Substrate Moiety Research Articles

DFT Studies on the Mechanism of Ligand-Regulated Palladium-Catalyzed Iodide-Assisted Hydrocarbonylation of Olefins with Formic Acid: Favored Reaction Routes and Selectivities.

DFT calculations have been performed to gain insight into the mechanism of hydrocarbonylation of olefins and the origin of regio- and chemoselectivity. It is shown that the most feasible mechanism involves five steps: (i) decomposition of acetic formic anhydride, (ii) hydropalladation of olefins, (iii) CO migratory insertion, (iv) iodide-assisted acetate-formate exchange, and (v) formylation or carboxylation. Importantly, carboxylation proceeds via the decomposition of anhydride, followed by reductive elimination instead of direct hydrolysis of anhydride. For phosphine-ligated palladium catalysis, on one hand, the lower stability of the transition state leading to 1,2-hydropalladation could be attributed to H···H steric hindrance. On the other hand, the high chemoselectivity for the aldehyde is ascribed to increased π back-donation effect and ligand-substrate noncovalent interactions, which stabilize the transition state and hence reduce the energy barrier. For ferrocenyl phosphine-ligated palladium catalysis, significant C-H···π interaction between the substrate and proximal phenyl moiety of the phenylphosphine and π-π interaction between formate and phenyl moiety can facilitate the carboxylation process. This in-depth mechanistic insight can account for reactivity and selectivity at an atomistic level and have implications for designing new generations of palladium catalysts.

Computational Insights into the Photoinduced Dimeric Gold-Catalyzed Divergent Dechloroalkylation of gem-Dichloroalkanes with Alkenes.

The employment of dinuclear Au(I) catalysts in photomediated modern organic transformations has attracted significant attention over the past decade, which commonly demonstrates unique catalytic performance compared with the corresponding mononuclear gold complexes. Nevertheless, detailed mechanisms of dinuclear gold catalysis remain ambiguous, and further mechanistic understanding is highly desirable. Herein, computational studies were carried out to gain mechanistic insights into the photoinduced dinuclear gold-catalyzed divergent dechloroalkylation of gem-dichloroalkanes. Computational results suggest that a proton transfer from the additive, Hantzsch ester (HE), to the base, guanidine, could lead to an ionic pair complex, which is ready to undergo excitation under blue light irradiation to result in the corresponding triplet excited state. Then, the excited complex might undergo oxidative quenching with the dinuclear gold photocatalyst [AuI-AuI]2+, via a single-electron-transfer (SET) step to afford an unusual [Au1/2-Au1/2]+ dinuclear species. The corresponding mononuclear gold catalyst, [AuI]+, however, is not ready to enable the analogous step to give a [Au0] species, which might account for the unique characteristics of dinuclear gold catalysis. Subsequently, the formed [Au1/2-Au1/2]+ intermediate could trigger a Cl-atom transfer from dichloromethane in an inner-sphere manner to furnish a critical chloromethyl radical. Next, the resulting chloromethyl radical could attack the alkenyl moiety of substrates to generate the corresponding alkyl radicals. Then, three possible mechanistic pathways were explored to rationalize the substrate-dependent divergent transformations in this protocol. The main factors responsible for the diversified transformations were discussed.

Substrate scope driven optimization of an encapsulated hydroformylation catalyst.

Caged complexes can provide impressive selective catalysts. Due to the complex shapes of such caged catalysts, however, the level of selectivity control of a single substrate cannot be extrapolated to other substrates. Herein, the substrate scope using 41 terminal alkene substrates is investigated in the hydroformylation reaction with an encapsulated rhodium catalyst [Rh(H)(CO)3(P(mPy3(ZnTPP)3))] (CAT1). For all substrates, the amount of branched products formed was higher with CAT1 than with the unencapsulated reference catalyst [Rh(H)(CO)2(P(mPy3))2] (CAT2) (linear/branched ratio between 2.14 and 0.12 for CAT1 and linear/branched ratio between 6.22 and 0.59 for CAT2). Interestingly, the level of cage induced selectivity depends strongly on the substrate structure that is converted. Analysis of the substrate scope combined with DFT calculations suggests that noncovalent interactions between the substrate moieties and cage walls play a key role in controlling the regioselectivity. Consequently, these supramolecular interactions were further optimized by replacing the ZnTPP building block with a zinc porphyrin analog that contained OiPr substituents on the meta position of the aryl rings. The resulting caged catalyst, CAT4, converted substrates with even higher branched selectivity.

