Pentafluorophenyl Ester Research Articles

Polymer Free Volume-Controlled Molecular Clock and Emitter for Multicolored Transient Data Display in Advanced Photonic Cryptography.

The booming demand on data security has aroused great interest for developing smart materials with temporal display feature and dynamic multicolor fluorescence. However, it remains challenging to implement both features on most responsive molecules. Herein, we construct a polymer free volume-controlled "molecular clock and emitter" via covalently embedding a multi-stimuli responsive molecular switch (i.e., spiropyran) into a polymer network (i.e., poly(pentafluorophenyl acrylate)) with programmable crosslink density and free volume. By the aminolysis of pentafluorophenyl ester with different amount of diamine crosslinkers, pPFPA-co-SP networks with controllable crosslink densities are generated, which have different confinement effects on the rate constant of SP/MC isomerization, thus leading to time-dependent photochromism. In addition, PTF1, a fluorescent probe that is sensitive to polymer rigidity, is introduced to further endow pPFPA-co-SP system with phototunable dynamic full-color emission. Therefore, relying on their synergistical responses to the rigidity of the polymer network, we have successfully developed a versatile molecular clock and emitter via an "one stone two birds" manner, which shows time-dependent data display along with dynamic multicolor fluorescence switching, providing great potential for advanced encryption and anticounterfeiting with a high security level.

Polymer Free Volume‐Controlled Molecular Clock and Emitter for Multicolored Transient Data Display in Advanced Photonic Cryptography

AbstractThe booming demand on data security has aroused great interest for developing smart materials with temporal display feature and dynamic multicolor fluorescence. However, it remains challenging to implement both features on most responsive molecules. Herein, we construct a polymer free volume‐controlled “molecular clock and emitter” via covalently embedding a multi‐stimuli responsive molecular switch (i.e., spiropyran) into a polymer network (i.e., poly(pentafluorophenyl acrylate)) with programmable crosslink density and free volume. By the aminolysis of pentafluorophenyl ester with different amount of diamine crosslinkers, pPFPA‐co‐SP networks with controllable crosslink densities are generated, which have different confinement effects on the rate constant of SP/MC isomerization, thus leading to time‐dependent photochromism. In addition, PTF1, a fluorescent probe that is sensitive to polymer rigidity, is introduced to further endow pPFPA‐co‐SP system with phototunable dynamic full‐color emission. Therefore, relying on their synergistical responses to the rigidity of the polymer network, we have successfully developed a versatile molecular clock and emitter via an “one stone two birds” manner, which shows time‐dependent data display along with dynamic multicolor fluorescence switching, providing great potential for advanced encryption and anticounterfeiting with a high security level.

Derivatives of (5-Oxooxazolidin-4-yl)acetic acids in aspartic acid α-carboxyl protection: a word of caution

Isomeric products could be isolated in a reaction of pentafluorophenyl ester of (S)-2-(3-((benzyloxy)-carbonyl)-5-oxooxazolidin-4-yl)acetic acid with aminoacid esters. One product is an expected dipeptide, the isomeric one is an N-hydroxymethylamino succinimide – a product of methylene bridge cleavavge. Steric bulkness of aminoacid esters favors the formation of a peptide, however the reaction selectivity is quite unpredicatable. Moreover, the precise structure assignement requires high-temperature NMR experiments.

Dual-reactive single-chain polymer nanoparticles for orthogonal functionalization through active ester and click chemistry

Glucose has been extensively studied as a targeting ligand on nanoparticles for biomedical nanoparticles. A promising nanocarrier platform are single-chain polymer nanoparticles (SCNPs). SCNPs are well-defined 5–20 nm semi-flexible nano-objects, formed by intramolecularly crosslinked linear polymers. Functionality can be incorporated by introducing labile pentafluorophenyl (PFP) esters in the polymer backbone, which can be readily substituted by functional amine-ligands. However, not all ligands are compatible with PFP-chemistry, requiring different ligation strategies for increasing versatility of surface functionalization. Here, we combine active PFP-ester chemistry with copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry to yield dual-reactive SCNPs. First, the SCNPs are functionalized with increasing amounts of 1-amino-3-butyne groups through PFP-chemistry, leading to a range of butyne-SCNPs with increasing terminal alkyne-density. Subsequently, 3-azido-propylglucose is conjugated through the glucose C1- or C6-position by CuAAC click chemistry, yielding two sets of glyco-SCNPs. Cellular uptake is evaluated in HeLa cancer cells, revealing increased uptake upon higher glucose-surface density, with no apparent positional dependance. The general conjugation strategy proposed here can be readily extended to incorporate a wide variety of functional molecules to create vast libraries of multifunctional SCNPs.

