含氟香豆素透明质酸衍生物的合成及其荧光性能

Synthesis and Fluorescence Properties of Hyaluronic Acid Derivatives Containing Fluorinated Coumarin

以间氨基苯酚与三氟乙酰乙酸乙酯反应生成4-三氟甲基-7-氨基香豆素,其与氯乙酰氯反应生成4-三氟甲基-7-氯乙酰氨基香豆素。该化合物与透明质酸钠反应得到了含氟香豆素透明质酸衍生物。利用荧光光谱等分析技术研究了浓度、pH值和温度变化对该透明质酸衍生物荧光强度的影响,同时研究了金属离子对其荧光强度的影响。结果表明,一定浓度范围内,荧光强度随透明质酸衍生物浓度增大而逐渐增强;在pH值为3.86～8.85范围内,其荧光强度较为稳定;在10～80℃范围内,其荧光强度随温度的升高而逐渐减弱;在常见干扰离子存在下,Fe3+对其荧光强度有较为显著的影响,其荧光强度显著降低。这为探索透明质酸在生命机体内的药物载体机理及其靶向作用提供良好的实验基础。

4-Trifluoromethyl-7-amino coumarin obtained from m-aminophenol and ethyl trifluoroacetoacetate, further reacted with chloroacetic chloride to generate 4-trifluoromethyl-7-chloro-acetylamino coumarin. Then, the product was treated with sodium hyaluronate to give hyaluronic acid derivatives containing fluorinated coumarin. The influences of concentration, pH and temperature on fluorescence intensity of hyaluronic acid derivatives were studied. The influence of different metal ions on fluorescence intensity of hyaluronic acid derivatives was also investigated. The results show that the fluorescence intensity of hyaluronic acid derivatives is enhanced with increased concentration, kept stable when the pH ranges from 3.86 to 8.85, and decreased when temperature increased from 10 ℃ to 80 ℃. In addition, Fe^3＋ leads to significantly reduced fluorescence intensity of hyaluronic acid derivatives in the presence of other interfering metal ions. These provide good experimental basis to explore the mechanism as well as the targeting behavior of hyaluronic acid as drug carrier.