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Enzymes are increasingly explored for use in asymmetric synthesis1-3, but their applications are generally limited by the reactions available to naturally occurring enzymes. Recently, interest in photocatalysis4 has spurred the discovery of novel reactivity from known enzymes5. However, so far photoinduced enzymatic catalysis6 has not been used for the cross-coupling of two molecules. For example, the intermolecular coupling of alkenes with α-halo carbonyl compounds through a visible-light-induced radical hydroalkylation, which could provide access to important γ-chiral carbonyl compounds, has not yet been achieved by enzymes. The major challenges are the inherent poor photoreactivity of enzymes and the difficulty in achieving stereochemical control of the remote prochiral radical intermediate7. Here we report a visible-light-induced intermolecular radical hydroalkylation of terminal alkenes that does not occur naturally, catalysed by an 'ene' reductase using readily available α-halo carbonyl compounds as reactants. This method provides an efficient approach to the synthesis of various carbonyl compounds bearing a γ-stereocentre with excellent yields and enantioselectivities (up to 99 per cent yield with 99 per cent enantiomeric excess), which otherwise are difficult to access using chemocatalysis. Mechanistic studies suggest that the formation of the complex of the substrates (α-halo carbonyl compounds) and the 'ene' reductase triggers the enantioselective photoinduced radical reaction. Our work further expands the reactivity repertoire of biocatalytic, synthetically useful asymmetric transformations by the merger of photocatalysis and enzyme catalysis.
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Alquenos/química , Alquenos/metabolismo , Hidrógeno/química , Hidrógeno/metabolismo , Luz , Oxidorreductasas/metabolismo , Procesos Fotoquímicos/efectos de la radiación , Alcoholes/química , Alcoholes/metabolismo , Alquilación/efectos de la radiación , Biocatálisis/efectos de la radiación , Biomasa , Carboxiliasas/metabolismo , Flavinas/metabolismo , Modelos Químicos , Modelos Moleculares , EstereoisomerismoRESUMEN
We report the macrocyclic ring size-electronic structure-electrophilic reactivity correlation of mononuclear nonheme iron(III)-peroxo complexes bearing N-tetramethylated cyclam analogues (n-TMC), [FeIII(O2)(12-TMC)]+ (1), [FeIII(O2)(13-TMC)]+ (2), and [FeIII(O2)(14-TMC)]+ (3), as a model study of Rieske oxygenases. The Fe(III)-peroxo complexes show the same δ and pseudo-σ bonds between iron and the peroxo ligand. However, the strength of these interactions varies depending on the ring size of the n-TMC ligands; the overall Fe-O bond strength and the strength of the Fe-O2 δ bond increase gradually as the ring size of the n-TMC ligands becomes smaller, such as from 14-TMC to 13-TMC to 12-TMC. MCD spectroscopy plays a key role in assigning the characteristic low-energy δ â δ* LMCT band, which provides direct insight into the strength of the Fe-O2 δ bond and which, in turn, is correlated with the superoxo character of the iron-peroxo group. In oxidation reactions, reactivities of 1-3 toward hydrocarbon C-H bond activation are compared, revealing the reactivity order of 1 > 2 > 3; the [FeIII(O2)(n-TMC)]+ complex with a smaller n-TMC ring size, 12-TMC, is much more reactive than that with a larger n-TMC ring size, 14-TMC. DFT analysis shows that the Fe(III)-peroxo complex is not reactive toward C-H bonds, but it is the end-on Fe(II)-superoxo valence tautomer that is responsible for the observed reactivity. The hydrogen atom abstraction (HAA) reactivity of these intermediates is correlated with the overall donicity of the n-TMC ligand, which modulates the energy of the singly occupied π* superoxo frontier orbital that serves as the electron acceptor in the HAA reaction. The implications of these results for the mechanism of Rieske oxygenases are further discussed.