Design, Preparation, and Implementation of Axially Chiral Benzotetramisoles as Lewis Base Catalysts for Asymmetric Cycloadditions

AbstractDeveloping novel catalysts with potent activity is of great importance in organocatalysis. In this study, we designed and prepared a new class of benzotetramisole Lewis base catalysts (AxBTM) that have both central and axial chirality. This unique feature of these catalysts results in a three‐dimensional microenvironment with multi‐layers of chirality. The performance of the developed catalysts was tested in a series of cycloaddition reactions. These included the AxBTM‐catalyzed (2+2) cycloaddition between α‐fluoro‐α‐aryl anhydride with imines or oxindoles, and the sequential gold/AxBTM‐catalyzed (4+2) cycloaddition of enynamides with pentafluorophenyl esters. The interplay between axial and central chirality had a collaborative effect in regulating the stereochemistry in these cycloadditions, leading to high levels of stereoselectivity that would otherwise be challenging to achieve using conventional BTM catalysts. However, the (2+2) and (4+2) cycloadditions have different predilections for axial and central chirality combinations.

Design, Preparation, and Implementation of Axially Chiral Benzotetramisoles as Lewis Base Catalysts for Asymmetric Cycloadditions.

Developing novel catalysts with potent activity is of great importance in organocatalysis. In this study, we designed and prepared a new class of benzotetramisole Lewis base catalysts (AxBTM) that have both central and axial chirality. This unique feature of these catalysts results in a three-dimensional microenvironment with multi-layers of chirality. The performance of the developed catalysts was tested in a series of cycloaddition reactions. These included the AxBTM-catalyzed (2+2) cycloaddition between α-fluoro-α-aryl anhydride with imines or oxindoles, and the sequential gold/AxBTM-catalyzed (4+2) cycloaddition of enynamides with pentafluorophenyl esters. The interplay between axial and central chirality had a collaborative effect in regulating the stereochemistry in these cycloadditions, leading to high levels of stereoselectivity that would otherwise be challenging to achieve using conventional BTM catalysts. However, the (2+2) and (4+2) cycloadditions have different predilections for axial and central chirality combinations.

Inverse Vulcanization of Activated Norbornenyl Esters – A Versatile Platform for Functional Sulfur Polymers

Elemental sulfur has shown to be a promising alternative feedstock for development of novel polymeric materials with high sulfur content. However, the utilization of inverse vulcanized polymers is restricted by the limitation of functional comonomers suitable for an inverse vulcanization. Control over properties and structure of inverse vulcanized polymers still poses a challenge to current research due to the dynamic nature of sulfur‐sulfur bonds and high temperature of inverse vulcanization reactions. In here, we report for the first time the inverse vulcanization of norbornenyl pentafluorophenyl ester (NB‐PFPE), allowing for post‐modification of inverse vulcanized polymers via amidation of reactive PFP esters to yield high sulfur content polymers under mild conditions. Amidation of the precursor material with three functional primary amines (α‐amino‐ω‐methoxy polyethylene glycol, aminopropyl trimethoxy silane, allylamine) was investigated. The resulting materials were applicable as sulfur containing poly(ethylene glycol) nanoparticles in aqueous environment. Cross‐linked mercury adsorbents, sulfur surface coatings, and high‐sulfur content networks with predictable thermal properties were achievable using aminopropyl trimethoxy silane and allylamine for post‐polymerization modification, respectively. With the broad range of different amines available and applicable for post‐polymerization modification, the versatility of poly(sulfur‐random‐NB‐PFPE) as a platform precursor polymer for novel specialized sulfur containing materials was showcased.

Inverse Vulcanization of Activated Norbornenyl Esters-A Versatile Platform for Functional Sulfur Polymers.

