Intermediate Building Blocks Research Articles

Visualizing 13C-Labeled Metabolites in Maize Root Tips with Mass Spectrometry Imaging.

Tracing in vivo isotope-labeled metabolites has been used to study metabolic pathways or flux analysis. However, metabolic differences between the cells have been often ignored in these studies due to the limitation of solvent-based extraction. Here we demonstrate that the mass spectrometry imaging of in vivo isotope-labeled metabolites, referred to as MSIi, can provide important insights into metabolic dynamics with cellular resolution that may supplement the traditional metabolomics and flux analysis. Developing maize root tips are adopted as a model system for MSIi by supplementing 200 mM [U-13C]glucose in 0.1x Hoagland medium. MSIi data sets were acquired for longitudinal sections of newly grown maize root tips after growing 5 days in the medium. A total of 56 metabolite features were determined to have been 13C-labeled based on accurate mass and the number of carbon matching with the metabolite databases. Simple sugars and their derivatives were fully labeled, but some small metabolites were partially labeled with a significant amount of fully unlabeled metabolites still present, suggesting the recycling of "old" metabolites in the newly grown tissues. Some distinct localizations were found, including the low abundance of hexose and its derivatives in the meristem, the high abundance of amino acids in the meristem, and the localization to epidermal and endodermal cells for lipids and their intermediates. Fatty acids and lipids were slow in metabolic turnover and showed various isotopologue distributions with intermediate building blocks, which may provide flux information for their biosynthesis.

Computational insights into aqueous speciation of metal-oxide nanoclusters: an in-depth study of the Keggin phosphomolybdate.

Herein, we present a new computational methodology that unlocks the prediction of the complex multi-species multi-equilibria processes involved in the formation of complex metal-oxo nanoclusters. Relying on our recently introduced method named POMSimulator, we extended its capabilities and challenged its accuracy with the well-known phosphomolybdate [PMo12O40]3- Keggin anion system. We show how the use of statistical techniques enabled the processing of a vast number of speciation models and their associated systems of non-linear equations efficiently and in a scalable manner. Subsequently, this approach is applied to generate statistically averaged speciation diagrams and their associated error bars. Then, we unveil the previously unreported speciation phase diagram under varying [Mo]/[P] ratios vs. pH. Our findings align well with experimental data, indicating the prevalence of the Keggin {PMo12} as the primary species at low pH, but the lacunary {PMo11}and Strandberg {P2Mo5} anions also emerge as major species at other concentration ratios. Finally, from 7 × 104 speciation models we inferred a plausible reaction network across the diverse nuclearities present within the system, which underlines the role of trimers as key intermediate building blocks.

Comparative techno-economic and energy analyses of integrated biorefinery processes of furfural and 5-hydroxymethylfurfural from biomass residue

For efficient feedstock and energy utilization, integrated biorefinery processes are applied to furfural production from bagasse to convert furfural residue into 5-hydroxymethylfurfural (HMF)—an important intermediate building block for the production of various biochemicals. Here, a techno-economic analysis of the integrated processes of furfural and HMF production combined with electricity generation under different scenarios was performed to identify the most suitable process design. Simulations revealed that using the whole bagasse in the biorefinery plant and recycling 50% waste from the HMF production to recover unreacted sugar (scenario 2) achieved the maximum furfural and HMF production with minimum CO2 emission, compared with integrated processes without sugar recycling (scenario 1), with 80% (scenario 3) and 60% biomass (scenario 4) bypassed to the biorefinery, and with a standalone combined heat and power system (scenario 5). Moreover, heat integration improved the efficiency of biorefinery plant (scenario 2), with an energy recovery potential of 71%, leading to the maximum profit at 11% internal rate of return. However, the high operating cost associated with the requirement of solvents and catalysts for HMF production represents the largest cost distribution in the proposed integrated processes. Sensitivity analysis revealed that solvent cost was the most important parameter for economic benefit. In addition, improving technological efficiency in the pretreatment and HMF production phases can enhance product yield, thereby benefiting the profitability of this process.

ResNet-LDDMM: Advancing the LDDMM Framework Using Deep Residual Networks.

