Dual Photoredox and Nickel Catalysis in Regioselective Diacylation: Exploring the Versatility of Nickel Oxidation States in Allene Activation.

We present a nickel-catalyzed regioselective radical diacylation of allenes with ketoacids to produce 1,4-dione products by dual photoredox and nickel catalysis. This integrated approach merges redox-active oxidative addition and reductive elimination steps with migratory insertion. The acyl radical generated in the photoredox cycle sequentially adds to Ni(I) and Ni(II) intermediates following a Ni(I)-Ni(II)-Ni(II)-Ni(III)-Ni(I) catalytic cycle. This methodology, supported by DFT calculations, demonstrates the potential of nickel catalysis in the creation of complex molecular architectures.

Succinic acid production from softwood with genome-edited Corynebacterium glutamicum using the CRISPR-Cpf1 system.

Corynebacterium glutamicum is a useful microbe that can be used for producing succinic acid under anaerobic conditions. In this study, we generated a knock-out mutant of the lactate dehydrogenase 1 gene (ΔldhA-6) and co-expressed the succinic acid transporter (Psod:SucE- ΔldhA) using the CRISPR-Cpf1 genome editing system. The highly efficient HPAC (hydrogen peroxide and acetic acid) pretreatment method was employed for the enzymatic hydrolysis of softwood (Pinus densiflora) and subsequently utilized for production of succinic acid. Upon evaluating a 1%-5% hydrolysate concentration range, optimal succinic acid production with the ΔldhA mutant was achieved at a 4% hydrolysate concentration. This resulted in 14.82 g L-1 succinic acid production over 6 h. No production of acetic acid and lactic acid was detected during the fermentation. The co-expression transformant, [Psod:SucE-ΔldhA] produced 17.70 g L-1 succinic acid in 6 h. In the fed-batch system, 39.67 g L-1 succinic acid was produced over 48 h. During the fermentation, the strain consumed 100% and 73% of glucose and xylose, respectively. The yield of succinic acid from the sugars consumed was approximately 0.77 g succinic acid/g sugars. These results indicate that the production of succinic acid from softwood holds potential applications in alternative biochemical processes.

Value-Added Products from Coffee Waste: A Review.

Coffee waste is often viewed as a problem, but it can be converted into value-added products if managed with clean technologies and long-term waste management strategies. Several compounds, including lipids, lignin, cellulose and hemicelluloses, tannins, antioxidants, caffeine, polyphenols, carotenoids, flavonoids, and biofuel can be extracted or produced through recycling, recovery, or energy valorization. In this review, we will discuss the potential uses of by-products generated from the waste derived from coffee production, including coffee leaves and flowers from cultivation; coffee pulps, husks, and silverskin from coffee processing; and spent coffee grounds (SCGs) from post-consumption. The full utilization of these coffee by-products can be achieved by establishing suitable infrastructure and building networks between scientists, business organizations, and policymakers, thus reducing the economic and environmental burdens of coffee processing in a sustainable manner.

Converting textile waste into value-added chemicals: An integrated bio-refinery process.

The rate of textile waste generation worldwide has increased dramatically due to a rise in clothing consumption and production. Here, conversion of cotton-based, colored cotton-based, and blended cotton-polyethylene terephthalate (PET) textile waste materials into value-added chemicals (bioethanol, sorbitol, lactic acid, terephthalic acid (TPA), and ethylene glycol (EG)) via enzymatic hydrolysis and fermentation was investigated. In order to enhance the efficiency of enzymatic saccharification, effective pretreatment methods for each type of textile waste were developed, respectively. A high glucose yield of 99.1% was obtained from white cotton-based textile waste after NaOH pretreatment. Furthermore, the digestibility of the cellulose in colored cotton-based textile wastes was increased 1.38-1.75 times because of the removal of dye materials by HPAC-NaOH pretreatment. The blended cotton-PET samples showed good hydrolysis efficiency following PET removal via NaOH-ethanol pretreatment, with a glucose yield of 92.49%. The sugar content produced via enzymatic hydrolysis was then converted into key platform chemicals (bioethanol, sorbitol, and lactic acid) via fermentation or hydrogenation. The maximum ethanol yield was achieved with the white T-shirt sample (537 mL/kg substrate), which was 3.2, 2.1, and 2.6 times higher than those obtained with rice straw, pine wood, and oak wood, respectively. Glucose was selectively converted into sorbitol and LA at a yield of 70% and 83.67%, respectively. TPA and EG were produced from blended cotton-PET via NaOH-ethanol pretreatment. The integrated biorefinery process proposed here demonstrates significant potential for valorization of textile waste.

