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Developing heterogeneous photocatalysts for the applications in harsh conditions is of high importance but challenging. Herein, by converting the imine linkages into quinoline groups of triphenylamine incorporated covalent organic frameworks (COFs), two photosensitive COFs, namely TFPA-TAPT-COF-Q and TFPA-TPB-COF-Q, are successfully constructed. The obtained quinoline-linked COFs display improved stability and photocatalytic activity, making them suitable photocatalysts for photocatalytic reactions under harsh conditions, as verified by the recyclable photocatalytic reactions of organic acid involving oxidative decarboxylation and organic base involving benzylamine coupling. Under strong oxidative condition, the quinoline-linked COFs show a high efficiency up to 11831.6 μmol·g −1 ·h −1 and a long-term recyclable usability for photocatalytic production of H 2 O 2 , while the pristine imine-linked COFs are less catalytically active and easily decomposed in these harsh conditions. The results demonstrate that enhancing the linkage robustness of photoactive COFs is a promising strategy to construct heterogeneous catalysts for photocatalytic reactions under harsh conditions. The development of heterogeneous photocatalysts applicable under harsh conditions is challenging. Here the authors report the conversion of imine linkages into quinoline groups in triphenylamine incorporated photosensitive covalent organic frameworks to develop robust heterogeneous photocatalysts for photocatalytic applications in harsh conditions.

The enzymatic decarboxylation of fatty acids (FAs) represents an advance toward the development of biological routes to produce drop-in hydrocarbons. The current mechanism for the P450-catalyzed decarboxylation has been largely established from the bacterial cytochrome P450 OleTJE. Herein, we describe OleTPRN, a poly-unsaturated alkene-producing decarboxylase that outrivals the functional properties of the model enzyme and exploits a distinct molecular mechanism for substrate binding and chemoselectivity. In addition to the high conversion rates into alkenes from a broad range of saturated FAs without dependence on high salt concentrations, OleTPRN can also efficiently produce alkenes from unsaturated (oleic and linoleic) acids, the most abundant FAs found in nature. OleTPRN performs carbon–carbon cleavage by a catalytic itinerary that involves hydrogen-atom transfer by the heme-ferryl intermediate Compound I and features a hydrophobic cradle at the distal region of the substrate-binding pocket, not found in OleTJE, which is proposed to play a role in the productive binding of long-chain FAs and favors the rapid release of products from the metabolism of short-chain FAs. Moreover, it is shown that the dimeric configuration of OleTPRN is involved in the stabilization of the A-A’ helical motif, a second-coordination sphere of the substrate, which contributes to the proper accommodation of the aliphatic tail in the distal and medial active-site pocket. These findings provide an alternative molecular mechanism for alkene production by P450 peroxygenases, creating new opportunities for biological production of renewable hydrocarbons.

Mitochondrial NAD-malic enzyme (ME) and/or cytosolic/plastidic NADP-ME combined with the cytosolic/plastidic pyruvate orthophosphate dikinase (PPDK) catalyze two key steps during light-period malate decarboxylation that underpin secondary CO₂ fixation in some Crassulacean acid metabolism (CAM) species. We report the generation and phenotypic characterization of transgenic RNA interference lines of the obligate CAM speciesKalanchoë fedtschenkoiwith reduced activities of NAD-ME or PPDK. Transgenic linerNAD-ME1had 8%, andrPPDK1had 5% of the wild-type level of activity, and showed dramatic changes in the light/dark cycle of CAM CO₂ fixation. In well-watered conditions, these lines fixed all of their CO₂ in the light; they thus performed C₃ photosynthesis. The alternative malate decarboxylase, NADP-ME, did not appear to compensate for the reduction in NAD-ME, suggesting that NAD-ME was the key decarboxylase for CAM. The activity of other CAM enzymes was reduced as a consequence of knocking out either NAD-ME or PPDK activity, particularly phosphoenolpyruvate carboxylase (PPC) and PPDK inrNAD-ME1. Furthermore, the circadian clock-controlled phosphorylation of PPC in the dark was reduced in both lines, especially inrNAD-ME1. This had the consequence that circadian rhythms of PPC phosphorylation, PPCkinasetranscript levels and activity, and the classic circadian rhythm of CAM CO₂ fixation were lost, or dampened toward arrhythmia, under constant light and temperature conditions. Surprisingly, oscillations in the transcript abundance of core circadian clock genes also became arrhythmic in therNAD-ME1line, suggesting that perturbing CAM inK. fedtschenkoifeeds back to perturb the central circadian clock.