Elemental sulfur has shown to be a promising alternative feedstock for development of novel polymeric materials with high sulfur content. However, the utilization of inverse vulcanized polymers is restricted by the limitation of functional comonomers suitable for an inverse vulcanization. Control over properties and structure of inverse vulcanized polymers still poses a challenge to current research due to the dynamic nature of sulfur-sulfur bonds and high temperature of inverse vulcanization reactions. In here, we report for the first time the inverse vulcanization of norbornenyl pentafluorophenyl ester (NB-PFPE), allowing for post-modification of inverse vulcanized polymers via amidation of reactive PFP esters to yield high sulfur content polymers under mild conditions. Amidation of the precursor material with three functional primary amines (α-amino-ω-methoxy polyethylene glycol, aminopropyl trimethoxy silane, allylamine) was investigated. The resulting materials were applicable as sulfur containing poly(ethylene glycol) nanoparticles in aqueous environment. Cross-linked mercury adsorbents, sulfur surface coatings, and high-sulfur content networks with predictable thermal properties were achievable using aminopropyl trimethoxy silane and allylamine for post-polymerization modification, respectively. With the broad range of different amines available and applicable for post-polymerization modification, the versatility of poly(sulfur-random-NB-PFPE) as a platform precursor polymer for novel specialized sulfur containing materials was showcased.

Well-Tailored Norbornene-Based Fluorinated Copolymers toward Modulating Icephobicity and Mechanical Robustness.

Well-tailored construction of icephobic surfaces with mechanical robustness and investigation of the structure-property relationships at the molecular level are highly desirable. Herein, a series of norbornene-based fluorinated polyolefin copolymers (FPOR-x) with varying norbornenyl dodecafluoroheptyl ester (NDFHE) molar fractions (0-100 mol %) were well-designed and fabricated via living ring-opening metathesis polymerization (ROMP) employing NDFHE and norbornenyl pentafluorophenyl ester (NPFPE) as the soft and hard segments, respectively. The mechanical and icephobic properties of the fluorinated copolymers can be regulated by adjusting the soft NDFHE contents. As a result, the well-designed norbornene-based copolymers exhibited a wide range of tunable mechanical properties, including tensile strength ranging from 0.2 to 26.4 MPa, elastic modulus ranging from 0.6 to 593.7 MPa, and breaking elongations ranging from 5718.7% to 3.7%, correlating with the proportion of soft NDFHE content. Furthermore, the synergistic interplay between soft and hard segments, particularly the hardness in the majority and softness in the minority or vice versa, could achieve a significant difference in the local modulus and enhance the propagations of cracks within the three-phase regions (soft regions/hard regions/ice), ultimately leading to a significant reduction in ice shear strength. Notably, FPOR-25% with a tensile strength of 12.0 MPa and an elastic modulus of 227.5 MPa exhibited a remarkably low ice shear strength of 57.7 kPa. This study not only highlights the relationship between the polymer molecular structure and surface icephobic properties but also breaks the limitations of icephobic surfaces with a low modulus.

Solution and Solvent-Free Stopper Exchange Reactions for the Preparation of Pillar[5]arene-containing [2] and [3]Rotaxanes.

Diamine reagents have been used to functionalize a [2]rotaxane building block bearing an activated pentafluorophenyl ester stopper. Upon a first acylation, an intermediate host-guest complex with a terminal amine function is obtained. Dissociation of the intermediate occurs in solution and acylation of the released axle generates a [2]rotaxane with an elongated axle subunit. In contrast, the corresponding [3]rotaxane can be obtained if the reaction conditions are appropriate to stabilize the inclusion complex of the mono-amine intermediate and the pillar[5]arene. This is the case when the stopper exchange is performed under mechanochemical solvent-free conditions. Alternatively, if the newly introduced terminal amide group is large enough to prevent the dissociation, the second acylation provides exclusively a [3]rotaxane. On the other hand, detailed conformational analysis has been also carried out by variable temperature NMR investigations. A complete understanding of the shuttling motions of the pillar[5]arene subunit along the axles of the rotaxanes reported therein has been achieved with the help of density functional theory calculations.

Access to Functionalized Materials by Metal-Free Ring-Opening Metathesis Polymerization of Active Esters and Divergent Postpolymerization Modification.

Metal-free ring-opening metathesis polymerization (MF-ROMP) is an emerging polymerization strategy that provides access to ROMP materials by using organic initiators and photoredox catalysts. Unlike metal-mediated ROMP, MF-ROMP is not highly tolerant toward functionalized monomers. Herein, we report that pentafluorophenyl esters are polymerizable under MF-ROMP conditions to produce homopolymers, statistical copolymers, and block copolymers. Amine coupling agents were then used to install a range of functional groups via acyl substitution including alkynes, amino acid derivatives, fluorophores, and redox active moieties. Overall, these findings provide a framework to prepare functionalized ROMP polymers without the risk of metal contamination.

