Synthesis And Properties Of NIR Luminescent Cationic Fluorescent Probes Based On Benzothiadiazole And Thieno[3,2-b] Thiophene

Photodynamic therapy（PDT）,which has the characteristics of non-invasiveness,negligible drug resistance,small side effects,and precise spatiotemporal manipulation,achieves the therapeutic effect by triggering apoptosis through reactive oxygen species（ROS）generated by photosensitizers（PSs）after light irradiation.Although a large number of photosensitizers have been developed,these photosensitizers still suffer from aggregation-caused quenching（ACQ）,low ROS generation efficiency,and poor tumor targeting.RNA plays an important role in gene expression and protein synthesis,and observing these processes is beneficial for the diagnosis and treatment of diseases.Visualization of these processes can be achieved by imaging RNA with fluorescent probes.However,most of the reported fluorescent probes for RNA have defects such as short emission wavelengths,small Stokes shift,poor selectivity,low sensitivity,and poor membrane permeability.Herein,we developed near-infrared（NIR）fluorescent probes for PDT and RNA recognition,the main research contents are:（1）A fluorescent probe TBZTI with D-π-A structure was designed and synthesized using triphenylamine and benzothiadiazole as electron donors and indolium salt as an electron acceptor.TBZTI,with a 730 nm NIR emission wavelength and a 180 nm Stokes shift,has aggregation-induced emission（AIE）effect,and its intramolecular charge transfer（ICT）is verified by solvation effects and density functional theory（DFT）calculations.Under light irradiation,TBZTI has higher singlet oxygen（¹O₂）generation efficiency than Rose Bengal（RB）,and the phototoxic cell survival rate is 32.4%and only 13.5%cells survive apoptosis in flow cytometry at 2μM TBZTI,showing an ideal photodynamic effect at the cellular level.Having a colocalization coefficient of 0.92 with Lyso-Tracker Green,TBZTI can target lysosomes well,and its particle size distribution and fluorescence imaging in mice validate its ability to target tumors via enhanced permeability and retention effect（EPR）.Furthermore,TBZTI can significantly inhibit the growth of tumors in mice without causing damage to the main organs of mice,and has the potential to be used as a photosensitizer in clinical research of PDT.（2）A fluorescent probe PCTP with D-π-A structure was designed and synthesized using9-phenylcarbazole as an electron donor and pyridinium salt as an electron acceptor.PCTP has a 710 nm NIR emission wavelength and a large Stokes shift（285 nm）,and its ICT is verified by solvation effects and DFT calculations.PCTP can recognize RNA in vivo and in vitro,showing high selectivity and sensitivity to RNA.After binding with RNA,the fluorescence intensity of PCTP increased by 52.2 times,and the detection limit of RNA was 2.17μg/m L.Moreover,PCTP can effectively penetrate the cell membrane and enter the cells for real-time imaging,showing high photostability,and can track the proliferation of 4T1 cells in vitro up to 11 generations,and track the growth of mouse tumor for more than 22 days.Therefore,PCTP provides a potential tool for RNA imaging and long-term cell growth tracking.