4‐Oxo‐β‐Lactams as Novel Inhibitors for Rhomboid Proteases

Posted on 15 September 2023 by

Rhomboid proteases are serine proteases that reside inside the lipid bilayer of a membrane. They are implicated in several diseases. We here report 4-oxo-β-lactam as a new scaffold for covalent rhomboid inhibitors and activity-based probes.

Abstract

Intramembrane serine proteases (rhomboid proteases) are involved in a variety of biological processes and are implicated in several diseases. Here, we report 4-oxo-β-lactams as a novel scaffold for inhibition of rhomboids. We show that they covalently react with the active site and that the covalent bond is sufficiently stable for detection of the covalent rhomboid-lactam complex. 4-Oxo-β-lactams may therefore find future use as both inhibitors and activity-based probes for rhomboid proteases.

Palladium‐Catalyzed [4+2] Cycloaddition of Vinyl Benzoxazinanones with 1,3‐Indanedione: Approach to Spiro‐Tetrahydroquinoline Scaffolds

Posted on 15 September 2023 by nQinglang Wei, nLiang Tu, nSen Li, nYongsheng Zheng, nJikai Liun

A palladium catalyzed decarboxylative [4+2] cycloaddition of vinyl benzoxazinanones with 1,3-indanedione was developed, affording a series of biologically potential spiro-tetrahydroquinolines. Gram-scale synthesis and product elaboration demonstrated the utility of this method. The product demonstrated exhibited potency in inhibiting MDA-MB-231 cell line.

Abstract

A palladium catalyzed decarboxylative [4+2] cycloaddition of vinyl benzoxazinanones with 2-arylidene indan-1,3-dione has been established, which afford a series of bioactive spiro-tetrahydroquinolines (27 examples) in moderate to good yield (up to 87 %) with high diastereoselectivities. The synthetic utility of this reaction was demonstrated by gram-scale synthesis. Compounds synthesized by this method potently inhibited proliferation in a panel of cancer cell lines. Particularly, the most potent compounds 3 ae, 3 ah, 3 aj and 3 fa displayed selective inhibition of MDA-MB-231 breast carcinoma cells with IC₅₀ values of 1.292, 0.6118, 0.6558, 1.656 and 2.215 μM, respectively.

Facile One‐Pot Three Component Synthesis, Characterization, and Molecular Docking Simulations of Novel α‐Aminophosphonate Derivatives Based Pyrazole Moiety as Potential Antimicrobial Agent

Posted on 15 September 2023 by

Abstract

An efficient method has been developed for the synthesis of novel α-aminophosphonates (AAP) (3 a–m) through a one-pot three-component reaction of 1,3-disubstituted-1H-pyrazol-5-amine, aromatic aldehydes, and phosphite using lithium perchlorate as catalyst. All newly synthesized compounds were characterized via different spectroscopic techniques. The synthesized compounds′ mode of action was investigated using molecular docking against the outer membrane protein A (OMPA) and exo-1,3-β-glucanase, with interpreting their pharmacokinetics aspects. The results of the antimicrobial effectiveness of these compounds revealed a broad spectrum of their biocidal activity and this in-vitro study was in line with the in- silico results. Additionally, it has been demonstrated that these compounds exhibited a minimum inhibitory concentration (MIC) with significant activity at low concentrations (7.5–30.0 mg/mL). Further, the radical scavenging (DPPH^*) activity of the synthesized compounds fluctuated, with compounds 3 h, 3 a, and 3 f showing the highest antioxidant activity. Overall, the formulated compounds can be employed as antimicrobial and antioxidant agents in medical applications.

Vinyl Phosphonates as Photopharmacological Agents: Laser‐Induced Cis‐Trans Isomerization and Butyrylcholinesterase Activity

Posted on 15 September 2023 by

Photoswitchable and bioactive: We report vinyl phosphonates with laser-induced cis to trans isomerization via a C=C bond. Cis isomers of the compounds possess some butyrylcholinesterase inhibition, while laser-induced trans isomers demonstrate steep inhibition increase. The presented vinyl phosphonates are highly requested objects for photopharmacology, as they ensure a unique combination of photoswitchable and bioactive properties.

Abstract

Photoswitchable molecules are highly requested compounds in various fields and, in particular, biomedicine. The urgent modern task of photopharmacology (an emerging approach in medicine) is the design of molecules that have both photoswitchable and bioactive properties. In this study, we present vinyl phosphonates – diene compounds with ethyl and isopropyl substituents on the phosphonate group. Both compounds demonstrated laser-induced cis-trans isomerization via a C=C bond after irradiation at 266 nm. The photoisomerization quantum yield was 17 % and 20 % for compounds with ethyl and isopropyl groups, respectively. The main advantage of the presented vinyl phosphonates is their bioactivity, unlike other photoswitchable molecules. Rather efficient butyrylcholinesterase inhibition by both presented compounds was demonstrated by IPC-Micro analysis. The notable butyrylcholinesterase inhibition increase by 5 and 9 times was found for the vinyl phosphonates after laser irradiation. Such a sizeable difference in inhibition values for different isomeric states is a critical factor, which opens the way toward promising applications of vinyl phosphonates as photopharmacological agents.

