Production Of Fine Chemicals Research Articles

A brief overview of global biotechnology

Biotechnology is an innovative, interdisciplinary field that impacts many different sectors, including agriculture, veterinary, medicine, pharmaceutical and fine chemicals production. It is emerging as one of the leading technologies for the transition towards carbon-free society and for solving critical societal challenges comprising health protection, food and energy supply, and environmental protection. Professional networks such as EBTNA (European Biotechnology Thematic Network Association) are important to disseminate knowledge and raise awareness of biotechnology as one of the key enabling technologies for sustainable production.

Advances of bioelectrocatalysis by oxidoreductases

<p indent=0mm>Bioelectrocatalysis attracts much attention with the advantages of high selectivity, high efficiency, no byproduct and environmental friendliness. Electrification of industrial biotechnology is challenging for the different operating conditions and catalysts of electrochemical and biochemical reactions. In this review, we present the state-of-the-art information on enzymatic electrosynthesis for the production of fine chemicals. Multidisciplinary strategies of electrode surface modification and enzyme immobilization have been integrated in electrocatalytic devices with various applications in biosensors and bioelectrocatalysis. However, the efficiency of bioelectrosynthesis is determined by the intramolecular electron transfer rate, and interfacial electron transfer rate between the oxidoreductases and electrode. This review aims to summarize recent progresses on the mechanism studies of intramolecular electron transferof redox proteins, including tunneling, hopping, proton-coupled electron transfer, etc. Modular origin of electron transfer chain was also discussed from the perspective of the evolution of spatial adjacency network. Novel and efficient oxidoreductases with enhanced intramolecular and interfacial electron transfer rate can be obtained by protein engineering. The strategies for facilitating intramolecular electron transfer are addressed, which includes the regulation of co-evolved electron transfer network, the designs of molecular switch and the assembly of conductive modules. Oxidoreductases are engineered to improve their biocatalytic performance by using the tools of molecular evolution, modeling, structure prediction, and mutation. Co-evolved molecular switches controll proton-coupled electron transfer and regulate electron transfer inside the multi-center redox proteins. Assembly of surface-binding conductive peptides to oxidoreductases facilitates electricity-driven catalysis. Moreover, the modifications of oxidoreductases allow their predictable immobilization on functionalized electrode surface with improved stability, controlled orientation, surface coverage and enhanced electron transfer. After that, electron transfer within a series of well-defined peptides with orientation-controlled and surface-confined enzymes was addressed. Strategies also developed to increase the biocompatible active surface of electrodes and to promote charge transfer reactions. Nano- and macroporous electrodes based on metal nanoparticles, nanocarbon tubes, graphene, and metallic inverse opals have been designed and fabricated with predictable surface functionalities and electrochemical properties. Electrode/mediator/cofactor/enzyme conjugates can enhance the <italic>in vitro</italic> bioelectricity generation of cofactor. Screening of redox mediators for electrochemical regeneration of NADH was also summarized. Multifunctional surfaces of nano or meso-porous electrodes, where oxidoreductases were bounded to structured electrodes with necessary components (e.g., mediators, cofactor, etc.) with tailored properties, were summarized. Optimizations of functional electrode materials and surfaces can improve the efficiency of cofactor regeneration in the electrochemical reactor modules. Key challenges and future research for better bioelectrocatalysis are discussed and expected briefly. Mining and engineering of novel and robust enzymes from genomic and metagenomic libraries would benefit the bioelectrocatalysis. Based on genome mining, discovery of novel oxidoreductases from extreme microorganism provide thermophilic, alkalophilic, halophilic and organic solvent tolerant oxidoreductases. Reactors for bioelectrocatalysis are optimized to provide a platform for the production of chiral chemicals, which brings great promises for biomanufacturing. Further study of bio-inspired multi-enzyme immobilization which mimics quick electron transfer in multi-enzyme complex is suggested. A variety of approaches for bioelectrocatalysis have been successfully applied for the synthesis of chiral chemicals which are intermediates of fine chemicals and pharmaceuticals. Bioelectrosynthesis processes could replace many chemically catalyzed routes in the future, and aims to construct a new platform for more efficient and green biomanufacturing.

