Frame-Guided Synthesis of Polymeric Colloidal Discs
Journal of the American Chemical Society: Latest Articles (ACS Publications)
Authors: Na Qu, Zhang Luo, Shuping Zhao, and Bing Liu
feedproxy.google.com/~r/acs/jacsat/~3/2VCNLWnbFeg/jacs.0c08627
Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC)
Journal of Medicinal Chemistry: Latest Articles (ACS Publications)
Authors: Zhuming Zhang, Peter J. Connolly, Heng Keang Lim, Vineet Pande, Lieven Meerpoel, Christopher Teleha, Jonathan R. Branch, Janine Ondrus, Ian Hickson, Tammy Bush, Leopoldo Luistro, Kathryn Packman, James R. Bischoff, Salam Ibrahim, Christopher Parrett, Yolanda Chong, Marco M. Gottardis, and Gilles Bignan
feedproxy.google.com/~r/acs/jmcmar/~3/qS47QTXFlC0/acs.jmedchem.0c01563
Structure–Activity Relationship Study of Amidobenzimidazole Analogues Leading to Potent and Systemically Administrable Stimulator of Interferon Gene (STING) Agonists
Journal of Medicinal Chemistry: Latest Articles (ACS Publications)
Authors: Zilan Song, Xiyuan Wang, Yan Zhang, Wangting Gu, Ancheng Shen, Chunyong Ding, Han Li, Ruoxuan Xiao, Meiyu Geng, Zuoquan Xie, and Ao Zhang
feedproxy.google.com/~r/acs/jmcmar/~3/OxQz8HJRsCo/acs.jmedchem.0c01900
Hierarchically Porous Biocatalytic MOF Microreactor as a Versatile Platform towards Enhanced Multienzyme and Cofactor‐Dependent Biocatalysis
Hierarchically porous biocatalytic MOFs provide sufficient space for accommodation of enzymes to reorientate and spread in their lower surface energy state as well as to decrease the inherent barriers to accelerate the diffusion of reactants and intermediates. The promoted intermolecular correlation of enzymes and MOFs, and polyphenol coating, safeguards the enzymes from inactivation, showcasing their promise for diverse biotechnological applications.
Abstract
Metal‐organic frameworks (MOFs) have recently emerged as excellent hosting matrices for enzyme immobilization, offering superior physical and chemical protection for biocatalytic reactions. However, for multienzyme and cofactor‐dependent biocatalysis, the subtle orchestration of enzymes and cofactors is largely disrupted upon immobilizing in the rigid crystalline MOF network, which leads to a much reduced biocatalytic efficiency. Herein, we constructed hierarchically porous MOFs by controlled structural etching to enhance multienzyme and cofactor‐dependent enzyme biocatalysis. The expanded size of the pores can provide sufficient space for accommodated enzymes to reorientate and spread within MOFs in their lower surface energy state as well as to decrease the inherent barriers to accelerate the diffusion rate of reactants and intermediates. Moreover, the developed hierarchically porous MOFs demonstrated outstanding tolerance to inhospitable surroundings and recyclability.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Jieying Liang, Song Gao, Jian Liu, Muhammad Y. B. Zulkifli, Jiangtao Xu, Jason Scott, Vicki Chen, Jiafu Shi, Aditya Rawal, Kang Liang
doi.org/10.1002/anie.202014002
Acceptor Engineering for Optimized ROS Generation Facilitates Reprogramming Macrophages to M1 Phenotype in Photodynamic Immunotherapy
The ROS of type I mechanism generated from AIEgen photosensitizers can reeducate the tumor‐associated macrophages towards M1 phenotype, leading to a complete ablation of the tumor without recurrence through single PDT treatment.