Construction of a Pentacyclic Framework Enabled by Nickel Catalysis.

We present a novel nickel-catalyzed reaction of indole-tethered 2-alkynylphenol esters with various (hetero)aryl boronic acids, resulting in the synthesis of diversely functionalized pentacyclic benzofurocyclohepta[b]indole derivatives. This unprecedented cascade reaction involves the arylative cyclization of alkynes, nucleophilic attack of the indole moiety on the oxonium ion intermediate, 1,2-alkyl group migration, and aromatization. The synthesized molecules exhibit exceptional cytotoxicity against multiple cancer cell lines while maintaining biocompatibility toward healthy cells.

Photoredox Selective Homocoupling of Propargyl Bromides.

Since the alkynyl moiety is one of the most versatile synthons for many other functional groups, 1,5-diynes (Wurtz-type products of propargyl halides) would be valuable synthetic building blocks for the synthesis of complex functional molecules. However, despite the high and similar reactivity of propargyl radicals compared to allyl and benzyl derivative radicals, a photoredox Wurtz-type reaction of propargyl halides has not yet been developed. In this study, we developed the visible-light-induced selective homocoupling of propargyl bromides to form 1,5-diynes. Electrochemical and photophysical experiments showed that the key propargyl radical generation involves a reductive quenching cycle of the photoexcited [Ir(III)]* photocatalyst in the presence of N,N-dicyclohexylmethylamine. The product 1,5-diyne underwent one-step conversion to the functionalized indole derivative via Rh-catalyzed coupling with N-phenylacetamide. These results indicated the high utility of the developed homocoupling method.

Boosted Heterogeneous Catalysis by Surface-Accumulated Excess Electrons of Non-Oxidized Bare Copper Nanoparticles on Electride Support.

Engineering active sites of metal nanoparticle-based heterogeneous catalysts is one of the most prerequisite approaches for the efficient production of chemicals, but the limited active sites and undesired oxidation on the metal nanoparticles still remain as key challenges. Here, it is reported that the negatively charged surface of copper nanoparticles on the 2D [Ca2 N]+ ∙e- electride provides the unrestricted active sites for catalytic selective sulfenylation of indoles and azaindoles with diaryl disulfides. Substantial electron transfer from the electride support to copper nanoparticles via electronic metal-support interactions results in the accumulation of excess electrons at the surface of copper nanoparticles. Moreover, the surface-accumulated excess electrons prohibit the oxidation of copper nanoparticle, thereby maintaining the metallic surface in a negatively charged state and activating both (aza)indoles and disulfides under mild conditions in the absence of any further additives. This study defines the role of excess electrons on the nanoparticle-based heterogeneous catalyst that can be rationalized in versatile systems.

Photocatalytic para-Selective C-H Functionalization of Anilines with Diazomalonates.

Visible-light-induced para-selective C-H functionalization of anilines over N-H insertion was developed using diazomalonates with the help of an Ir(III) photocatalyst. The para-selective radical-radical cross coupling proceeded via C-centered radical intermediates generated from both anilines and diazomalonates. The photochemistry of anilines could be extended to other N-heterocycles, such as indole and carbazole. The reaction pathway for the selective C-C coupling was validated by electrochemical and photophysical experiments as well as computational studies.

N-O Bond Activation by Energy Transfer Photocatalysis.