In deformable registration, the Riemannian framework - Large Deformation Diffeomorphic Metric Mapping, or LDDMM for short - has inspired numerous techniques for comparing, deforming, averaging and analyzing shapes or images. Grounded in flows of vector fields, akin to the equations of motion used in fluid dynamics, LDDMM algorithms solve the flow equation in the space of plausible deformations, i.e., diffeomorphisms. In this work, we make use of deep residual neural networks to solve the non-stationary ODE (flow equation) based on an Euler's discretization scheme. The central idea is to represent time-dependent velocity fields as fully connected ReLU neural networks (building blocks) and derive optimal weights by minimizing a regularized loss function. Computing minimizing paths between deformations, thus between shapes, turns to find optimal network parameters by back-propagating over the intermediate building blocks. Geometrically, at each time step, our algorithm searches for an optimal partition of the space into multiple polytopes, and then computes optimal velocity vectors as affine transformations on each of these polytopes. As a result, different parts of the shape, even if they are close (such as two fingers of a hand), can be made to belong to different polytopes, and therefore be moved in different directions without costing too much energy. Importantly, we show how diffeomorphic transformations, or more precisely bilipshitz transformations, are predicted by our registration algorithm. We illustrate these ideas on diverse registration problems of 3D shapes under complex topology-preserving transformations. We thus provide essential foundations for more advanced shape variability analysis under a novel joint geometric-neural networks Riemannian-like framework, i.e., ResNet-LDDMM.

Effect of Olive Kernel thermal treatment (torrefaction vs. slow pyrolysis) on the physicochemical characteristics and the CO2 or H2O gasification performance of as-prepared biochars

The thermochemical conversion of biomass through its gasification has been widely explored during the last decades. The generated bio-syngas mixture can be directly used as fuel in thermal engines and fuel cells or as intermediate building block to produce synthetic liquid fuels and/or value added chemicals at large scales. In the present work, the effect of Greek olive kernel (OK) thermal treatment (torrefaction at 300 °C vs. slow pyrolysis at 500 and 800 °C) on the physicochemical characteristics and CO2 or H2O gasification performance of as-produced biochars is examined. Both the pristine OK sample and biochars (OK300, OK500, OK800) were fully characterized by employing a variety of physicochemical methods. The results clearly revealed the beneficial effect of thermal pretreatment on the gasification performance of as-prepared biochars. Α close relationship between the physicochemical properties of fuel samples and gas production was disclosed. Carbon dioxide gasification leads mainly to CO with minor amounts of H2 and CH4, whereas steam gasification results in a mixture containing CO2, CO, H2 and CH4 with a H2/CO ratio varied between 1.3 and 2.3. The optimum gasification performance was obtained for the slowly pyrolyzed samples (OK500 and OK800), due to their higher carbon and ash content as well as to their higher porosity and less ordered structure compared to pristine (OK) and torrefied (OK300) samples.

Hydrogen Energy Production from Advanced Reforming Processes and Emerging Approaches

AbstractNo abstract.

Concept and challenges of modern biorefineries

International R&D community and technology developers for the last decades. However, despite intense efforts, real breakthrough has not been achieved yet. This has been mainly due to a biased view, focusing solely on a certain end product – for example cellulose pulp or ethanol and considering by-products as low value waste streams for energy applications. With the new wave of lignocellulosic biomass fractionation technologies being demonstrated at a pilot scale, success stories are closer than they have ever been. Biomass fractionation to high purity intermediate building blocks of cellulose to C6 sugars and hemicellulose to C5/C6 sugars and lignin, instead of just one main product, provides a way to produce a diversity of products and establish novel bio-based value chains. Especially important is the availability of higher purity lignin for different direct drop-in or after processing (depolymerization etc.) applications, which compared to the conventional lignins derived from pulp mills or ethanol refineries provides totally new applications and perspectives to enable the increased use of biobased raw materials in various industries. A biorefinery is a facility where different low-value renewable biomass materials are the feedstock to the processes where they are transformed, in multiple steps including fractionations, separations and conversions, to several higher-value bio-based products. Examples of these products can include fibres, food, feed, fine chemicals, transportation fuels and heat. A biorefinery can be formed by a single unit or can combine several facilities targeted for a single purpose that further process products as well as by-products or wastes of combined facilities. In biorefining one can find similarities to oil refining, with the exception that in oil refining the raw material comes from fossil resources. According to the International Energy Agency ‘Biorefineries will contribute significantly to the sustainable and efficient use of biomass resources, by providing a variety of products to different markets and sectors. They also have the potential to reduce conflicts and competition over land and feedstock, but it is necessary to measure and compare the benefits of biorefineries with other possible solutions to define the most sustainable option.’1 Although it is possible to produce the same products in a biorefinery as in an oil refinery, this is not the target, which instead is to produce products which can replace the products from oil refining.

