Selective Molecular Recognition of Biological and Medicinal Guests in Water by Cucurbit[n]uril Hosts

我提出的研究计划包括继续研究瓜环(CB[n]，n=5-8，10，14)与具有生物学和药用价值的客体的超分子主客体复合体(其他分子内的分子)。这项工作将更好地了解支配水中客体分子选择性分子识别的弱非共价力，并考虑CB[n]作为宿主在药物输送和释放、药物逆转、疾病生物标志物识别以及修复对水生态有毒性的药物和代谢物方面的潜在应用。环状CB[n]宿主由一个疏水空腔组成，该空腔通过两个收缩的极口进入。CB[7]主客体在水中与客体形成非常稳定的络合物，在每个开口处都能放置正电荷并填充内腔，从而使所有“高能”水分子被置换。*具有生物和医药价值的分子上的正电荷无处不在，通常用于提供包括受体蛋白在内的其他分子的选择性识别。客体的PKA(基态)和PKA*(激发态)值(酸强度)在CB[n]主客体中质子化的客体中增加，正在进行的研究集中于通过同时控制主体酸和酸的浓度来选择性地调节阳离子芳香染料客体的吸收和发射性能。这些嘉宾中的一些人表现得像一个有着激动态PKA的超级光酸*。

My proposed research program involves continuing investigations of supramolecular host-guest complexes (molecules inside other molecules) of the cucurbit[n]uril (CB[n], n = 5-8,10,14) host molecules with guests of biological and medicinal interest. The work will provide a better understanding of the weak non-covalent forces governing the selective molecular recognition of guest molecules in water, with a consideration of potential applications of CB[n] as hosts for drug delivery and release, drug reversal, the recognition of disease biomarkers, and remediation of drugs and metabolites which are toxic to the aquatic ecology. The cyclic CB[n] hosts are comprised of a hydrophobic cavity accessed through two constrictive polar portals. The CB[7] host in particular forms extraordinary stable complexes in water with guests which can position positive charges at each opening and fill the internal cavity such that all of the `high energy' water molecules are displaced.*Positive charges on molecules of biological and medicinal interest are ubiquitous and often serve to provide selective recognition by other molecules including receptor proteins.  The guest pKa (ground state) and pKa* (excited state) values (acid strength) increase for protonated guests within CB[n] hosts, and ongoing studies are focussed on selective tuning of absorption and emission properties of cationic aromatic dye guests by simultaneous controls of host and acid concentrations. Some of these guests behave as a "super" photoacid with an excited state pKa*