Functional and structural insights into the multi-step activation and catalytic mechanism of bacterial ExoY nucleotidyl cyclase toxins bound to actin-profilin.

ExoY virulence factors are members of a family of bacterial nucleotidyl cyclases (NCs) that are activated by specific eukaryotic cofactors and overproduce cyclic purine and pyrimidine nucleotides in host cells. ExoYs act as actin-activated NC toxins. Here, we explore the Vibrio nigripulchritudo Multifunctional-Autoprocessing Repeats-in-ToXin (MARTX) ExoY effector domain (Vn-ExoY) as a model for ExoY-type members that interact with monomeric (G-actin) instead of filamentous (F-actin) actin. Vn-ExoY exhibits moderate binding affinity to free or profilin-bound G-actin but can capture the G-actin:profilin complex, preventing its spontaneous or VASP- or formin-mediated assembly at F-actin barbed ends in vitro. This mechanism may prolong the activated cofactor-bound state of Vn-ExoY at sites of active actin cytoskeleton remodelling. We present a series of high-resolution crystal structures of nucleotide-free, 3'-deoxy-ATP- or 3'-deoxy-CTP-bound Vn-ExoY, activated by free or profilin-bound G-actin-ATP/-ADP, revealing that the cofactor only partially stabilises the nucleotide-binding pocket (NBP) of NC toxins. Substrate binding induces a large, previously-unidentified, closure of their NBP, confining catalytically important residues and metal cofactors around the substrate, and facilitating the recruitment of two metal ions to tightly coordinate the triphosphate moiety of purine or pyrimidine nucleotide substrates. We validate critical residues for both the purinyl and pyrimidinyl cyclase activity of NC toxins in Vn-ExoY and its distantly-related ExoY from Pseudomonas aeruginosa, which specifically interacts with F-actin. The data conclusively demonstrate that NC toxins employ a similar two-metal-ion mechanism for catalysing the cyclisation of nucleotides of different sizes. These structural insights into the dynamics of the actin-binding interface of actin-activated ExoYs and the multi-step activation of all NC toxins offer new perspectives for the specific inhibition of class II bacterial NC enzymes.

DEVELOPMENT AND APPLICATION OF STRUCTURE-ASSISTED ATOM-BASED DE NOVO MOLECULAR DESIGN (SAAD) APPROACH USING MATLAB

In the context of drug design and development, phytochemical and synthetic libraries are starting places for searching leads. However, knowing crystal structure of receptor may help scratching molecules that complements available interaction sites using de novo molecular design approaches. This research describes the implementation of genetic algorithm optimization technique for construction of molecular scaffold composed from sp2 carbon, oxygen and nitrogen atoms. Using Matlab, functions for molecule construction, crossover, mutation and fitness measurement were individually programmed. Fitness function was derived from AutoDock3.05 function which calculates molecular interaction energy with protein using grid map. The approach was successfully applied to design glutathione-S-transferase inhibitory molecule at sub-site of the binding pocket that is originally occupied by g-glutamyl and cysteinyl moieties of glutathione substrate. Starting from scratches, the approach was able to design molecular scaffolds complementarily filling the pocket.

Structural insights into a bacterial β-glucosidase capable of degrading sesaminol triglucoside to produce sesaminol: toward the understanding of the aglycone recognition mechanism by the C-terminal lid domain.

The sesaminol triglucoside (STG)-hydrolyzing β-glucosidase from Paenibacillus sp. (PSTG1), which belongs to glycoside hydrolase family 3 (GH3), is a promising catalyst for the industrial production of sesaminol. We determined the X-ray crystal structure of PSTG1 with bound glycerol molecule in the putative active site. PSTG1 monomer contained typical three domains of GH3 with the active site in domain 1 (TIM barrel). In addition, PSTG1 contained an additional domain (domain 4) at the C-terminus that interacts with the active site of the other protomer as a lid in the dimer unit. Interestingly, the interface of domain 4 and the active site forms a hydrophobic cavity probably for recognizing the hydrophobic aglycone moiety of substrate. The short flexible loop region of TIM barrel was found to be approaching the interface of domain 4 and the active site. We found that n-heptyl-β-D-thioglucopyranoside detergent acts as an inhibitor for PSTG1. Thus, we propose that the recognition of hydrophobic aglycone moiety is important for PSTG1-catalyzed reactions. Domain 4 might be a potential target for elucidating the aglycone recognition mechanism of PSTG1 as well as for engineering PSTG1 to create a further excellent enzyme to degrade STG more efficiently to produce sesaminol.