Abstract
Reprogramming tumor‐associated macrophages to an antitumor M1 phenotype by photodynamic therapy is a promising strategy to overcome the immunosuppression of tumor microenvironment for boosted immunotherapy. However, it remains unclear how the reactive oxygen species (ROS) generated from type I and II mechanisms, relate to the macrophage polarization efficacy. Herein, we design and synthesize three donor–acceptor structured photosensitizers with varied ROS‐generating efficiencies. Surprisingly, we discovered that the extracellular ROS generated from type I mechanism are mainly responsible for reprogramming the macrophages from a pro‐tumor type (M2) to an anti‐tumor state (M1). In vivo experiments prove that the photosensitizer can trigger photodynamic immunotherapy for effective suppression of the tumor growth, while the therapeutic outcome is abolished with depleted macrophages. Overall, our strategy highlights the designing guideline of macrophage‐activatable photosensitizers.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Guang Yang, Jen‐Shyang Ni, Yaxi Li, Menglei Zha, Yao Tu, Kai Li
doi.org/10.1002/anie.202013228
On‐POM Ring‐Opening Polymerisation of N‐Carboxyanhydrides
On‐POM polymerisation: An amino‐functionalised polyoxometalate (POM) acts as initiator for the ring‐opening polymerisation (ROP) of α‐amino acid N‐carboxyanhydrides (NCAs) under living polymerisation conditions. The resulting POM–peptide materials (POMlymers) possess bactericidal properties and prevent biofilm formation.
Abstract
The ring‐opening polymerisation of α‐amino acid N‐carboxyanhydrides (NCAs) offers a simple and scalable route to polypeptides with predicted and narrow molecular weight distributions. Here we show how polyoxometalates (POMs)—redox‐active molecular metal‐oxide anions—can serve as inorganic scaffold initiators for such NCA polymerisations. This “On‐POM polymerisation” strategy serves as an innovative platform to design hybrid materials with additive or synergistic properties stemming from the inorganic and polypeptide component parts. We have used this synthetic approach to synthesise a library of bactericidal poly(lysine)–POM hybrid derivatives that can be used to prevent biofilm formation. This versatile “On‐POM polymerisation” method provides a flexible synthetic approach for combining inorganic scaffolds with amino acids, and the potential to tailor and improve the specificity and performance of hybrid antimicrobial materials.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Héctor Soria‐Carrera, Isabel Franco‐Castillo, Pilar Romero, Santiago Martín, Jesús M. Fuente, Scott G. Mitchell, Rafael Martín‐Rapún
doi.org/10.1002/anie.202013563
Molecular Engineering of NIR‐II Fluorophores for Improved Biomedical Detection
Fluorescence imaging in the NIR‐II window has become a powerful method for biomedical research owing the combined merits of diminished background fluorescence and deep tissue penetration. NIR‐II fluorophores occupy a central position in this technology. This review discusses the strategies applied in the design of NIR‐II fluorophores and NIR‐II fluorescent probes.
Abstract
The development of fluorophores for the second near‐infrared window (NIR‐II, 1000–1700 nm) represents an emerging, significant, and vibrant field in analytic chemistry, chemical biology, and biomedical engineering. The wavelength, brightness, and stability are three crucial factors that determine the performance of an NIR‐II fluorophore. Up to now, significant progress has been made in the development of NIR‐II fluorescence molecular probes, including the synthesis of D‐A‐D and D‐π‐A fluorophores with improved NIR‐II fluorescence imaging performance and the construction of off–on probes and ratiometric probes via energy transfer or molecular structure modification. In this review, we summarize the most recent advances in molecular engineering design strategies of NIR‐II fluorophores and probes, then highlight a selection of bioimaging and biosensing applications. We also provide perspectives on potential challenges and opportunities in this emerging field
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Zuhai Lei, Fan Zhang
doi.org/10.1002/anie.202007040
A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors
An unusual reductase (mnOpccR) in phytosterol catabolism is found to catalyze the formation of 4‐HBC through two different routes. Inactivation or overexpression of mnOpccR leads to exclusive production of 4‐androstenedione (4‐AD) and 4‐HBC from phytosterols. By a two‐step synthesis, 4‐HBC can be further efficiently converted into progesterone (PG). This work provides two green and economical methods for 4‐AD and PG manufacturing.
