Metalloenzyme mechanisms correlated to their turnover number and metal lability

Metalloenzymes are involved in several different reactions and the metal can display distinct roles, such as redox chemistry or substrate activation. The activation mechanism is mainly described to occur by bond polarization upon coordination to the metal center. However, the disregard of the outer sphere mechanism can have a profound impact on the mechanism proposition of reactions. In the outer sphere coordination, the metal acts as an electrostatic activator in its hydrated form. Since hydration is crucial in this mechanism, metal lability is related to the proposition of an enzyme mechanism. In this review, we will evidence the impact of metal lability in the design of metalloenzyme mechanisms from EC 1–6, correlating some of the enzymes to their biomimetic compounds.