Extended Biocatalytic Halogenation Cascades Involving a Single‐Polypeptide Regeneration System for Diffusible FADH2

Posted on 15 September 2023 by nNicolai Montua, nNorbert Sewaldn

We constructed a bifunctional fusion protein for FADH₂ regeneration and successfully coexpressed it with different flavin-dependent halogenases, as well as a dioxygenase that converts 6-chlorotryptophan to 4-Cl-Kynurenine. The figure is a still life of a laboratory bench, with a single oversized E. coli bacterium hovering over an Erlenmeyer flask. Cell disruption is depicted in visual analogy to cracking an egg with the lysate appearing like egg yolk. The lysate in the flask contains all necessary enzymes for the biocatalytic cascade described in the paper rendered as ribbon structures with coloring consistent with the paper. Shown as permanent marker notes on the bench surface are a key reaction scheme as well as a “ToDo-list” that checks off some important goals of the research work. More information can be found in the Research article by N. Montua, N. Sewald.

A Calcination‐Free Sol‐Gel Method to Prepare TiO2‐Based Hybrid Semiconductors for Enhanced Visible Light‐Driven Hydrogen Production

Posted on 15 September 2023 by nKang Yang, nDan Wei, nChunman Jia, nJianwei Lin

The cover picture compares the structure of calcined (left) and non-calcined (right) rutile TiO2 doped with a molecule NA. The calcination process enlarges the pores in TiO2, reducing its surface area and hydrogen production efficiency under visible light. The “sad face” symbolizes the damaged pore structure. Conversely, doping TiO2 with NA without high-temperature calcination forms a covalent bond, resulting in smaller pores, larger surface area, and improved hydrogen production efficiency. The “smiley face” represents the structurally intact TiO2 hybrid material. More information can be found in the Research Article by Jianwei Li, Chunman Jia, and co-workers.

Late‐stage Ligand Modification After Coordination Strengthens Stereoselectively Self‐Assembled Hemiaminal Ether Complexes

Posted on 15 September 2023 by

Fragile hemiaminal ether linkages present in the backbone of koneramine ligands bound to copper(II) in stereoselectively self-assembled complexes were transformed into sturdy methylene linkages by late-stage ligand modification after coordination with the retention of coordination sphere.

Abstract

Fragile hemiaminal ether linkages present in the backbone of koneramines (L^ROR’), tridentate ligands, bound to copper(II) in stereoselectively self-assembled syn-[Cu(L^ROR’)X₂] complexes were transformed into sturdy methylene linkages to make corresponding rac-[Cu(L^RH)Cl₂] complexes by late-stage ligand modification after coordination with the retention of coordination sphere. The generality of stereoselective self-assembly of koneramine complexes is shown by utilising a number of metal ions, anions, amines, alcohols and thiols with complete characterisations.

Structure Identification of Dynamic Zinc(II)-Ligand Assemblies in Solution Based on Ligand Chirality

Posted on 15 September 2023 by Daiji Ogata

Chemistry Letters, Ahead of Print.

Covalent Organic Framework‐based Solid‐State Electrolytes, Electrode Materials, and Separators for Lithium‐ion Batteries

Posted on 14 September 2023 by

The increasing global energy consumption has led to the rapid development of renewable energy storage technologies. Lithium-ion batteries (LIBs) have been extensively studied and utilized for reliable, efficient, and sustainable energy storage. Nevertheless, designing new materials for LIB applications with high capacity and long-term stability is highly desired but remains a challenging task. Recently, covalent organic frameworks (COFs) have emerged as superior candidates for LIB applications due to their high porosity, well-defined pores, highly customizable structure, and tunable functionalities. These merits enable the preparation of tailored COFs with predesigned redox-active moieties and suitable porous channels that can improve the lithium-ion storage and transportation. This review summarizes the recent progress in the development of COFs and their composites for a variety of LIB applications, including (quasi) solid-state electrolytes, electrode materials, and separators. Finally, the challenges and potential future directions of employing COFs for LIBs are also discussed, further promoting the foundation of this class of exciting materials for future advances in energy-related applications.

Synthetic Routes to Imidates and Their Applications in Organic Transformation: Recent Progress

Posted on 14 September 2023 by nAndriani G. Chaidali, nIoannis N. Lykakisn

Imidates are important organic intermediates used in several synthetic transformations towards N-heterocycles, natural products and metal complexes with a potential catalytic effect. Herein, the recent synthetic approaches and diverse applications of imidates were categorized and summarized. A wide range of organic compounds, mainly nitriles, isocyanides, amides, imines, and alkynes are used as starting materials. This review also summarizes the latest synthetic approaches to imidates that have been developed the recent years and some of their significant applications in the field of organic synthesis.

Abstract

Recent synthetic approaches and diverse applications of imidates are presented in this review. These motifs are successfully used as intermediates in organic transformations, such as the synthesis of N-heterocycles, natural products and metal complexes with a potential catalytic effect. Consequently, many attempts have been made for the development of efficient and facile synthetic methods of imidates in the past few years, as a continuum of previous paths. A wide range of organic compounds can be used as starting materials for these syntheses, including nitriles, isocyanides, amides etc. which through simple and flexible processes are converted to the desired imidates. Herein, an exploration of the recent synthetic routes of imidates and their diverse applications in organic transformations has been categorized and summarized.