Development Of Biological Fluorescence Sensor For Sugar And Amino Acid With Boronic Acid

Saccharides are nature's conveyors of energy and therefore essential for cell survival. The breakdown of glucose transport has been correlated with certain diseases: renal glycosuria, cystic fibrosis, diabetes, and human cancer, seriously affected our normal life. One of the major challenges in the management of the diseases like diabetes is the monitoring of glucose concentrations. To develop a continuous monitoring system, it would be ideal to use an implantable device that is in constant contact with the biological fluid to give a continuous reading of glucose concentration. Chemical sensors do offer the advantage of higher stability and relatively easy manufacturing. Such a concept has already been put into test by companies such as sensors for medicine and Science. we are interested in the development of fluorescent sensor system for saccharides based on boronic acid - diol.Firstly, three monoboronic acid compounds comprise naphthalene withdifferent substituents were synthesized and prepared to be fluorescent sensors in 80% methanol/water buffered at PH 6.86, respectively. We tested the recognition between three sensory systems and D-glucose, studied the influence of the electron transfer to sensory sensitivity. From these research we got a conclusion that the electron-releasing substituents made the electronic cloud density of fluorophore increased and quenched the fluorescence intensity of fluorophore. When the boronic acid in receptor form a stable five-membered cyclic boronate esters with the saccharides, the direction of electron transfer was changed and result in the electronic cloud density of fluorophore decreased. Therefore, the fluorescence intensity was increased obviously. The electron-releasing substituents made sensity of the sensory system increased. On the contrary, electron-attracting substituents like sulfonic result in the decrease of the sensitivity of the sensors. According to these result, we can modulate the sensitivity of fluorescence sensors through import different substituents to change electron transfer, and get more sensitive sensor. This work can help us design and synthesize more sensitive sensory molecule, understand and prove the process of electron transfer in this kind of sensor.Furthermore, we studied the function of a small water soluble organic molecular fluorescence sensor. We found the D-fructose added into the sensory system result in the different fluorescence changing with pH titration compared with without D-fructose appeared. From these experiment we select pH=6.86 as the best condition for detect saccharide. We also studied the selectivity to saccharides of two different sensory system.Secondly, the function between boronic and sugar was imported into vesicular system, a vesicular fluorescent sensor based on phenylboronic acid-glucose recognition in aqueous DBBTAB vesicles containing ARS was prepared. The vesicular sensor enhanced the sensitivity for glucose about 7-8 fold compared with the corresponding aqueous solution, which is ascribed in enhancing the local concentrations of glucose on the surface of covesicles. This enhance of local concentrations made the sensitivity of fluorescence sensors increased, and the absolute fluorescent intensity enhanced obviously. We also designed and synthesized monoboronic acid compounds with different length tail-chain, and naphthalene imported as fluorophore. The monoboronic acid compounds were made to aggregate solution by dry film ultrasonic. We studied the different sensitivity of mononboronic acid sensor caused by the difference of aggregate figure, and found compound with long tail chain could form uniform sphere have more sensitivity. These research will help us to design more sensitive fluorescence sensors for saccharides. Based on these research, aggregation also can be employed as carrier for sensors to develop a new continuous glucose monitoring systems, and as an implantable device that is in constant contact with the biological fluid to give a continuous reading of glucose concentration.Finally, we attempt to use monoboronic acid sensor to detectα-amino acids. FT-IR spectrum were used to study the binding between boronic acid and glycin, and the model was proposed. We also studied the selectivity of the boronic acid sensor for four different compound withα-amino acid structure. These research can help us to design high sensitive fluorescent sensor based on boronic acid-α-amino acid recognition, and employed to detect or cure disease caused by disorder of amino acid metabolism. At the same time, a new field was opened for boronic acid fluorescent sensors.