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Ciclamas , Hierro , Hierro/química , Oxigenasas , Ligandos , Biomimética , Oxígeno/química , Hidrógeno , Compuestos FérricosRESUMEN
Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of natural products. The enzyme mechanism for the biaryl phenol coupling reaction of the bicyclic CCNPs remains unclear. Herein, we report the discovery of two new arabinofuranosylated bicyclic CCNPs cihanmycins (CHMs) A (1) and B (2) from Amycolatopsis cihanbeyliensis DSM 45679 and the identification of the CHM biosynthetic gene cluster (cih BGC) by heterologous expression in Streptomyces lividans SBT18 to afford CHMs C (3) and D (4). The structure of 1 was confirmed by X-ray diffraction analysis. Three cytochrome P450 enzyme (CYP)-encoding genes cih26, cih32, and cih33 were individually inactivated in the heterologous host to produce CHMs E (5), F (6), and G (7), respectively. The structures of 5 and 6 indicated that Cih26 was responsible for the hydroxylation and epoxidation of the cinnamoyl moiety, and Cih32 should catalyze the ß-hydroxylation of three amino acid residues. Cih33 and its homologues DmlH and EpcH were biochemically verified to convert CHM G (7) with a monocyclic structure to a bicyclic skeleton of CHM C (3) through an intramolecular C-O phenol coupling reaction. The substrate 7-bound crystal structure of DmlH not only established the structure of 7, which was difficult for NMR analysis for displaying anomalous splitting signals, but also provided the binding mode of macrocyclic peptides recognized by these intramolecular C-O coupling CYPs. In addition, computational studies revealed a water-mediated diradical mechanism for the C-O phenol coupling reaction. These findings have shed important mechanistic insights into the CYP-catalyzed phenol coupling reactions.
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The development of catalysts serves as the cornerstone of innovation in synthesis, as exemplified by the recent discovery of photoenzymes. However, the repertoire of naturally occurring enzymes repurposed by direct light excitation to catalyze new-to-nature photobiotransformations is currently limited to flavoproteins and keto-reductases. Herein, we shed light on imine reductases (IREDs) that catalyze the remote C(sp3)-C(sp3) bond formation, providing a previously elusive radical hydroalkylation of enamides for accessing chiral amines (45 examples with up to 99% enantiomeric excess). Beyond their natural function in catalyzing two-electron reductive amination reactions, upon direct visible-light excitation or in synergy with a synthetic photoredox catalyst, IREDs are repurposed to tune the non-natural photoinduced single-electron radical processes. By conducting wet mechanistic experiments and computational simulations, we unravel how engineered IREDs direct radical intermediates toward the productive and enantioselective pathway. This work represents a promising paradigm for harnessing nature's catalysts for new-to-nature asymmetric transformations that remain challenging through traditional chemocatalytic methods.
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Water network rearrangement from the ligand-unbound state to the ligand-bound state is known to have significant effects on the protein-ligand binding interactions, but most of the current machine learning-based scoring functions overlook these effects. In this study, we endeavor to construct a comprehensive and realistic deep learning model by incorporating water network information into both ligand-unbound and -bound states. In particular, extended connectivity interaction features were integrated into graph representation, and graph transformer operator was employed to extract features of the ligand-unbound and -bound states. Through these efforts, we developed a water network-augmented two-state model called ECIFGraph::HM-Holo-Apo. Our new model exhibits satisfactory performance in terms of scoring, ranking, docking, screening, and reverse screening power tests on the CASF-2016 benchmark. In addition, it can achieve superior performance in large-scale docking-based virtual screening tests on the DEKOIS2.0 data set. Our study highlights that the use of a water network-augmented two-state model can be an effective strategy to bolster the robustness and applicability of machine learning-based scoring functions, particularly for targets with hydrophilic or solvent-exposed binding pockets.
