Emerging and Re-emerging Warheads for Targeted Covalent Inhibitors: An Update

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(10), P. 7668 - 7758

Published: May 7, 2024

Covalent inhibitors and other types of covalent modalities have seen a revival in the past two decades, with variety new targeted drugs having been approved recent years. A key feature such molecules is an intrinsically reactive group, typically weak electrophile, which enables irreversible or reversible formation bond specific amino acid target protein. This often called "warhead", critical determinant ligand's activity, selectivity, general biological properties. In 2019, we summarized emerging re-emerging warhead chemistries to cysteine acids (Gehringer, M.; Laufer, S. A. J. Med. Chem. 62, 5673−5724; DOI: 10.1021/acs.jmedchem.8b01153). Since then, field has rapidly evolved. Here discuss progress on warheads made since our last Perspective their application medicinal chemistry chemical biology.

Language: Английский

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Recyclable, Malleable, and Strong Thermosets Enabled by Knoevenagel Adducts

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(14), P. 9920 - 9927

Published: April 1, 2024

Plastic recycling is critical for waste management and achieving a circular economy, but it entails difficult trade-offs between performance recyclability. Here, we report thermoset, poly(α-cyanocinnamate) (PCC), synthesized using Knoevenagel condensation terephthalaldehyde (TPA) triarm cyanoacetate star, that tackles this difficulty by harnessing its intrinsically conjugated dynamic chemical characteristics. PCCs exhibit extraordinary thermal mechanical properties with typical Tg of ∼178 °C, Young's modulus 3.8 GPa, tensile strength 102 MPa, along remarkable flexibility dimensional stabilities. Furthermore, end-of-life can be selectively degraded partially recycled back into one starting monomer TPA new production cycle or reprocessed through exchange aided chain-ends. This study lays the scientific groundwork design robust recyclable thermosets, transformative potential in plastic engineering.

Language: Английский

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Strengthening and Toughening Dynamic Covalent Thermosets via Hydrogen-Bonded Cross-Links

Macromolecules, Journal Year: 2024, Volume and Issue: 57(3), P. 1362 - 1369

Published: Feb. 5, 2024

Dynamic covalent thermosets have emerged as a next-generation sustainable plastic that combines the advantages of traditional and thermoplastics. However, dynamic generally suffer from trade-off between strength/stiffness ductility/toughness. Herein, strategy to simultaneously strengthen toughen thermosets, incorporation hydrogen-bonded (H-bonded) cross-links into networks, is reported. We designed polyimine network cross-linked by both imine bonds H-bonds, resulting in remalleable recyclable thermoset with high yield strength (ca. 55.2 MPa) Young's modulus 1.7 GPa) well ductility 72%) toughness 32.7 MJ m–3). When H-bonded are removed or replaced bonds, mechanical polyimines significantly declined, respectively. Therefore, this work provides an effective design principle for strong tough modularity recyclability.

Language: Английский

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Vinylogous Urea—Urethane Vitrimers: Accelerating and Inhibiting Network Dynamics through Hydrogen Bonding

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(9)

Published: Jan. 10, 2024

Vinylogous urethane (VU

Language: Английский

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Dynamic Covalent Bond-Based Polymer Chains Operating Reversibly with Temperature Changes

Molecules, Journal Year: 2024, Volume and Issue: 29(14), P. 3261 - 3261

Published: July 10, 2024

Dynamic bonds can facilitate reversible formation and dissociation of connections in response to external stimuli, endowing materials with shape memory self-healing capabilities. Temperature is an stimulus that be easily controlled through heat. covalent temperature reversibly connect, exchange, convert chains the polymer. In this review, we introduce dynamic operate without catalysts various ranges. The basic bonding mechanism kinetics are examined understand chemistry performed by equilibrium control. Furthermore, a recent synthesis method implements coupling based on polymers introduced. depending applied expand use polymers, providing predictions for development future smart materials.

