Model Studies Related to Haloperoxidases
- Model studies related to vanadium biochemistry: recent advances and perspectives

Haloperoxidases are enzymes which catalyze the oxidation of halides (Cl-, Br-, I-) by hydrogen peroxide, resulting in the halogenation of appropriate organic substrates.84 The presence of vanadium as an essential component for a haloperoxidase was discovered in the red algae Ascophyllum nodosum in 1984.85 Within these vanadium-dependent haloperoxidases, both vanadium bromoperoxidases, isolated mainly from algae, and vanadium chloroperoxidases, found essentially in fungi, have been subsequently identified.9

Recently, the crystal structure of a vanadium chloroperoxidase isolated from the fungus Curvularia inaequalis, was reported by Messerschmidt and Wever.86 The structural features of the active vanadium center seems to be characteristic of all such systems.9 The metal, in the V oxidation state, has a trigonal bipyramidal geometry, ligated by azide (a result of the azide-containing crystallization buffer), three non-protein oxygen atoms, and a histidine N atom. In the native structure the azide ligand, located in trans position to the histidine N atom, is apparently replaced by an OH group.9, 86

The finding of a specific function of vanadium in haloperoxidases allows new speculations, on its possible functions in higher organisms. Thyroid peroxidase is one of the best known animal haloperoxidases.84 As mentioned previously, vanadium deprivation increases thyroid weight and also affects the response of thyroid peroxidase activity.5,10 Perhaps, vanadium plays some role in the halogenating activity of this enzyme.

A great number of model studies have been performed recently, in an attempt to understand better the structural characteristics of the metal site as well as to elucidate the reaction mechanisms the vanadium-dependent haloperoxidases.

All the information so far accumulated shows that vanadium remains in the V oxidation state during the entire catalytic cycle and it has also been demonstrated that during the process one peroxide group is bonded to the metal.4,87 A variety of mechanistic studies has been performed using different vanadium/peroxide complexes as model systems.4,88-91 Some vanadium-based semi-synthetic and biomimetic models have also been assayed as catalysts for enantioselective oxidations.92

Recently, we have also initiated some model studies related to these natural systems, investigating the kinetics of the bromination of phenol red by the peroxovanadium(V) species generated by acid decomposition of [VO(O2)2(NH3)]- and [O{VO(O2)2}2]4-.93

Numerous model studies related to the characteristics of both the active vanadium (V) site and the catalytically inactive reduced oxovanadium(IV) site, have been also performed.4,14,94-97

One interesting aspect of the structure of the active site is the simultaneous presence of N- and O-donors and of V=O and V-OH groups. The ligand 8-hydroxyquinoline, the well-known analytical reagent oxine (HQ), is particularly interesting for model studies related to these systems and to other biologically relevant vanadium centers. It normally stabilizes chelate complexes of the types MQ2 and MQ3, generating MN2O2 or MN3O3 and, in certain cases, also MN2O3(OH) environments.

In spite of the fact that the simplest oxovanadium(IV) complex of oxine, VOQ2, has been widely investigated, several contradictory reports, mainly derived from its easily oxidability, are found in the literature. 12 In order to extend these studies, we have synthesized and characterized a series of VO2+ complexes with different derivatives of oxine. Those derived from 5,7-dihalogenated oxine are stable in air but show a very complex solution behavior that includes oxidation phenomena, ligand loss and interactions with solvents. 98 On the other hand, the presence of halogen atoms on the oxine ring has a negligible effect on the thermal stability of the complexes.99

A detailed study of the magnetic behavior of these complexes shows that a ferromagnetic interaction between the VO2+ groups becomes operative at temperatures below 40 K with an exchange integral J 2.73 cm-1. 100 These results constitute the first direct evidence of the formation of ...V=O...V=O... ferromagnetic chains in these and in similar oxovanadium(IV) complexes.12,100

Other related complexes that were also investigated in detail are the bis-chelated VO2+ species derived from 8-hydroxyquinoline-N-oxide.101 and from 7-iodo-8-hydroxyquinoline-5-sulfonic acid (the analytical reagent ferron).102

Some vanadium(V) species containing oxine or its derivatives as ligands are much more interesting in relation to the active site of haloperoxidases. The complex hydroxobis(8-hydroxyquinolinato)oxovanadium(V) (Figure 4a) can be considered as an "inorganic analog" of a carboxylic acid.12,103 Accordingly, it is possible to prepare salts (Figure 4b), esters (Figure 4c) and dimer anhydrides (Figure 4d). We obtained a great number of complexes of these types and characterized them thoroughly by different physicochemical methods,98,101,102,104,105 including detailed electrochemical studies.106,107

Another class of model system related to this biological site, in its reduced (inactive) form are the recently reported species cis-[VO(OH)(bipy)2]+ and cis-[VO(OH)(o-phen)2]+ which structural analysis, as the BF4- salts, showed the presence of a severely distorted octahedral coordination with the vanadium(IV) above the mean equatorial plane defined by three bipy (o-phen) N-atoms and the OH-group. The oxo group and the remaining N-atom of one of the organic ligands occupy the apical positions.108

Also, Schiff-base complexes of vanadium(V) and of oxovanadium(IV) have often been investigated as useful models for this and other biological systems containing the metal.109-115

Finally, it is worthy commenting that numerous model compounds developed for a better understanding of the activity and action of vanadium-dependent haloperoxidases and other biological systems containing this element are also reagents in modern organic synthesis.116

It is pertinent to emphasize that a number of model compounds investigated in relation to Amavadine, the natural vanadium complex present in the fungus Amanita muscaria (cf.117,118 and references therein), also have very interesting catalytic capabilities.119


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