The Construction Of Intelligent GPX Artificial Enzyme Of PH Sensitivity By Using Molecular Machine With Cucurbital [6] Urea As The Main Molecule

Glutathione peroxidase(GPx)is an important antioxidant enzymes that protect various organisms from oxidative stress by catalyzing the reduction of hydroperoxides(ROOH)at the expense of glutathione(GSH)in vivo.Imitating GPx functions has aroused great interest because of its excellent antioxidant properties.Up to now,a series of enzyme models based on small molecule,dendrimer,nano size assembly,gel,polymer and biological macromolecule have been constructed.After decades of development,some of these GPx mimics have displayed extraordinarily high activities that rival the native ones.On the other hand,the design and preparation of smart GPx mimics with controlled catalytic activity have also attracted increasing attention.These smart artificial enzymes were constructed by stimuli-responsive materials through changing their structures and properties in response to external stimuli such as temperature,pH,light and small molecules.Among these stimuli-responsive methods,the pH-responsive artificial enzymes have a bright future as potential medicines because the pH level in the human body varies with different organs,e.g.cancer and normal cells.Especially the ones that can be switched on/off around the neutral conditions are very mild and suitable for the human body.One important example is the design of cucurbit[6]uril(CB[6])based pH-responsive molecular machine which contains a CB[6] ‘bead' and a polyamine‘string'.CB[6],a member of cucurbit[n]uril family,has been studied extensively to have a very strong combining capacity with protonated diaminoalkanes.However,when the two nitrogen atoms are deprotonated,the binding constant with CB[6]decreases significantly.That is why this kind of molecular switch exhibits a strong response to pH change.Inspired by this work,we design and synthesized organoselenium compound 1which contains a catalytic selenium center and aniline,secondary amine and primary amine three different amino groups.Organoselenium compound 1 can form a molecular machine with CB[6].CB[6] slides to the alkyl chain between aniline and secondary amine on organoselenium compound 1 when the three amino groups of organoselenium compound 1 are all protonated.In this case,compound 1 did not show GPx activity obviously as the active site of compound 1 was encapsulated into CB[6] and therefore cannot bind to the substrate.However,CB[6] slides to the alkyl chain between primary amine and secondary amine on organoselenium compound 1when aniline and secondary amine are deprotonated.With the increase of pH the active site gradually exposed to solution,which caused a gradually increased GPx activity.As a result,the GPx activity can be switched on and off by controlling the slide of the host molecule in molecular machine through changing pH.By this way,a pH sensitive smart GPx mimic was constructed using cucurbit[6]uril based molecular machine.