Strain-Release-Controlled [4 + 2 + 1] Reaction of Cyclopropyl-Capped Diene-ynes/Diene-enes and Carbon Monoxide Catalyzed by Rhodium.

Achieving transition-metal-catalyzed reactions of diene-ynes/diene-enes and carbon monoxide (CO) to deliver [4 + 2 + 1] cycloadducts, rather than the kinetically favored [2 + 2 + 1] products, is challenging. Here, we report that this can be solved by adding a cyclopropyl (CP) cap to the diene moiety of the original substrates. The resulting CP-capped diene-ynes/diene-enes can react with CO under Rh catalysis to give [4 + 2 + 1] cycloadducts exclusively without forming [2 + 2 + 1] products. This reaction has a broad scope and can be used to synthesize useful 5/7 bicycles with a CP moiety. Of the same importance, the CP moiety in the [4 + 2 + 1] cycloadducts can act as an intermediate group for further transformations so that other challenging bicyclic 5/7 and tricyclic 5/7/5, 5/7/6, and 5/7/7 skeletons, some of which are widely found in natural products, can be accessed. The mechanism of this [4 + 2 + 1] reaction has been investigated by quantum chemical calculations, and the role of the CP group in avoiding the possible side [2 + 2 + 1] reaction has been identified, showing that the [4 + 2 + 1] is controlled by releasing the ring strain in the methylenecyclopropyl (MCP) group (about 7 kcal/mol) in the CP-capped dienes.

AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis

Macrocyclization is an important process that affords morphed scaffold in biosynthesis of bioactive natural products. Nature has adapted diverse biosynthetic strategies to form macrocycles. In this work, we report the identification and characterization of a small enzyme AvmM that can catalyze the construction of a 16-membered macrocyclic ring in the biosynthesis of alchivemycin A (1). We show through in vivo gene deletion, in vitro biochemical assay and isotope labelling experiments that AvmM catalyzes tandem dehydration and Michael-type addition to generate the core scaffold of 1. Mechanistic studies by crystallography, DFT calculations and MD simulations of AvmM reveal that the reactions are achieved with assistance from the special tenuazonic acid like moiety of substrate. Our results thus uncover an uncharacterized macrocyclization strategy in natural product biosynthesis.

Structural insight into a molecular mechanism of methenyltetrahydrofolate cyclohydrolase from Methylobacterium extorquens AM1

Bioconversion of the C1 compounds into value-added products is one of the CO2-reducing strategies. In particular, because CO2 can be easily converted into formate, the efficient and direct bioconversion of CO2 through formate assimilation is attracting attention. The tetrahydrofolate (THF) cycle is the highly efficient reconstructed formate assimilation pathway, and 5,10-methenyltetrahydrofolate cyclohydrolase (FchA) is an essential enzyme involved in the THF cycle. In this study, a kinetic analysis of FchA from Methylobacterium extorquens AM1 (MeFchA) was performed and revealed that the enzyme has much higher cyclization than hydrolyzation activity, making it an optimal enzyme for formate assimilation. The crystal structure of MeFchA in the apo- and the THF-complexed forms was also determined, revealing that the substrate-binding site of the enzyme has three differently charged regions to stabilize the three differently charged moieties of the formyl-THF substrate. The residues involved in the substrate binding were also verified through site-directed mutagenesis. This study provides a biochemical and structural basis for the molecular mechanism underlying formate assimilation.

Computational Study of the Rh/phanephos-Catalyzed Enantioselective [2+2+2] Cyclization of Enediyne, Affording Lactone-Fused Cyclohexadiene Bearing a Quaternary Bridgehead Carbon

Abstract The mechanism of the Rh/phanephos-catalyzed enantioselective [2+2+2] cyclization of an ester-tethered enediyne, which produces a lactone-fused cyclohexadiene bearing an all-carbon quaternary bridgehead carbon, was computationally analyzed using density functional theory (DFT) calculations. This study suggests that the initial oxidative coupling occurs with the 1,6-diyne moiety rather than the 1,6-enyne moiety of the enediyne substrate, and the subsequent insertion of the pendant alkene into the resultant rhodacyclopentadiene intermediate is the enantioselectivity determining step. Further, it is suggested that the experimentally favored enantiomer should be produced through endo-mode alkene insertion followed by two-step reductive elimination. Moreover, DFT calculations show that the Rh/2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) catalyst enables the [2+2+2] cyclization of an enediyne bearing a methyl substituent at the propiolate terminus, which is not feasible using the Rh/phanephos catalyst.

