The function of metalloproteins can be directly linked to the local environment around the metallo-cofactor. This environment includes direct covalent interactions of amino acid residues and the metal ion, as well as non-covalent interactions proximal to the metal center. The non-covalent interactions include hydrogen bonds (H-bonds) from amino acid residues, as well as extended H-bonding networks that include structural water molecules. Synthetic systems have been designed that include non-covalent interactions within their secondary coordination sphere, however it is often difficult to control and predict these interactions. In this dissertation, an approach has been employed to model the active sites of metalloproteins that utilizes bio-conjugates of metal complexes immobilized within a protein host. Using biotin-streptavidin (Sav) technology, artificial metalloproteins (ArMs) have been prepared that leverage the attributes of protein chemistry with the versatility of synthetic chemistry. Using this approach, control over the primary coordination sphere was demonstrated by developing artificial metalloproteins containing Type I Cu centers like those found in cupredoxins. These ArMs utilize a series of biotinylated CuII complexes with spacers between the biotin and the metal complex of variable length that controlled the location of the metal ion within Sav. Anchoring these CuII complexes within Sav S112C allowed for the study of a series of 4-coordinate Cu complexes with a coordinated thiolate ligand. In addition to controlling the primary coordination sphere, the secondary coordination sphere can be controlled by altering the H-bonding interactions to ligands bound to the Cu center. This control was initially shown through equilibrium binding studies of CuII-azido complexes. X-ray diffraction (XRD) measurements showed the azido ligand H-bonded to residues and/or structural water molecules within Sav WT. These H-bonds were further employed to stabilize reactive CuII–OOH species. CuII–OOH species are known to be highly unstable at room temperature but confinement within Sav WT rendered stable complexes with a half-life of over 1 day. The CuII–OOH species was also generated in crystallo and the structure revealed an O–O ligand coordinated to the Cu center. In addition, the CuII–OOH unit is involved in an H-bonding network: the proximal O-atom is H-bonded to a structural water molecule and the distal O-atom is H-bonded to the N49 residue. This is the only example of a structurally characterized Cu-peroxido species that has an H-bond to the distal and proximal oxygen atoms. A series of Sav variants were used to systematically delete H-bonding interactions to the hydroperoxido ligand. Removal of the H-bond to the distal O-atom of the hydroperoxido ligand did not affect solution stability, while removal of the H-bond to the proximal O-atom drastically reduced the stability of the CuII–OOH and elicited reactivity with an external substrate. For Cu-proteins such as LPMOs, these findings support the premise that H-bonds to the distal O-atom are necessary to produce reactive species.