Cross-coupling between two similar or identical functional groups to form a new C–C bond is a powerful tool to rapidly assemble complex molecules from readily available building units, as seen with olefin cross-metathesis or various types of cross-electrophile coupling 1 , 2 . The Kolbe electrolysis involves the oxidative electrochemical decarboxylation of alkyl carboxylic acids to their corresponding radical species followed by recombination to generate a new C–C bond 3 – 12 . As one of the oldest known C sp 3 –C sp 3 bond-forming reactions, it holds incredible promise for organic synthesis, yet its use has been almost non-existent. From the perspective of synthesis design, this transformation could allow one to agnostically execute syntheses without regard to polarity or neighbouring functionality just by coupling ubiquitous carboxylates 13 . In practice, this promise is undermined by the strongly oxidative electrolytic protocol used traditionally since the nineteenth century 5 , thereby severely limiting its scope. Here, we show how a mildly reductive Ni-electrocatalytic system can couple two different carboxylates by means of in situ generated redox-active esters, termed doubly decarboxylative cross-coupling. This operationally simple method can be used to heterocouple primary, secondary and even certain tertiary redox-active esters, thereby opening up a powerful new approach for synthesis. The reaction, which cannot be mimicked using stoichiometric metal reductants or photochemical conditions, tolerates a range of functional groups, is scalable and is used for the synthesis of 32 known compounds, reducing overall step counts by 73%. An Ni-electrocatalytic system can couple two different carboxylates using doubly decarboxylative cross-coupling, tolerating a range of functional groups, being scalable, used for the synthesis of 32 known compounds and reducing overall step counts by 73%.

Isocitrate dehydrogenase (IDH) enzymes catalyse the oxidative decarboxylation of isocitrate and therefore play key roles in the Krebs cycle and cellular homoeostasis. Major advances in cancer genetics over the past decade have revealed that the genes encoding IDHs are frequently mutated in a variety of human malignancies, including gliomas, acute myeloid leukaemia, cholangiocarcinoma, chondrosarcoma and thyroid carcinoma. A series of seminal studies further elucidated the biological impact of the IDH mutation and uncovered the potential role of IDH mutants in oncogenesis. Notably, the neomorphic activity of the IDH mutants establishes distinctive patterns in cancer metabolism, epigenetic shift and therapy resistance. Novel molecular targeting approaches have been developed to improve the efficacy of therapeutics against IDH-mutated cancers. Here we provide an overview of the latest findings in IDH-mutated human malignancies, with a focus on glioma, discussing unique biological signatures and proceedings in translational research.

Reactions that enable carbon–nitrogen, carbon–oxygen and carbon–carbon bond formation lie at the heart of synthetic chemistry. However, substrate prefunctionalization is often needed to effect such transformations without forcing reaction conditions. The development of direct coupling methods for abundant feedstock chemicals is therefore highly desirable for the rapid construction of complex molecular scaffolds. Here we report a copper-mediated, net-oxidative decarboxylative coupling of carboxylic acids with diverse nucleophiles under visible-light irradiation. Preliminary mechanistic studies suggest that the relevant chromophore in this reaction is a Cu( ii ) carboxylate species assembled in situ. We propose that visible-light excitation to a ligand-to-metal charge transfer (LMCT) state results in a radical decarboxylation process that initiates the oxidative cross-coupling. The reaction is applicable to a wide variety of coupling partners, including complex drug molecules, suggesting that this strategy for cross-nucleophile coupling would facilitate rapid compound library synthesis for the discovery of new pharmaceutical agents. Direct coupling methods, which do not require substrate prefunctionalization, are highly desirable for the construction of complex molecular scaffolds. Now, a photochemical method has been developed for the direct decarboxylative coupling of carboxylic acids with diverse nitrogen, oxygen and carbon nucleophiles, taking advantage of the photochemistry of copper(II) carboxylate complexes assembled in situ.

