Construction And Sensing Application Of Activatable Fluorescence/MR Imaging Molecules

More and more attention has been attached on molecular imaging, because it can realize non-invasive and real-time observation of physiological and pathological processes in cell and also on the molecular level, possessing the unique advantages for early desease screening, accurate diagnosis, the development of drugs and new drug development and so on. The two keys to molecular imaging are choices of imaging technology and probe design. The current concerns are the high sensitivity of the fluorescence imaging and the representation of three-dimensional anatomical information of MRI with high spatial resolution. Construction of polychromatic luminescence molecules, simulating life system identification process to monitor in situ the biological molecules related in cell or tissue with high sensitivity and high resolution image, facilitate the study on physiological reaction process and pathogenesis of organisms. In this dissertation, a series responsive fluorescent and MR imaging sensor molecules has been constructed through regulating the elements influencing the probe response, and also studied their image application in cells and mouse models.Tow single-molecular FRET luminescence imaging probes based on the traditional fluorescent dyes and lanthanide luminescent complexes have been synthesized. Probe Cou-RhB acts as binary complementary color luminescent molecules, as the change of solution pH from neutral to acid, its luminescence presented by the blue-white-orange color change, such three-color luminescence was achieved with fixed excitation wavelength. Probe Cou-Rh6G-Eu is a three-primary-colors luminescent molecule, its luminescence rendered by the red-blue-green color change as the change of pH, to achieve continuously adjustable multicolor emission based on the three-primary-color emission at fixed excitation wavelength. CIE color coordinates were established to attain the pH directly according to luminous color of the solution. Cell viability assay showed that the probe Cou-RhB and Cou-Rh6G-Eu have good biocompatibility, they also have been used for the ratio detection of intracellular pH by multicolor fluorescence imaging.2-amino-1,8-naphthyridine derivatives acting as base analogs were embedded into rhodamine and luminescence rare earth macrocyclic complexes molecular structures to construct two cases of small molecule probes for luminescence imaging for nucleotides. In aqueous solution, the formation of multiple hydrogen bonding between nucleotide bases and the naphthyridine incorporated into the lactam ring of the probe RBS induced spiro ring to open up, achieved rhodamine-based dye for polynucleotide molecule colorimetric and fluorescent dual modes sensing, Confocal fluorescence imaging experiments showed that RBS has low cytotoxicity and can be used for fluorescence image analysis of intraceliular nucleotides. Naphthyridine group in the probe Eu/Tb-ANAMD not only acts as complementary hydrogen bonding sites to nucletides base, but also coordinates to rare earth ions to be served as an antenna molecule to sensitize rare earth luminescence. In the presence of GMP, the PET effects of nucleic acid bases block the naphthyridine sensitization to Eu/Tb, resulting in the luminescence quenching. Synergy Coordination role of phosphate on the rare earth ions increased selective response to GMP.Grafted2-amino-1,8-naphthyridine derivatives to the typical Gd-based macrocyclic acid MRI contrast agent molecular structure to construct two cases of MRI contrast agent for selective relaxation response towards purine nucleotides. With the triple complementary hydrogen bonding between guanine base and naphthyridine group of contrast agent, and also the coordination of phosphate to Gd, Gd-ANAMD showed selective relaxation response to GMP. Due to the kosmotropes characteristic of phosphate radical, reduced the exchange rate between inner and outer sphere water molecular, resulting in the low relaxivity. Contrast agent Gd-NAPTA showed "turn-on" relaxation response for GTP and ATP. Transient fluorescence spectra assay showed that the inner coordinated water number increase on Gd center was the main reason for the relaxivity increasement of the contrast agent. MCF-7cell viability experiments showed that Gd-ANAMD and Gd-NAPTA had minimal cell toxicity, MRI showed a continuous enhancement effect on mouse models.