A radical shift toward energy transfer photocatalysis from electron transfer photocatalysis under visible-light photoirradiation is often due to the greener prospects of atom and process economy. Recent advances in energy transfer photocatalysis embrace unique strategies for direct small-molecule activation and sometimes extraordinary chemical bond formation in the absence of additional/sacrificial reagents. Selective energy transfer photocatalysis requires careful selection of substrates and photocatalysts for a perfect match with respect to their triplet energies while having incompatible redox potentials to prevent competitive electron transfer pathways. Substrates containing labile N-O bonds are potential targets for generating reactive key intermediates via photocatalysis to access a variety of functionalized molecules. Typically, the differential electron densities of N and O heteroatoms have been exploited for generation of either N- or O-centered radical intermediates from the functionalized substrates by the electron transfer pathway. However, the latest developments involve direct N-O bond homolysis via energy transfer to generate both N- and O-centered radicals for their subsequent utilization in diverse organic transformations, also in the absence of sacrificial redox reagents. In this Account, we highlight our key contributions in the field of N-O bond activation via energy transfer photocatalysis to generate reactive radical intermediates, with coverage of useful mechanistic insights. More specifically, well-designed N-O bond-containing substrates such as 1,2,4-oxadiazolines, oxime esters, N-indolyl carbonates, and N-enoxybenzotriazoles were successfully utilized in versatile transformations involving selective energy transfer over electron transfer from photocatalysts with high triplet state energy. Direct access to reactive N-, O-, and C-centered (if decarboxylation follows) radical intermediates was achieved for diverse cross-couplings and rearrangement processes. In particular, a variety of open-shell nitrogen reactive intermediates, including N(sp2) and N(sp3) radicals and nitrenes, have been utilized. Notably, diversified transformations of identical substrates have been achieved through careful control of the reaction conditions. 1,2,4-Oxadiazolines were converted into spiro-azolactams through iminyl intermediates in the presence of 1O2, benzimidazoles, or sulfoximines with external sulfoxide reagent through triplet nitrene intermediates under inert conditions. Besides, oxime esters underwent either intramolecular C(sp3)-N radical-radical coupling or intermolecular C(sp3)-N radical-radical coupling by a combined energy transfer-hydrogen atom transfer strategy. Furthermore, a series of electrochemical and photophysical experiments as well as computational studies were performed to substantiate the proposed selective energy-transfer-driven reaction pathways. We hope that this Account will serve as a guide for the rational design of selective energy transfer processes through the activation of further labile chemical bonds.

Nickel-Catalyzed Enantioselective Synthesis of 2,3,4-Trisubstituted 3-Pyrrolines.

The development of synthetic methods to produce highly functionalized chiral 3-pyrrolines is of indisputable importance because of their prevalence in natural and synthetic bioactive molecules. Unfortunately, previous general cycloaddition approaches using allenoates, could not synthesize 3,4-disubstituted 3-pyrrolines. Herein, an original approach to yield 2,3,4-trisubstituted 3-pyrrolines with chirality at the 2-position is presented. A NiII /Fc-i-PrPHOX catalytic system facilitated a redox-neutral highly stereoselective process that exhibited an enantioselectivity of up to 99 %. Enantioenriched 3-pyrrolines can be converted to other valuable classes of N-heterocycles.

Energy Transfer Photocatalytic Radical Rearrangement in N-Indolyl Carbonates.

A new type of sp3-like N-centered radical has been generated by selective energy transfer catalysis. Upon photoexcitation, homolytic N-O bond cleavage of N-indolyl carbonate in the presence of an Ir complex produced N- and O-centered radicals. The high spin density at the C3 position of indole led to radical recombination with the O-centered radical, affording valuable 3-oxyindole derivatives without decarboxylation. Transformations of the desired products into various molecules were also demonstrated.

Non-oxidized bare copper nanoparticles with surface excess electrons in air.

Copper (Cu) nanoparticles (NPs) have received extensive interest owing to their advantageous properties compared with their bulk counterparts. Although the natural oxidation of Cu NPs can be alleviated by passivating the surfaces with additional moieties, obtaining non-oxidized bare Cu NPs in air remains challenging. Here we report that bare Cu NPs with surface excess electrons retain their non-oxidized state over several months in ambient air. Cu NPs grown on an electride support with excellent electron transfer ability are encapsulated by the surface-accumulated excess electrons, exhibiting an ultralow work function of ~3.2 eV. Atomic-scale structural and chemical analyses confirm the absence of Cu oxide moiety at the outermost surface of air-exposed bare Cu NPs. Theoretical energetics clarify that the surface-accumulated excess electrons suppress the oxygen adsorption and consequently prohibit the infiltration of oxygen into the Cu lattice, provoking the endothermic reaction for oxidation process. Our results will further stimulate the practical use of metal NPs in versatile applications.

