Construction Of Ratiometric Optical Probes For Biological Imaging Of Methylglyoxal

Methylglyoxal（MGO）is an endogenous dicarbonyl compound produced by the conversion of glucose,alcohols and protein metabolism,among other pathways,and is an indicator for assessing a variety of disease states.MGO can cause endogenous damage and generate harmful products by reacting with proteins and DNA,causing cellular and biological toxicity and leading to related health problems.MGO concentrations are increased in in vivo models of diabetes and associated vascular complications,renal failure,Alzheimer’s disease and Parkinson’s disease,while high concentrations of MGO also lead to increased frequency of cardiovascular disease,oxidative stress,dyslipidemia,cell shedding,apoptosis and DNA strand breaks.Therefore,the study of MGO-related physiological functions and real-time tracing of in vivo concentrations are of great importance for human health and early diagnosis and treatment of diseases.Fluorescent probes have received much attention in the detection of MGO due to their high sensitivity,non-invasive nature and excellent spatial and temporal resolution.Although various chromophore-based MGO fluorescent probes have been reported,these fluorescent probes still face some problems,such as most MGO probes respond to MGO by fluorescence"turn-on"and emit wavelengths in the UV-Vis region less than 550 nm,which are easily affected by the instrument state,light scattering and in vivo microenvironment in imaging applications.To address the above-mentioned problems of MGO optical probes,this paper aims to achieve accurate detection of MGO in cells and in vivo,and to design and synthesize optical probes with near-infrared emission and absorption characteristics with ratiometric response effect by linking MGO recognition groups to isophorone and BODIPY chromophores to achieve fluorescence and photoacoustic imaging of MGO in cells and in vivo mice.The main research includes:In Chapter 2,we selected the isophorone backbone with good biocompatibility,large Stokes shift and NIR emission as the chromophore and o-phenylenediamine（OPD）as the response group of MGO,and the OPD group was bridged with the fluorophore via ethylene to obtain the fluorescent probe FL_MGO with D-π-A structure.in PBS solvent,FL_MGO had excellent ratiometric response behavior to MGO cellular experiments further demonstrated the excellent ratiometric response of the probe and enabled the detection and imaging of intracellular MGO.The above results provide research ideas for the design of MGO-responsive near-infrared ratiometric fluorescent probes,which are expected to facilitate the research of fluorescent probes in MGO and its related diseases.In Chapter 3,to address the current situation that it is difficult to image MGO in vivo,we designed and synthesized photoacoustic probes PA_MGO1-2 with near-infrared ratiometric response capability by selecting BODIPY,which is biocompatible and easy to modify,as the chromophore and OPD as the response group.The results show that the probe PA_MGO2 has specific response to MGO,and the maximum absorption wavelength after responding with MGO is shifted from It is expected to achieve the detection of MGO in the near-infrared region.PA_MGO2 is the first PA probe that can detect MGO in the brain through the blood-brain barrier and is expected to be used in the study of MGO and AD.In Chapter 4,considering the superior penetration depth and imaging effect of photoacoustic probes with absorption wavelengths greater than 950 nm in the Near infrared regionⅡregion,we obtained the BODIPY dimer by ethylene bridging and designed and synthesized the photoacoustic probe DPA_MGO with ratiometric response capability in the Near infrared regionⅡregion by conjugating the MGO response group to this dimer.The results showed that DPA_MGO was blue-shifted from 1050 nm to 980 nm before and after the reaction with MGO,and absorbed in both Near infrared regionⅡregions.We successfully applied this probe to in situ PA imaging of MGO in the brain of AD model mice.This study provides a new research idea for the synthesis of PA probes in the Near infrared region Ⅱ region.