The Application Of Fluorescent Probes Based On Oxazine And Thiazide For The Detection In Alzheimer's Disease

Alzheimer's disease?AD?,one of the particularly common neurodegenerativediseases,poses great threat on the physical and mental health of the elderly.Although the pathological mechanism of AD remains unclear,numerous researchers propose a series of pathogenesis hypothesis,including amyloid cascade hypothesis,oxidative stress hypothesis,and metal homeostasis disturbances hypothesis and so on.A wide range of fluorescent probes are used in the detection of AD pathological proteins due to their advantages such as low price,simple synthesis,convenient use,fast response and so on.In addition,relevant evidence suggests that the pathogenesis of AD is closely associated with reactive oxygen species?ROS?and copper???ions,and it is particularly important to the detection of ROS or Cu²⁺and explores their correlation with AD.Hypochlorous acid?HOCl?is the most common type of reactive oxygen species,which is widespread in the brain of AD.Therefore,the development of highly selective and sensitive fluorescent probes for the rapid detection of HOCl and Cu²⁺is increasingly important.Firstly,we designed and synthesized two fluorescent probes BC-2 and BC-3 for specifically detecting HOCl,taking advantage of remarkable fluorescence change between the reduced form and oxidized form of oxazine 1.The two probes BC-2 and BC-3 released fluorophore oxazine 1 in the presence of HOCl,accompanying with significant fluorescence intensity increase in NIR emission and remarkable colour change from colourless to blue.It is worth noting that the probe BC-3 exhibited high selectivity,sensitivity and rapid response towards HOCl both in cells and in mouse models.Subsequently,the fluorescent probe BC-1 based on oxazine 1 was developed for the selective sensing of Cu²⁺.The probe BC-1 showed good water solubility,high selectivity and excellent sensitivity.And the detection limit was estimated to be 1.93nM.It is worth noting that probe BC-1 is capable of permeating cell membrane and detecting Cu²⁺in living cells,indicating the great potential of probe BC-1 in the biological system for the detection of analytes.Although the pathological mechanism of AD remains unclear,two pathologicalhallmarks?A?and Tau?are critical to understand the progression of AD.Methyleneblue?MB?as a photosensitizer can produce highly reactive oxygen species?¹O₂?under 650 nm laser light,leading to degrading A?aggregates and reducing biologicaltoxicity.Furthermore,MB is also a small molecule compound inhibiting Tau aggregation.Therefore,the fluorescent probe MB-2 and MB-3 were constructed by the reduced form of MB and aniline through an amide bond.The probe MB-3exhibited high selectivity toward HOCl and little interference against various substances.More importantly,MB released from MB-3?containing 10?M HOCl?,could disaggregate misfolded A?protein and inhibit the aggregation of Tau.