Swellable Templated Copolymers

描述(申请人提供)：我们已经制备了一种可膨胀的模板共聚物，它在咖啡因存在的情况下选择性地识别茶碱，咖啡因是一种与茶碱不同的化合物，只有一个甲基。该共聚物包括10~20摩尔-%的识别单体和5-摩尔-%的交联剂。其余为N-异丙基丙烯酰胺或N-丙基丙烯酰胺。这种聚合物经历热相变，在热相变温度以上从溶液中出来。分子识别发生在热相变之上。我们已经证明茶碱在室温和中性pH下对0.1微摩尔以下的茶碱有反应。这些共聚物是稳定的，易于大量制备。它们为设计生物医学应用的传感器和执行器提供了新的可能性。它们可用于药物或内源性化合物的连续传感。它们可以用作药物输送系统中的执行器。它们可能被用于化学触发的捕获化合物的输送。这个应用程序有两个特定的目标。第一个具体目标是合成一种选择性识别谷氨酰胺的共聚物，并将这种材料整合到能够在线监测发酵液中谷氨酰胺的传感器中。提出了两种传感方案。一种是测量嵌入在水凝胶中的共聚微球组成的膜的浊度变化。浊度的变化是因为共聚物的膨胀和收缩改变了折射率。浑浊度可以使用为光通信开发的组件通过光纤远程测量。第二种方法是在共聚物中加入给体和受体荧光团，使共聚物的溶胀和收缩改变荧光共振能量转移的程度，从而改变供体和受体荧光的比例。二是论证了在生理条件下化学触发传递捕获的靶分子的可行性。触发分子将是茶碱。在不同的释放条件下，荧光靶分子的释放速率将作为时间的函数进行监测。

DESCRIPTION (provided by applicant): We have prepared a swellable templated copolymer that selectively recognizes theophylline in the presence of caffeine, a compound that differs from theophylline by a single methyl group. The copolymer includes 10 to 20 mole-% recognition monomer and 5 mole-% crosslinker. The rest is N-isopropylacrylamide or n-propylacrylamide. This polymer undergoes a thermal phase transition, coming out of solution above the thermal phase transition temperature. Molecular recognition occurs above the thermal phase transition. We have demonstrated response to theophylline below 0.1 micromolar at room temperature and neutral pH. These copolymers are stable and easily prepared in large quantities. They offer new possibilites for designing sensors and actuators for biomedical applications. They can be used for continuous sensing of drugs or endogenous compounds. They can be employed as actuators in drug delivery systems. They can potentially be used for chemically triggered delivery of trapped compounds. This application has two specific aims. The first specific aim is to synthesize a copolymer that selectively recognizes glutamine and to incorporate this material into a sensor that is capable of in situ monitoring of glutamine in fermentation broths. Two sensing schemes are proposed. One involves measuring changes in the turbidity of membranes consisting of copolymer microspheres embedded in a hydrogel. Turbidity changes because swelling and shrinking changes copolymer refractive index. The turbidity can be measured remotely through optical fibers using components developed for optical telecommunications. The second involves incorporating donor and acceptor fluorophores into the copolymer at levels such that swelling and shrinking change the extent of fluorescence resonance energy transfer, leading to a change in the ratio of donor to acceptor fluorescence. The second is to demonstrate the feasibility of chemically triggered delivery of trapped target molecules under physiological conditions. The trigger molecule will be theophylline. The rate of release of fluorescent target molecules will be monitored as a function of time for different release conditions.