Language: Английский

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Green and clean synthesis of 4-arylideneisoxazol-5-ones using NaCl aqueous solution

Sustainable Chemistry for the Environment, Journal Year: 2024, Volume and Issue: 5, P. 100066 - 100066

Published: Jan. 6, 2024

The one-pot, three-component cyclization reaction a wide variety of aryl/heteroaryl aldehydes, hydroxylamine hydrochloride, and β-keto ester compounds was performed in simple manner. reactions carried out the presence sodium chloride (NaCl) as profitable, green, efficient catalyst at room temperature. Optimization experiments indicate that amount 17 mol% loaded NaCl is sufficient to catalyze reaction. Among advantages this NaCl-catalyzed method are availability catalyst, no need for synthesis several steps, commercially available reactants, use aqueous conditions, clean synthesis, non-inflammable medium, environmental pollution, safety, cost-effectiveness, pot-economy, optimum efficiency, carbon economy steps. Due absence harmful solvents, an abundant, low-cost, useful water solvent, considered green synthesis.

Language: Английский

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Activation of Anthraquinone’s Electrophilicity by Light for a Dynamic C–O Bond

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 1799 - 1805

Published: Jan. 11, 2024

Coupling of photoswitching with dynamic covalent chemistry enables control the formation and cleavage bonds by light irradiation. peri-Aryloxyanthraquinones feature an exclusive ability to switch electrophilicity interconversion between para- ana-quinone isomers, which was used for first time implementation a C–O bond. Photogenerated ana-isomers undergo concerted oxa-Michael addition phenols give hitherto unknown 4-hydroxy-10,10-diaryloxyanthracen-9-ones. These species were found be in equilibrium corresponding ana-quinones, thus forming system new type. Withdrawal colored ana-quinones from equilibria visible irradiation resulted two para-quinones "locked" aryloxy groups.

Language: Английский

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Catalyst‐Free Dynamic Covalent C=C/C=N Metathesis Reaction for Associative Covalent Adaptable Networks

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Covalent adaptable networks (CANs), leveraging the dynamic exchange of covalent bonds, emerge as a promising material to address challenge irreversible cross-linking in thermosetting polymers. In this work, we explore introduction catalyst-free and associative C=C/C=N metathesis reaction into polyurethanes, creating CANs with superior stability, solvent resistance, thermal/mechanical properties. By incorporating reaction, stress-relaxation is significantly accelerated compared imine-bond-only networks, rate adjustable by modifying substituents ortho position double bonds. The obtained plasticity enables recycle without altering chemical structure or mechanical properties, also found be vital for achieving shape memory functions complex spatial structures. This new crosslinker polymer has potential accelerate ongoing exploration malleable functional thermoset

Language: Английский

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Dynamic Chemistry Toolbox for Advanced Sustainable Materials

Advanced Science, Journal Year: 2024, Volume and Issue: 11(14)

Published: Feb. 6, 2024

Abstract Developing dynamic chemistry for polymeric materials offers chemical solutions to solve key problems associated with current plastics. Mechanical performance and function are equally important in material design because the former determines application scope latter enables recycling hence sustainability. However, it is a long‐term challenge balance subtle trade‐off between mechanical robustness properties single material. The rise of chemistry, including supramolecular covalent provides many opportunities versatile molecular tools designing constitutionally that can adapt, repair, recycle. Facing growing social need developing advanced sustainable without compromising properties, recent progress showing how toolbox be explored enable high‐performance by engineering strategies discussed here. state art milestones summarized discussed, followed an outlook toward future challenges present this field.

Language: Английский

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Dual reactivity based dynamic covalent chemistry: mechanisms and applications

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(87), P. 12943 - 12958

Published: Jan. 1, 2023

Dynamic covalent chemistry (DCC) focuses on the reversible formation, breakage, and exchange of bonds assemblies, setting a bridge between irreversible organic synthesis supramolecular finding wide utility. In order to enhance structural functional diversity complexity, different types dynamic reactions (DCRs) are placed in one vessel, encompassing orthogonal DCC without crosstalk communicating with shared reactive group. As means adding tautomers, widespread chemistry, interconnected DCRs combining features DCRs, concept dual reactivity based underlying mechanistic insights summarized. The manipulation distinct structurally diverse ring-chain tautomers allows selective activation switching reaction pathways corresponding (C-N, C-O, C-S) assemblies. coupling photoswitches further enables light-mediated formation scission multiple bonds. To showcase capability DCC, versatile applications polymers luminescent materials presented, paving way for future functionalization studies.

Language: Английский

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