Dehalogenation Reactions Research Articles

Estimating dehalogenation reactivity of nanoscale zero-valent iron by simple colorimetric assay by way of 4-chlorophenol reduction

Estimating dehalogenation reactivity of nanoscale zero-valent iron by simple colorimetric assay by way of 4-chlorophenol reduction

Radiohalogenated Neopentyl Derivatives: A Novel Scaffold for Radioiodinated and astatinated Compounds of High Stability to In Vivo Dehalogenation

Astatine-211 (211At) is an α-emitting radionuclide appropriate for medical use. To expand the application of 211At-labeled compounds to radiotheranostics, we developed neopentyl derivatives as a novel scaffold for radioiodination and astatination. The stability, biodistribution, and metabolism of 125I-labeled neopentyl derivatives were evaluated. The biodistribution of a 211At-labeled compound was compared with its 125I-labeled counterpart. Two iodinated neopentyl derivatives with a nitroimidazole group were synthesized; N-[2,2-bis(hydroxymethyl)-2-(iodomethyl)ethyl]-2-nitroimidazole (BHIN) and N-[2,2-diethyl2-(iodomethyl)ethyl]-2-nitroimidazole (DEIN). The radioiodination was conducted by reacting their sulfonyl precursors with Na[125I]I. The stability to the nucleophilic substitution was evaluated in a 10 mM glutathione solution at pH 7.4 for 24 h. The biodistribution of [125I]BHIN or [125I]DEIN was evaluated in normal male mice. Urine samples collected for 6 h after injection were analyzed by a reversed-phase HPLC. [211At]N-[2,2-bis(hydroxymethyl)2-(astatomethyl)ethyl]-2-nitroimidazole ([211At]BHAN) was prepared under the procedure similar to [125I]BHIN and was subjected to biodistribution study in normal male mice. Both 125I-labeled compounds were obtained in 40 to 90% radiochemical yields and over 98% radiochemical purities after HPLC purification. Both 125I-labeled compounds remained stable after incubation in a glutathione solution for 24 h (>95%), indicating that the two radioiodinated compounds possess high stability to the nucleophilic substitution reaction. In biodistribution study, while [125I]DEIN showed high radioactivity levels in the neck (10.60 ± 0.03 %ID at 24 h), such radioactivity was hardly observed with [125I]BHIN (0.03 ± 0.02 %ID at 24 h). Both radioiodinated compounds were mainly excreted into urine. The analysis of urine samples indicated that while the majority of the radioactivity was present as [125I]I- for [125I]DEIN, [125I]BHIN showed the majority of the radioactivity as the glucuronide-conjugate. [211At]BHAN was obtained in about 14% radiochemical yields and over 98% radiochemical purities after HPLC purification. [211At]BHAN exhibited the pharmacokinetics similar to [125I]BHIN with low radioactivity levels in the neck and the stomach. Both 125I-labeled compounds possessed high stability to the nucleophilic substitution. The presence of the hydroxyl groups in BHIN provided further stabilization to the enzymatic dehalogenation reaction. [125I]BHIN and [211At]BHAN exhibited similar pharmacokinetics each other with dehalogenation being hardly observed. These findings indicate that the neopentyl derivatives would serve as a useful scaffold to develop a radiotheranostic pair consisting of radioiodinated and 211At-labeled compounds.

Surface Restraint Synthesis of an Organic-Inorganic Hybrid Layer for Dendrite-Free Lithium Metal Anode.

Li metal is considered to be the most attractive anode for next-generation batteries because of its high specific capacity and low reduction potential. However, uncontrolled Li dendrite growth and low Coulombic efficiency cause severe capacity decay and safety issues. Here we propose a LiCl contained inorganic-organic hybrid layer on Li metal surface by a surface restraint dehalogenation reaction, which is highly uniform and features lithiophilic property as well as high ionic conductivity that can inhibit Li dendrite growth effectively. Consequently, the surface protected Li metal electrodes enable Li | Li symmetric cells to maintaina stable and low overpotential of 20 mV at a current density of 1 mA cm-2 after cycling over 3000 h, and enable Li | LiFePO4 pouch cell to decay only 0.05% in capacity per cycle at 5.0 C for 500 cycles, indicating excellent cycle stability and high rate capability. This work offers a simple and facile method to protect Li metal anode and promise a potential direction for industrialization of Li metal batteries.

