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葫芦[n]uril （CB[n], n = 5-8,10,14）宿主分子的超分子主客体复合物（其他分子内的分子），以及具有生物学和医学意义的客体。这项工作将更好地理解控制水中客体分子选择性分子识别的弱非共价力，并考虑到CB[n]作为药物传递和释放、药物逆转、疾病生物标志物识别以及对水生生态有毒的药物和代谢物的修复的潜在应用。环状CB[n]宿主由一个疏水腔组成，通过两个收缩的极性门户进入。特别是CB[7]宿主在水中与客体形成非常稳定的复合物，客体可以在每个开口定位正电荷并填充内部腔，这样所有的“高能”水分子都被置换。*具有生物学和医学意义的分子上的正电荷是普遍存在的，通常用于提供其他分子（包括受体蛋白）的选择性识别。在CB[n]宿主中，质子化的客体pKa（基态）和pKa*（激发态）值（酸强度）增加，正在进行的研究主要集中在通过同时控制宿主和酸浓度来选择性调节阳离子芳香染料客体的吸收和发射特性。其中一些客体表现为具有激发态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*