A comparison of the thermal conversion behaviour of marine kerogens isolated from oil shales by NaOH-HCl and HCl-HF methods

The inherent reactivity of kerogens isolated from marine oil shales has not been extensively studied. Determining the conversion and products of demineralized oil shales simplifies modelling of oil shale pyrolysis because the complications introduced by the mineral matter are removed. Accordingly, the reactive behaviour of demineralized products (kerogens) isolated from two marine oil shales (type II kerogen) by NaOH-HCl and HCl-HF methods have been compared with each other and with those of untreated shales. Pyrolysis experiments have been carried out under N2 and H2 in a sealed system, and also in a flow through autoclave system, which is closer to practical pyrolysis conditions, at temperatures in the range 355 °C to 425 °C. The two isolation methods gave a similar conversion in sealed autoclaves and the only major difference was the higher asphaltol yield for the NaOH-HCl kerogens, so that asphaltol yield cannot be used to characterize the intrinsic reactivity of the shale organic matter. The El-Lajjun shale gave higher conversion to organic materials than the kerogens but the opposite was noted for Julia Creek, especially for pyrolysis under N2.Pyrolysis experiments in a flow through system gave similar overall conversion for the kerogens and their untreated shales but the yields of condensates for the Julia Creek shale were significantly lower for the oil shales than for the kerogens. The chemical complexity of the condensates from the flow through experiments was much greater than that for the CH2Cl2 soluble samples from the sealed autoclave pyrolysis experiments.The product compositions for the NaOH-HCl and HCl-HF kerogens were, as for the total yields, very similar, suggesting that the NaOH-HCl method is a valuable alternative in countries where the use of HF is severely restricted. Further, determining the reactive behaviour of kerogens isolated by two different methods makes it likely that features of the reactivity common to both types of kerogens are features of organic matter reactivity rather than of the isolation method and thus provides a firm foundation for future work. The isolated kerogen could also be considered as a source material for the production of fine chemicals and other applications.

Bromotrimethylsilane as a selective reagent for the synthesis of bromohydrins.

Bromotrimethylsilane (TMSBr) is a very efficient reagent in the solvent-free conversion of glycerol into bromohydrins, useful intermediates in the production of fine chemicals. As glycerol is a relevant by-product in biodiesel production, TMSBr has been also tested as a mediator in transesterification in acidic conditions, providing FAME from castor oil in good yields, along with bromohydrins from glycerol. Subsequently the glycerol conversion was optimized and depending on the reaction conditions, glycerol can be selectively converted into α-monobromohydrin (1-MBH) or α,γ-dibromohydrin (1,3-DBH) in very good yields.

Continuous Crystallization Processes in Pharmaceutical Manufacturing: A Review

This scientific paper presents an overview of continuous solution crystallization in the pharmaceutical industry. Since the specific knowledge spectrum of precipitation is very broad, topics covering the following were analyzed and assessed in detail: a comparison between batch and continuous crystallizers, their engineering advantages/disadvantages, the introduction of the solid form structuring to continuously oriented chemical production, and the usage of the online process analytical technology (PAT) methodologies in interacting functional systems. Furthermore, mechanistic multiscale modeling, whose understanding is of decisive importance for further control application development, was thoroughly discussed as well. The multiscale modeling section also includes the simulation of processes and the optimization of crystallizers. In the last section, model-based predictive control (MPC) is considered, which also covers the intensification approach methods in the field of crystal formation and the introduction of new, highly potential continuous systems, e.g. the coiled flow inverter (CFI) crystallizer, in industry and academia. In the mentioned main sections, individual theme-related articles are collected, discussed, and compared; therefore, a reader can get acquainted with pieces of research, their found results, which have been developed until now, and various emerging perspectives. With regard to the importance of crystallization in the pharmaceutical industry, a reader can already find literature on continuous crystallization. However, due to the growing tendency toward the synthesis of products with specific properties which cannot be achieved with conventional approaches, more attention has been paid in the present work to the establishment of continuous systems for the production of specific fine chemicals. In addition, continuous crystallization could also enable more efficient and “on-demand” production, modeling for optimization, MPC, and intensification approaches. A review of the literature classifying studies according to the choice of a continuous system and their description was omitted in this study, as such reviews are already available in the literature.

