Insights into the Relationship of Catalytic Activity and Structure: A Comparison Study of Three Carbonic Anhydrase Mimics

Abstract

Density functional theory (DFT) calculations were used to study the mechanism of CO 2 hydrolysis by Zn-(1,5,9-triazacyclododecane) and Zn-cyclam and evaluate the associated thermodynamic and kinetic parameters. Microkinetic models were then built based on the kinetics and thermodynamics derived from first principles. Both catalysts showed very similar behavior to Zn-cyclen, which we have reported previously, but with multiple distinctions. The intrinsic reaction rate constants for Zn-(1,5,9-triazacyclododecane) and Zn-cyclam were calculated to be 2693 and 4623 M −1 s −1 , respectively, which is in reasonable agreement with experimental values reported or estimated. The CO 2 adsorption step was found to be a ratelimiting step for all three catalysts. Zn-cyclam has the lowest barrier for this step due to the highest pK a or nucleophilicity of the Zn-OH − form, and , therefore, the highest intrinsic activity. However, the observed reaction rate constant also depends on the availability of the catalyst. The decrease in the observed reaction rate constant over 0-12 ms was ascribed to the decrease in the concentration of the catalytic form, Zn-OH − , which was primarily converted to Zn-HCO 3 − . The reaction rate constant of Zn-cyclam dropped much faster than those of Zn-cyclen and Zn-(1,5,9-triazacyclododecane) due to lower energy of the Zn-HCO 3 − form. The conversion of CO 2 at 1000 ms as a function of pH was calculated to compare the relative activity of these catalysts, and Zn-cyclen was found to be the best catalyst.

Kinetic Study of CO2 Hydration by Small-Molecule Catalysts with A Second Coordination Sphere that Mimic the Effect of the Thr-199 Residue of Carbonic Anhydrase

“…That is, in the Ni and Cu compounds, the central metal has a higher acidity than that of the Zn complex, and thus, they form strong bonds with bicarbonate, making it difficult to substitute water molecules. Looking closely at the formation mechanism of the bicarbonate intermediate of CA, as reported by Lindskog, Zn 2+ is capable of monodentate as well as bidentate bonding with bicarbonate ( Figure 5) [33,45]. Increasing…”

Computational Insights into Biomimetic CO2 Hydration Activities of (Poly)borate Ions

“…Lipscomb and Lindskog mechanisms have been reported for bicarbonate ion formation from OH – .CO 2 complex during enzyme catalyzed CO 2 hydration. − In Lipscomb mechanism, proton transfer takes place for bicarbonate ion formation while in Lindskog mechanism, OH – ·CO 2 complex rotates to change the metal–oxygen (M-O) coordination for bicarbonate formation. − Transition state for Lipscomb mechanism is represented as TS2 while transition state for Lindskog mechanism is represented as TS2′ in our study. Proton moved away from O atom of IM2 complex to attain the transition state TS2 following the Lipscomb mechanism.…”

Quantum mechanical investigation on the hydroxycarbonylation of styrene using a palladium complex catalyst

“…The methods used here are widely applicable to theoretical investigations of chemical reactions [23][24][25][26][27][28][29][30]. The Chemcraft program [32] was used for drawing illustrations.…”