Cleavage Of Carbon-halogen Bond Research Articles

Charge-Separated Reactive Intermediates from the UV Photodissociation of Chlorobenzene in Solution.

Although ultraviolet (UV)-induced photochemical cleavage of carbon–halogen bonds in gaseous halocarbons is mostly homolytic, the photolysis of chlorobenzene in solution has been proposed to produce a phenyl cation, c-C6H5+, which is a highly reactive intermediate of potential use in chemical synthesis and N2 activation. Any evidence for such a route to phenyl cations is indirect, with uncertainty remaining about the possible mechanism. Here, ultrafast transient absorption spectroscopy of UV-excited (λ = 240 and 270 nm) chlorobenzene solutions in fluorinated (perfluorohexane) and protic (ethanol and 2,2,2-trifluoroethanol) solvents reveals a broad electronic absorption band centered at 540 nm that is assigned to an isomer of chlorobenzene with both charge-separated and triplet-spin carbene character. This spectroscopic feature is weaker, or absent, when experiments are conducted in cyclohexane. The intermediate isomer of chlorobenzene has a solvent-dependent lifetime of 30–110 ps, determined by reaction with the solvent or quenching to a lower-lying singlet state. Evidence is presented for dissociation to ortho-benzyne, but the intermediate could also be a precursor to phenyl cation formation.

Improvement in the Environmental Stability of Haloalkane Dehalogenase with Self-Assembly Directed Nano-Hybrid with Iron Phosphate

Haloalkane dehalogenase (DhaA) catalyzes the hydrolysis of halogenated compounds through the cleavage of carbon halogen bonds. However, the low activity, poor environmental stability, and difficult recycling of free DhaA greatly increases the economic cost of practical application. Inspired by the organic–inorganic hybrid system, an iron-based hybrid nanocomposite biocatalyst FeHN@DhaA is successfully constructed to enhance its environmental tolerability. A series of characterization methods demonstrate that the synthesized enzyme–metal iron complexes exhibit granular nanostructures with good crystallinity. Under optimized conditions, the activity recovery and the effective encapsulation yield of FeHN@DhaA are 138.54% and 87.21%, respectively. Moreover, it not only exhibits excellent immobilized enzymatic properties but also reveals better tolerance to extreme acid, and is alkali compared with the free DhaA. In addition, the immobilized enzyme FeHN@DhaA can be easily recovered and has a satisfactory reusability, retaining 57.8% of relative activity after five reaction cycles. The results of this study might present an alternative immobilized DhaA-based clean biotechnology for the decontamination of organochlorine pollutants.

A DFT and SERS study of synergistic roles of thermodynamics and kinetics during the electrocatalytic reduction of benzyl chloride at silver cathodes

The reductive cleavage of carbon-halogen bonds is one of the classical model systems of concerted versus non-concerted bond breaking electron transfer in molecular electrochemistry, but most studies did not consider the influence of adsorption of reaction intermediates on this phenomenon. We performed density functional theory (DFT) calculations to understand the electrochemical reduction of benzyl chloride at silver electrodes through predicting the surface adsorption effect of the reactant and of follow-up intermediates and analyzing the energetics of the overall dissociative electron transfer. The ensuing DFT calculations of surface-enhanced Raman spectroscopic (SERS) signals provided some key information for characterizing different surface species at different potentials at the molecular level. The most intense and broad spectral peak observed near 800 cm−1 in the electrochemical SERS was thus assigned to the CH2 wagging vibration closely associated with the co-adsorption of benzyl radical and chlorine. After the dissociation of the C-Cl benzyl chloride bond, the chloride anion adsorbs at the three-fold hollow site on silver electrodes, as indicated by a low vibrational frequency and a weak Raman signal. Conversely, the formed benzyl radical intermediate is found to adsorb at the top site with the characteristic vibrational frequency and strong Raman intensity. DFT calculations further confirmed that the kinetic effect underlying the electrocatalytic activity of silver electrodes is closely associated with the intrinsic energy barrier and the dissociative adsorption state of benzyl radical and chlorine on silver electrodes. Finally, we discuss the fundamental meaning of the kinetic rate constant of the first-step dissociative electron transfer for benzyl chloride on silver electrodes based on the different electron transfer models, indicating the synergistic roles of thermodynamics and kinetics.