Recent Progress in Electrocatalytic Glycerol Oxidation

Glycerol, as the major by‐product of biodiesel, can be oxidized into diverse value‐added chemical products via either traditional chemical methods or electrochemical routes. Electrocatalytic glycerol oxidation reaction (GOR) driven by renewable‐derived electricity (e.g., wind and solar) is a promising pathway for fine chemicals production. In an electrochemical cell, GOR can be coupled with various cathodic reactions, including hydrogen evolution reaction (HER), CO2 reduction reaction (CO2RR), and oxygen reduction reaction (ORR); in this manner, different benefits of either energy effectiveness or additional value‐added products can be obtained depending on the cathode reduction reaction selected. Comprehensively understanding of electrocatalytic GOR and the associated processes is of great significance to promote its industrial application. Herein, recent progress of GOR is focused on. The background of biomass‐derived glycerol valorization to energy and value‐added chemicals as well as the electrochemical conversion techniques via GOR is introduced. Then, the electrocatalytic reaction pathways, the potential application of GOR, and the measurement method for products are also discussed and summarized. Special emphasis is put on the design and the development of high‐selectivity and high‐activity electrocatalysts for GOR. Finally, the challenges and the future prospects in the fields of GOR are highlighted.

Acid hydrolysis conditions for the production of fine chemicals from Gracilaria birdiae alga biomass

Gracilaria birdiae is a tropical agarophytes species of red seaweed that is rich in carbohydrates and presents a great potential for mariculture and economic use. However, it is still understudied as a potential renewable resource. In this study, the hydrolysis conditions of G. birdiae algal biomass, reaction time, and sulfuric acid concentration for obtaining monosaccharides, organic acids, and furanic compounds were optimized. Glucose and galactose concentrations were found to be more affected by algal biomass concentration, while the production of 5-hydroxymethylfurfural (5-HMF) and organic acid were most affected by sulfuric acid concentration. The most suitable conditions to produce glucose (28.56 ± 0.72 g·L−1) and galactose (108.03 ± 1.32 g·L−1) were at 121 °C, with sulfuric acid 1.3 mol·L−1, 841.59 g·L−1 of algal biomass and time of 20 min. For cellobiose (25.39 ± 0.43 g·L−1), the condition was sulfuric acid 0.6 mol·L−1, 680 g·L−1 of biomass, and 10 min. For 5-HMF (19.82 ± 0.43 g·L−1), it was sulfuric acid 0.6 mol·L−1, 680 g·L−1 of biomass and 30 min. Finally, for levulinic (38.88 ± 0.58 g·L−1) and formic acids (26.75 ± 0.54 g·L−1) and, the best conditions were sulfuric acid 2.0 mol·L−1, 680 g·L−1 of biomass and 30 min. Thus being, Gracilaria birdiae is a promising renewable resource to produce fine chemicals and fermentable compounds by optimizing its acid hydrolysis conditions.

A comparative study on the chemo-enzymatic upgrading of renewable biomass to 5-Hydroxymethylfurfural

ABSTRACT 5-hydroxymethylfurfural (HMF) obtained from renewable biomass-derived carbohydrates is a potential sustainable substitute to petroleum-based building blocks. In the present work, we constituted a comparative study on the production of HMF from two widely available real biomasses in India- Agave americana and Casuarina equisetifolia. In the initial hydrolysis studies for the production of reducing sugars, 649.5 mg/g of fructose was obtained from the hydrolysis of 5% (w/v) A. americana biomass by the enzyme inulinase in 3 h at 50°C. Similarly, upon hydrolysis of 15% (w/v) C. equisetifolia biomass by the lignocellulolytic enzymes (laccase, cellulase and xylanase) from Trichoderma atroviride, 456.65 mg/g of reducing sugars was released in 24 h at 30°C. Subsequently, the dehydration of the obtained reducing sugars to HMF was achieved with titanium dioxide as the catalyst. The dehydration of A. americana-derived fructose at 140°C led to a maximum HMF yield of 92.6% in 15 min with 10% catalyst load. Contrarily, upon optimizing the process parameters for dehydration of C. equisetifolia derived reducing sugars, the maximum HMF yield of 85.7% was obtained at 110°C in 25 min with a TiO2 concentration of 10%. This study reports for the first time the utilization of C. equisetifolia biomass for HMF production and thus, by utilizing these inexpensive, abundantly available and highly functionalized polysaccharides, a strategical approach can be developed for the production of fine chemicals, eliminating the need of fossil-based chemicals. Implications: The catalytic upgrading of lignocellulosic biomass into high-valued platform chemicals like 5-Hydroxymethylfurfural (HMF) implies an extremely significant challenge to the attempts of establishing a green economy. Casuarina equisetifolia and Agave americana represents a sustainable feedstock for the production of HMF through catalytic integration. The present work describes a two-step reaction process where the initial depolymerization step comprises of an enzymatic hydrolysis followed by a chemical-catalyst mediated dehydration process. The utilization of a biocatalytic approach followed by mild chemical catalyst eliminates the need of hazardous chemical conversion processes. Thus, the HMF produced via sustainable can bridge the gap between carbohydrate chemistry and petroleum-based industrial chemistry because of the wide range of chemical intermediates and end-products that can be derived from this compound.

