Synthesis, Structure, Spectral Characteristics And Applications Of Rhodamine B-based Fluorescent Probes And Derivatives Of Pyrazoline,1,2,4-triazole And Thiazolo[3,2-b][1,2,4|Triazole

Section1:Disruption of copper homeostasis in cells, the deficiency or excess of copper, will cause severe dysfunction, and even result in many diseases. Mercury, as a toxic heavy metal element, will damage the human brain and nervous system, renal system, immune system, reproductive system, etc. Moreover, mercury and copper are heavy metal environmental pollutants. Therefore, the quantitative detection of metal ions, such as Cu2+and Hg2+, is of great importance. Fluorescence analysis is more sensitive than colorimetric and spectrophotometric method. Compared to conventional detection methods for the quantitative analysis of meal ions, such as atomic absorption spectroscopy, inductively coupled plasma mass spectroscopy (ICPMS), the fluorescence detection method is more convenient and does not require complicated, multistep sample preparation or sophisticated instrument. Rhodamine B fluorescent probes have excellent photophysical properties, such as high fluorescence quantum yield, large absorption coefficient, long emission wavelength and little interference of background fluorescence.In Section1of this paper, we designed and synthesized four rhodamine B fluorescent probes for the detection of Cu2+and Hg2+, respectively, which were characterized by IR, NMR, HRESIMS and/or single-crystal X-ray diffraction. We studied the selectivity for Cu2+or Hg2+, the interference of other metal ions and/or anions, and the effect of time and pH to fluorescent intensity. We also discussed the binding mode or the mechanism of the reaction by titration spectrum and Job method, furthermore, we committed to applying the probes to locate and image the intracellular metal ions, or to detect metal ions in the blood.Chapter1, to elucidate the importance of detection of metal ions and the advantages of fluorescent analysis and rhodamine fluorescent probes, we reviewed the research and applications of rhodamine B fluorescent probes in recent years. And we described our work in Section1briefly.Chapter2, we designed and synthesized three novel highly sensitive and selective rhodamine B fluorescent probes for Cu2+.(E)-3',6'-bis(diethylamino)-2-((6-methoxy-4-oxo-4H-chromen-3-yl)methyleneamino)spiro[isoindoline-1,9'-xanthen]-3-one, as Cu2+fluorescent probe, interacted with Cu2+. Cu2+induced spirocycle opening of the probe, and caused nearly40-fold enhancement of fluorescence, while other ten metal ions caused no significant or little enhancement of fluorescence.(E)-3',6'-bis(diethylamino)-2-((6-chloro-4-oxo-4H-chromen-3-yl)methyleneamino) spiro[isoindoline-1,9'-xanthen]-3-one is more sensitive and selective for detecting Cu2+, and has higher fluorescence quantum yield, larger absorption coefficient than the former probe, but the binding mode with Cu2+is similar to the former one. Cu2+also caused large enhancement of fluorescence, while other metal ions caused no enhancement of fluorescence and no obvious interference basically. Using the two probes for detecting and imaging the intracellular Cu2+of living HeLa cells, we found the latter probe was easier to penetrate the membrane, and could imagine the cells in shorter time than the former one. In addition, we synthesized a novel rhodamine B derivative conjugating with1,2,4-triazole subunit. After investigating the absorption and fluorescent spectrum, we found this rhodamine B-1,2,4-triazole conjugate showed excellent selectivity to Cu2+, and caused nearly120-fold enhancement of fluorescence in buffered solution. Moreover, this probe could recognize Cu2+by both colorimetric and fluorescent method, the fluorescent detection limit of which for Cu2+was10-8M level, and it also had much larger stability constant with Cu2+and much higher quantum yield than the former two probes. Rhodamine B-1,2,4-triazole conjugate could also be used as Cu2+probe to monitoring intracellular Cu2+Chapter3, another novel rhodamine B derivative was synthesized, which exhibited excellent selectivity to Hg2+as fluorescent probe, and had very large absorption coefficient and high quantum yield. Its fluorescent detection limit for Hg2+was10-8M level. Section2.We devoted our effort to synthesizing diverse and multifunctional small organic molecules. The derivatives of pyrazoline,1,2,4-triazole and thiazolo[3,2-b][1,2,4]-triazole have been widely used for the research and applications in the fields of electroluminescence, photoluminescence and biological activities in recent years. Ferrocene has distinctive "sandwich" structure and special physical and chemical properties, which is widely applied for the biological research, the development of materials and chiral catalysts, etc. Therefore, we synthesized several series of novel derivatives of pyrazoline,1,2,4-triazole and thiazolo[3,2-b][1,2,4]-triazole conjugating ferrocenyl group respectively. In addition, we prepared a series of ribavirin carbohydrozide derivatives, and evaluated their preliminary biological activities.Chapter1, we reviewed the applications and synthetic methods of derivatives of pyrazoline,1,2,4-triazole and thiazolo[3,2-b][1,2,4]-triazole, and also summarized the properties and applications of ferrocene and its derivatives. We concisely introduced the content of our work in Section2.Chapter2, we synthesized a series of novel5-aryl-3-ferrocenyl-l-(4-aryl thiazolidine-2-yl)-pyrazoline derivatives, which were characterized by IR, NMR and HRESIMS respectively, and two of which were characterized single-crystal X-ray diffraction. We also investigated the mechanism of the cyclization of pyrazoline ring and their absorption and fluorescent characteristics.Chapter3, novel1-ferrocenyl-2-(3-substituted-1H-1,2,4-triazol-5-ylthio) ethanone derivatives were systhesized and characterized by IR, NMR and HRESIMS respectively.3-Phenyl substituted derivative was characterized by single-crystal X-ray diffraction. We also studied all their absorption and fluorescent spectrum.Chapter4, a series of novel6-ferrocenyl-2-substituted-thiazolo[3,2-b][1,2,4]-triazole were synthesized and characterized by IR, NMR, HRESIMS and single-crystal X-ray diffraction.Chapter5, we synthesized a series of novel ribavirin hydrozone derivatives and evaluated their preliminary biological activities, and we found that one of the compounds inhibited the growth of A549cells.