Heteroatom‐Doped Porous Carbon Materials with Unprecedented High Volumetric Capacitive Performance

AbstractThe design of carbon‐based materials with a high mass density and large porosity has always been a challenging goal, since they fulfill the demands of next‐generation supercapacitors and other electrochemical devices. We report a new class of high‐density heteroatom‐doped porous carbon that can be used as an aqueous‐based supercapacitor material. The material was synthesized by an in situ dehalogenation reaction between a halogenated conjugated diene and nitrogen‐containing nucleophiles. Under the given conditions, pyridinium salts can only continue to perform the dehalogenation if there is residue water remaining from the starting materials. The obtained carbon materials are highly doped by various heteroatoms, leading to high densities, abundant multimodal pores, and an excellent volumetric capacitive performance. Porous carbon tri‐doped with nitrogen, phosphorous, and oxygen exhibits a high packing density (2.13 g cm−3) and an exceptional volumetric energy density (36.8 Wh L−1) in alkaline electrolytes, making it competitive to even some Ni‐MH cells.

Heteroatom-Doped Porous Carbon Materials with Unprecedented High Volumetric Capacitive Performance.

The design of carbon-based materials with a high mass density and large porosity has always been a challenging goal, since they fulfill the demands of next-generation supercapacitors and other electrochemical devices. We report a new class of high-density heteroatom-doped porous carbon that can be used as an aqueous-based supercapacitor material. The material was synthesized by an in situ dehalogenation reaction between a halogenated conjugated diene and nitrogen-containing nucleophiles. Under the given conditions, pyridinium salts can only continue to perform the dehalogenation if there is residue water remaining from the starting materials. The obtained carbon materials are highly doped by various heteroatoms, leading to high densities, abundant multimodal pores, and an excellent volumetric capacitive performance. Porous carbon tri-doped with nitrogen, phosphorous, and oxygen exhibits a high packing density (2.13 g cm-3 ) and an exceptional volumetric energy density (36.8 Wh L-1 ) in alkaline electrolytes, making it competitive to even some Ni-MH cells.

Iodine mediated in situ generation of R-Se-I: application towards the construction of pyrano[4,3-b]quinoline heterocycles and fluorescence properties.

In this paper, we report the iodine mediated in situ generation of R-Se-I and further its application towards the construction of pyrano[4,3-b]quinolin-1-one derivatives. The structural elaboration of 1-chloro-8-methyl-3-phenylbenzo[b][1,6]naphthyridine 6 was successfully achieved by Sonogashira, Suzuki coupling and dehalogenation reactions. Finally, the synthesized compounds 4a, 5a, 5b, 6, and 7a-7c were studied for photophysical properties including UV-absorption, fluorescence, and quantum yield studies. The synthesized pyranoquinoline derivatives showed λmax, Fmax and Φf values in the range of 391-447 nm, 436-486 nm and 0.004-0.301, respectively in chloroform solvent.

Mitochondria targeted and NADH triggered photodynamic activity of chloromethyl modified Ru(ii) complexes under hypoxic conditions.

Three chloromethyl-modified Ru(ii) complexes were designed and synthesized as mitochondria targeting photosensitizers, which can generate carbon radicals in the presence of NADH under visible light irradiation, cause DNA cleavage and covalent binding in Ar-saturated solutions, and lead to apoptosis of human ovarian carcinoma SKOV-3 cells under hypoxic conditions (3% O2), demonstrating a new mode of type I mechanism to overcome the limitation of hypoxia in photodynamic therapy (PDT).