Insight into the nucleoside transport and inhibition of human ENT1

The human equilibrative nucleoside transporter 1 (hENT1) is an effective controller of adenosine signaling by regulating its extracellular and intracellular concentration, and has become a solid drug target of clinical used adenosine reuptake inhibitors (AdoRIs). Currently, the mechanisms of adenosine transport and inhibition for hENT1 remain unclear, which greatly limits the in-depth understanding of its inner workings as well as the development of novel inhibitors. In this work, the dynamic details of hENT1 underlie adenosine transport and the inhibition mechanism of the non-nucleoside AdoRIs dilazep both were investigated by comparative long-time unbiased molecular dynamics simulations. The calculation results show that the conformational transitions of hENT1 from the outward open to metastable occluded state are mainly driven by TM1, TM2, TM7 and TM9. One of the trimethoxyphenyl rings in dilazep serves as the adenosyl moiety of the endogenous adenosine substrate to competitively occupy the orthosteric site of hENT1. Due to extensive and various VDW interactions with N30, M33, M84, P308 and F334, the other trimethoxyphenyl ring is stuck in the opportunistic site near the extracellular side preventing the complete occlusion of thin gate simultaneously. Obviously, dilazep shows significant inhibitory activity by disrupting the local induce-fit action in substrate binding cavity and blocking the transport cycle of whole protein. This study not only reveals the nucleoside transport mechanism by hENT1 at atomic level, but also provides structural guidance for the subsequent design of novel non-nucleoside AdoRIs with enhanced pharmacologic properties.

An activator-induced quencher-detachment-based turn-on probe with a cationic substrate moiety for acetylcholinesterase.

We report a choline ester-grafted turn-on fluorescence probe to detect acetylcholinesterase (AChE) in living cells. The AChE-mediated hydrolysis of the choline ester moiety producing carboxylate initiates the activation of the Cy5 fluorophore quenched by an intramolecular nucleophilic mercapto group. The probe has the advantages of high AChE affinity and low cytotoxicity.

Rapid and Sensitive Detection of Cancer Cells with Activatable Fluorescent Probes for Enzyme Activity.

Fluorescence (FL)-guided detection of cancer is one of the most promising approaches to achieve intraoperative assessment of surgical margins. Enzymes, such as aminopeptidase, carboxypeptidase, and glycosidase, whose activities are increased in cancer, have attracted great interest as imaging targets for rapid and sensitive visualization of cancerous tissues with fluorescent probes. Activatable probes, which are initially nonfluorescent but become strongly fluorescent upon rapid one-step cleavage of their substrate moiety by the target enzyme, are especially promising for practical clinical application during surgical or endoscopic procedures due to the highly amplified FL change generated by enzyme-catalyzed turnover at lesion sites. Here, we describe robust protocols for using activatable fluorescent probes targeting cancer-associated enzyme activities to visualize cultured cancer cells, metastatic cancer in a mouse model, and cancerous lesions in surgical specimens from patients.

Nonspecific Heme-Binding Cyclase, AbmU, Catalyzes [4 + 2] Cycloaddition during Neoabyssomicin Biosynthesis.

Diels–Alder (DA) [4 + 2]-cycloaddition reactions rank among the most powerful transformations in synthetic organic chemistry; biosynthetic examples, however, are few and far between. We report here a heme-binding cyclase, AbmU, that catalyzes an essential [4 + 2] cycloaddition during neoabyssomicin scaffold assembly. In vivo genetic and in vitro biochemical analyses strongly suggest that AbmU catalyzes an intramolecular and stereoselective [4 + 2] cycloaddition to form a spirotetronate skeleton from an acyclic substrate featuring both a terminal 1,3-diene and an exo-methylene group. Biochemical assays and X-ray diffraction analyses reveal that AbmU binds nonspecifically to a heme b cofactor and that this association does not play a catalytic role in AbmU catalysis. A detailed study of the AbmU crystal structure reveals a unique mode of substrate binding and reaction catalysis; His160 forms a H-bond with the C-1 carbonyl O-atom of the acyclic substrate, and the imidazole of the same amino acid directs the tetronate moiety of acyclic substrate toward the terminal Δ10,11, Δ12,13-diene moiety, thereby facilitating intramolecular DA chemistry. Our findings expand upon what is known about mechanistic diversities available to biosynthetic [4 + 2] cyclases and help to lay the foundation for the use of AbmU in possible industrial applications.