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Proteínas , Agua , Ligandos , Bases de Datos de Proteínas , Simulación del Acoplamiento Molecular , Proteínas/metabolismo , Unión ProteicaRESUMEN
Improving the generalization ability of scoring functions remains a major challenge in protein-ligand binding affinity prediction. Many machine learning methods are limited by their reliance on single-modal representations, hindering a comprehensive understanding of protein-ligand interactions. We introduce a graph-neural-network-based scoring function that utilizes a triplet contrastive learning loss to improve protein-ligand representations. In this model, three-dimensional complex representations and the fusion of two-dimensional ligand and coarse-grained pocket representations converge while distancing from decoy representations in latent space. After rigorous validation on multiple external data sets, our model exhibits commendable generalization capabilities compared to those of other deep learning-based scoring functions, marking it as a promising tool in the realm of drug discovery. In the future, our training framework can be extended to other biophysical- and biochemical-related problems such as protein-protein interaction and protein mutation prediction.
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Descubrimiento de Drogas , Aprendizaje Automático , Ligandos , Mutación , Redes Neurales de la ComputaciónRESUMEN
Flavoenzymes can mediate a large variety of oxidation reactions through the activation of oxygen. However, the O2 activation chemistry of flavin enzymes is not yet fully exploited. Normally, the O2 activation occurs at the C4a site of the flavin cofactor, yielding the flavin C4a-(hydro)hydroperoxyl species in monooxygenases or oxidases. Using extensive MD simulations, QM/MM calculations and QM calculations, our studies reveal the formation of the common nucleophilic species, Flavin-N5OOH, in two distinct flavoenzymes (RutA and EncM). Our studies show that Flavin-N5OOH acts as a powerful nucleophile that promotes C-N cleavage of uracil in RutA, and a powerful base in the deprotonation of substrates in EncM. We reason that Flavin-N5OOH can be a common reactive species in the superfamily of flavoenzymes, which accomplish generally selective general base catalysis and C-X (X=N, S, Cl, O) cleavage reactions that are otherwise challenging with solvated hydroxide ion base. These results expand our understanding of the chemistry and catalysis of flavoenzymes.
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Flavinas , Oxigenasas de Función Mixta , Flavinas/metabolismo , Oxigenasas de Función Mixta/metabolismo , Oxidación-Reducción , Oxidorreductasas , Compuestos OrgánicosRESUMEN
Repurposing enzymes to catalyze non-natural asymmetric transformations that are difficult to achieve using traditional chemical methods is of significant importance. Although radical C-O bond formation has emerged as a powerful approach for constructing oxygen-containing compounds, controlling the stereochemistry poses a great challenge. Here we present the development of a dual bio-/photo-catalytic system comprising an ene-reductase and an organic dye for achieving stereoselective lactonizations. By integrating directed evolution and photoinduced single electron oxidation, we repurposed engineered ene-reductases to steer non-natural radical C-O formations (one C-O bond for hydrolactonizations and lactonization-alkylations while two C-O bonds for lactonization-oxygenations). This dual catalysis gave a new approach to a diverse array of enantioenhanced 5- and 6-membered lactones with vicinal stereocenters, part of which bears a quaternary stereocenter (up to 99 % enantiomeric excess, up to 12.9 : 1 diastereomeric ratio). Detailed mechanistic studies, including computational simulations, uncovered the synergistic effect of the enzyme and the externally added organophotoredox catalyst Rh6G.