Principles and Advances in Supramolecular Catalysis

Highly efficient aqueous artificial-light-harvesting systems (ALHSs) were successfully fabricated based on the supramolecular assembly of naphthalenyl-phenylacrylonitrile derivative (NPT), water-soluble pillar [5]arene (WP5), and three kinds of pigments (4,7-di(2-thienyl)-2,1,3-benzothiadiazole (DBT), Eosin Y (ESY), and sulforhodamine-101 (SR101)). The assembled ALHSs perform a high energy-transfer-efficiency (ΦETE) and antenna effect (90.9% and 40.6 for WP5⊃NPT-DBT, 81.5% and 39.1 for WP5⊃NPT-ESY as well as 71.3% and 38.4 for WP5⊃NPT-SR101), suggesting that the energy of WP5⊃NPT complex has been effectively transferred to pigment acceptors (DBT, ESY, and SR101). Notably, during the energy-transfer process of WP5⊃NPT-SR101 ALHS, a white light emission (ΦQY = 24.21%) could be achieved by tuning the molar-ratio of [NPT]/[SR101] to 250:1, which is close to that of natural light-harvesting system, displaying a promising application in simulating natural light-harvesting system. Furthermore, the WP5⊃NPT-SR101 ALHS was successfully utilized as nanoreactors to catalyze the free-radical dehalogenation reactions of 2-bromo-acetophenone, 2-bromo-4′-methylacetophenone, and 2-bromo-4′-nitroacetophenone with the yields of 92%, 90% as well as 95%, which realized the energy transformation from solar-energy to chemical-energy, displaying a potential prospect in the field of artificial photosynthesis systems.

A complete bioconversion cascade for dehalogenation and denitration by bacterial flavin–dependent enzymes

Halogenated phenol and nitrophenols are toxic compounds that are widely accumulated in the environment. Enzymes in the had operon from the bacterium Ralstonia pickettii DTP0602 have the potential for application as biocatalysts in the degradation of many of these toxic chemicals. HadA monooxygenase previously was identified as a two-component reduced FAD (FADH-)-utilizing monooxygenase with dual activities of dehalogenation and denitration. However, the partner enzymes of HadA, that is, the flavin reductase and quinone reductase that provide the FADH- for HadA and reduce quinone to hydroquinone, remain to be identified. In this report, we overexpressed and purified the flavin reductases, HadB and HadX, to investigate their functional and catalytic properties. Our results indicated that HadB is an FMN-dependent quinone reductase that converts the quinone products from HadA to hydroquinone compounds that are more stable and can be assimilated by downstream enzymes in the pathway. Transient kinetics indicated that HadB prefers NADH and menadione as the electron donor and acceptor, respectively. We found that HadX is an FAD-bound flavin reductase, which can generate FADH- for HadA to catalyze dehalogenation or denitration reactions. Thermodynamic and transient kinetic experiments revealed that HadX prefers to bind FAD over FADH- and that HadX can transfer FADH- from HadX to HadA via free diffusion. Moreover, HadX rapidly catalyzed NADH-mediated reduction of flavin and provided the FADH- for a monooxygenase of a different system. Combination of all three flavin-dependent enzymes, i.e. HadA/HadB/HadX, reconstituted an effective dehalogenation and denitration cascade, which may be useful for future bioremediation applications.

Development of Fluorescent Assay for Monitoring of Dehalogenase Activity.

The rapid accumulation of sequence data and powerful protein engineering techniques providing large mutant libraries have greatly heightened interest in efficient methods for biochemical characterization of proteins. Herein is reported a continuous assay for screening of enzymatic activity. The assay is developed and tested with the model enzymes haloalkane dehalogenases and relies upon a fluorescent change of a derivative of 8-hydroxypyrene-1,3,6-trisulphonic acid due to the pH drop associated with the dehalogenation reactions. The assay is performed in a microplate format using a purified enzyme, cell-free extract or intact cells, making the analysis quick and simple. The method exhibits high sensitivity with a limit of detection of 0.06 mM. The assay is successfully validated with gas chromatography and then applied for screening of 12 haloalkane dehalogenases with the environmental pollutant bis(2-chloroethyl) ether and chemical warfare agent sulfur mustard. Six enzymes exhibited detectable activity with both substrates. The within-day variability of the assay for five replicates (n = 5) was 21%.

Metal-Organic-Framework-Derived Co3 S4 Hollow Nanoboxes for the Selective Reduction of Nitroarenes.

MOF-derived Co3 S4 /CN hollow nanoboxes (CN=nitrogen-doped carbon) was used to catalyze the chemoselective reduction of nitroarenes to anilines under mild reaction conditions with H2 as the reducing agent. The catalyst provides high conversion efficiencies and selectivities for a variety of nitroarene substrates that contain electron-donating or electron-withdrawing substituents under mild reaction conditions (in methanol at 60 °C). Further, the nanobox inhibits both dehalogenation and vinyl hydrogenation reactions, which are common limitations of state-of-the-art Pd-based catalysts. Because the reactions result in pure aniline products, the need for separation by column chromatography is eliminated. The resulting anilines are easily separated from the methanolic reaction solution in just three simple steps (centrifugation, decantation, and drying). If employed in industrial processes, catalysts of this kind would significantly reduce the amount of waste organic solvent generated and thus satisfy the need for sustainable chemical processes.