Crystal Structures of the C-Glycosyltransferase UGT708C1 from Buckwheat Provide Insights into the Mechanism of C-Glycosylation.

C-Glycosyltransferases (CGTs) catalyze the formation of C-glycosidic bonds for the biosynthesis of C-glycosides, but the underlying mechanism is unclear. This process improves the solubility and bioavailability of specialized metabolites, which play important roles in plant growth and development and represent rich resources for drug discovery. Here, we performed functional and structural studies of the CGT UGT708C1 from buckwheat (Fagopyrum esculentum). Enzymatic analysis showed that UGT708C1 is capable of utilizing both UDP-galactose and UDP-glucose as sugar donors. Our structural studies of UGT708C1 complexed with UDP-glucose and UDP identified the key roles of Asp382, Gln383, Thr151, and Thr150 in recognizing the sugar moiety of the donor substrate and Phe130, Tyr102, and Phe198 in binding and stabilizing the acceptor. A systematic site-directed mutagenesis study confirmed the important roles of these residues. Further structural analysis combined with molecular dynamics simulations revealed that phloretin binds to the acceptor binding pocket in a bent state with a precise spatial disposition and complementarity. These findings provide insights into a catalytic mechanism for CGTs.

Exploiting the rationale behind substrate recognition by promiscuous thermophilic NDP-sugar pyrophosphorylase for expanding glycorandomization: an in silico study

The fundamental substrates for protein glycosylation are provided by a group of enzymes known as NDP-sugar pyrophosphorylases (NSPases) which utilize nucleotide triphosphate (NTP) and sugar 1-phosphate to catalyze the formation of nucleotide diphospho-sugar (NDP-sugar). The promiscuous nature of NSPases is often exploited during chemoenzymatic glycorandomization in the pursuit of novel therapeutics. However, till date, the number of inherently promiscuous NSPases reported and the rationale behind their promiscuity is meager. In this study, we have identified a set of NSPases from a hyperthermophilic archaeon Pyrococcus horikoshii OT3 to identify probable candidates for glycorandomization. We identified a set of NSPases that include both substrate-specific and substrate-promiscuous NSPases with a visible predominance of the latter group. The rationale behind the promiscuity (or specificity) vividly lies in the repertoire of amino acid residues that assemble the active site for recognition of the substrate moiety. Furthermore, the absence of a function-specific auxiliary domain promotes substrate promiscuity in NSPases. This study, thus, provides a novel set of thermophilic NSPases that can be employed for chemoenzymatic glycorandomization. More importantly, identification of the residues that render substrate promiscuity (or specificity) would assist in sequence-based rational engineering of NSPases for enhanced glycorandomization. Communicated by Ramaswamy H. Sarma

A General Approach to Enzyme-Responsive Liposomes.

Liposomes are effective nanocarriers due to their ability to deliver encapsulated drugs to diseased cells. Nevertheless, liposome delivery would be improved by enhancing the ability to control the release of contents at the target site. While various stimuli have been explored for triggering liposome release, enzymes provide excellent targets due to their common overexpression in diseased cells. We present a general approach to enzyme-responsive liposomes exploiting targets that are commonly aberrant in disease, including esterases, phosphatases, and β-galactosidases. Responsive lipids correlating with each enzyme family were designed and synthesized bearing an enzyme substrate moiety attached via a self-immolating linker to a non-bilayer lipid scaffold, such that enzymatic hydrolysis triggers lipid decomposition to disrupt membrane integrity and release contents. Liposome dye leakage assays demonstrated that each enzyme-responsive liposome yielded significant content release upon enzymatic treatment compared to minimal release in controls. Results also showed that fine-tuning liposome composition was critical for controlling release. DLS analysis showed particle size increases in the cases of esterase- and β-galactosidase-responsive lipids, supporting alterations to membrane properties. These results showcase an effective modular strategy that can be tailored to target different enzymes, providing a promising new avenue for advancing liposomal drug delivery.