Abstract
4‐Androstenedione (4‐AD) and progesterone (PG) are two of the most important precursors for synthesis of steroid drugs, however their current manufacturing processes suffer from low efficiency and severe environmental issues. In this study, we decipher a dual‐role reductase (mnOpccR) in the phytosterols catabolism, which engages in two different metabolic branches to produce the key intermediate 20‐hydroxymethyl pregn‐4‐ene‐3‐one (4‐HBC) through a 4‐e reduction of 3‐oxo‐4‐pregnene‐20‐carboxyl‐CoA (3‐OPC‐CoA) and 2‐e reduction of 3‐oxo‐4‐pregnene‐20‐carboxyl aldehyde (3‐OPA), respectively. Inactivation or overexpression of mnOpccR in the Mycobacterium neoaurum can achieve exclusive production of either 4‐AD or 4‐HBC from phytosterols. By utilizing a two‐step synthesis, 4‐HBC can be efficiently converted into PG in a scalable manner (100 gram scale). This study deciphers a pivotal biosynthetic mechanism of phytosterol catabolism and provides very efficient production routes of 4‐AD and PG.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Haidong Peng, Yaya Wang, Kai Jiang, Xinru Chen, Wenlu Zhang, Yanan Zhang, Zixin Deng, Xudong Qu
doi.org/10.1002/anie.202015462
Activating Lattice Oxygen at the Twisted Surface in a Mesoporous CeO2 Single Crystal for Efficient and Durable Catalytic CO Oxidation
Well‐defined active sites are created at the surface in mesoporous CeO2 single crystals at the 2 cm scale. Complete CO oxidation with air at 67 °C is demonstrated with no degradation observed after operation of 300 hours.
Abstract
Activating lattice oxygen linked to active sites at surface remains a fundamental challenge in many catalytic reactions. Here we create well‐defined surface by directly growing porous CeO2 single crystals at 2 cm scale and confining Pt in lattice to construct isolated Pt1/CeO2 sites at a continuously twisted surface in a monolith. We demonstrate significantly enhanced activation of lattice oxygen linked to Pt ions in contrast to Ce ions in local structures. We show complete CO oxidation with air at 67 °C without degradation being observed after operation of 300 hours. The isolated Pt1/CeO2 sites at twisted surfaces not only contribute to the chemisorption of CO but also effectively activate the lattice oxygen linked to Pt ion for CO oxidation. The current work would open a new route to activate lattice oxygen by incorporating well‐defined active structures confined at the surfaces.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Yongchun Xiao, Hao Li, Kui Xie
doi.org/10.1002/anie.202013633
Synthesis of Enantiopure 6,11‐Methylene Lipoxin B4 Methyl Ester
A flexible convergent enantioselective total synthesis of a rigid lipoxin B4 analog incorporating a 6, 11‐methylene bridge has been developed. C1–C12 aldehyde and C13–C20 ketophosphonate underwent highly efficient key Horner olefination. A final six‐step sequence delivered the target compound displaying all stereogenic centers with standard lipoxin B4 configurations.
Abstract
The synthesis of Lipoxin B4 analogs (LXB4) to gain access to stabilized inflammation resolving compounds is an actual field of research. Focusing on variation and stabilization of the conjugated E,Z,E,E C6–C13 tetraene moiety of natural LXB4, a methylene bridge introduced between C6 and C11 suppresses any Z/E isomerization of the C8–C9 olefin. Intending to enable prospective structure variations in connection with the C1–C5 and C14–C20 fragments, a convergent total synthesis has been developed. Optically active C1–C12 building blocks were build‐up from cycloheptatriene 1‐carbonester (C6–C11, C21) and glutaryl chloride (C1–C5) using Friedel‐Crafts‐type acylation and chiral HPLC. The C13–C20 segment had been generated via a five‐step sequence starting from heptanoyl chloride. Horner key olefination enabled the assembly of the carbon backbone. A final five‐step sequence including a chelate Cram reduction of the unsaturated ketone moiety afforded the target 6,11‐methylene LXB4 methyl ester.
Wiley: European Journal of Organic Chemistry: Table of Contents
Authors: Lukas Trippe, Analuisa Nava, Andrea Frank, Udo Nubbemeyer
doi.org/10.1002/ejoc.202001591
Reactions of a 3‐Phenyl‐1‐trifluoromethyl‐prop‐2‐yne Iminium Salt with Furans, Thiophenes, and Pyrroles
Reactions of a novel propyne iminium salt, N,N‐dimethyl 3‐phenyl‐1‐trifluoromethyl‐propyne iminium triflate, with electron‐rich heteroaromatic ring systems (furans, thiophenes, pyrroles) are reported. The 1‐CF3‐propyne iminium ion can act as a highly reactive ambident electrophile, giving rise to simple electrophilic heteroaromatic ring substitution products, and as a 1,3‐biselectrophile leading to C2+C3‐CF3 annulation products.