Liquid chromatography/isotope ratio mass spectrometry analysis of halogenated benzoates for characterization of the underlying degradation reaction in Thauera chlorobenzoica CB-1T.

Halogenated benzoic acids occur in the environment due to their widespread agricultural and pharmaceutical use. Compound-specific stable isotope analysis (CSIA) has developed over the last decades for investigation of in situ transformation and reaction mechanisms of environmental pollutants amenable by gas chromatography (GC). As polar compounds are unsuitable for GC analysis we developed a method to perform liquid chromatography (LC)/CSIA for halogenated benzoates. LC/isotope ratio mass spectrometry (IRMS) utilizing a LC-Surveyor pump coupled to a MAT 253 isotope ratio mass spectrometer via a LC-Isolink interface was applied. For chromatographic separation a YMC-Triart C18 column and a potassium hydrogen phosphate buffer (150mM, pH7.0, 40°C, 200μL mL-1 ) were used, followed by wet oxidation deploying 1.5molL-1 ortho-phosphoric acid and 200g L-1 sodium peroxodisulfate at 75μL mL-1 . Separation of benzoate and halogenated benzoates could be achieved in less than 40min over a concentration range of 2 orders of magnitude. Under these conditions the dehalogenation reaction of Thauera chlorobenzoica 3CB-1T using 3-chloro-, 3-bromo- and 4-chlorobenzoic acid was investigated resulting in inverse carbon isotope fractionation for meta-substituted benzoic acids and minor normal fractionation for para-substituted benzoic acids. Together with the respective growth rates this led to the assumption that dehalogenation of para-halobenzoic acids follows a different mechanism from that of meta-halobenzoic acids. A new LC/IRMS method for the quantitative determination of halogenated benzoates was developed and used to investigate the in vivo transformation pathways of these compounds, providing some insights into degradation and removal of these widespread compounds by T. chlorobenzoica 3CB-1T .

Acetylene‐Mediated Synthesis of Supported Pt Nanocatalyst for Selective Hydrogenation of Halonitrobenzene

AbstractWe demonstrated that acetylene was a unique reducing agent for aqueous synthesis of ultrasmall Pt nanoparticles (NPs) supported on carbon nanotube (CNT) with high stability. Multiple techniques including X‐ray absorption fine structure (XAFS) were employed to fully characterize this Pt catalyst. The in‐situ generated olefins from acetylene closely wrapped the Pt NPs, and turned into a very thin carbon shell in the subsequent calcination step. The carbon shell not only endowed the Pt NPs with extraordinary thermal stability, but also significantly improved the catalytic selectivity in hydrogenation of halogenated nitrobenzene by eliminating the dehalogenation reaction. Also, the acetylene‐mediated preparation method is readily scalable due to its convenience and environmental friendliness.

The Cationic Residue Coordinated to the N1/2O‐Position of FMN in the Nitroreductase Family is Highly Conserved yet not Central to Catalysis