Computational study on the mechanism of metal‐free photochemical borylation of aryl halides

AbstractC‐radical borylation is a significant approach for the construction of carbonboron bond. Photochemical borylation of aryl halides successfully applied this strategy. However, precise mechanisms, such as the generation of aryl radicals and the role of base additive (TMDAM) and water, remain controversy in these reactions. In this study, photochemical borylation of aryl halides has been researched by density functional theory (DFT) calculations. Indeed, the homolytic cleavage of the CX bond under irradiation with UV‐light is a key step for generation of aryl radicals. Nevertheless, the generation of aryl radicals may also undergo the process of single electron transfer and the heterolytic carbonhalogen bond cleavage sequence, and the latter is favorable during the reaction.

Palladium(II)‐Catalyzed Direct Arylations of Quinoxalin‐2(1H)‐ones with Arylsulfonyl Chlorides

AbstractA palladium‐catalyzed desulfitative coupling of quinoxalin‐2(1H)‐ones with arylsulfonyl chlorides is described. C3‐Arylquinoxalin‐2(1H)‐ones are readily accessible by reacting various arylsulfonyl chloride derivatives with quinoxalin‐2(1H)‐ones. The arylsulfonyl chloride undergoes palladium‐catalyzed C−S and S−Cl bond cleavage, which leads to direct desulfitative cross‐coupling with the quinoxalin‐2(H)‐one. Chloro‐ and fluoro‐aryl sulfonyl chlorides are successfully coupled with quinoxalin‐2(1H)‐ones without carbon–halogen bond cleavage.

Electrochemically activated carbon-halogen bond cleavage and C-C coupling monitored by in situ shell-isolated nanoparticle-enhanced Raman spectroscopy.

The electroreductive cleavage of carbon-halogen bonds has attracted increasing attention in both electrosynthesis and pollution remediation. Herein, by employing the in situ electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique, we have successfully investigated the electroreductive dehalogenation process of aryl halides with the thiol group on a smooth Au electrode in aqueous solution at different pH values. The obtained potential-dependent Raman spectra directly reveal a mixture of the reduction products 4,4'-biphenyldithiol (BPDT) and thiophenol (TP). The conversion ratios of the C-Cl and C-Br bonds at pH = 7 are 37% and 55%, respectively. Furthermore, quantitative analysis of the intensity variations of ν(C-Cl), ν(C-Br) and aromatic ν(CC) stretching modes suggests electroreductive dehalogenation via both direct electron transfer reduction and electrocatalytic hydrodehalogenation. Molecular evidence for the C-C cross coupling process through TP reaction with benzene free radical intermediates is found at negative potentials, which leads to the increasing selectivity of biphenyl products.

Conjugation of haloalkane dehalogenase DhaA with arabinogalactan to increase its stability

Haloalkane dehalogenase DhaA can catalyze the hydrolytic cleavage of carbonhalogen bonds, along with production of the corresponding alcohol, a proton and a halide. However, DhaA suffers from poor environmental tolerance, such as sensitivity to high temperature, low pH and hypersaline. Arabinogalactan (AG) is a hydrophilic polysaccharide with highly branched long chains. DhaA was conjugated with AG to improve the environmental stability of DhaA in the present study. Each DhaA was averagely conjugated with 4∼5 AG molecules. Conjugation of AG essentially maintained the enzymatic activity of DhaA (91.4 %) without apparent structural alteration. The hydration layer formed by AG could reduce the solvent accessible area of DhaA and slow the protonation process, thereby improving the pH and high salt stability of DhaA. In particular, the remaining activities of the conjugate (AG-DhaA) were 35.3 % after treatment at pH4.0 for 1 h, and 80.8 % in 1 M NaCl after treatment for 16 h. As compared with DhaA, AG-DhaA showed slightly different kinetic parameters (K M of 1.90 μmol/L and k cat of 2.60 s -1).

