Synthesis,Optical Properties And Biological Activity Of Quinazolinone-Pyridine-Triphenylamine Compounds

Quinazolinones,which are widely found in natural products and pharmaceutical fragments,exhibited a variety of excellent properties such as antibacterial,anticancer and antioxidant.In addition,some quinazolinones show good optical properties and can be used as organic probes for bioimaging.However,due to the simple structure and short emission wavelengths,currently reported quinazolinone-based luminescent materials are not suitable for further applications,such as solvatochromic fluorescence imaging,two-photon fluorescence imaging,high-resolution imaging and photodynamic therapy.Therefore,it is essential to design and discover new quinazolinones with excellent photophysical properties to expand their biological imaging applications.In this thesis,a series of quinazolinone-pyridine fluorescent molecules with long wavelength emission were designed and synthesized through introducing vinyltriphenylamine group modification.The photophysical properties of these compounds were investigated,and their applications in biological imaging and photodynamic therapy were further explored.A dual functional fluorescent probe with cellular localization imaging and photodynamic therapy activities was obtained.The main work is divided into the following three aspects.1)Three quinazolinone-pyridine-triphenylamine conjugates were designed and synthesized.These visible light excited complexes showed long wavelength emission(The maximum emission wavelength was 650 nm).The photophysical properties and biological imaging activities of these compounds were further investigated.The results showed that three fluorescent probes exhibited large Stokes shifts.It is found that methoxy group with different position in complexes showed a significant impact on the photophysical properties of the compounds.By comparison,the fluorescent probe with methoxy group showed weak fluorescence intensity than the unsubstituted complex.In addition,complexes with methoxy group,especially the complex with methoxy group at triphenylamine moiety,showed a larger Stokes shift,which showed good bioimaging application.2)Photoinduced active oxygen species generation by two fluorescent probes with methoxy group was further investigated in dichloromethane and dimethyl sulfoxide solutions.The active oxygen species and carbon center radical were detected through electron paramagnetic resonance spectroscopy after visible light irradiation of the solution of two compounds,which indicated that energy exchange or electron transfer process may occurred between the complexes and solvent under illumination conditions.That may be the reason for their reduced fluorescence intensity.In addition,cytotoxicity testing and biological imaging experiments indicated that 5b was mainly distributed in lipid droplets and showed high cytotoxicity;5c exhibited a low cytotoxicity in dark condition,which was a good candidate for biological imaging.During continuous cell dynamic imaging by laser irradiation,it was found that cells treated with 5c showed obvious morphological changes such as membrane rupture and cell vesiculation,while the morphology of the nucleus remained basically unchanged with subsequent cell death.It was speculated that 5c may induce ferroptosis after light irradiation.3)In order to further improve the localization of compounds in the endoplasmic reticulum(ER),quinazolinone-pyridine-triphenylamine conjugates with Ts NH group were designed.After trying three synthetic routes for the synthesis of quinazolinone based probes containing Ts NH groups,we finally chose a well-established click reaction from alkynyl groups and azides to construct the target molecule containing Ts NH group.