Modeling the Azadithiolate Cofactor

The dithiolate cofactor has been proposed to be SCH2NHCH2S [15], although protein crystallography cannot distinguish between N, O, and C. 1,3-Propane-dithiol is unknown biologically, so despite its routine chemical character, this species is no more plausible as the cofactor than the hetero-substituted derivatives. 

Structural and acid-base studies on the diiron azadithiolato complexes show that the basicity of the amine is diminished versus EtjN in the same solvent [37, 42]. Theoretical calculations suggest that the reduced basicity is arises from an electronic interaction between the nitrogen lone pair and the C-S a orbital (Fig. 12.4). The conjugate acid of this weakly basic amine would be capable of protonating a weakly basic iron hydride to generate hydrogen. 

It is well known from classical organometallic chemistry that non-coordinating amine bases affect the behavior of H2 complexes [44]. The azadithiolate motif has been exploited in the design of new catalysts for hydrogen oxidation, as described in the next section on [NiFe] hydrogenases [45]. 

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