1.2- Dithiolenes enzyme mechanisms

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). 

Subsequently, RR was used to successfully detect structural changes between the oxidized and reduced forms of both DMSOR and BSOR that are consistent with the proposed oxygen atom transfer mechanism of the catalytic reaction (95, 97). These experiments make use of the readily measurable isotopic shifts in vibration frequency between ieO=Mo and lsO=Mo to follow the fate of the oxygen atom removed from DMSO (or BSO) by the Mo. In this way, the clean transfer of 180 from DMSlsO to Mo(IV) to yield the oxidized form of the active site as Mo(VI)=180 was directly observed as well as the substrate-bound intermediate, (DMS180)Mo(IV). Further discussion of the technique of RR applied to metal dithiolenes and dithiolene-containing enzymes is included in Chapter 4 in this volume (98). 

A range of chemical analogs of the catalytic centers of Mo and W dithiolene-containing enzymes (pterins) have been prepared. In particular, the rich chemistry of multisulfur transition metal systems allows ligand redox, internal electron transfer, and intermediate redox states. Such redox flexibility may facihtate coupled proton/electron transfer and/or 0x0-transfer mechanisms, which are employed by Mo and W enzymes. 

Catalytic and single-turnover experiments with the R. sphaeroides DMSO reductase, 0-labeled DMSO and l,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane as an oxygen atom acceptor have been used to demonstrate that the enzyme is an oxotransferase. Complementary resonance Raman studies have been interpreted on the basis of a direct mechanism for OAT, with the active site cycling between mono-oxo-Mo(VI) and des-oxo-Mo(IV) forms via a DMSO-bound Mo(IV) intermediate. Both MPT dithiolene groups stay firmly attached to the molybdenum throughout the catalytic cycle. However, EPR and UV/visible spectroscopic evidence has been interpreted on the basis of the species formed upon the addition of DMS to oxidized... 

Metallodithiolene complexes have long been of interest due to their unusual properties, unique geometric and electronic structures, non-innocent behaviour and potential applications. Several of these attributes are no doubt important in the function of Mo-MPT enzymes. Indeed, Rothery et aZ. have argued that the dithiolene ligand(s) are primary determinants of enzyme reactivity and mechanism. 

The initial contribution to this volume provides a detailed overview of how spectroscopy and computations have been used in concert to probe the canonical members of each pyranopterin Mo enzyme family, as well as the pyranopterin dithiolene ligand itself. The discussion focuses on how a combination of enzyme geometric structure, spectroscopy and biochemical data have been used to arrive at an understanding of electronic structure contributions to reactivity in all of the major pyranopterin Mo enzyme families. A unique aspect of this discussion is that spectroscopic studies on relevant small molecule model compounds have been melded with analogous studies on the enzyme systems to arrive at a sophisticated description of active site electronic structure. As the field moves forward, it will become increasingly important to understand the structure, function and reaction mechanisms for the numerous non-canonical [ie. beyond sulfite oxidase, xanthine oxidase, DMSO reductase) pyranopterin Mo enzymes. 

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