Conjugation with inulin improves the environmental stability of haloalkane dehalogenase DhaA

Haloalkane dehalogenase DhaA catalyzes the hydrolytic cleavage of carbon-halogen bonds and produces alcohol, a proton and a halide. However, DhaA suffers from the poor environmental stability, such as sensitivity to high temperature, low pH, hypersaline and organic solvent. In order to improve the environmental stability of DhaA, DhaA was covalently conjugated with inulin, a hydrophilic polysaccharide in the present study. Each DhaA was averagely conjugated with 7∼8 inulin molecules. The conjugated inulin could form a hydration layer around DhaA, which increased the conformational rigidity and decreased the entropy of the enzyme. Conjugation of inulin maintained 75.5 % of the enzymatic activity of DhaA and slightly altered the structure of DhaA. As compared with DhaA, the conjugate (inu-DhaA) showed slightly different kinetic parameters (Km of 2.9 μmol/L and Kcat of 1.0 s−1). Inulin conjugation could delay the structural unfolding and/or slow the protonation process of DhaA under undesirable environment, including the long-term storage, low pH, hypersaline and organic solvent stability. As a result, the environmental stability of DhaA was markedly increased upon conjugation with inulin. Thus, inulin conjugation was an effective approach to enhance the environmental stability of DhaA.

Dehalogenases for pollutant degradation in brief: A mini review

Dehalogenases are microbial enzyme catalysed the cleavage of carbon-halogen bond of halogenated organic compounds. It has potential use in the area of biotechnology such as bioremediation and chemical industry. Halogenated organic compounds can be found in a considerable amount in the environment due to utilization in agriculture and industry, such as pesticides and herbicides. The presence of halogenated compound in the environment have been implicated on the health and natural ecosystem. Microbial dehalogenation is a significant method to tackle this problem. This review intends to briefly describe the microbial dehalogenases in relation to the environment where they are isolated. The basic information about dehalogenases in relation to dehalogenation mechanisms, classification, sources and the transportation of these pollutants into bacterial cytoplasm will be described. We also summarised readily available synthetic halogenated organic compound in the environment.

Catabolic Reductive Dehalogenase Substrate Complex Structures Underpin Rational Repurposing of Substrate Scope.

Reductive dehalogenases are responsible for the reductive cleavage of carbon-halogen bonds during organohalide respiration. A variety of mechanisms have been proposed for these cobalamin and [4Fe-4S] containing enzymes, including organocobalt, radical, or cobalt-halide adduct based catalysis. The latter was proposed for the oxygen-tolerant Nitratireductor pacificus pht-3B catabolic reductive dehalogenase (NpRdhA). Here, we present the first substrate bound NpRdhA crystal structures, confirming a direct cobalt–halogen interaction is established and providing a rationale for substrate preference. Product formation is observed in crystallo due to X-ray photoreduction. Protein engineering enables rational alteration of substrate preference, providing a future blue print for the application of this and related enzymes in bioremediation.

Direct Electrochemical Reduction of Acetochlor at Carbon and Silver Cathodes in Dimethylformamide

Cyclic voltammetry and controlled-potential (bulk) electrolysis have been employed to investigate the direct electrochemical reduction of acetochlor (1) at carbon and silver cathodes in dimethylformamide. Voltammograms of 1 exhibit a single irreversible cathodic peak at both cathode materials. Catalytic properties of silver towards carbon–halogen bond cleavage are evidenced by a positive shift in the reduction of acetochlor as compared to the more inert glassy carbon electrode. Voltammograms in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), and comparisons of calculated relative interaction energies between acetochlor, possible intermediates, and deschloroacetochlor in the presence of different proton donors, suggest strong hydrogen-bonding interactions between HFIP and a carbanion intermediate. Addition of HFIP to electrolysis conditions promotes complete reduction at both cathode materials, with formation of deschloroacetochlor in high yields. In deuterium labelling studies, the use of DMF-d7 led to no evidence for deuterium atom incorporation. However, when HFIP-OD or D2O were employed as a proton source, substantial amounts of deuterated deschloroacetochlor were observed. A mechanism for the reduction of acetochlor is proposed, in which radical intermediates do not play a significant role in reduction, rather a carbanion intermediate pathway is followed.

Flavin-dependent dehalogenases.

Flavin-dependent dehalogenases use flavin as a cofactor to catalyze carbon-halogen (C-X) bond cleavage from halogenated compounds which are mainly distributed as persistent environmental pollutants via anthropogenic activities. The accumulation of these compounds results in adaptation of bacteria to evolve metabolic pathways to metabolize the agents for four decades. Flavin-dependent enzymes have been evolved to catalyze dehalogenation in addition to its basal function. Apart from bacterial biodegradation, flavin-dependent dehalogenases also naturally appear in cellular metabolisms of higher organisms such as in human thyroid hormone. Although the removal of halogen is required in various applications, the usage of dehalogenases remains limited. In-depth understanding of their enzymatic mechanisms is useful for development of dehalogenases applications. Three main types of flavin-dependent dehalogenases are classified based on their reaction mechanisms reported to date: (1) flavin-dependent O2-utilizing dehalogenases; (2) flavin-dependent reductive dehalogenases; and (3) non-redox flavin-dependent dehalogenases. In this chapter, the catalytic properties, substrate scope, protein structures, enzymatic mechanisms, enzyme engineering, and also development of enzymes for novel applications are discussed.