Oxidation of 5-Chloromethylfurfural (CMF) to 2,5-Diformylfuran (DFF).

2,5-Diformylfuran (DFF) is an important biorenewable building block, namely for the manufacture of new polymers that may replace existing materials derived from limited fossil fuel resources. The current reported methods for the preparation of DFF are mainly derived from the oxidation of 5-hydroxymethylfurfural (HMF) and, to a lesser extent, directly from fructose. 5-Chloromethylfurfural (CMF) has been considered an alternative to HMF as an intermediate building block due to its advantages regarding stability, polarity, and availability from glucose and cellulose. The only reported method for the transformation of CMF to DFF is restricted to the use of DMSO as the solvent and oxidant. We envisioned that the transformation could be performed using more attractive conditions. To that end, we explored the oxidation of CMF to DFF by screening several oxidants such as H2O2, oxone, and pyridine N-oxide (PNO); different heating methods, namely thermal and microwave irradiation (MWI); and also flow conditions. The combination of PNO (4 equiv.) and Cu(OTf)2 (0.5 equiv.) in acetonitrile was identified as the best system, which lead to the formation of DFF in 54% yield under MWI for 5 min at 160 °C. Consequently, a range of different heterogeneous copper catalysts were tested, which allowed for catalyst reuse. Similar results were also observed under flow conditions using copper immobilized on silica under thermal heating at 160 °C for a residence time of 2.7 min. Finally, HMF and 5,5′-oxybis(5-methylene-2-furaldehyde) (OBMF) were the only byproducts identified under the reaction conditions studied.

Abstract 4081: Stromal autophagy is required for the growth of cutaneous melanoma

Abstract Through degrading bulk cytoplasmic materials into intermediate building blocks, autophagy refuels metabolism and maintains homeostasis under starvation and stress conditions. The context-dependent role of autophagy in cancer cells during tumorigenesis and tumor progression has been explored over the past decade; however, studies of autophagy in relation to the tumor microenvironment are still lacking. In this study, we investigated the role of autophagy in the cancer-associated fibroblasts (CAFs), a major component of the microenvironment that is important for the growth and development of cutaneous melanoma. Analysis of clinical biopsies revealed high levels of autophagy in fibroblasts that surrounded melanoma cells, but not in the non-tumor adjacent area. Fibroblasts co-cultured with any of multiple melanoma cell lines, but not melanocytes, also showed increased autophagic flux, which requires transforming growth factor beta (TGF-β) signaling. Knocking down autophagy-related (ATG) genes ATG5 or ATG7 in fibroblasts did not impair their proliferation in vitro, but inhibited the growth of co-engrafted melanoma cells in vivo. Further, by introducing intradermal melanoma allografts into mice that harbored fibroblast-specific Atg7 deletion, we observed remarkable tumor growth retardation. In order to mimic anti-autophagy therapy for patients, we generated mice that allowed conditional Atg7 depletion in their entire bodies, and found significant tumor growth suppression. Atg7 knockout mice contained elevated plasma levels of immune cell attractants, including CXCL9, CXCL10 and MCP-1. By inhibiting these cytokines/chemokines with atorvastatin, tumor growth in Atg7 knockout mice was completely rescued; while, there was no effect of atorvastatin on control mice. Taken together, our data show that through modulating the tumor microenvironment, stromal autophagy plays an important role during melanoma growth and development. Our findings indicate that stromal autophagy may represent a valuable therapeutic target that might induce less side effects and systemic toxicity. Citation Format: Ran Ellen Zhang, Natalie J. Guo, Nithya Krishnan, David Jelinek, Gizem Karsli Uzunbas, Xiaoqi Xie, Arek Gertych, Janice M. Mehnert, Beatrice Knudsen, Eileen White, Hilary A. Coller. Stromal autophagy is required for the growth of cutaneous melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4081.

Hexamethylenediamine (HMDA) from fossil- vs. bio-based routes: an economic and life cycle assessment comparative study

A series of biobased routes are critically scrutinized for the production of hexamethylenediamine (HMDA) using 5-hydroxymethylene furfural (HMF) as intermediate building block.

Characterization and photocatalytic study of tantalum oxide nanoparticles prepared by the hydrolysis of tantalum oxo-ethoxide Ta8(μ3-O)2(μ-O)8(μ-OEt)6(OEt)14.