Abstract
Reactions of a novel propyne iminium salt, N,N‐dimethyl 3‐phenyl‐1‐trifluoromethyl‐propyne iminium triflate, with electron‐rich heteroaromatic ring systems (furans, thiophenes, pyrroles) are reported. The 1‐CF3‐propyne iminium ion can act as a highly reactive ambident electrophile, giving rise to simple electrophilic heteroaromatic ring substitution products, and as a 1,3‐biselectrophile leading to C2+C3‐CF3 annulation products. Moreover, it is an electron‐deficient alkyne which was found to afford double [2+2] cycloaddition products with 2,5‐dimethylfuran and 2,5‐dimethylthiophene. The obtained molecular structures include CF3‐containing compounds with cyclopenta[b]furan, cyclopenta[b]thiophene, cyclopenta[c]thiophene, cyclopenta[b]pyrrole, cyclopenta[c]pyrrole, 3H‐pyrrolizine, and 1,4‐dihydrocyclopenta[b]pyrrole ring systems. Analogous reactions of 1,3(or 1,4)‐phenylenebis(1‐CF3‐propyne iminium) salts with furans, pyrroles or thiophenes in a 2 : 1 stoichiometry lead to phenylene‐tethered condensed heterocycles of the same type.
Wiley: European Journal of Organic Chemistry: Table of Contents
Authors: Thomas Schneider, Georg Heinrich, Raphael Koch, Gerhard Maas
doi.org/10.1002/ejoc.202001577
Visible Light‐Driven Efficient Synthesis of Amides from Alcohols using Cu−N−TiO2 Heterogeneous Photocatalyst
A simple and practical method for direct amide synthesis from alcohols and amines using an in situ generated active ester of N‐hydroxyimide with the earlier developed robust and recyclable Cu−N−TiO2 catalyst, at room temperature, using oxygen as a sole oxidant under visible light is discussed. The application of this amidation reaction has been successfully demonstrated for the synthesis of moclobemide, an antidepressant drug, and an analog of the itopride drug on a gram scale.
Abstract
Amides were synthesized from alcohols and amines in high yields using an in situ generated active ester of N‐hydroxyimide with our developed Cu−N−TiO2 catalyst at room temperature using oxygen as a sole oxidant under visible light. The catalyst can be easily prepared, robust, and recycled four times without a considerable change in catalytic activity. This developed protocol applies to a wide substrate scope and has good functional group tolerance. The application of this amidation reaction has been successfully demonstrated for the synthesis of moclobemide, an antidepressant drug, and an analog of the itopride drug on a gram scale.
Wiley: European Journal of Organic Chemistry: Table of Contents
Authors: Krishnadipti Singha., Subhash Chandra Ghosh., Asit Baran Panda.
doi.org/10.1002/ejoc.202001466
Transition Metal Complexes as Catalysts for the Electroconversion of CO2: An Organometallic Perspective
This review article illustrates and categorizes the currently favored molecular mechanisms for the electrochemically induced transformation of CO2 promoted by homogeneous transition metal complexes. The resulting insights are corroborated by the concepts and elementary steps of organometallic catalysis to derive strategies to broaden the molecular diversity of products.
Abstract
The electrocatalytic transformation of carbon dioxide has been a topic of interest in the field of CO2 utilization for a long time. Recently, the area has seen increasing dynamics as an alternative strategy to catalytic hydrogenation for CO2 reduction. While many studies focus on the direct electron transfer to the CO2 molecule at the electrode material, molecular transition metal complexes in solution offer the possibility to act as catalysts for the electron transfer. C1 compounds such as carbon monoxide, formate, and methanol are often targeted as the main products, but more elaborate transformations are also possible within the coordination sphere of the metal center. This perspective article will cover selected examples to illustrate and categorize the currently favored mechanisms for the electrochemically induced transformation of CO2 promoted by homogeneous transition metal complexes. The insights will be corroborated with the concepts and elementary steps of organometallic catalysis to derive potential strategies to broaden the molecular diversity of possible products.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Niklas W. Kinzel, Christophe Werlé, Walter Leitner
doi.org/10.1002/anie.202006988
Genetically Encoded and Biologically Produced All‐DNA Nanomedicine Based on One‐Pot Assembly of DNA Dendrimers for Targeted Gene Regulation
A genetically encoded all‐DNA nanomedicine with targeted gene regulation property was produced from E. coli after a range of bioprocessing. This study provides a new approach for production of DNA nanomedicines, which will greatly promote their clinical applications in the future.
