Based On The Design, Synthesis And Application Of BODIPY Derivatives

Fluorescent probes have many advantages over traditional detection methods,such as high sensitivity,multiple output signals,easy operation,on-site real-time detection.They are widely used in chemical,medical research,food analysis,disease treatment and so on.4,4-difluoro-4-bora-3a,4a-diaza-s-indacene?BODIPY?is widely used because of its excellent properties,including photostability,high quantum yield,and wide pH detection range.BODIPY and its derivatives can be used as fluorescent probes to detect cations,anions,and biological macromolecules.The work reported in this dissertation is focused on the rational design and synthesis of fluorescent probes based on BODIPY and investigation on their applications in biology and analytical chemistry.?1?A new coumarin-BODIPY based fluorescent probe 1 was synthesized,which can simultaneously detect CN^-and F^-by ICT sensing mechanism.In the mixture solution of acetonitrile and Tris-HCl buffer?V/V=95:5,pH=7.5?,F^-could induce red shift from 349 to412 nm and 585 to 593 nm in absorption spectra and fluorescence quenching completely.However,addition of CN^-could lead to the absorption band of probe 1 disappearing,meanwhile,a new absorption band around 412 nm was appeared.Moreover,CN^-could lead to emission band at 604 nm quenching completely with appearance of a new emission band around 492 nm.The detection limit of probe 1 for F^-and CN^-were 0.43?M and 1.9?M,respectively.?2?A BODIPY-hemicyanine turn-on fluorescent probe 2 was synthesized,which showed high selectivity and sensitivity for CN^-detection,and the detection limit was 59 nM in aqueous solution.The nucleophilic addition of CN^-reduced the?conjugate system and restored the fluorescent unit of BODIPY.Combined its fast kinetics and wide pH range,probe 2 could be a good approach for the real-time,on-spot,selectiveand sensitive detection of CN^-in the complicated systems.Moreover,probe 2 was successfully applied to detect CN^-on paper test strips with satisfactory results.?3?A novel ratiometric fluorescent probe 3 based on BODIPY was synthesized,which cloud detect Cu²⁺by using BODIPY as the fluorescent signal group and 2-pyridyl ester as the recognition site.This probe exhibits high selectivity and sensitivity towards Cu²⁺through the hydrolysis reaction between probe 3 and Cu²⁺,which is confirmed by ¹H NMR and mass spectrum analysis.The limit of detection was calculated to be 0.08?M.Moreover,this probe could be used for Cu²⁺detection on filter paper with excellent results.?4?As one of the most typical secondary structures,?-sheet has a crucial influence on the function of proteins,using fluorescence techniques to study the interaction between?-sheets and proteins?receptors?has great scientific significance and practical value,the synthesis of protein secondary structure mimics is also the difficulty in peptide chemistry.Using unnatural amino acids as templates to induce?-sheet structure in small peptides is most advantageous,because these templates eliminated most of the entropic penalty associated with chain reversal due to their U shape,however,to the best of our knowledge,none of these compounds have been reported to be fluorescent.This project is firstly proposed using BODIPY as research object for the development of fluorescent?-turn mimics,since it not only would lead to short conformationally restricted peptides,but also could be easily detected and studied using fluorescence techniques.On this basis,designing and synthesizing different bioactive?-sheet mimics to explore their biomedical applications as fluorescent probes.The concrete content includes:Design and synthesis of fluorescent?-turn mimics based on BODIPY;Synthesizing somatostatin analogues as examples to explore the application prospect of fluorescent?-turn mimics,the mechanisms of interaction between somatostatin analogues.Finally,generalize this technology to research other field of peptide-protprotein-protein interactions for providing useful information in designing potential drug candidates.Somatostain analogue-1 has been successfully synthesized by solid phase synthesis,and subsequent work is still in progress.