Design And Synthesis Of D-A Type Aiegens With Near-Infrared Emission And Their Application In Phototheranostics

The performance of conventional near-infrared（NIR）organic phototheranostics agents is severely weakened in high concentration or aggregated state due to the aggregation-caused quenching（ACQ）effect.Aggregation-induced emission（AIE）is totally opposed to ACQ.AIE luminogens（AIEgens）with NIR emission have been widely used in phototheranostics because of their enhanced fluorescence intensity in high concentrations or aggregated states,the large Stokes shift,and superior resistance to photobleaching.NIR AIEgens with freely movable molecular rotors or vibrators were expected to be regulated to reach a balance between radiative and nonradiative decays to achieve multimodal phototheranostics.Therefore,in this thesis,we designed and synthesized a series of NIR AIEgens through various molecular engineering strategies and investigated their phototheranostics properties.The main contents are as follows:1、Three D-A-D type AIEgens 2TPA-HPy,2TPA-FPy,and 2DSP-FPy were synthesized by introducing fluorine chain and optimizing electron donor moiety.Photophysical tests showed that 2TPA-FPy with fluorine-substituted alkyl chains exhibited significantly red-shifted emission and enhanced type I reactive oxygen species（ROS）production capacity compared to 2TPA-HPy with hydrogen-substituted alkyl chains.Further optimizing the donor in 2TPA-FPy by donor engineering,the maximal emission wavelength of the obtained 2DSP-FPy was effectively red-shifted to NIR window and the efficient ROS generation ability was maintained.2、Two D-A-D type NIR AIEgens 2TPA-PTCF and 2DSP-PTCF with large Stokes shifts and bright NIR-II emission were obtained through acceptor engineering to enhance the electron-withdrawing capacity of the acceptor.After fabrication into nanoparticles（NPs）,both 2TPA-PTCF NPs and 2DSP-PTCF NPs exhibited large Stokes shifts,efficient type I ROS production capability,excellent photothermal conversion efficiency（PCE）,moderate NIR fluorescence brightness.2DSP-PTCF NPs exhibited a red-shifted absorption maxima,higher molar extinction coefficient(1.15×10⁵ L/mol cm^-1),larger PCE（57%）as well as higher cellular uptake levels in a variety of cancer cells due to the stronger D-A interactions,compared to 2TPA-PTCF NPs.The effectiveness of improving the photophysical properties and enhancing cellular uptake of other phototheranostic agents by using this strategy was further validated in AIEgens TPA-TCF NPs and DSP-TCF NPs.NIR fluorescence imaging-guided multimodal cancer therapy both in living cells and live small animals was successfully realized by using 2DSP-PTCF NPs.3、To enrich the A-D-A type AIEgens for NIR phototheranostics,two NIR-II AIEgens LA5 NPs and LA6 NPs with bright NIR-II emission（4.2%,2.3%）,excellent resistance against photobleaching,high ROS generation and PCE（74%,75%）were synthesized.LA6 NPs showed longer emission maximum at 1040 nm due to the introduction of fluorine atoms.LA6 NPs were expected to achieve multimodal phototheranostics of deep tumors with higher spatial resolution and signal-to-noise ratio.