Haloperoxidase reactivity

Vanadium. Vanadyl complexes of the three ligands 14, 24, and 28 were prepared from vanadyl sulfate and the metal-free ligands. They have the expected spectroscopic properties, and this is confirmed by the X-ray crystal structure of the vanadyl complex of 24, which is shown in Fig. 23(a) and has metal-donor bond distances in the expected range. In terms of reactivity, these complexes are rather unspectacular. No haloperoxidase reactivity was observed, and oxidation of alkanes and alkenes is rather sluggish (138). This is not unexpected since with the pentadentate ligands there is no free site at the vanadium(IV) center for metal-substrate interaction. The same is true for the vanadium(V) oxo-peroxo complexes with tetradentate coordination of the pentadentate ligand. 

Heme-dependent haloperoxidases generate HOX as reactive species from H2O2 and X, which represents an X+ equivalent capable of undergoing electrophilic addition at electron-rich centers [270,271]. Aprototype biocatalyst of this group is the chloroperoxidase from Caldariomyces Jumago [272]. In many natural systems, such enzymes are responsible for the halogenation of electron-rich aromatic cores. 

Zampella G, Fantucci P, Pecoraro VL, De Gioia L (2005) Reactivity of Peroxo Forms of the Vanadium Haloperoxidase Cofactor. A DFT Investigation. J Am Chem Soc 127 953... 

The emphasis of this review chapter will be on the reactivity of the vanadium haloperoxidases. A brief summary of the molecular properties of these en-... 

Hamstra, B.J., G.J. Colpas, and V.L. Pecoraro. 1998. Reactivity of dioxovanadium(V) complexes with hydrogen peroxide Implications for vanadium haloperoxidase. Inorg. Chem. 37 949-955. 

The haloperoxidases are a class of enzymes that catalyze the oxidation of halides via a reactive peroxometal active site. These enzymes are named according to the most electronegative halide they are able to oxidize. Hence, a bromoperoxidase can oxidize bromide and iodide but not chloride, whereas a chloroperoxidase can oxidize all three. Haloperoxidases are found in most living organisms and predominately fall into two classes the iron heme-based and vanadium-dependent enzymes. Of these, heme-based enzymes are found in mammals, where they provide a vital... 

This book does not follow a chronological sequence but rather builds up in a hierarchy of complexity. Some basic principles of 51V NMR spectroscopy are discussed this is followed by a description of the self-condensation reactions of vanadate itself. The reactions with simple monodentate ligands are then described, and this proceeds to more complicated systems such as diols, -hydroxy acids, amino acids, peptides, and so on. Aspects of this sequence are later revisited but with interest now directed toward the influence of ligand electronic properties on coordination and reactivity. The influences of ligands, particularly those of hydrogen peroxide and hydroxyl amine, on heteroligand reactivity are compared and contrasted. There is a brief discussion of the vanadium-dependent haloperoxidases and model systems. There is also some discussion of vanadium in the environment and of some technological applications. Because vanadium pollution is inextricably linked to vanadium(V) chemistry, some discussion of vanadium as a pollutant is provided. This book provides only a very brief discussion of vanadium oxidation states other than V(V) and also does not discuss vanadium redox activity, except in a peripheral manner where required. It does, however, briefly cover the catalytic reactions of peroxovanadates and haloperoxidases model compounds. 

Because the reactivity of a cyclopropane closely resembles that of an olefinic double bond [2], haloperoxidases (chloroperoxidase from Cadariomyces fumago, bromoperoxidase from Penicillus capitalus) add readily to the ring of cyclopropanes la,b in the presence of halide ions and hydrogen peroxide to... 

A novel class of haloperoxidases, in which a heme prosthetic group was absent, was detected in brown algae (Phaeophyceae) by Vilter and coworkers (13-15). These publications escaped the attention of most biochemists involved in peroxidase research. Only when some of this work was published in the journal Phytochemistry (16) was there as increasing awareness of these findings. A clue for the involvement of vanadium was also published (16). It was shown that the bromoperoxidase could be inactivated at low pH and reactivated by vanadate. These results were subsequently confirmed (17, 18) when it was shown that vanadium was present in a number of bromoperoxidases from different sources and was essential for enzymatic activity. To date, these sources include the enzymes from the brown seaweed Ascophyllum nodosum... 

Fig. 25.3. Detection of a two-step cascade reaction by observing single hypobromite reaction events, (a) Reaction mechanism. The haloperoxidase enzyme produces hypobromite. These reactive oxygen species react with aminophenyl fluorescein (APF) in a secondary reaction to yield the highly fluorescent dye fluorescein, (b) Representative part of a fluorescence intensity time trace. Every intensity burst corresponds to one reaction event between hypobromite and APF. (c) Histogram of the time-averaged activities of approximately 100 individual enzymes, obtained by measuring the secondary reaction between hypobromite and APF. (d) Frequency of observing individual reaction events as a function of distance from the enzyme. At distances farther than the diffraction limit, a considerable number of reaction events occurs indicating that the secondary reaction takes place in solution following the release of most of the hypobromite from the enzyme...

After Mo, vanadium is the second most abundant transition metal in the ocean and is certainly beneficial and probably essential for man. It is used in the form of a V prosthetic group in V-dependent haloperoxidases, which utilise hydrogen peroxide to oxidise a halide ion into a reactive electrophilic intermediate. There has been extensive debate as to whether a final transition metal ion is an essential trace element, as was originally proposed over 50 years ago — it has been widely accepted as an essential element for over 30 years. We discuss Mo and W together with V and Cr in Chapter 17. 

Unfortunately, direct epoxidation of alkenes by metal-free haloperoxidases led to racemic epoxides [1331, 1332]. Since the reaction only takes place in the presence of a short-chain carboxylic acid (e.g., acetate or propionate), it is believed to proceed via an enzymatically generated peroxycarboxylic acid, which subsequently oxidizes the alkene without the aid of the enzyme. This mechanism has a close analogy to the lipase-catalyzed epoxidation of alkenes (Sect 3.1.5) and halogenation reactions catalyzed by haloperoxidases (Sect. 2.7.1), where enzyme catalysis is only involved in the formation of a reactive intermediate, which in turn converts the substrate in a spontaneous (nonenzymatic) foUowup reaction. 

Redox reactions with synthetic potential have been developed by use of dialkyl phosphonate, early transition metals, and lanthanides. The Lewis acidic nature of metallic compounds is another key factor in their reactivities in addition to the redox properties. Controlling the metal-based redox systems leads to greater selectivities in their electron transfer reactions. Likewise, fine-tuning the ligands coordinated to metals results in more efficient redox systems. These approaches yield a variety of fruitful redox reactions for organic synthesis as observed in the ligand coupling and haloperoxidase-inspired reactions. 

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