Insights into Structural Transformations of Lignin Toward High Reactivity During Choline Chloride/Formic Acid Deep Eutectic Solvents Pretreatment

Understanding lignin structural transformations during DES pretreatment would facilitate to produce lignin with tailor-made properties based on intended applications. To unravel the structural variant of lignin in the DES, the alkali lignin (AL) was pretreated in choline chloride/formic acid (ChCl/FA) (the ratio of 1:2) at 80-120 oC. Characterization of the AL and regenerated lignin samples were determined to understand lignin structure, such as linkage in lignin, phenolic OH content, molecular weight, and aromatic products. ChCl/FA DES pretreatment resulted in large amounts of the dissociation of β-O-4' bonds, partial cleavage of carbon-carbon bonds (i.e., β-β′, β-5′), dehydration of hydroxyl radicals in lignin’s side-chain, and demethoxylation reaction. Furthermore, various monomeric phenols derived from AL were also determined in spite of low combined yields, which facilitate the production of fine chemicals in the future. Detailed unmasking of lignin structural transformation during the DES process is conducive to the optimizing preparation of homogeneous lignin with low molecular weight.

Transition Metal-Free Synthesis of Carbamates Using CO2 as the Carbon Source.

Utilization of carbon dioxide as a C1 synthon is highly attractive for the synthesis of valuable chemicals. However, activation of CO2 is highly challenging, owing to its thermodynamic stability and kinetic inertness. With this in mind, several strategies have been developed for the generation of carbon-heteroatom bonds. Among these, formation of C-N bonds is highly attractive, especially, when carbamates can be synthesized directly from CO2 . This Minireview focuses on transition metal-free approaches for the fixation of CO2 to generate carbamates for the production of fine chemicals and pharmaceuticals. Within the past decade, transition metal-free approaches have gained increasing attention, but traditional reviews have rarely focused on these approaches. Direct comparisons between such methods have been even more scarce. This Minireview seeks to address this discrepancy.

Harnessing Photoexcited Redox Centers of Semiconductor Photocatalysts for Advanced Synthetic Chemistry

Solar photocatalysis is emerging as an environment‐friendly and sustainable energy approach for the production of fine chemicals and pharmaceuticals with high industrial and academic importance. Due to photochemical stability, tunable redox capability, and facile recyclability, semiconductor photocatalysts display remarkable advantages over molecular photocatalysts, thus attracting increasing attention. More importantly, photoexcited hole–electron pairs on semiconductor photocatalysts can accomplish two aligned redox reactions on the same semiconductor surface, resulting in unique designs of several semiconductor photocatalysis models. This review surveys recent advances in rational harnessing of photoexcited hole–electron pairs in semiconductor photocatalysts for oxidative and reductive synthetic transformations for chemical and pharmaceutical production. Depending on the catalytic behavior of the photogenerated redox centers, there are three major semiconductor photoredox reaction modes: 1) photoexcited hole‐induced oxidations, 2) photoexcited electron‐induced reductions, and 3) photoexcited electron–hole pairs co‐induced redox‐neutral reactions. The characteristics, reaction scopes, and mechanisms of these three semiconductor photocatalysis modes are discussed. Finally, the major challenges and future opportunities regarding the rational design of photoexcited redox centers in advanced synthetic chemistry are provided.