Enzymes of the nitroreductase structural superfamily form an α+β fold and exist as homodimers with active sites formed at the dimer interface. Although these enzymes contain many conserved residues, their flavin chemistry and catalytic activities are wide‐ranging. For instance, nitroreductase (NfsB) and flavin mononucleotide (FMN) reductases exclusively promote reaction by concurrent transfer of two electrons while iodotyrosine dehalogenase (IYD) and 5,6‐dimethylbenzimidazole synthase (BluB) primarily promote reaction by two single electron transfers. A cationic residue (Arg/Lys) coordinates the N1/2O of the bound FMN throughout the superfamily regardless of their catalytic specificity. To test the necessity of such a highly conserved residue, the candidate residue in IYD (Arg38) was alternatively mutated to a neutral (Gln) and anionic (Glu) derivative. Additionally, the catalytic necessity of an Arg over a Lys was evaluated. The affinity of the R38K and R38Q IYD mutants for iodotyrosine (I‐Tyr) decreased by 11‐ and 46‐fold respectively, compared to that of the wild‐type IYD. In addition, the dehalogenation reaction promoted by R38K and R38Q IYD were suppressed by ~10 and 20‐fold. The most extreme substitution of R38E exhibited no detectable dehalogenation activity but did not prevent FMN from binding to the active site. The R38E IYD also produced a 78‐fold decrease in I‐Tyr affinity.The Arg38 mutations did not, however, alter the FMN chemistry of IYD suggesting that the Arg/Lys at the N1/2O‐position of FMN is not crucial in regulating the one versus two electron transfer process. All variants had comparable FMNox/FMNhq midpoint potentials relative to that of wild‐type IYD. The one electron chemistry of IYD is only expressed in the presence of its substrate or an inert substrate mimic such as fluorotyrosine (F‐Tyr). In the presence of F‐Tyr, the R38Q and R38E variants exhibited an increase of ~50 mV for the midpoint potential of the FMNox/FMNsq couple. In addition, the R38Q and R38E variants registered an increase in the FMNsq/FMNhq midpoint potential of ~50 mV and ~90 mV respectively. Although the R38K IYD had a FMNox/FMNsq midpoint potential comparable to that of the native enzyme, its FMNsq/FMNhq mid‐point potential also increased by ~50 mV. We anticipate similar results with the other model nitroreductases (NfsB and BluB) in this investigation.Support or Funding InformationJHU Provost's Postdoctoral Fellowship and Discovery AwardThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fabricating hierarchically porous carbon with well-defined open pores via polymer dehalogenation for high-performance supercapacitor

Improving specific energy of supercapacitors (SCs) at high power has been intensively investigated as a hot and challengeable topic. In this work, hierarchically porous carbon (HPC) materials with well-defined meso-/macro-pores are reported via the dehalogenation reaction of polyvinyl fluoride (PVDF) by NaNH2. The pore hierarchy is achievable mainly because of the coupled effects of NaNH2 activation and the template/bubbling effects of byproducts of NaF and NH3. Electron microscopy studies and Brunauer–Emmett–Teller (BET) measurements confirm that the structures of HPC samples contain multiple-scale pores assembled in a hierarchical pattern, and most of their volumes are contributed by mesopores. Aqueous symmetric supercapacitors (ASSCs) were fabricated using HPC-M7 materials, achieving an ultrahigh specific energy of 18.8 Wh kg−1 at specific power of 986.8 W kg−1. Remarkably, at the ultrahigh power of 14.3 kW kg−1, the HPC-ASSCs still output a very high specific energy of 16.7 Wh kg−1, which means the ASSCs can be charged or discharged within 4 s. The outstanding rate capacitive performance is mainly benefited from the hierarchical porous structure that allows highly efficient ion diffusion.

Tris(pentafluoroethyl)stannane: Tin Hydride Chemistry with an Electron-Deficient Stannane.

A versatile two-step synthesis of tris(pentafluoroethyl)stannane, HSn(C2 F5 )3 , is presented. Electron-withdrawing C2 F5 groups significantly influence the polarity of the tin-hydrogen bond, which allows facile deprotonation of the compound, even in water. The utility of this electron-deficient stannane was illustrated in hydrostannylations of alkenes and alkynes, as well as in dehalogenation reactions. The remarkably high reactivity of HSn(C2 F5 )3 is demonstrated in fast hydrostannylations, even in the absence of activators, whereby the regioselectivity of this process turns out to be solvent dependent. It is of great advantage that in dehalogenation reactions volatile halogenotris(pentafluoroethyl)stannanes, XSn(C2 F5 )3 (X=I, Br), are formed that allow facile separation of the tin-containing byproducts from the reaction mixtures.

