Development Of Triazolyl Fluorescence Glyco-Chemosensors And Bioactive Glycolipid Derivatives By Click Chemistry

Carbohydrate is the one of most important cellular signaling components in organisms, which is involved in numerous biological and pathological processes. Sugar-based efficient development of functional glyco-compounds is currently of much interest. This thesis describes the construction of fluorescence glyco-chemosensors for ion sensing both in solution and with live cells and of bioactive glycolipid derivatives as potential anticancer agents based on the rapid and efficient click chemistry; the thesis is divided into the following two parts:Part Ⅰ:Fluorescent chemosensors, regarded as high selectivity, sensitivity and rapidly responsive molecular devices, are widely applied in detection of environmental pollutants including heavy metal ions. This part first reviews recent progresses in the development and application of fluorescence sensors based on sugar skeletons, and then proposes the design rationale of the sensors developed in this study. A series of fluorescence glyco-chemosensors were synthesized via a click reaction (Cu(Ⅰ)-catalyzed azide-alkyne1,3-dipolar cycloaddition reaction). Triazolyl coumarins (the receptor-fluorophore regime) were modified on different substitution sites (C2,3; C3,4and C4,6) of a sugar skeleton. Interestingly, reverse fluorescence responses of these probes to a same heavy metal, silver(Ⅰ), due to the different substitution patterns, were found. When the C3,4-substituted sensor bound to silver, the fluorescence of which was quenched due to heavy metal effects. However, the fluorescence of C2,3-substitued sensor enhanced probably because of the chelating enhance fluorescence (CHEF) mechanism. The C2,3-substitued sensor was determined to bind with silver ion forming a2:1complex, and a computational study proposed the optimal binding mode. The sensor was found to be able to image silver ions internalized by a cancer cell line, and was not toxic to the cell line used.Additionally, two classes of anion sensors based on bis-triazolyl scaffolds were designed. The first class of which embodies a bis-triazolyl glycosyl amino acid skeleton, which is construced based on a PET (photoinduced electron transfer)"receptor-spacer-fluorophore" system. The bis-triazolyl amino acid motif serves as the ion receptor and a glucoside as spacer. A dimethyl naphthalene fluorophore was used to modify the C1site of the sugar skeleton. The sensor possessed good selectivity towards cooper ion among other cations used. The fluorescence of the sensor quenched after binding with copper ion, whereas the coordination system could be further broken after addition of cyanide ion leading to recovery of the fluorescence of the sensor. The second class of sensors was based on the introduction of bis-triazolyl motifs onto an indoleaminyl core, which reversibly responded to copper ion and fluoride ion. The coordination-dissociation enabled both the fluorimetric and colorimetric change of the sensor. These two types of fluorescent glyco-sensors might provide insight into the further development of green chemosensors for detection of ions in the environment.Part Ⅱ:Glycolipids are important component of the cell membrane, as a class of natural amphiphilic compound. They possess a range of bioactivities such as anti-tumor, anti-mircobial and antiviral effects. In this part, a series of glycolipid derivatives were prepared via click reaction. The cytotoxicity of these compound towards multiple myeloma cells were tested. The mixtures of different epimeric glycolipids with a same chain length showed better suppressive effect against the growth of cancer cells than either single epimer, probably suggesting a synergistic effect.