Stepwise Functionalization of a Pillar[5]arene-Containing [2]Rotaxane with Pentafluorophenyl Ester Stoppers.

Invited for the cover of this issue are the group of Iwona and Jean-François Nierengarten from the University of Strasbourg (LIMA, UMR 7042, CNRS) and collaborators from the University of Carthage. The image depicts a sky of umbrellas floating in the air to illustrate the protective effect allowing the efficient mono-acylation of a symmetrical rotaxane building block with two pentafluorophenyl ester stoppers. Read the full text of the article at 10.1002/chem.2023003501.

Stepwise Functionalization of a Pillar[5]arene-Containing [2]Rotaxane with Pentafluorophenyl Ester Stoppers.

Detailed investigations into the stepwise bis-functionalization of a pillar[5]arene-containing rotaxane building block have been carried out. Upon a first stopper exchange, the pillar[5]arene moiety of the mono-acylated product is preferentially located close to its reactive pentafluorophenyl ester stopper, thus limiting the accessibility to the reactive carbonyl group by the nucleophilic reagents. Selective mono-functionalization is thus very efficient. Introduction of a second stopper is then possible to generate dissymmetrical rotaxanes with different amide stoppers. Moreover, when dethreading is possible upon the second acylation, the pillar[5]arene plays the role of a protecting group allowing the synthesis of dissymmetrical axles that are particularly difficult to prepare under statistical conditions. Finally, detailed conformation analysis of the rotaxanes revealed that the position of the pillar[5]arene moiety on its axle subunit is mainly governed by polar interactions in nonpolar organic solvents, whereas solvophobic effects play a major role in polar solvents.

Multifunctional Poly(2-ethyl-2-oxazoline) Copolymers Containing Dithiolane and Pentafluorophenyl Esters as Effective Reactive Linkers for Gold Surface Coatings.

Surface functionalization with biological macromolecules is an important task for the development of sensor materials, whereby the interaction with other biological materials should be suppressed. In this work, we developed a novel multifunctional poly(2-ethyl-2-oxazoline)-dithiolane conjugate as a versatile linker for gold surface immobilization of amine-containing biomolecules, containing poly(2-ethyl-2-oxazoline) as antifouling polymer, dithiolane for surface immobilization, and activated esters for protein conjugation. First, a well-defined carboxylic acid containing copoly(2-ethyl-2-oxazoline) was synthesized by cationic ring-opening copolymerization of 2-ethyl-2-oxazoline with a methyl ester-containing 2-oxazoline monomer, followed by postpolymerization modifications. The side-chain carboxylic groups were then converted to amine-reactive pentafluorophenyl (PFP) ester groups. Part of the PFP groups was used for the attachment of the dithiolane moiety, which can efficiently bind to gold surfaces. The final copolymer contained 1.4 mol% of dithiolane groups and 4.5 mol% of PFP groups. The copolymer structure was confirmed by several analytical techniques, including NMR spectroscopy and size-exclusion chromatography. The kinetics of the PFP ester aminolysis and hydrolysis demonstrated significantly faster amidation compared to hydrolysis, which is essential for subsequent protein conjugation. Successful coating of gold surfaces with the polymer was confirmed by spectroscopic ellipsometry, showing a polymer brush thickness of 4.77 nm. Subsequent modification of the coated surfaces was achieved using bovine serum albumin as a model protein. This study introduces a novel reactive polymer linker for gold surface functionalization and offers a versatile polymer platform for various applications including biosensing and surface functionalization.

Umpolung Isomerization in Radical Copolymerization of Benzyl Vinyl Ether with Pentafluorophenylacrylate Leading to Degradable AAB Periodic Copolymers

AbstractThis study revealed that benzyl vinyl ether (BnVE) shows a peculiar isomerization propagation in its radical copolymerization with an electron‐deficient acrylate carrying a pentafluorophenyl group (PFA). The co‐monomer pair inherently exhibits the cross‐over propagation feature due to the large difference in the electron density. However, the radical species of PFA was found to undergo a backward isomerization to the penultimate BnVE pendant giving a benzyl radical species prior to propagation with BnVE. The isomerization brings a drastic change in the character of the growing radical species from electrophilic to nucleophilic, and thus the isomerized benzyl radial species propagates with PFA. Consequently, the two monomers were consumed in the order AAB (A: PFA; B: BnVE) and the unique periodic consumption was confirmed by the pseudo‐reactivity ratios calculated by the penultimate model: r11=0.174 and r21=6600 for PFA (M1) with BnVE (M2). The pentafluorophenyl ester groups of the resulting copolymers are transformed into ester and amide groups by post‐polymerization alcoholysis and aminolysis modifications. The unique isomerization in the AAB sequence allowed the periodic introduction of a benzyl ether structure in the backbone leading to efficient degradation under acid conditions.

