The Construction Of PH-sensitive Smart Glutathione Peroxidase And Its PH Responsiveness

Glutathione peroxidase(GPx)catalyses the reduction of hydroperoxides(ROOH)at the expense of tripeptide glutathione(GSH)and maintains the metabolic balance of reactive oxygen species(ROS)in vivo to protect various organisms from oxidative stresses and to reduce the risk of a range of related diseases.In the design of artificial enzymes,GPx has attracted much attention because of the outstanding antioxidant ability.A series of GPx mimics have been successful constructed in the past thirty years including organoselenium/tellurium compounds,host molecules modified by selenium catalytic centres,nanoenzyme models and genetic engineering models.Up to now,some of these GPx mimics have shown satisfying enzymatic properties that rival the native ones.In recent years,the design and preparation of smart GPx mimics with controlled catalytic activity have attracted increasing attention.The smart GPx mimics can be constructed by the materials that are responsive to the external stimuli such as temperature,light and pH.The development of pH responsive molecular machines provides an opportunity to construct pH sensitive GPx mimics.Such smart GPx mimics are promising in the future as potential medicines because the pH level in human body is varied in different cells and organs.Inspired by the above works,we want to develop a pH sensitive GPx model by using a pH responsive molecular switch formed by CB[6] and organoselenium compound.Herein,we designed organoselenium compound 1 and 2 as GPx models,which contain two primary amine groups and diselenide catalytic center(compound 1)or selenide catalytic center(compound 2).In the presence of CB[6],the GPx mimics form 1:1 host-guest pseudorotaxane complexes when the amine groups are diprotonated.In this case,the mimics cannot show GPx activity since the active sites are encapsulated into the hydrophobic cavity of CB[6].As the primary amine groups are gradually deprotonated with the rise of pH,the binding ability of CB[6] with compound 1 and 2 significantly decreases.As a result,the active sites expose to solution,causing an increase of GPx activity.Thus,the catalytic activity of the GPx model can be switched on/off through changing the pH.