Ta8(μ3-O)2(μ-O)8(μ-OEt)6(OEt)14 (1) was obtained by the controlled hydrolysis of tantalum ethoxide Ta(OEt)5 in the presence of ammonia. Compound 1 is considered as the intermediate building block in the sol–gel polymerization of Ta(OEt)5. Further hydrolysis of compound 1 yielded nanoparticles of Ta2O5, which were characterized by various techniques such as TGA-DTA-DSC, UV–vis DRS, XRD, SEM, TEM, particle size analyzer (DLS) and the Brunauer–Emmett–Teller (BET) method. The band gap of the particles was calculated by using the Tauc plot. The photocatalytic activity of Ta2O5 nanoparticles was tested by the degradation of the organic dye rhodamine B.

Lactic acid as a platform chemical in the biobased economy: the role of chemocatalysis

Upcoming bio-refineries will be at the heart of the manufacture of future transportation fuels, chemicals and materials. A narrow number of platform molecules are envisioned to bridge nature's abundant polysaccharide feedstock to the production of added-value chemicals and intermediate building blocks. Such platform molecules are well-chosen to lie at the base of a large product assortment, while their formation should be straightforward from the refined biomass, practical and energy efficient, without unnecessary loss of carbon atoms. Lactic acid has been identified as one such high potential platform. Despite its established fermentation route, sustainability issues – like gypsum waste and cost factors due to multi-step purification and separation requirements – will arise as soon as the necessary orders of magnitude larger volumes are needed. Innovative production routes to lactic acid and its esters are therefore under development, converting sugars and glycerol in the presence of chemocatalysts. Moreover, catalysis is one of the fundamental routes to convert lactic acid into a range of useful chemicals in a platform approach. This contribution attempts a critical overview of all advances in the field of homogeneous and heterogeneous catalysis and recognises a great potential of some of these chemocatalytic approaches to produce and transform lactic acid as well as some other promising α-hydroxy acids.

Hierarchical self-assembly of star-shaped organometallic crystalline-coil block copolymers in solution

We describe the stepwise hierarchical self-assembly of star-shaped organometallic crystalline-coil block copolymers with four arms, poly(ethylene oxide)-block-poly(ferrocenyldimethylsilane) [PEO50-b-PFDMSx]4, into anisotropic superstructures of up to several μm in length. The process takes place in mixtures of a common solvent for both blocks (THF) and a non-solvent for the organometallic PFDMS block (acetone, EtOH). In both cases, spherical intermediates could be identified via light scattering (DLS) and electron microscopic techniques (SEM, TEM, and cryo-TEM). Materials with weight fractions of PFDMS in the range of 64–80% have been used and, depending on the selective co-solvent, several “triggers” to induce the formation of anisotropic superstructures have been identified: the content of the selective co-solvent (acetone, EtOH), the temperature (EtOH), and the overall star block copolymer concentration (EtOH). In addition, the processes are, to a certain extent, reversible. Whereas in THF–EtOH solvent mixtures crystalline vesicles seem to serve as intermediate building blocks, in the case of THF–acetone mixtures large-compound micelles without any intrinsic fine structure are observed initially. Nevertheless, after further agglomeration into superstructures, an undulated tubular morphology is observed and a partially crystalline nature can be confirmed by X-ray analysis (WAXS).

Synthesis and characterization of new mono-, bis-, and tris-oxamato proligands

This communication presents the synthesis and the characterization of new organic molecules bearing up to three N-phenyl-oxalamic acid ethyl esters. The syntheses are based on Sonogashira-type cross-coupling reactions with preformed oxalamic ester intermediate building blocks. The short synthetic pathways lead easily to valuable potential oxamato-bridging ligands with overall interesting yields.

Two approaches to the synthesis of 9-oxo-and 10-hydroxy-2E-decenoic acids, important components of queen substance and royal jelly of honeybees Apis mellifera

Two approaches to the synthesis of 9-oxo-and 10-hydroxy-2E-decenoic acids, biologically active components of queen substance and royal jelly of honeybees, respectively, were proposed starting with allyl bromide and 1,7-octadiene and using chemo-and regioselective transformations of the common intermediate building block 7-octen-1-ylacetate.

Complex Oligosaccharide Investigations: Synthesis of an Octasaccharide Incorporating the Dimeric Lex Structure of PSGL‐1.