Umpolung Isomerization in Radical Copolymerization of Benzyl Vinyl Ether with Pentafluorophenylacrylate Leading to Degradable AAB Periodic Copolymers.

This study revealed that benzyl vinyl ether (BnVE) shows a peculiar isomerization propagation in its radical copolymerization with an electron-deficient acrylate carrying a pentafluorophenyl group (PFA). The co-monomer pair inherently exhibits the cross-over propagation feature due to the large difference in the electron density. However, the radical species of PFA was found to undergo a backward isomerization to the penultimate BnVE pendant giving a benzyl radical species prior to propagation with BnVE. The isomerization brings a drastic change in the character of the growing radical species from electrophilic to nucleophilic, and thus the isomerized benzyl radial species propagates with PFA. Consequently, the two monomers were consumed in the order AAB (A: PFA; B: BnVE) and the unique periodic consumption was confirmed by the pseudo-reactivity ratios calculated by the penultimate model: r11 =0.174 and r21 =6600 for PFA (M1 ) with BnVE (M2 ). The pentafluorophenyl ester groups of the resulting copolymers are transformed into ester and amide groups by post-polymerization alcoholysis and aminolysis modifications. The unique isomerization in the AAB sequence allowed the periodic introduction of a benzyl ether structure in the backbone leading to efficient degradation under acid conditions.

Cooperative Isothiourea/Iridium-Catalyzed Asymmetric Annulation Reactions of Vinyl Aziridines with Pentafluorophenyl Esters

Chiral γ-lactam-containing skeletons are important motifs in bioactive natural products, pharmaceuticals, and bioactive molecules. Herein, we report a general and modular platform to access chiral γ-lactam compounds via an ITU/Ir cooperatively catalyzed [3 + 2] asymmetric annulation reaction of vinyl aziridines with pentafluorophenyl esters. Through the Lewis base and transition metal cooperative catalytic regime, a broad range of optically active γ-lactams were generated in good yields (up to 92%) with high asymmetric induction (up to 98% ee). Furthermore, the utility of this synthetic protocol was also demonstrated by the expedient preparation of diverse enantioenriched architectures.

One-Step Preparation of Semiconductor/Dielectric Bilayer Structures for the Simulation of Flexible Bionic Photonic Synapses.

Flexible synaptic devices with information sensing, processing, and storage functions are indispensable in the development of wearable artificial intelligence electronic systems. Here, a semiconductor/dielectric bilayer structure was prepared by a one-step deposition method and used for the first time in a flexible biomimetic photonic synaptic transistor device. Specifically, poly(3-hexylthiophene)-block-poly(phenyl isocyanide) with pentafluorophenyl ester (P3HT-b-PPI(5F)) was prepared as the device active layer, where the P3HT segment served as a carrier transport channel and optical gate and the PPI(5F) segment was used for charge trapping. Various biomimetic synaptic behaviors, such as excitatory postsynaptic currents, paired-pulse facilitation, and short-term/long-term memory, were successfully simulated under green light stimulation. An ultra-low energy consumption of 1.82 fJ was achieved with a greatly reduced operating voltage. Further, the "Morse-code" optical decoding was simulated using the excellent synaptic plasticity of the device. In addition, flexible synaptic devices were prepared by a one-step deposition method and can be well-affixed to arbitrary substrates. This has promising applications in the field of wearable bionic electronics.