Fluorescent substrates for haloalkane dehalogenases: Novel probes for mechanistic studies and protein labeling

Haloalkane dehalogenases are enzymes that catalyze the cleavage of carbon-halogen bonds in halogenated compounds. They serve as model enzymes for studying structure–function relationships of >100.000 members of the α/β-hydrolase superfamily. Detailed kinetic analysis of their reaction is crucial for understanding the reaction mechanism and developing novel concepts in protein engineering. Fluorescent substrates, which change their fluorescence properties during a catalytic cycle, may serve as attractive molecular probes for studying the mechanism of enzyme catalysis. In this work, we present the development of the first fluorescent substrates for this enzyme family based on coumarin and BODIPY chromophores. Steady-state and pre-steady-state kinetics with two of the most active haloalkane dehalogenases, DmmA and LinB, revealed that both fluorescent substrates provided specificity constant two orders of magnitude higher (0.14–12.6 μM−1 s−1) than previously reported representative substrates for the haloalkane dehalogenase family (0.00005–0.014 μM−1 s−1). Stopped-flow fluorescence/FRET analysis enabled for the first time monitoring of all individual reaction steps within a single experiment: (i) substrate binding, (ii–iii) two subsequent chemical steps and (iv) product release. The newly introduced fluorescent molecules are potent probes for fast steady-state kinetic profiling. In combination with rapid mixing techniques, they provide highly valuable information about individual kinetic steps and mechanism of haloalkane dehalogenases. Additionally, these molecules offer high specificity and efficiency for protein labeling and can serve as probes for studying protein hydration and dynamics as well as potential markers for cell imaging.

Cu-Catalyzed Carbonylative Silylation of Alkyl Halides: Efficient Access to Acylsilanes.

A Cu-catalyzed carbonylative silylation of unactivated alkyl halides has been developed, enabling efficient synthesis of alkyl-substituted acylsilanes in high yield. A variety of functional groups are tolerated under the mild reaction conditions, and primary, secondary, and tertiary alkyl halides are all applicable. The practical utility of this method has been demonstrated in the synthesis of acylsilanes bearing different silyl groups as well as in situ reduction of a product to the corresponding α-hydroxylsilane in one pot. Mechanistic experiments indicate that a silylcopper intermediate activates alkyl halides by single electron transfer to form alkyl radical intermediates and that carbon-halogen bond cleavage is not involved in the rate-determining step.

Hot Electron-Induced Carbon–Halogen Bond Cleavage Monitored by in Situ Surface-Enhanced Raman Spectroscopy

The activation of the carbon–halogen (C–X) bond is of great significance in chemical synthesis. Herein, we report on in situ surface-enhanced Raman spectroscopic monitoring of hot electron-induced ...

Metal–Organic Self-Assembled Trefoil Knots for C—Br Bond Activation

Synthesizing molecular knots that mimic the catalytic functionality of stereospecific or stereoselective enzymes are an intriguing task in chemistry. Synthetic anion receptors even with moderate halide binding affinities may catalyze chemical reactions involving carbon–halogen bond cleavage. Herein we report isostructural self-assembled trefoil molecular knots (Cu-TK, Cd-TK, Zn-TK) based on Cu(II), Cd(II), and Zn(II) that are capable of binding and stabilizing bromide within their central cavity and are capable of catalyzing C–Br bond cleavage. We also describe the role of noncovalent interactions between the knots and bromide as well as the size and shape of the knots on their catalytic efficiency. Among the studied three knots, Cu-TK was found to be more effective than Zn-TK and Cd-TK in catalyzing C–Br bond cleavage. The catalytic efficiency of the knots toward C–Br bond cleavage was found to be related to a balance between their attractive electrostatic interactions with bromide as well as cavity size...

Coulomb explosion imaging of CH3I and CH2ClI photodissociation dynamics.

