Critical Roles of Exchange and Superexchange Interactions in Dictating Electron Transfer and Reactivity in Metalloenzymes.

Electron transfer (ET) is a fundamental process in transition-metal-dependent metalloenzymes. In these enzymes, the spin-spin interactions within the same metal center and/or between different metal sites can play a pivotal role in the catalytic cycle and reactivity. This Perspective highlights that the exchange and/or superexchange interactions can intrinsically modulate the inner-sphere and long-range electron transfer, thus controlling the mechanism and activity of metalloenzymes. For mixed-valence diiron oxygenases, the spin-regulated inner-sphere ET can be dictated by exchange interactions, leading to efficient O-O bond activations. Likewise, the spin-regulated inner-sphere ET can be enhanced by both exchange and superexchange interactions in [Fe4S4]-dependent SAM enzymes, which enable the efficient cleavage of the S─C(γ) or S─C5' bond of SAM. In addition to inner-sphere ET, superexchange interactions may modulate the long-range ET between metalloenzymes. We anticipate that the exchange and superexchange enhanced reactivity could be applicable in other important metalloenzymes, such as Photosystem II and nitrogenases.