The efficacy of l -dopa treatment for Parkinson's disease is hugely variable between individuals, depending on the composition of their microbiota. l -Dopa is decarboxylated into active dopamine, but if the gut microbiota metabolize l -dopa before it crosses the blood-brain barrier, medication is ineffective. Maini Rekdal et al. found that different species of bacterium are involved in l -dopa metabolism (see the Perspective by O'Neill). Tyrosine decarboxylase (TDC) from Enterococcus faecalis and dopamine dehydroxylase (Dadh) from Eggerthella lenta A2 sequentially metabolized l -dopa into m -tyramine. The microbial l -dopa decarboxylase can be inactivated by ( S )-α-fluoromethyltyrosine (AFMT), which indicates possibilities for developing combinations of Parkinson's drugs to circumvent microbial inactivation. Science , this issue p. eaau6323 ; see also p. 1030 An interspecies metabolic pathway allows human gut bacteria to metabolize the Parkinson’s drug levodopa. The human gut microbiota metabolizes the Parkinson’s disease medication Levodopa ( l -dopa), potentially reducing drug availability and causing side effects. However, the organisms, genes, and enzymes responsible for this activity in patients and their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway for gut bacterial l -dopa metabolism. Conversion of l -dopa to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase from Enterococcus faecalis is followed by transformation of dopamine to m -tyramine by a molybdenum-dependent dehydroxylase from Eggerthella lenta . These enzymes predict drug metabolism in complex human gut microbiotas. Although a drug that targets host aromatic amino acid decarboxylase does not prevent gut microbial l -dopa decarboxylation, we identified a compound that inhibits this activity in Parkinson’s patient microbiotas and increases l -dopa bioavailability in mice.

In this study, a photocatalytic late‐stage decarboxylative functionalization strategy utilizing gem‐boryl,silyl (gem‐B,Si) alkene as a versatile coupling partner is reported. This light‐driven transformation enables the direct conversion of structurally simple and complex carboxylic acids into synthetically valuable molecules with Csp3 carbon bearing both Bpin and SiMe3 groups under mild conditions. This methodology provides a powerful platform for the selective, programmable, late‐stage modification of bioactive molecules, natural products, and fatty acid derivatives, enabling access to a diverse array of functionalized, chiral Csp3‐rich molecules with potential applications across materials science and chemistry. A photocatalytic, late‐stage decarboxylative functionalization of carboxylic acids using gem‐borylsilyl alkenes is described. This transformation enables the direct decarboxylative /radical addition of bioactive, naturally occurring, and fatty acids to gem‐B,Si alkenes, delivering synthetically valuable alkylboron,silayl under mild, visible‐light conditions. A powerful platform for late‐stage diversification.

The C‐terminal decarboxylation of peptides provides an important opportunity to synthesize modern peptide pharmaceuticals that contain C‐terminal amides. This transformation can be achieved by electrochemical oxidation; however, the standard implementation depends on oxidation potential for selectivity which may represent a challenge when amino acid residues containing electroactive side chains are present. To address this limitation, an alternative mechanistic paradigm has been introduced for selective decarboxylation of a C‐terminal carboxylate, one that relies on a chelation event. In a proof‐of‐principle experiment used to probe and define the viability of this mechanism, it is demonstrated that the combination of an iron mediator and a C‐terminal glutamate residue can be used to conduct the reaction in the presence of the more electron‐rich tyrosine residue frequently found in medicinally active peptides. Investigations into the reaction specifics and the scope/limitations provide key insights into the reaction mechanism and how such processes can be optimized. The success of the method highlighted here points to a more general binding‐based approach to drive C‐terminal decarboxylation that utilizes a functional group motif not possible at any other position in a peptide. Chemoselectivity in electrochemical oxidations is largely influenced by oxidation potential which represents a challenge for selectively oxidizing higher potential functional groups in complex substrates. Herein, a molecular binding strategy that selectively oxidizes the C‐terminal acid of a model peptide containing an electron‐rich tyrosine residue by exploiting a binding event between a dicarboxylate and an iron mediator is reported.

Extra ATP required in C4 photosynthesis for the CO2-concentrating mechanism probably comes from cyclic electron transport (CET). As metabolic ATP : NADPH requirements in mesophyll (M) and bundle-sheath (BS) cells differ among C4 subtypes, the subtypes may differ in the extent to which CET operates in these cells. We present an analytical model for cell-type-specific CET and linear electron transport. Modelled NADPH and ATP production were compared with requirements. For malic-enzyme (ME) subtypes, c. 50% of electron flux is CET, occurring predominantly in BS cells for standard NADP-ME species, but in a ratio of c. 6 : 4 in BS :M cells for NAD-ME species. Some C4 acids follow a secondary decarboxylation route, which is obligatory, in the form of ‘aspartate-malate’, for the NADP-ME subtype, but facultative, in the form of phosphoenolpyruvate-carboxykinase (PEP-CK), for the NAD-ME subtype. The percentage for secondary decarboxylation is c. 25% and that for 3-phosphoglycerate reduction in BS cells is c. 40%; but these values vary with species. The ‘pure’ PEP-CK type is unrealistic because its is impossible to fulfilATP : NADPH requirements in BS cells. The standard PEP-CK subtype requires negligible CET, and thus has the highest intrinsic quantum yields and deserves further studies in the context of improving canopy productivity.