Asymmetric Open-Closed Dimer Mechanism of Polyhydroxyalkanoate Synthase PhaC.

SummaryBiodegradable polyester polyhydroxyalkanoate (PHA) is a promising bioplastic material for industrial use as a replacement for petroleum-based plastics. PHA synthase PhaC forms an active dimer to polymerize acyl moieties from the substrate acyl-coenzyme A (CoA) into PHA polymers. Here we present the crystal structure of the catalytic domain of PhaC from Chromobacterium sp. USM2, bound to CoA. The structure reveals an asymmetric dimer, in which one protomer adopts an open conformation bound to CoA, whereas the other adopts a closed conformation in a CoA-free form. The open conformation is stabilized by the asymmetric dimerization and enables PhaC to accommodate CoA and also to create the product egress path. The bound CoA molecule has its β-mercaptoethanolamine moiety extended into the active site with the terminal SH group close to active center Cys291, enabling formation of the reaction intermediate by acylation of Cys291.

Computational Insights into the Divergent Regioselectivities for Nickel‐Catalyzed Dicarbofunctionalization of Allyl Moiety of N‐Allyl‐2‐aminopyrimidine

AbstractHerein, the origins of organohalide‐dependent regioselectivities for Ni‐catalyzed dicarbofunctionalization of allyl moiety of N‐allyl‐2‐aminopyrimidine were explored by computational studies. When aryl iodides are used for the dicarbofunctionalization, the detailed reaction mechanistic pathway follows the sequential oxidative addition (OA), migratory insertion (MI), β‐H elimination, H‐migration, transmetalation, and reductive elimination (RE) to afford the 1,3‐dicarbofunctionalization products. Due to the presence of chelation of the pyrimidinyl moiety of substrate with Ni, the competitive β‐H elimination leading to the product of Heck reaction is less favourable and thus the regioselective β‐H elimination occurs. The formation of thermodynamically more stable intermediate is the driving force for the subsequent H‐migration. When alkenyl bromides are used, alternative regioselectivity to give 1,2‐dicarbofunctionalization products is obtained and the proposed mechanistic pathway proceeds sequentially via OA, MI, transmetalation, and RE. The main reason accounting for the different regioselectivity between aryl iodides and alkenyl bromides involved in dicarbofunctionalization is revealed. In addition, the reversed 2,1‐regioselectivity achieved by using alkynyl halides in the Ni‐catalyzed dicarbofunctionalization is via sequential steps of OA, transmetalation, MI, and RE. The mechanistic difference that the migratory insertion step is unlikely to occur after OA, which is in contrast to the other two mechanistic pathways, is rationalized.

Allylic hydrocarbon polymers complexed with Fe(II)(salen) as a ultrahigh oxygen-scavenging and active packaging film

Abstract Macromolecular metal complexes provide a molecular-based synergy function of organic polymers and combined metal complexes. A new category of macromolecular complexes includes catalytically active metal complexes immobilized by organic polymers containing reactive substrate moieties in their repeating units. Here, we describe the extremely efficient oxidation of allylic hydrocarbon polymers with the attached iron complex catalyst, as well as the efficient oxygen-consumption or oxygen-scavenging function of the matrix polymer film. The less toxic N,N´-di(salicylaldehyde)ethylenediiminatoiron(II) complex was combined with or fixed onto a series of allylic hydrocarbon polymers as both the oxidative substrate and the film matrix, i.e. poly(1,2-butadiene), polynorbornene, poly(5-vinyl-2-norbornene), poly(2,5-norboenadiene), poly(dicyclopentadiene), and poly(5-ethylidene-2-norbornene). Ultra-high oxygen-scavenging capacity up to 300 mL (oxygen gas at STP)/g(film) was achieved, based on the oxidative consumption of the allylic bond (particularly of poly(5-ethylidene-2-norbornene)), which was more than three times that of the previously reported highest oxygen-scavenging polymers. These oxygen-scavenging films are based on the high reactivity of polymer-metal complexes that provides an innovative development in the area of active packaging polymer films that facilitate cost-effective performance, safety, and sustainability.