The metalloenzyme carbonic anhydrase maintains acid-base balance and aids carbon dioxide transport in the body. Our efforts to investigate synthetic mimics to understand the mechanism and key steps in the catalytic cycle will be discussed. Two activity descriptors have been previously been highlighted to describe the catalytic activity of carbonic anhydrase mimics. The first is the pKa/ acidity of the LM(OH2) species which affects the deprotonation step in the CA mechanism. The second is the electron density of the metal center which affects the bicarbonate release step of the mechanism. These two properties are naturally inversely related and, therefore, have not been investigated independently to understand the degree of impact each has on a mimic system. With the series of Cu(II) complex studied herein, the impact of these two properties were decoupled from one another and the metal electron density alone is investigated by functionalizing the ligand scaffold with different functional groups.