A Rapid Assessing Method of Drug Susceptibility Using Flow Cytometry for Mycobacterium tuberculosis Isolates Resistant to Isoniazid, Rifampin, and Ethambutol.

BACKGROUND: The current conventional drug susceptibility test (DST) for Mycobacterium tuberculosis (Mtb) takes several weeks of incubation to obtain results. As a rapid method, molecular DST requires only a few days to get the results but does not fully cover the phenotypic resistance. A new rapid method based on the ability of viable Mtb bacilli to hydrolyze fluorescein diacetate to free fluorescein with detection of fluorescent mycobacteria by flow cytometric analysis, was recently developed. METHODS: To evaluate this cytometric method, we tested 39 clinical isolates which were susceptible or resistant to isoniazid (INH) or rifampin (RIF), or ethambutol (EMB) by phenotypic or molecular DST methods and compared the results. RESULTS: The susceptibility was determined by measuring the viability rate of Mtb and all the isolates which were tested with INH, RIF, and EMB showed susceptibility results concordant with those by the phenotypic solid and liquid media methods. The isolates having no mutations in the molecular DST but resistance in the conventional phenotypic DST were also resistant in this cytometric method. These results suggest that the flow cytometric DST method is faster than conventional agar phenotypic DST and may complement the results of molecular DST. CONCLUSION: In conclusion, the cytometric method could provide quick and more accurate information that would help clinicians to choose more effective drugs.

Ni-Catalyzed Reductive Coupling of Alkynes and Amides to Access Multi-Functionalized Indoles.

A nickel-catalyzed reductive coupling of alkynes and amides, followed by base-free transmetalation, proceeded selectively in the presence of an uncommon bidentate primary aminophosphine ligand to access highly functionalized indoles comprising biologically important trifluoromethyl groups and challenging electron-rich alkenyl groups at the 2- and 3-positions, respectively. Indole molecules were installed within natural products or drug molecules under mild conditions, and a trifluoromethylated analogue of a drug molecule (pravadoline) was also synthesized.

Sustainable radical approaches for cross electrophile coupling to synthesize trifluoromethyl- and allyl-substituted tert-alcohols.

Trifluoromethylated molecules have gained privileged recognition among the medicinal and pharmaceutical chemists. Sustainable photoredox- and electrochemical processes were employed to facilitate the relatively less explored radical cross-electrophile coupling to access trifluoromethyl- and allyl-substituted tert-alcohols. Reactions proceed through trifluoromethyl ketyl radical and allyl radical intermediates, which undergo challenging radical-radical cross-coupling. The developed transformations are mild and chemo-selective to give cross-coupled products and deliver a wide range of valuable trifluoromethyl- and allyl-containing tertiary alcohols. Both processes can also be applied for the synthesis of amine variant containing trifluoromethyl and allyl moiety, which is considered as amide bioisostere.

Boosting Photoredox Catalysis Using a Two-Dimensional Electride as a Persistent Electron Donor.

Electrides, which have excess anionic electrons, are solid-state sources of solvated electrons that can be used as powerful reducing agents for organic syntheses. However, the abrupt decomposition of electrides in organic solvents makes controlling the transfer inefficient, thereby limiting the utilization of their superior electron-donating ability. Here, we demonstrate the efficient reductive transformation strategy which combines the stable two-dimensional [Gd2C]2+·2e- electride electron donor and cyclometalated Pt(II) complex photocatalysts. Strongly localized anionic electrons at the interlayer space in the [Gd2C]2+·2e- electride are released via moderate alcoholysis in 2,2,2-trifluoroethanol, enabling persistent electron donation. The Pt(II) complexes are adsorbed onto the surface of the [Gd2C]2+·2e- electride and rapidly capture the released electrons at a rate of 107 s-1 upon photoexcitation. The one-electron-reduced Pt complex is electrochemically stable enough to deliver the electron to substrates in the bulk, which completes the photoredox cycle. The key benefit of this system is the suppression of undesirable charge recombination because back electron transfer is prohibited due to the irreversible disruption of the electride after the electron transfer. These desirable properties collectively serve as the photoredox catalysis principle for the reductive generation of the benzyl radical from benzyl halide, which is the key intermediate for dehalogenated or homocoupled products.

Complementary Reactivity in Selective Radical Processes: Electrochemistry of Oxadiazolines to Quinazolinones.

