Studies Of Small Biomolecules' Fluorescent Probes Based On Two-photon Fluorescence And Up-convertion Luminescence

Fluorescent imaging with its high sensitivity,low toxicity,rich information feedback,high temporal-spatial resolution and convenient operation and other advantages,plays an increasingly prominent role in the field such as active species detection,drug research and controlled-release,the diagnosis and treatment of serious diseases.To explore the relevance between intracellular redox balance and gene mutations,metabolism,human disease including diabetes,cardiovascular disease and cancer,and body's aging and death,we urgently need to develop fluorescent probes with high selectivity,rapid response,good stability and excellent performance for the detection and imaging of the active biological species.Fluorescent probes based on two-photon fluorescent organic molecules or lanthanide up-conversion nano particles can be excited with near-infrared light,therefore,they usually exhibit good biological tissue penetration ability,little background fluorescence interference and have high application value in the biomedical field.In addition,compare with traditional near-infrared fluorescent probe,these fluorescent probes also have the properties of good photostability,ease of synthesis and preparation,negligible photobleaching and high spatial resolution.In this dissertation,we have strategically designed a series of fluorescent probes of great significance with 1,8-naphthalimide and other two-photon fluorophore and lanthanide doped up-conversion nano particles,which were used for the detection and imaging of thiols related active biological molecules.The dissertation is mainly divided into eight parts:1.The research background of fluorescence imaging is concisely reviewed.The physiologic research significance and current research progress of fluorescent probes for thiols related active species are introduced.And the applications of up-conversion fluorescent materials in the detection and imaging of thiols related active species are also discussed.2.A ratiometric fluorescent probe with multi-channel excitation was designed and synthesized based on merocyanine fluorophore of ICT fluorescence mechanism,which shows an appropriate lipid-water partition coefficient,low cytotoxicity and the imaging ability of cysteine of endogenous cells.3.The first ratiometric two-photon fluorescent probe for H₂S₂ was designed and synthesized with 1,8-naphthylamine as fluorophore.This probe not only has the general characters of ratiometric fluorescent probe,but also shows high quantum yield,good selectivity,quick response towards H₂S₂,little pH affect,low cytotoxicity,negligible interference from interfering species and excellent performance of endogenous H₂S₂ imaging.4.Based on the work in the previous chapter and the progress in the research of H₂S₂fluorescent probes,we have designed and synthesized the mitochondria and lysosome targeted ratiometric two-photon fluorescent probes by applying a modular strategy in which the fluorescent probe was divided into three parts,targeted groups,fluorophore and recognition group.5.A cobalt oxyhydroxide functionalized up-conversion nanoparticle system was designed as the first ratiometric fluorescent probe for AA detection.The ratio of the intensity of the up-conversion luminescence at 475 nm to that at 654 nm shows rapid response to AA.Furthermore,this probe could be applied to detect intracellular AA.6.Based on the work in the previous chapter,a two-photon sensor platform for quick detection of AA was designed and prepared by applying 1,8-naphthalimide as fluorophore and cobalt oxyhydroxide nanosheets to play the role of recognition group.We also have demonstrated the prominent sensing performance of this sensor platform,including excellent two-photon induced fluorescence properties,convenient fabrication pathway,specific response to AA,wider linear range and high stability.7.Four dinuclear lanthanide mesocates were fabricated,and Yb-complex shows multi-channel continuous fluorescence response to Al³⁺and Cu²⁺in physiological buffer.We have also studied the excellent catalytic performance of these lanthanide mesocates in the coupling reaction between epoxides and CO₂.8.The summary,including the conclusion of experimental results,the analysis of problems and deficiencies of the fluorescent probe reported in this paper,and the prospect of fluorescent probes for cellular active species.