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Particulate methane monooxygenase (pMMO) plays a critical role in catalyzing the conversion of methane to methanol, constituting the initial step in the C1 metabolic pathway within methanotrophic bacteria. However, the membrane-bound pMMO's structure and catalytic mechanism, notably the copper's valence state and genuine active site for methane oxidation, have remained elusive. Based on the recently characterized structure of membrane-bound pMMO, extensive computational studies were conducted to address these long-standing issues. A comprehensive analysis comparing the quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulated structures with cryo-EM data indicates that both the CuC and CuD sites tend to stay in the Cu(I) valence state within the membrane environment. Additionally, the concurrent presence of Cu(I) at both CuC and CuD sites leads to the significant reduction of the ligand-binding cavity situated between them, making it less likely to accommodate a reductant molecule such as durohydroquinone (DQH2). Subsequent QM/MM calculations reveal that the CuD(I) site is more reactive than the CuC(I) site in oxygen activation, en route to H2O2 formation and the generation of Cu(II)-Oâ¢- species. Finally, our simulations demonstrate that the natural reductant ubiquinol (CoQH2) assumes a productive binding conformation at the CuD(I) site but not at the CuC(I) site. This provides evidence that the true active site of membrane-bound pMMOs may be CuD rather than CuC. These findings clarify pMMO's catalytic mechanism and emphasize the membrane environment's pivotal role in modulating the coordination structure and the activity of copper centers within pMMO.
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Cobre , Sustancias Reductoras , Cobre/química , Peróxido de Hidrógeno , Metano/química , Oxidación-Reducción , Oxigenasas/metabolismoRESUMEN
P450 TleB catalyzes the oxidative cyclization of the dipeptide N-methylvalyl-tryptophanol into indolactam V through selective intramolecular C-H bond amination at the indole C4 position. Understanding its catalytic mechanism is instrumental for the engineering or design of P450-catalyzed C-H amination reactions. Using multiscale computational methods, we show that the reaction proceeds through a diradical pathway, involving a hydrogen atom transfer (HAT) from N1-H to Cpd I, a conformational transformation of the substrate radical species, and a second HAT from N13-H to Cpd II. Intriguingly, the conformational transformation is found to be the key to enabling efficient and selective C-N coupling between N13 and C4 in the subsequent diradical coupling reaction. The underlined conformational transformation is triggered by the first HAT, which proceeds with an energy-demanding indole ring flip and is followed by the facile approach of the N13-H group to Cpd II. Detailed analysis shows that the internal electric field (IEF) from the protein environment plays key roles in the transformation process, which not only provides the driving force but also stabilizes the flipped conformation of the indole radical. Our simulations provide a clear picture of how the P450 enzyme can smartly modulate the selective C-N coupling reaction. The present findings are in line with all available experimental data, highlighting the crucial role of substrate dynamics in controlling this highly valuable reaction.
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Sistema Enzimático del Citocromo P-450 , Simulación de Dinámica Molecular , Sistema Enzimático del Citocromo P-450/metabolismo , Conformación Molecular , Oxidación-Reducción , IndolesRESUMEN
Boron-based nonmetallic materials (such as B2O3 and BN) emerge as promising catalysts for selective oxidation of light alkanes by O2 to form value-added products, resulting from their unique advantage in suppressing CO2 formation. However, the site requirements and reaction mechanism of these boron-based catalysts are still in vigorous debate, especially for methane (the most stable and abundant alkane). Here, we show that hexagonal BN (h-BN) exhibits high selectivities to formaldehyde and CO in catalyzing aerobic oxidation of methane, similar to Al2O3-supported B2O3 catalysts, while h-BN requires an extra induction period to reach a steady state. According to various structural characterizations, we find that active boron oxide species are gradually formed in situ on the surface of h-BN, which accounts for the observed induction period. Unexpectedly, kinetic studies on the effects of void space, catalyst loading, and methane conversion all indicate that h-BN merely acts as a radical generator to induce gas-phase radical reactions of methane oxidation, in contrast to the predominant surface reactions on B2O3/Al2O3 catalysts. Consequently, a revised kinetic model is developed to accurately describe the gas-phase radical feature of methane oxidation over h-BN. With the aid of in situ synchrotron vacuum ultraviolet photoionization mass spectroscopy, the methyl radical (CH3â¢) is further verified as the primary reactive species that triggers the gas-phase methane oxidation network. Theoretical calculations elucidate that the moderate H-abstraction ability of predominant CH3⢠and CH3OO⢠radicals renders an easier control of the methane oxidation selectivity compared to other oxygen-containing radicals generally proposed for such processes, bringing deeper understanding of the excellent anti-overoxidation ability of boron-based catalysts.