Electrochemistry has recently emerged as a sustainable approach for efficiently generating radical intermediates utilizing eco-friendly electric energy. An electrochemical process was developed to transform 1,2,4-oxadiazolines under mild conditions. The electrochemical N-O bond cleavage at a controlled oxidation potential led to the selective synthesis of quinazolinone derivatives that could not be obtained by photocatalytic radical processes, indicating complementary reactivities in radical processes. The electrochemical reaction pathways were fully revealed by density functional theory-based investigations.

Hydrolysis pattern analysis of xylem tissues of woody plants pretreated with hydrogen peroxide and acetic acid: rapid saccharification of softwood for economical bioconversion.

BACKGROUND: Woody plants with high glucose content are alternative bioresources for the production of biofuels and biochemicals. Various pretreatment methods may be used to reduce the effects of retardation factors such as lignin interference and cellulose structural recalcitrance on the degradation of the lignocellulose material of woody plants. RESULTS: A hydrogen peroxide-acetic acid (HPAC) pretreatment was used to reduce the lignin content of several types of woody plants, and the effect of the cellulose structural recalcitrance on the enzymatic hydrolysis was analyzed. The cellulose structural recalcitrance and the degradation patterns of the wood fibers in the xylem tissues of Quercus acutissima (hardwood) resulted in greater retardation in the enzymatic saccharification than those in the tracheids of Pinus densiflora (softwood). In addition to the HPAC pretreatment, the application of supplementary enzymes (7.5 FPU cellulase for 24 h) further increased the hydrolysis rate of P. densiflora from 61.42 to 91.94% whereas the same effect was not observed for Q. acutissima. It was also observed that endoxylanase synergism significantly affected the hydrolysis of P. densiflora. However, this synergistic effect was lower for other supplementary enzymes. The maximum concentration of the reducing sugars produced from 10% softwood was 89.17 g L-1 after 36 h of hydrolysis with 15 FPU cellulase and other supplementary enzymes. Approximately 80 mg mL-1 of reducing sugars was produced with the addition of 7.5 FPU cellulase and other supplementary enzymes after 36 h, achieving rapid saccharification. CONCLUSION: HPAC pretreatment removed the interference of lignin, reduced structural recalcitrance of cellulose in the P. densiflora, and enabled rapid saccharification of the woody plants including a high concentration of insoluble substrates with only low amounts of cellulase. HPAC pretreatment may be a viable alternative for the cost-efficient production of biofuels or biochemicals from softwood plant tissues.

Understanding and Improving Photocatalytic Activity of Pd-Loaded BiVO4 Microspheres: Application to Visible Light-Induced Suzuki-Miyaura Coupling Reaction.

The effective utilization of visible light is required for exploiting photocatalytic reactions in indoor and outdoor environments. In this study, Pd-supported BiVO4 microspheres (Pd-BiVO4) were prepared for visible light-induced photocatalytic reactions. Under irradiation with a white light-emitting diode, the obtained Pd-BiVO4 composite exhibited considerably improved catalytic activity for the decomposition of an organic dye compared with other BiVO4 catalysts. The Pd-BiVO4 composite was also effective for catalytic organic transformation via the visible light-induced Suzuki-Miyaura coupling reaction. The photogenerated electrons in the conduction band of BiVO4 flowed to the Pd nanoparticles and amplified cross-coupling reaction. The influence of the crystal structure and grain size of BiVO4 and the role of the deposited Pd nanoparticles were fully investigated to elucidate the visible light activity of the catalyst. This system highlights the possibility of an indoor light source with low energy density for sustainable organic transformations.

Nickel-Catalyzed trans-Carboamination across Internal Alkynes to Access Multifunctionalized Indoles.

A Ni-catalyzed reaction was developed for the synthesis of multifunctionalized indoles. The reaction proceeded through oxidative cyclization of the Ni(0)/P^N complex with an enyne system, 2-alkynyl anilinoacrylate, to provide a nickelacycle intermediate. The trans-carboamination around the internal alkyne was achieved by syn/anti-rotation of the Ni-carbenoid intermediate formed by C-N bond cleavage of the nickelacycle, and 3-alkenylated indoles were formed by C-N bond-forming reductive elimination. Notably, the synthesized indoles could be successfully transformed to functionalized carbazoles.