Rection-activated Fluorescent Probe For Disease Diagnosis And The Other Related Fluorescent Probe: Design, Synthesis And Application

In the present work, three series of reaction-activated fluorescent probes were desiged and synthesized. Because of the rearrangement of fluorophore’s electron density, probe and reaction product can produce two different wavelengths of fluorescence emission peak. Therefore, probe can detect the substrate in ratiometric way, which greatly improves the accuracy and reliability of the detection results.1. Based on the clinical metabolic study that Amonafide was mainly metabolized by N-acetyltransferase II to Acetyl-Amonafide, we designed and synthesized N-acetyltransferase II specific probe Amonafide. Both Amonafide and Acetyl-amonafide can be excited at 350 nm, but the maximum emission wavelength is at 580 nm and 460 nm respectively. The more important thing is that the metabolism product Acetyl-amonafide has a high fluorescence quantum yield (0.72). Through enzyme and cell experiments, it was also proved that the probe had high selectivity and sensitivity (1 nM) for N-acetyltransferase II. Next, the probe was successfully applied in HepG2 fluorescence imaging. These will lay the foundation of personalized medicine.2. Based on the hypoxia prodrug moiety of p-nitrobenzyl, a selective ratiometric fluorescent sensor (RHP) for the detection of microenvironment hypoxia was designed and synthesized. RHP can be selectively activated by bioreductive enzymes (NTR) and results in an evident blue to green fluorescent emission wavelength change in both solution phases and in cell lines, which might be the first fluorescent ratiometric probe for hypoxia in solid tumors. By hypoxia/aerobic experiments, it showed that when the GrHy/GrAr and BlHy/BlAr ratio value is above 45, the cells are in a hypoxic environment. RHP can be used as a probe for the diagnosis of hypoxia in early stage of solid tumors.Some prodrugs which based on amonafide and activated by hypoxia were also synthesized.3. Based on benzothiazole compounds (HBTBC), fluorescent probes of Pd (0) was designed and synthesized. Because of the Stokes shift value is up to 120 nm before and after the reaction, the detection resulted had higher reliability and accuracy.Pd (0) fluorescent probe (OHBT) was based on Tsuji-Trost allylic oxidative insertion reaction. After reaction between OHBT and Pd, the maximum emission wavelength was shifted from 410 nm to 550 nm. OHBT had a high selectivity to Pd(0). The Pd can also be detected by solid fluorescence through a given method. OHBT was successfully applied in residual Pd detection in the Suzuki reaction.