THE NATURALLY AVAILABLE PHYTO-PRODUCTS OF INDIAN MEDICINAL PLANTS AGAINST ADULTICIDAL ACTIVITY OF HUMAN VECTOR MOSQUITOES

Globally, most of the research community’s consideration for the control of vectors has moved from synthetic chemical pesticides to naturally available phyto-products. In the present investigation, we attempted to evaluate the bio efficacy of various floral extracts and its derived major phyto-compounds against adulticidal activity with different concentrations against the adults of medically important vector mosquitoes Aedes aegypti and Culex quinquefasciatus. The major phyto-chemical compounds of N. brachiata, L. crustacea and O. corniculata leaf extracts were analyzed with GC and Mass Spectroscopy. N. brachiata leaf methanol extract had a total of 10 bio-active compounds acquiring 100% and the major bio-active compounds were 1,4-benzenedicarboxylic acid, bis(2-ethylhexyl) ester (31.03%) and phthalic acid, hexadecyl 2,3,4,5-tetrafluorobenzyl ester (1.86%). Therefore, L. crustacea leaf methanol extract had a total of 10 bio-active compounds acquiring 100% and the major bio-active compounds were 2-acetylamino-2-cyano-acetamide (22.3%) and Phosphorin, 2,4,6-tris(1,1-dimethylethyl)- (28.96%). Similarly, O. corniculata leaf methanol extract had a total of 15 bio-active compounds acquiring 100% and the major bio-active compounds were Succinic acid, 2-methylpent-3-yl pentafluorophenyl ester (18.95%) and 1,2-Cyclohexanedicarboxylic acid, di(2-fluorophenyl) ester (19.91%). The efficacies of the phyto-products were assessed under laboratory conditions. The LC50/ LC90 values of leaf methanol extracts of N. brachiata, L. crustacea and O. corniculata and its derived major phyto-compounds 1,4-Benzenedicarboxylic acid, bis(2-ethylhexyl) ester, Phthalic acid, hexadecyl 2,3,4,5-tetrafluorobenzyl ester, 2-Acetylamino-2-cyano-acetamide, Phosphorin, 2,4,6-tris(1,1-dimethylethyl)-, Succinic acid, 2-methylpent-3-yl pentafluorophenyl ester and 1,2-Cyclohexanedicarboxylic acid, di(2-fluorophenyl) ester were tested against adults of vector mosquitoes Aedes aegypti and Culex quinquefasciatus of results were 84.82/168.78, 88.46/182.55, 92.30/174.63, 94.51/175.44, 96.42/174.84, 98.58/186.62 and 12.71/23.86, 11.23/22.82, 12.46/23.06, 12.34/23.37, 12.96/24.34, 12.89/23.85, 11.84/23.27, 12.36/23.79, 11.42/21.90, 11.34/21.93, 10.67/20.93 and 10.85/21.47 µg/ml, respectively. The outcomes of this present investigation well clearly indicated that the leaf methanol extracts of N. brachiata, L. crustacea and O. corniculata and its derived major phyto-compounds 1,4-Benzenedicarboxylic acid, bis(2-ethylhexyl) ester, Phthalic acid, hexadecyl 2,3,4,5-tetrafluorobenzyl ester, 2-Acetylamino-2-cyano-acetamide, Phosphorin, 2,4,6-tris(1,1-dimethylethyl)-, Succinic acid, 2-methylpent-3-yl pentafluorophenyl ester and 1,2-Cyclohexanedicarboxylic acid, di(2-fluorophenyl) ester had the potential effects on selected medical pests Ae. aegypti and Cx. quinquefasciatus. The findings of outputs as possible role battle with Ae. aegypti and C. quinquefasciatus. Further studies regarding the application selected phyto-products in the field application which will give the way for development of newer phyto-mosquitocide.

Strategic design of lysine-targeted irreversible covalent NDM-1 inhibitors

New Delhi metallo-β-lactamase 1 (NDM-1) can hydrolyze most β-lactam antibiotics, which is the major factor for drug resistance of Gram-negative bacteria. The binding of most reversible inhibitors to NDM-1 is relatively weak due to the shallow active pocket of NDM-1. Alternatively, irreversible covalent inhibitors can prevent their dissociation from the target, leading to permanent inactivation of the protein. Herein, we report a series of irreversible covalent inhibitors of NDM-1 targeting the conserved Lys211 in the active pocket. Several methods, including mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fluorescent labeling, and coumarin probe were used to demonstrate that pentafluorophenyl ester formed a covalent bond with Lys211. Moreover, our target inhibitor, in combination with meropenem, achieved an antibacterial effect on drug-resistant bacteria, along with an excellent safety profile. Our new strategy in designing lysine-targeted irreversible covalent NDM-1 inhibitors provides a potential option for the clinical treatment of Gram-negative bacteria.