Cyclodextrin‐Derived Mimic of Glutathione Peroxidase Exhibiting Enzymatic Specificity and High Catalytic Efficiency

To elucidate the relationships between molecular recognition and catalytic ability, we chose three assay systems using three different thiol substrates, glutathione (GSH), 3‐carboxyl‐4‐nitrobenzenethiol (CNBSH), and 4‐nitrobenzenethiol (NBSH), to investigate the glutathione peroxidase (GPx) activities of 2,2′‐ditellurobis(2‐deoxy‐β‐cyclodextrin) (2‐TeCD) in the presence of a variety of structurally distinct hydroperoxides (ROOH), H2O2, tert‐butyl peroxide (tBuOOH), and cumene peroxide (CuOOH), as the oxidative reagent. A comparative study of the three assay systems revealed that the cyclodextrin moiety of the GPx mimic 2‐TeCD endows the molecule with selectivity for ROOH and thiol substrates, and hydrophobic interactions are the most important driving forces in 2‐TeCD complexation. Furthermore, in the novel NBSH assay system, 2‐TeCD can catalyze the reduction of ROOH about 3.4×105times more efficiently than diphenyl diselenide (PhSeSePh), and its second‐order rate constants for thiol are similar to some of those of native GPx. This comparative study confirms that efficient binding of the substrate is essential for the catalytic ability of the GPx mimic, and that NBSH is the preferred thiol substrate of 2‐TeCD among the chosen thiol substrates. Importantly, the proposed mode of action of 2‐TeCD imitates the role played by several possible noncovalent interactions between enzymes and substrates in influencing catalysis and binding.