Mild oxidants such as [Fe(C5Me5)(2)](+) accelerate the activation of H-2 by [Fe-2[(SCH2)(2)NBn](CO)(3)-(dppv)(PMe3)](+) ([1](+)), despite the fact that the ferrocenium cation is incapable of oxidizing [1](+). The reaction is first-order in [1](+) and [H-2] but independent of the E-1/2 and concentration of the oxidant. The analogous reaction occurs with D-2 and proceeds with an inverse kinetic isotope effect of 0.75(8). The activation of H-2 is further enhanced with the tetracarbonyl [Fe-2[(SCH2)(2)NBn](CO)(4)(dppn)](+) ([2](+)), the first crystallographically characterized model for the H-ox of the active site containing an amine cofactor. These studies point to rate-determining binding of H-2 followed by proton-coupled electron transfer. Relative to that by [1](+), the rate of H-2 activation by [2](+)/Fc(+) is enhanced by a factor of 10(4) at 25 degrees C.