Light-Mediated Carboxylation Using Carbon Dioxide.

Carbon dioxide is a green and sustainable one-carbon source, which could be utilized in the production of various fine chemicals. In recent studies, the light-mediated carboxylation employing CO2 has received considerable attention. The photocarboxylation of substrates with CO2 to build novel C-C bonds is introduced in this Minireview. The article is arranged based on the light-driven reactive intermediates, including CO2 radical anion, substrate radical anions, carbanions, and M-C species. Most of the cases are under the topic of photoredox catalysis, with single electron transfer as the main driving force. Some non-catalytic examples are also discussed to provide more mechanistic insights.

Preparation of Chiral Photosensitive Organocatalysts and Their Application for the Enantioselective Synthesis of 1,2-Diamines.

Chiral phosphoric acid based organocatalysis and visible-light photocatalysis have both emerged as promising technologies for the sustainable production of fine chemicals. In this context, we have envisioned the design and the synthesis of a new class of chimeric catalytic entities that would feature both catalytic capabilities. Given their multitask nature, such catalysts would be particularly attractive for the development of new catalytic transformations, tandem processes in particular. Toward this goal, several BINOL-based chiral phosphoric acid backbones presenting one or two visible-light-sensitive thioxanthone moieties have been prepared and studied. The utility of these new photoactive chiral organocatalysts is then demonstrated in the enantioselective tandem three-component electrophilic amination of enecarbamates. Of note, the C1-symmetric organo/photocatalyst has shown a better catalytic activity than those presenting a C2 symmetry.

An enhanced toluene dioxygenase platform for the production of cis-1,2-dihydrocatechol in Escherichia coli BW25113 lacking glycerol dehydrogenase activity

The compound cis-1,2-dihydrocatechol (DHC) is highly valuable since it finds wide application in the production of fine chemicals and bioactive compounds with medical relevance. The biotechnological process to generate DHC involves a dearomatizing dihydroxylation reaction catalyzed by toluene dioxygenase (TDO) from P. putida F1, employing benzene as substrate. We aimed to enhance the biotechnological E. coli BW25113 platform for DHC production by identifying the key operational parameters positively influencing the final isolated yield. Thereby, we observed an unreported downstream reaction, generating catechol from DHC, affecting, in a negative manner, the final titer for the product. Expression temperature for the TDO-system showed to have the highest influence in terms of final isolated yield. A KEIO-collection-based screening approach highlighted glycerol dehydrogenase (GldA) as the main responsible enzyme for the undesired reaction. We transferred the TDO-system to E. coli BW25113 ΔgldA and applied the enhanced operational set-up on it. This enhanced platform enabled the production of 1.41 g L−1 DHC in isolated yield, which represents a two-fold increase compared with the starting working conditions. To our knowledge, this is the highest DHC production accomplished in recombinant E. coli at semi-preparative scale, providing a robust and accessible biotechnological platform for DHC synthesis.

Hybrid Inorganic-Biological Systems: Faradaic and Quantum Efficiency, Necessary but Not Sufficient

Adam J. Rieth is a postdoctoral scholar in the Nocera group at Harvard University. He completed his undergraduate studies at the University of North Carolina at Chapel Hill, in his hometown. He then earned his Ph.D. in the laboratory of Prof. Mircea Dincă at the Massachusetts Institute of Technology, where he designed metal-organic frameworks for water harvesting. For the past year in the Nocera group, he has investigated the mechanisms and kinetics of photochemical processes that activate strong bonds. Daniel G. Nocera is the Patterson Rockwood Professor of Energy at Harvard University. He created the field of proton-coupled electron transfer (PCET) at a mechanistic level with the first kinetics measurements and theory of PCET. From this platform, he invented the Artificial Leaf and Bionic Leaf for the solar-driven fixation of carbon dioxide from air in the form of biomass and liquid fuels at energy efficiencies that are 10× greater than natural photosynthesis. He has since elaborated the Bionic Leaf for the solar-driven fixation of nitrogen from air for distributed and carbon-negative ammonia (and fertilizer) synthesis.

