTf)3 resulted in a versatile catalytic system for the synthesis of various dialkoxymethane ethers. This new catalytic reaction provides the first synthetic example for the selective conversion of carbon dioxide and hydrogen into a formaldehyde oxidation level, thus opening access to new molecular structures using this important C1 source.