The synthesis of an octasaccharide containing the dimeric Lex oligosaccharide structure found in PSGL-1 carbohydrate chains is reported. Several approaches were investigated employing regioselective and stereoselective glycosylation procedures, and a novel Lewisx trisaccharide donor, 7, was prepared and utilized as a key intermediate building block in the scheme developed for the construction of octasaccharide 3. Toward the preparation of 7, investigations into the influence of different protecting groups upon the relative reactivities of disaccharide acceptor moieties, 25 or 26, and the fucosyl donors, 10 and 11, were conducted using similar glycosylating conditions. Dramatic differences were noted between the effects of electron-donating and electron-withdrawing groups upon the reactivity of the acceptor hydroxyl. A similar effect upon the glycosylating capability of the donor molecule was, likewise, observed. The repeat use of donor 7 was instrumental in the synthesis of the desired dimeric octasacchar...

Complex oligosaccharide investigations: synthesis of an octasaccharide incorporating the dimeric Le(x) structure of PSGL-1.

The synthesis of an octasaccharide containing the dimeric Le(x) oligosaccharide structure found in PSGL-1 carbohydrate chains is reported. Several approaches were investigated employing regioselective and stereoselective glycosylation procedures, and a novel Lewis(x) trisaccharide donor, 7, was prepared and utilized as a key intermediate building block in the scheme developed for the construction of octasaccharide 3. Toward the preparation of 7, investigations into the influence of different protecting groups upon the relative reactivities of disaccharide acceptor moieties, 25 or 26, and the fucosyl donors, 10 and 11, were conducted using similar glycosylating conditions. Dramatic differences were noted between the effects of electron-donating and electron-withdrawing groups upon the reactivity of the acceptor hydroxyl. A similar effect upon the glycosylating capability of the donor molecule was, likewise, observed. The repeat use of donor 7 was instrumental in the synthesis of the desired dimeric octasaccharide structure 3. The structure and purity of 3 and important intermediates were fully characterized by DQF-COSY, TOCSY, ROESY, and ESI mass spectroscopy.

Synthesis of the 3′-terminal half of yeast alanine transfer ribonucleic acid (tRNAAla) by the phosphotriester approach in solution. Part 2

The preparation, by the phosphotriester approach in solution, of the 3′-terminal decaribonucleoside nonaphosphate [UpCpGpUpCpCpApCpCpA (48)], nonadecaribonucleoside octadecaphosphate [ApUpUpCpCpGpGpApCpUpCpGpUpCpCpApCpCpA (49)], and heptatriacontaribonucleoside hexatriacontaphosphate [GpGpApGpApGpGpUpCpUpCpCpGpGpTpψpCpGpApUpUpCpCpGpGpApCpUpCpGpUpCpCpApCpCpA (50)] sequences of yeast alanine transfer ribonucleic acid are described. With the exception of the 3′-terminal adenosine residue which was protected as its 2′,3′-O-methoxymethylene [Mm] derivative, the 2′-hydroxy functions were protected with 4-methoxytetrahydropyran-4-yl [Mthp] groups. The 5′-hydroxy functions of intermediate building blocks were protected with 2-(dibromomethyl)benzoyl [Dbmb (2)], 2-(isopropylthiomethoxymethyl)benzoyl [Ptmt (3)] or 9-phenylxanthen-9-yl [Px (4)] groups. The base residue of the adenosine, cytidine, guanosine, uridine, pseudouridine and 5-methyluridine building blocks were protected as in (5), (6), (7), (8), (9), and (10), respectively. Internucleotide linkages were protected with the 2-chlorophenyl group, and the 2,4-dinitrobenzyl (Dnb) group was used for the temporary protection of 3′-phosphodiester functions. The first phosphorylation step (leading to 3′-phosphodiester intermediates) was carried out by treatment with 2-chlorophenyl bis(1,2,4-triazoyl)phosphate (11) in the presence of 1-methylimidazole in tetrahydrofuran followed by triethylamine and water. 1-(Mesitylene-2-sulphonyl)-3-nitro-1,2,4-triazole [MSNT (15)] was used as the condensing agent in the second phosphorylation step. The final unblocking procedure involved treatment with (i)N1,N1,N3,N3-tetramethylguanidinium E-2-nitrobenzaldehyde oximate in dioxane–acetonitrile–water, (ii) concentrated aqueous ammonia, and (iii) 0.01 M hydrochloric acid.