Selenium Organic Fluorescent Molecular Probe Design, Synthesis And Biological Applications

Mercury is an environmentally and physiologically toxic heavy metal element whose toxicity, even at very low concentrations, has been recognized. Long-term exposure to this metal leads to permanent deterioration of the central nervous and endocrine system in the human body, since mercury easily passes through biological membranes, such as skin, respiratory, and gastrointestinal tissues. Therefore, mercury is widely studied in terms of its bioavailability, bioaccumulation, and cellular toxicity.Numerous free radicals are generated in the course of biology metabolism. Superoxide anion radicals (O2-·), hydroxyl radicals (HO·), ROO·and NO·are some typical ones. They have important relation with aging and many diseases. It is reported that appropriate level of reactive oxygen species (ROS) could help to build biological immune system. Once the internal redox status was destructed by some factors, unregulated production of ROS results in oxidative stress, and subsequent buildup of free radical damage to protein, lipids, and nucleic acids. Recent studies demonstrated that ROS can cause many diseases such as heart disease, cancer, malignancy and so on. Thus, studing on chemsensors for detecting internal redox cycle has an important physiological and pathological significance.Besides, various bio-active molecules are indispensable component of organism. They also take part in various life activities. Thus, studies on bio-active molecules including nucleic acid, protein, peptide, and other bio-active ingredients play an important role in life science. Recent years, more and more studies focus on detecting bio-active molecules. Among these methods, using fluorescent probes has many advantages such as high sensitivity, high selectivity and easy to operate. Besides, what is more attractive is that fluorescent probes can penetrate into cells without any damage, and combine with bio-active molecules to form strongly fluorescent substance. With the help of confocal microscopic imaging, visualizing and real-time detecting of bio-active molecules can be achieved. Recent years, imaging of living cells has made great progress, and fluorescent probe has become the most important tool because of its advantages.Based on the changes in spectrum characters of the fluorescent probes reacting with reactive oxygen species or bio-active molecules, we have achieved the detection of these ingredients. The designed fluorescent probes were also applied to confocal imaging of several kinds of cells. We carried out two aspects of investigation:First, inspired by the antitoxic function of selenium for heavy metal ions, we designed an organoselenium fluorescent probe (FSe-1) for mercury. The reaction of FSe-1 and Hg2+ is an irreversible deselenation mechanism based on the selenophilic character of mercury. Just for the selenium atom active sites and the strong affinity between Se and Hg, FSe-1 exhibits an ultrahigh selectivity and sensitivity for Hg2+ detecting. The experimental results proved that the selectivity of FSe-1 for Hg2+ ions over other relevant metal ions and bioanalytes, as well as an enhancement in sensitivity up to 1.0 nM, which is lower than the current EPA standard for drinking water. Furthermore, the new probe is successfully applied to the imaging of mercury ions in RAW 264.7 cells with high sensitivity and selectivity.Second, oxygen which is the key substance for aerobic metabolism provides the necessary energy of life activities. As the energy-releasing reduction of oxygen to water generates partially reduced reactive oxygen species (ROS) intermediates that can exert widely divergent physiological and pathological effects. Thus, studing on internal redox cycle has an important physiological and pathological significance. Recently, based on the medicinal value of selenium-containing compounds, amount of organoselenium drugs were synthesized. Based on the well antioxidate effect of selenium-countaining antihypertensive agent HoMePASe, we designed and synthesized two novel near-IR organoselenium fluorescent probes for reversible detecting internal redox cycles. Furthermore, we will image redox cycles in living cells using confocal laser-scanning microscope.