Surprising Condensation Reactions of the Azadithiolate Cofactor

Azadithiolate, a cofactor found in all [FeFe]-hydrogenases, is shown to undergo acid-catalyzed rearrangement. Fe-2[(SCH2)(2)NH](CO)(6) self-condenses to give Fe-6[(SCH2)(3)N](2)(CO)(17). The reaction, which is driven by loss of NH4+, illustrates the exchange of the amine group. X-ray crystallography reveals that three Fe-2(SR)(2)(CO)(x) butterfly subunits interconnected by the aminotrithiolate [N(CH2S)(3)](3-). Mechanistic studies reveal that Fe-2[(SCH2)(2)NR](CO)(6) participate in a range of amine exchange reactions, enabling new methodologies for modifying the adt cofactor. Ru-2[(SCH2)(2)NH](CO)(6) also rearranges, but proceeds further to give derivatives with Ru-alkyl bonds Ru-6[(SCH2)(3)N][(SCH2)(2)NCH2]S(CO)(17) and [Ru-2[(SCH2)(2)NCH2](CO)(5)](2)S.

Automated summary

Azadithiolate, a cofactor in all [FeFe]-hydrogenases, undergoes acid-catalyzed rearrangement. The reaction results in the exchange of the amine group and leads to the formation of Fe-6[(SCH2)(3)N](2)(CO)(17). X-ray crystallography shows the structure of the interconnected Fe-2(SR)(2)(CO)(x) butterfly subunits. Further studies reveal the participation of Fe-2[(SCH2)(2)NR](CO)(6) in various amine exchange reactions.