Insights into the molecular mechanism of dehalogenation catalyzed by D-2-haloacid dehalogenase from crystal structures

D-2-haloacid dehalogenases (D-DEXs) catalyse the hydrolytic dehalogenation of D-2-haloacids, releasing halide ions and producing the corresponding 2-hydroxyacids. A structure-guided elucidation of the catalytic mechanism of this dehalogenation reaction has not been reported yet. Here, we report the catalytic mechanism of a D-DEX, HadD AJ1 from Pseudomonas putida AJ1/23, which was elucidated by X-ray crystallographic analysis and the H218O incorporation experiment. HadD AJ1 is an α-helical hydrolase that forms a homotetramer with its monomer including two structurally axisymmetric repeats. The product-bound complex structure was trapped with L-lactic acid in the active site, which is framed by the structurally related helices between two repeats. Site-directed mutagenesis confirmed the importance of the residues lining the binding pocket in stabilizing the enzyme-substrate complex. Asp205 acts as a key catalytic residue and is responsible for activating a water molecule along with Asn131. Then, the hydroxyl group of the water molecule directly attacks the C2 atom of the substrate to release the halogen ion instead of forming an enzyme-substrate ester intermediate as observed in L-2-haloacid dehalogenases. The newly revealed structural and mechanistic information on D-DEX may inspire structure-based mutagenesis to engineer highly efficient haloacid dehalogenases.

Binding of anions in triply interlocked coordination catenanes and dynamic allostery for dehalogenation reactions.

By synergistic combination of multicomponent self-assembly and template-directed approaches, triply interlocked metal organic catenanes that consist of two isolated chirally identical tetrahedrons were constructed and stabilized as thermodynamic minima. In the presence of suitable template anions, the structural conversion from the isolated tetrahedral conformers into locked catenanes occurred via the cleavage of an intrinsically reversible coordination bond in each of the tetrahedrons, followed by the reengineering and interlocking of two fragments with the regeneration of the broken coordination bonds. The presence of several kinds of individual pocket that were attributed to the triply interlocked patterns enabled the possibility of encapsulating different anions, allowing the dynamic allostery between the unlocked/locked conformers to promote the dehalogenation reaction of 3-bromo-cyclohexene efficiently, as with the use of dehalogenase enzymes. The interlocked structures could be unlocked into two individual tetrahedrons through removal of the well-matched anion templates. The stability and reversibility of the locked/unlocked structures were further confirmed by the catching/releasing process that accompanied emission switching, providing opportunities for the system to be a dynamic molecular logic system.

KINETICS OF 2-CHLORO-4-NITROANILINE HYDROGENATION OVER SUPPORTED PLATINUM AND PALLADIUM CATALYSTS IN WATER SOLUTION OF 2-PROPANOL

The kinetics of liquid-phase hydrogenation of 2-chloro-4-nitroaniline over supported platinum and palladium catalysts in the aqueous solution of 2-propanol (0.68 mole fraction) was studied. Dependences of changes in concentration of participants vs the reaction time was obtained. The orders of reaction with respect to hydrogen and initial reagent were zero and the first. The palladium catalysts in comparison with platinum catalysts absorbed more amount of hydrogen. The products of dehalogenation reaction are main by-products. The platinum catalysts, as rules, more active in the conversion of the nitro group and selective with respect to chloroamine. The chloroaniline hydrogenation over the studied catalysts proceeded on sequential scheme. So, the chloroamine was dehalogenated. The values of the rate constants for all catalyst samples were varied depending on the total metal content. It was found that low-percentage platinum catalysts allow to achieve high selectivity of hydrogenation of HNC with respect to CFDA while maintaining the values of the observed rates of hydrogen absorption the similar as palladium catalysts. It is known that the kinetic regularities of catalytic reactions are associated with the structural and physicochemical characteristics of the catalysts. In particular, palladium and platinum have different electronic structures and behave is different in the catalytic reaction. Structure characteristics have value for the reaction kinetics also. The obtained data are consistent with these facts. However, some assumption appeared, that when the nature of the solvent varies, the same catalyst can behave differently. So, determination the relationship between the structure and activity of the catalyst only is not sufficiently correct for liquid-phase systems, without including the effect of the nature of the solvent.Forcitation:Latypova A.R., Krasnov A.I., Sharonov N.Yu., Safarov I.M., Lefedova O.V. Kinetics of 2-chloro-4-nitroaniline hydrogenation over supported platinum and palladium catalysts in water solution of 2-propanol. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2018. V. 61. N 1. P. 42-48

Cover Feature: Flavin‐N5 Covalent Intermediate in a Nonredox Dehalogenation Reaction Catalyzed by an Atypical Flavoenzyme

Cover Feature: Flavin‐N5 Covalent Intermediate in a Nonredox Dehalogenation Reaction Catalyzed by an Atypical Flavoenzyme