The evolution of oxidative metabolism has shaped life on Earth, driving biodiversitication from anaerobic microbes to complex aerobic organisms. However, dioxygen is a double-edged sword: essential for life, yet a contributor to oxidative stress and cellular damage. Several classes of metalloenzymes readily activate molecular oxygen for the stereoselective oxidation of organic substrates. Cambialistic enzymes are metalloenzymes that despite sharing a conserved protein host, can incorporate different metals to perform their selective transformations. In these systems, the identity of the metal ion(s) within the active sites is an important determinant of activity. Beyond the metal ion(s), activity is tuned by the ligands that comprise the primary coordination sphere, and the non-covalent interactions within the secondary coordination sphere that often controls substrate anchoring and site-selectivity. Cambialistic enzymes are exemplified by the quercetin dioxygenases (QueD), which catalyze the oxidative cleavage of quercetin, a flavonoid found in plants. However, the identities of the mechanistic intermediates involved in these transformations are still unclear, in part due to their transient nature. Furthermore, the metallocofactors in many naturally occurring QueD enzymes have yet to be identified, but metal-substituted variants with varying catalytic rates and activities have been characterized prompting investigations into metal-based functional switching. Here, we present developments in a series of artificial metalloproteins (ArMs) designed to mimic structural aspects of the active sites found in QueD enzymes and to stabilize mechanistically relevant intermediates generated during QueD turnover. Crystallographic, spectroscopic and thermodynamic results will be discussed and compared to what is known of the naturally occurring variants.