The photodissociation dynamics of CH3I and CH2ClI at 272 nm were investigated by time-resolved Coulomb explosion imaging, with an intense non-resonant 815 nm probe pulse. Fragment ion momenta over a wide m/z range were recorded simultaneously by coupling a velocity map imaging spectrometer with a pixel imaging mass spectrometry camera. For both molecules, delay-dependent pump-probe features were assigned to ultraviolet-induced carbon-iodine bond cleavage followed by Coulomb explosion. Multi-mass imaging also allowed the sequential cleavage of both carbon-halogen bonds in CH2ClI to be investigated. Furthermore, delay-dependent relative fragment momenta of a pair of ions were directly determined using recoil-frame covariance analysis. These results are complementary to conventional velocity map imaging experiments and demonstrate the application of time-resolved Coulomb explosion imaging to photoinduced real-time molecular motion.

Au@Pd Bimetallic Nanocatalyst for Carbon-Halogen Bond Cleavage: An Old Story with New Insight into How the Activity of Pd is Influenced by Au.

AuPd bimetallic nanocatalysts exhibit superior catalytic performance in the cleavage of carbon-halogen bonds (C-X) in the hazardous halogenated pollutants. A better understanding of how Au atoms promote the reactivity of Pd sites rather than vaguely interpreting as bimetallic effect and determining which type of Pd sites are necessary for these reactions are crucial factors for the design of atomically precise nanocatalysts that make full use of both the Pd and Au atoms. Herein, we systematically manipulated the coordination number of Pd-Pd, d-orbital occupation state, and the Au-Pd interface of the Pd reactive centers and studied the structure-activity relationship of Au-Pd in the catalyzed cleavage of C-X bonds. It is revealed that Au enhanced the activity of Pd atoms primarily by increasing the occupation state of Pd d-orbitals. Meanwhile, among the Pd sites formed on the Au surface, five to seven contiguous Pd atoms, three or four adjacent Pd atoms, and isolated Pd atoms were found to be the most active in the cleavage of C-Cl, C-Br, and C-I bonds, respectively. Besides, neighboring Au atoms directly contribute to the weakening of the C-Br/C-I bond. This work provides new insight into the rational design of bimetallic metal catalysts with specific catalytic properties.

Palladium-catalyzed intermolecular coupling of 2-haloallylic acetates with simple phenols, and sequential formation of benzofuran derivatives through the intramolecular cyclization

We accomplished the synthesis of 2-substituted benzofuran derivatives by the palladium-catalyzed reaction of 2-haloallylic acetates with simple phenols in the presence of a base. The reaction proceeded through the intermolecular attack of the nucleophile on the central carbon atom of the π-allyl group, carbon-halogen bond cleavage, and sequential intramolecular cyclization.

Functional and Catalytic Characterization of the Detoxifying Enzyme Haloalkane Dehalogenase from Rhizobium leguminosarum.

Haloalkane dehalogenases (EC 3.8.1.5, HLDs) are α/β-hydrolases which catalyze the irreversible cleavage of carbon-halogen bonds of haloalkanes, producing an alcohol, a halide and a hydrogen ion. Haloalkanes are acutely toxic to animals and humans and their toxic effects are mainly observed in the liver, kidneys and central nervous system. In the present work, the haloalkane dehalogenase from Rhizobium leguminosarum bv. trifolii (DrlA) was characterized. Reverse transcription polymerase chain reaction analysis and enzyme activity assays revealed that the DrlA gene expression in R. leguminosarum bv. trifolii is induced by 1,2- dibromoethane (1,2-DBE) during the early exponential phase. The gene of the enzyme was isolated, cloned and expressed in E. coli Rosetta (DE3). Recombinant DrlA displays its high catalytic activity towards 1,2-DBE and the long-chain haloalkane 1-iodohexane. Limited activity was observed for other aliphatic and cyclic haloalkanes, indicating that the enzyme displays restricted substrate specificity, compared to other bacterial HLDs. Homology modelling and phylogenetic analysis suggested that the enzyme belongs to the HLD-II subfamily and shares the same overall fold and domain organization as other bacterial HLDs, however major variations were identified at the hydrophobic substrate-binding cavity, the cap domain and the entrance of the main tunnel that affect the size of the active site pocket and the substrate recognition mechanism. This work sheds new light on the environmental fate and toxicity of 1,2-DBE and provides new knowledge on the structure, function and diversity of HLDs for developing applications in toxicology.