七元瓜环对阿糖胞苷稳定性的影响  

Encapsulation of Cytarabine in Cucurbit[7]uril and Its Effects on Stability of the Drug

作　　者：黄英[1,2] 宋桂先 唐青[1] 王娟 陶朱[1] 薛赛凤 张建新[3] 

机构地区：[1]贵州大学西南药用生物资源教育部工程研究中心 [2]贵州省大环化学与超分子化学重点实验室 [3]贵州省中国科学院天然产物化学重点实验室,贵阳550025

出　　处：《高等学校化学学报》2014年第6期1224-1228,共5页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21202026);国家重大科学仪器设备开发专项项目(批准号:2011YQ120035);贵州省科技厅国际合作项目(批准号:黔科合外G字[2012]7003号);教育部春晖计划(批准号:Z2011034);贵州省英才培育项目(批准号:2012154)资助~~

摘　　要：研究了七元瓜环(Q[7])与抗癌药物阿糖胞苷(Ara-C)的不同质子化存在形式之间的超分子相互作用,探讨了超分子包合作用对药物电离平衡常数及药物稳定性的影响.结果表明,Q[7]使得Ara-C的pK a降低了约0.3个单位,Q[7]与Ara-C的2种存在形式(Ara-C+及Ara-C)均可形成1∶1的主客体包结配合物,Ara-C以其嘧啶环进入Q[7]空腔,而核糖环位于瓜环端口发生相互作用;Q[7]与Ara-C作用后对药物起到保护性载体的作用,从而提高了药物的稳定性.The interaction of cucurbit[7]uril（Q[7]） with cytarabine（Ara-C） in different proton forms were studied by ultraviolet absorption spectroscopy and 1 H NMR technique in details. Complexation by Q[7] has also been investigated to cause pKa shifts and stability of drug. The results showed that Q[7] encapsulated the Ara-C and shifted its pKa value by down to 0. 3 units. Ara-C in different proton forms with Q[7] informed 1 ： 1 inclusion complexes, and the formation constants were （9. 48±0. 29）×103 L/ mol and （6. 30±0. 04）×103 L/ mol for the Q[7]-Ara-C＋ system and Q[7]-Ara-C system, respectively. Moreover, The formation of inclu-sion complexes between Q[7] with Ara-C was confirmed by 1 H NMR, the pyrimidine moiety of Ara-C were entrapped in the cavity of the host and the D-ribose ring was likely located at the outside cucurbituril cavity. In addition, stability studies were investigated by initial uniform rate experiment. The results revealed that complexation of Ara-C with Q[7] offers a major improvement in drug stability.

关 键 词：阿糖胞苷 七元瓜环 主客体配合物 稳定性 

分 类 号：O625[理学—有机化学]