A simulated annealing optimization algorithm based nonlinear model predictive control strategy with application

Batch reactors are widely used in the production of fine chemicals, polymers, pharmaceuticals and other specialty products. For certain exothermic reactions, the transient operation of the reactor with respect to small changes in critical parameters like coolant temperature and initial composition of the reactants can lead runaway condition of the reactor. In order to avoid the hazards associated with runaway situations, it is imperative to operate the reactor by means of an efficient controller. This work presents a nonlinear model predictive control (NMPC) strategy based on simulated annealing (SA) for the temperature control of a batch reactor involving a highly exothermic runaway reaction. The efficacy of the proposed strategy is studied through simulation for the temperature control of the reactor in which a highly parametric sensitive exothermic reaction of hydrolysis of acetic anhydride with sulfuric acid as catalyst and acetic acid as a solvent is carried out. The controller is found effective in averting the runaway behavior with the smooth and quick attainment of the desired operating condition. The results demonstrate the better performance of the SA based NMPC over the linear model predictive controller (LMPC).

Use of a methylotrophic organism for production of fine chemicals from methanol

Use of a methylotrophic organism for production of fine chemicals from methanol

5-Hydroxymethylfurfural Hydrodeoxygenation to 2,5-Dimethylfuran in Continuous-Flow System over Ni on Nitrogen-Doped Carbon

Waste lignocellulosic biomass is sustainable and an alternative feedstock to fossil resources. Among the lignocellulosic derived compounds, 2,5-dimethylfuran (DMF) is a promising building block for chemicals, e.g., p-xylene, and a valuable biofuel. DMF can be obtained from 5-hydroxymethylfurfural (HMF) via catalytic deoxygenation using non-noble metals such as Ni in the presence of H2. Herein, we present the synthesis of DMF from HMF using 35 wt.% Ni on nitrogen-doped carbon pellets (35Ni/NDC) as a catalyst in a continuous flow system. The conversion of HMF to DMF was studied at different hydrogen pressures, reaction temperatures, and space times. At the best reaction conditions, i.e., 423 K, 8.0 MPa, and space time 6.4 kgNi h kgHMF−1, the 35Ni/NDC catalyst exhibited high catalytic activity with HMF conversion of 99 mol% and 80 mol% of DMF. These findings can potentially contribute to the transition toward the production of sustainable fine chemicals and liquid transportation fuels.

Highly efficient perylene-based polymer photocatalyst/biocatalyst systems for l-glutamate production under solar light

The selective production of fine chemicals using inexpensive solar light continues to be a challenge. As a means to achieve this we report herein the synthesis and development of a perylene-based solar-light-driven photocatalyst (PDA–DAA) obtained by the covalent bonding of perylene tetracarboxylic dianhydride (PDA) with a 2,6-diamino-anthraquinone (DAA) molecule. The photocatalyst/biocatalyst coupled system developed using PDA–DAA as a photocatalyst functions in a highly efficient manner, leading to high NADH regeneration (80.12%), followed by its consumption in exclusive production of l-glutamate (94.16%) from α-ketoglutarate. The present research highlights the development and application of the PDA–DAA photocatalyst for direct formation of l-glutamate under solar light.

Highly selective aromatic ring hydrogenation of lignin-derived compounds over macroporous Ru/Nb2O5 with the lost acidity at room temperature

Selective aromatic ring hydrogenation is an important process for the valorization of lignin and designing the high active and selective catalyst is still a challenge. At present, it is reported that such catalysts generally have some shortcomings including strict reaction conditions, complicated catalyst preparation and low reaction efficiency. Herein, Ru/Nb2O5 catalyst with the macropore structure prepared by an incipient wetness impregnation method could effectively promote the aromatic rings hydrogenation of various lignin-derived compounds under extremely mild condition (30 °C). The resulting aliphatic compounds with the high yield provided abundant raw materials for the production of fine chemicals and biofuels. In this case, further experiments revealed that it was H2 rather than solvents provided the only hydrogen source. A relatively low bond energy of Ru0 in Ru/Nb2O5 promoted the formation of active hydrogen from H2. Due to the acid loss of Ru/Nb2O5 catalyst, the hydrodeoxygenation reaction did not occur. Moreover, the catalyst was investigated under different influence parameters in order to obtain the optimal reaction conditions (30 °C, 3 MPa H2). The application of Ru/Nb2O5 catalyst may provide a promising approach to the value-added utilization of lignin-derived fragments.