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The antibacterial agents deoxynybomycin (DNM) and nybomycin (NM) have a unique tetracyclic structure featuring an angularly fused 4-oxazoline ring. Here, we report the identification of key enzymes responsible for forming the 4-oxazoline ring in Embleya hyalina NBRC 13850 by comparative bioinformatics analysis of the biosynthetic gene clusters encoding structurally similar natural products DNM, deoxynyboquinone (DNQ), and diazaquinomycins (DAQs). The N-methyltransferase DnmS plays a crucial role in catalyzing the N-dimethylation of a tricyclic precursor prenybomycin to generate NM D; subsequently, the Fe(II)/α-ketoglutarate-dependent dioxygenase (Fe/αKGD) DnmT catalyzes the formation of a 4-oxazoline ring from NM D to produce DNM; finally, a second Fe/αKGD DnmU catalyzes the C-12 hydroxylation of DNM to yield NM. Strikingly, DnmT is shown to display unexpected functions to also catalyze the decomposition of the 4-oxazoline ring and the N-demethylation, thereby converting DNM back to prenybomycin, to putatively serve as a manner to control the intracellular yield of DNM. Structure modeling, site-directed mutagenesis, and quantum mechanics calculations provide mechanistic insights into the DnmT-catalyzed reactions. This work expands our understanding of the functional diversity of Fe/αKGDs in natural product biosynthesis.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Quinolonas , Catálisis , Compuestos Ferrosos/químicaRESUMEN
The practical catalytic enantioselective cis-dihydroxylation of olefins that utilize earth-abundant first-row transition metal catalysts under environmentally friendly conditions is an important yet challenging task. Inspired by the cis-dihydroxylation reactions catalyzed by Rieske dioxygenases and non-heme iron models, we report the biologically inspired cis-dihydroxylation catalysis that employs an inexpensive and readily available mononuclear non-heme manganese complex bearing a tetradentate nitrogen-donor ligand and aqueous hydrogen peroxide (H2O2) and potassium peroxymonosulfate (KHSO5) as terminal oxidants. A wide range of olefins are efficiently oxidized to enantioenriched cis-diols in practically useful yields with excellent cis-dihydroxylation selectivity and enantioselectivity (up to 99% ee). Mechanistic studies, such as isotopically 18O-labeled water experiments, and density functional theory (DFT) calculations support that a manganese(V)-oxo-hydroxo (HO-MnVâO) species, which is formed via the water-assisted heterolytic O-O bond cleavage of putative manganese(III)-hydroperoxide and manganese(III)-peroxysulfate precursors, is the active oxidant that effects the cis-dihydroxylation of olefins; this is reminiscent of the frequently postulated iron(V)-oxo-hydroxo (HO-FeVâO) species in the catalytic arene and alkene cis-dihydroxylation reactions by Rieske dioxygenases and synthetic non-heme iron models. Further, DFT calculations for the mechanism of the HO-MnVâO-mediated enantioselective cis-dihydroxylation of olefins reveal that the first oxo attack step controls the enantioselectivity, which exhibits a high preference for cis-dihydroxylation over epoxidation. In this study, we are able to replicate both the catalytic function and the key chemical principles of Rieske dioxygenases in mononuclear non-heme manganese-catalyzed enantioselective cis-dihydroxylation of olefins.