Abstract
All‐DNA nanomedicines have emerged as potential anti‐tumor drugs. DNA nanotechnology provides all‐DNA nanomedicines with unlimited possibilities in controlling the diversification of size, shape, and loads of the therapeutic motifs. As DNA is a biological polymer, it is possible to genetically encode and produce the all‐DNA nanomedicines in living bacteria. Herein, DNA‐dendrimer‐based nanomedicines are designed to adapt to the biological production, which is constructed by the flexible 3‐arm building blocks to enable a highly efficient one‐pot DNA assembly. For the first time, a DNA nanomedicine, D4‐3‐As‐DzSur, is successfully genetically encoded, biotechnologically produced, and directly self‐assembled. The performance of the biologically produced D4‐3‐As‐DzSur in targeted gene regulation has been confirmed by in vitro and in vivo studies. The biological production capability will fulfill the low‐cost and large‐scale production of all‐DNA nanomedicines and promote clinical applications.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Jingxiong Lu, Pengchao Hu, Lingyan Cao, Zixiang Wei, Fan Xiao, Zhe Chen, Yan Li, Leilei Tian
doi.org/10.1002/anie.202012916
Atomically Precise Preorganization of Open Metal Sites on Gold Nanoclusters with High Catalytic Performance
A stable Au23 nanocluster with preorganized open sites has been conducted through surface geometric mismatch strategy. The 35 % accessibility of Au23 was confirmed by luminescent titration with 2‐naphthalenethiol. The preorganized open sites make intact Au23 a high‐performance catalyst for aerobic oxidation of benzyl alcohol.
Abstract
Gold nanoclusters with surface open sites are crucial for practical applications in catalysis. We have developed a surface geometric mismatch strategy by using mixed ligands of different type of hindrance. When bulky phosphine Ph3P and planar dipyridyl amine (Hdpa) are simultaneously used, steric repulsion between the ligands will reduce the ligand coverage of gold clusters. A well‐defined access granted gold nanocluster [Au23(Ph3P)10(dpa)2Cl](SO3CF3)2 (Au23, dpa=dipyridylamido) has been successfully synthesized. Single crystal structural determination reveals that Au23 has eight uncoordinated gold atoms in the shape of a distorted bicapped triangular prism. The accessibility of the exposed Au atoms has been confirmed quantitatively by luminescent titration with 2‐naphthalenethiol. This cluster has excellent performance toward selective oxidation of benzyl alcohol to benzaldehyde and demonstrates excellent stability due to the protection of negatively charged multidentate ligand dpa.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Shang‐Fu Yuan, Zhen Lei, Zong‐Jie Guan, Quan‐Ming Wang
doi.org/10.1002/anie.202012499
Kinetic Barriers and Microscopic Mechanisms of Noble Gas Adsorption by Nanoporous γ‐Mg(BH4)2 Obtained by Means of Sub‐Second X‐Ray Diffraction
The sub‐second crystal structure analysis of noble gas uptake by nanoporous γ‐Mg(BH4)2 sheds light on its diffusion mechanisms and activation barriers. It resolves two kinetic barriers for noble gas adsorption: one with diffusion along the 1D channels and the other by diffusion between the channels via a smaller aperture.
