Molybdenum complexes enzyme mechanisms

Recent papers describe models for molybdenum-containing enzymes [106], Certain vanadium complexes have been described to mimic the binding site reactions of vanadium haloperoxidases [62, 107], Scheme XI.20 demonstrates the mechanism of active species formation in bromoperoxidase proposed on the basis of the investigation of model reactions [108],... 

Nitrogenase, as must now become clear, is a complex enzyme of two component proteins which requires ATP, a reductant, a reducible substrate, Mg " " as an activator, and an anaerobic environment to function. To this complexity must be added the difficulty that the component proteins have no enzymatic half reactions . There are, perhaps, four main questions to decide about the mechanism (1) the role(s) of the two component proteins (2) the role(s) of ATP (3) the nature of the active site(s) and (4) the mechanism of N2 reduction. Despite the complexities and difficulties mentioned above, progress in the last 15 years has partly answered all these questions. The Fe protein mediates an ATP-dependent electron transfer from the donor to the MoFe protein which contains the active site. MgATP binds and induces a conformational change in the Fe protein which lowers its redox potential. FeMoco, the molybdenum cofactor, which may be part of the active site of N2 reduction, has been isolated and partly characterized, while an intermediate in N2 reduction has recently been discovered (Thorneley ct al., 1978). The next part of this chapter describes the evidence for these claims. This evidence involves the noncatalytic reactions of the individual proteins, their... 

Further work has been reported - with Fe-Mo models for nitro-genase, and a molecular mechanism has been proposed for the action of molybdenum in enzymes. In all reactions catalysed by Mo enzymes, the product and substrate differ by two electrons and two protons (or some multiple thereof). The co-ordination chemistry of Mo suggests that there is a distinct relationship between acid-base and redox properties of Mo complexes, and that a coupled electron-proton transfer (to or from substrate) may be mediated by Mo in enzymes. Each of the molybdenum enzymes (nitrogenase, nitrate reductase, xanthine oxidase, aldehyde oxidase, and sulphite oxidase) is discussed and it is shown that a simple molecular mechanism embodying coupled proton-electron transfer can explain many key experimental observations. 

Mo(V) complex disproportionates as it dissociates to produce mononuclear Mo (IV) and Mo (VI). As Mo (IV) and Mo (VI) are directly interconvertible by an oxo transfer reaction, they are viable participants in catalytic cycles. A dinuclear Mo(V) species of this nature can thus supply either the oxidizing or reducing member of this couple and presents a mechanism by which molybdenum enzymes can channel reducing or oxidizing power. Several inorganic reactions have recently been explained using this scheme (80, 81). To date, however, Reaction 12 only applies when the ligand is a dithiocarbamate or dithiophosphate. Nevertheless, were there known dinuclear active sites in enzymes, this would be an important mechanism to consider. 

The electrochemical transformation of a molybdenum nitrosyl complex [Mo(NO)(dttd)J [dttd = 1,2-bis(2-mercaptophenylthio)ethane] (30) is rather interesting (119). Ethylene is released from the backbone of the sulfur ligand upon electrochemical reduction. The resulting nitrosyl bis(dithiolene) complex reacts with O2 to give free nitrite and a Mo-oxo complex. Multielectron reduction of 30 in the presence of protons releases ethylene and the NO bond is cleaved, forming ammonia and a Mo-oxo complex (Scheme 15). The proposed reaction mechanism involves successive proton-coupled electron-transfer steps reminiscent of schemes proposed for Mo enzymes (120). 

Vitamins are substances essential for a healthy life humans must ingest vitamins via their diet because there is no mechanism for their biosynthesis in the body. There are 14 vitamins - the name was coined when the first vitamin chemically identified (vitamin Bi in 1910) turned out to be an amine - a vital amine. A typical vitamin is folic acid, a complex molecule in which the functionally important unit is the bicyclic pyrazino[2,3- f pyrimidine (pteridine) ring system, and its arylaminomethyl substituent. Folic acid is converted in the body into tetrahydrofolic acid (FH4) which is crucial in carrying one-carbon units, at various oxidation levels, for example in the biosynthesis of purines, and is mandatory for healthy development of the foetus during pregnancy. Other essential co-factors that contain pteridine units must and can be biosynthesised in humans - without them we cannot survive - aud are incorporated into oxygen-transfer enzymes based on molybdenum, in which the metal is liganded by a complex ene-dithiolate. 

Rich P, Hille R (1999) Mechanism of formamide hydroxylation catalyzed by a molybdenum-dithiolate complex A model for xanthine oxidase reactivity. J Phys Chem B 103 5406-5412 Rich P, Hille R (2002) Oxo, thioxo, and telluroxo Mo-enedithiolate models for xanthine oxidase Understanding the basis of enzyme reactivity. J Am Chem Soc 124 6796-6797... 

---