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Dioxigenasas , Peróxido de Hidrógeno/química , Manganeso , Oxidación-Reducción , Alquenos/química , Estereoisomerismo , Hierro/química , Oxidantes , Catálisis , AguaRESUMEN
Mononuclear nonheme iron enzymes catalyze a large variety of oxidative transformations responsible for various biosynthesis and metabolism processes. Unlike their P450 counterparts, non-heme enzymes generally possess flexible and variable coordination architecture, which can endow rich reactivity for non-heme enzymes. This Concept highlights that the coordination dynamics of iron can be a key player in controlling the activity and selectivity of non-heme enzymes. In ergothioneine synthase EgtB, the coordination switch of the sulfoxide radical species enables the efficient and selective C-S coupling reaction. In iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenases, the conformational flip of ferryl-oxo intermediate can be extensively involved in selective oxidation reactions. Especially, the five-coordinate ferryl-oxo species may allow the substrate coordination via O or N atom, which may facilitate the C-O or C-N coupling reactions via stabilizing the transition states and inhibiting the unwanted hydroxylation reactions.
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Hierro , Oxigenasas , Hierro/química , Oxidación-Reducción , Oxigenasas/química , Catálisis , Conformación MolecularRESUMEN
This Account describes the manner whereby nature controls the Fenton-type reaction of O-O homolysis of hydrogen peroxide and harnesses it to carry out various useful oxidative transformations in metalloenzymes. H2O2 acts as the cosubstrate for the heme-dependent peroxidases, P450BM3, P450SPα, P450BSß, and the P450 decarboxylase OleT, as well as the nonheme enzymes HppE and the copper-dependent lytic polysaccharide monooxygenases (LPMOs). Whereas heme peroxidases use the Poulos-Kraut heterolytic mechanism for H2O2 activation, some heme enzymes prefer the alternative Fenton-type mechanism, which produces â¢OH radical intermediates. The fate of the â¢OH radical is controlled by the protein environment, using tight H-bonding networks around H2O2. The so-generated â¢OH radical is constrained by the surrounding H-bonding interactions, the orientation of which is targeted to perform H-abstraction from the Fe(III)-OH group and thereby leading to the formation of the active species, called Compound I (Cpd I), Por+â¢Fe(IV)âO, which performs oxidation of the substrate. Alternatively, for the nonheme HppE enzyme, the O-O homolysis catalyzed by the resting state Fe(II) generates an Fe(III)-OH species that effectively constrains the â¢OH radical species by a tight H-bonding network. The so-formed H-bonded â¢OH radical acts directly as the oxidant, since it is oriented to perform H-abstraction from the C-H bond of the substrate (S)-2-HPP. The Fenton-type H2O2 activation is strongly suggested by computations to occur also in copper-dependent LPMOs and pMMO. In LPMOs, the Cu(I)-catalyzed O-O homolysis of the H2O2 cosubstrate generates an â¢OH radical that abstracts a hydrogen atom from Cu(II)-OH and forms thereby the active species of the enzyme, Cu(II)-Oâ¢. Such Fenton-type O-O activation can be shared by both the O2-dependent activations of LPMOs and pMMOs, in which the O2 cosubstrate may be reduced to H2O2 by external reductants. Our studies show that, generally, the H2O2 activation is highly dependent on the protein environment, as well as on the presence/absence of substrates. Since H2O2 is a highly flexible and hydrophilic molecule, the absence of suitable substrates may lead to unproductive binding or even to the release of H2O2 from the active site, as has been suggested in P450cam and LPMOs, whereas the presence of the substrate seems to play a role in steering a Fenton-type H2O2 activation. In the absence of a substrate, the hydrophilic active site of P450BM3 disfavors the binding and activation of H2O2 and protects thereby the enzyme from the damage by the Fenton reaction. Due to the distinct coordination and reaction environment, the Fenton-type H2O2 activation mechanism by enzymes differs from the reaction in synthetic systems. In nonenzymatic reactions, the H-bonding networks are quite dynamic and flexible and the reactivity of H2O2 is not strategically constrained as in the enzymatic environment. As such, our Account describes the controlled Fenton-type mechanism in metalloenzymes, and the role of the protein environment in constraining the â¢OH radical against oxidative damage, while directing it to perform useful oxidative transformations.