Abstract
Gas adsorption by porous frameworks sometimes results in structure “breathing”, “pores opening/closing”, “negative gas adsorption”, and other phenomena. Time‐dependent diffraction can address both kinetics of the guest uptake and structural response of the host framework. Using sub‐second in situ powder X‐ray diffraction, three intracrystalline diffusion scenarios have been evaluated from the isothermal kinetics of Ar, Kr, and Xe adsorption by nanoporous γ‐Mg(BH4)2. These scenarios are dictated by two possible simultaneous transport mechanisms: diffusion through the intra‐ (i) and interchannel apertures (ii) of γ‐Mg(BH4)2 crystal structure. The contribution of (i) and (ii) changes depending on the kinetic diameter of the noble gas molecule and temperature regime. The lowest single activation barrier for the smallest Ar suggests equal diffusion of the atoms trough both pathways. Contrary, for the medium sized Kr we resolve the contributions of two parallel transport mechanisms, which tentatively can be attributed to the smaller barrier of the migration paths via the channel like pores and the higher barrier for the diffusion via narrow aperture between these channels. The largest Xe atoms diffuse only along 1D channels and show the highest single activation barrier.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Iurii Dovgaliuk, Irena Senkovska, Xiao Li, Vadim Dyadkin, Yaroslav Filinchuk, Dmitry Chernyshov
doi.org/10.1002/anie.202015019
Bile Acid Tethered Docetaxel‐Based Nanomicelles Mitigate Tumor Progression through Epigenetic Changes
Phosphocholine derivative of docetaxel‐conjugated lithocholic acid can form stable sub‐100 nm nanomicelles (DTX‐PC NMs). DTX‐PC NMs exhibit superior tolerance and pharmacokinetics over FDA‐approved formulation. DTX‐PC NMs can retard tumor progression in murine models and induce upregulation of tumor suppressor genes. Superior pharmacokinetic profiling in non‐human primates makes them an ideal platform for clinical applications.
Abstract
In this study, we describe the engineering of sub‐100 nm nanomicelles (DTX‐PC NMs) derived from phosphocholine derivative of docetaxel (DTX)‐conjugated lithocholic acid (DTX‐PC) and poly(ethylene glycol)‐tethered lithocholic acid. Administration of DTX‐PC NMs decelerate tumor progression and increase the mice survivability compared to Taxotere (DTX‐TS), the FDA‐approved formulation of DTX. Unlike DTX‐TS, DTX‐PC NMs do not cause any systemic toxicity and slow the decay rate of plasma DTX concentration in rodents and non‐rodent species including non‐human primates. We further demonstrate that DTX‐PC NMs target demethylation of CpG islands of Sparcl1 (a tumor suppressor gene) by suppressing DNA methyltransferase activity and increase the expression of Sparcl1 that leads to tumor regression. Therefore, this unique system has the potential to improve the quality of life in cancer patients and can be translated as a next‐generation chemotherapeutic.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Vedagopuram Sreekanth, Animesh Kar, Sandeep Kumar, Sanjay Pal, Poonam Yadav, Yamini Sharma, Varsha Komalla, Harsh Sharma, Radhey Shyam, Ravi Datta Sharma, Arnab Mukhopadhyay, Sagar Sengupta, Ujjaini Dasgupta, Avinash Bajaj
doi.org/10.1002/anie.202015173
Novel β‐Glucocerebrosidase Activators That Bind to a New Pocket at a Dimer Interface and Induce Dimerization
A first crystal structure for a novel GCase activator is obtained and a novel non‐inhibitory binding mode at a dimer interface, rationalizing the observed structure–activity relationship, is identified. Mechanistic insights and key information for future drug discovery efforts towards GCase activation are provided.
Abstract
Genetic, preclinical and clinical data link Parkinson’s disease and Gaucher’s disease and provide a rational entry point to disease modification therapy via enhancement of β‐Glucocerebrosidase (GCase) activity. We discovered a new class of pyrrolo[2,3‐b]pyrazine activators effecting both Vmax and Km. They bind to human GCase and increase substrate metabolism in the lysosome in a cellular assay. We obtained the first crystal structure for an activator and identified a novel non‐inhibitory binding mode at the interface of a dimer, rationalizing the observed structure–activity relationship (SAR). The compound binds GCase inducing formation of a dimeric state at both endoplasmic reticulum (ER) and lysosomal pHs, as confirmed by analytical ultracentrifugation. Importantly, the pyrrolo[2,3‐b]pyrazines have central nervous system (CNS) drug‐like properties. Our findings are important for future drug discovery efforts in the field of GCase activation and provide a deeper mechanistic understanding of the requirements for enzymatic activation, pointing to the relevance of dimerization.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Joerg Benz, Arne C. Rufer, Sylwia Huber, Andreas Ehler, Melanie Hug, Andreas Topp, Wolfgang Guba, Eva Carolina Hofmann, Ravi Jagasia, Rosa María Rodríguez Sarmiento
doi.org/10.1002/anie.202013890
Ultrathin Two‐Dimensional Nanostructures: Surface Defects for Morphology‐Driven Enhanced Semiconductor SERS
The down‐sizing of metal oxide semiconductors to ultrathin nanosheets creates intrinsic crystalline defects which alters the electronic structure of the semiconductor and activates SERS performance as a result of promoted charge‐transfer efficiency and charge‐transfer pathways.
Abstract
Two‐dimensional (2D) semiconductors have recently become attractive candidate substrates for surface‐enhanced Raman spectroscopy, exhibiting good semiconductor‐based SERS sensing for a wider variety of application scenarios. However, the underlying mechanism remains unclear. Herein, we propose that surface defects play a vital role in the magnification of the SERS performances of 2D semiconductors. As a prototype material, ultrathin WO3 nanosheets is used to demonstrate that surface defect sites and the resulting increased charge‐carrier density can induce strong charge‐transfer interactions at the substrate‐molecule interface, thereby improving the sensitivity of the SERS substrate by 100 times with high reproducibility. Further work with other metal oxides suggests the reduced dimension of 2D materials can be advantageous in promoting SERS sensing for multiple probe molecules.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Ge Song, Wenbin Gong, Shan Cong, Zhigang Zhao
doi.org/10.1002/anie.202015306
Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions
The (R) enantiomer of Praziquantel is more active against schistosomiasis (bilharzia, snail fever). The cheaper, commonly used, racemate can be deracemized via a conglomerate derivative to this enantiomer, which is obtained in 98 % ee using a flow system in which Pd‐catalyzed high‐temperature racemization is coupled to low‐temperature cycled crystallization.
Abstract
An efficient deracemization method for conversion of the racemate to the desirable (R)‐enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 °C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5–15 °C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)‐enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Giulio Valenti, Paul Tinnemans, Iaroslav Baglai, Willem L. Noorduin, Bernard Kaptein, Michel Leeman, Joop H. ter Horst, Richard M. Kellogg
doi.org/10.1002/anie.202013502
Solid, Noncovalent Formulation of Biocatalysts for Rapid and Accurate Submilligram Dosing to Microtiter Plates
Organic Process Research & Development: Latest Articles (ACS Publications)
Authors: Jesse T. C. Brown, Noah P. Tu, and Ryan M. Phelan
feedproxy.google.com/~r/acs/oprdfk/~3/fKWmTb-dfSI/acs.oprd.0c00443
Photocatalytic Radical Ortho-Dearomative Cyclization: Access to Spiro[4.5]deca-1,7,9-trien-6-ones
The Journal of Organic Chemistry: Latest Articles (ACS Publications)
Authors: Wuheng Dong, Yao Yuan, Caiyun Liang, Feng Wu, Siyuan Zhang, Xiaomin Xie, and Zhaoguo Zhang
feedproxy.google.com/~r/acs/joceah/~3/e5QhDm982Sg/acs.joc.0c02477
Difluoromethylation of Alkyl Bromides and Iodides with TMSCF2H
The Journal of Organic Chemistry: Latest Articles (ACS Publications)
Authors: Haiwei Zhao, Changhui Lu, Simon Herbert, Wei Zhang, and Qilong Shen
feedproxy.google.com/~r/acs/joceah/~3/x_XEF7Gu9Gw/acs.joc.0c02783
Nanosized CdS as a Reusable Photocatalyst: The Study of Different Reaction Pathways between Tertiary Amines and Aryl Sulfonyl Chlorides through Visible-Light-Induced N-Dealkylation and C–H Activation Processes
The Journal of Organic Chemistry: Latest Articles (ACS Publications)
Authors: Somayeh Firoozi and Mona Hosseini-Sarvari
feedproxy.google.com/~r/acs/joceah/~3/yYwQ-5JiP8Y/acs.joc.0c02263
Enantioselective Total Synthesis of Nitraria Alkaloids: (+)-Nitramine, (+)-Isonitramine, (−)-Isonitramine, and (−)-Sibirine via Asymmetric Phase-Transfer Catalytic α-Allylations of α-Carboxylactams
The Journal of Organic Chemistry: Latest Articles (ACS Publications)
Authors: Jewon Yang, Yohan Park, Sehun Yang, Geumwoo Lee, Min Woo Ha, Mi-hyun Kim, Suckchang Hong, and Hyeung-geun Park
feedproxy.google.com/~r/acs/joceah/~3/4hEE-3t3FJY/acs.joc.0c02573