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Peróxido de Hidrógeno , Metaloproteínas , Cobre/química , Compuestos Férricos , Hemo/química , Peróxido de Hidrógeno/química , Metaloproteínas/metabolismo , Oxidación-Reducción , Peroxidasas/metabolismoRESUMEN
Lightweight, low-cost, and simple systems for magnetic field sensing are in high demand. Here, we demonstrate such a magnetic field sensing system by integrating a light source, detector, magnetic fluid (MF), and plastic optical fiber (POF). Two bifunctional AlGaInP diodes with identical multiple-quantum well structures separately function as the light source and the detector of the sensing system due to the partial overlap between the electroluminescence and responsivity spectra. Magnetic field sensing is realized by changing the amount of reflected light due to the change in reflection coefficient of the POF/MF interface caused by the ambient magnetic field. The chip-integrated POF magnetic field sensor exhibits a reliable operation with a detection range from 10 Gs to 400 Gs. The results indicate that the chip-integrated POF sensor is promising for magnetic field sensing.
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Dual-functioning multiple quantum well (MQW) diodes can simultaneously transmit and receive information through visible light. Here, we report vertically stacked red, green, and blue (RGB) MQW diodes for light detection and display applications. Both blue and green MQW diodes are monolithically integrated with distributed Bragg reflector (DBR) filters to realize the separation of light. The versatile RGB MQW transmitter/receiver system not only creates full-color display but also effectively separates RGB light into various colors. These results open feasible routes to generate multifunctional device for the development of full-color display and light receiver.
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The combination of plastic optical fiber (POF) with monolithically integrated transmitter and receiver is becoming increasingly attractive for the development of miniature optoelectronic sensing systems. Here, we propose a temperature sensing system by integrating a GaN optoelectronic chip with a POF and aluminum (Al) reflector. Owing to the overlap between electroluminescence and responsivity spectra of multiple quantum well (MQW) diodes, both the transmitter and the receiver having identical MQW structures are monolithically integrated on a tiny GaN chip by using the same fabrication process flow. Environmental temperature change leads to thermal deformation in the Al reflector, which reflects the transmitted light back with a light pulse. The reflected light is coupled into the guided POF again and sensed by the on-chip receiver. Finally, the temperature information is read out as electrical signals. When the ambient temperature changes from 20.1°C to 100°C, the optically induced electrical signal decreases from -3.04 µA to -3.13 µA. The results suggest that the monolithically integrated GaN device offers a promising option for optoelectronic temperature sensing systems.
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A palladium-catalyzed multicomponent cascade reaction of aryl iodides, oxanorbornadiene, and diborns to access (Z)-alkenylborons is reported. This transformation proceeds through the sequential carbopalladation/boronation/retro-Diels-Alder domino reaction. The oxanorbornadiene used in this reaction serves as an acetylene surrogate, which is generated via a retro-Diels-Alder reaction. Such a stereoselective and scalable approach has a wide range of functional group tolerance and good substrate universality.
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Amylomaltases (AMs) play important roles in glycogen and maltose metabolism. However, the molecular mechanism is elusive. Here, we investigated the conformational dynamics of the 250s loop and catalytic mechanism of Thermus aquaticus TaAM using path-metadynamics and QM/MM MD simulations. The results demonstrate that the transition of the 250s loop from an open to closed conformation promotes polysaccharide sliding, leading to the ideal positioning of the acid/base. Furthermore, the conformational dynamics can also modulate the selectivity of hydrolysis and transglycosylation. The closed conformation of the 250s loop enables the tight packing of the active site for transglycosylation, reducing the energy penalty and efficiently preventing the penetration of water into the active site. Conversely, the partially closed conformation for hydrolysis results in a loosely packed active site, destabilizing the transition state. These computational findings guide mutation experiments and enable the identification of mutants with an improved disproportionation/hydrolysis ratio. The present mechanism is in line with experimental data, highlighting the critical role of conformational dynamics in regulating the catalytic reactivity of GHs.