Exploring Aromatic Donor-Acceptor Interactions in Water

描述（由申请人提供）：但是我们能让它在水中起作用吗？化学家们现在正在探索超越共价键的分子结构设计。从大自然中获得灵感，折叠或自组装的分子正在从第一性原理设计出来。创造在水中折叠和组装的分子系统目前是一个主要挑战，尽管一旦创造出来，这样的系统将能够以前所未有的方式与生物结构和分子相互作用。我们早期的折叠体研究证实，芳香的供体-受体相互作用可以在水中作为一种非常强的稳定相互作用，产生折叠、堆叠的结构（Lokey和Iverson， Nature, 1995,375, 303-5.），称为折叠体。最近，我们有了一个令人兴奋的发现，富电子芳香单元链会特异性地识别水溶液中缺电子芳香单元的互补链，从而形成稳定的双链（Gabriel和Iverson， J. of Am）。化学。Soc。[j] .农业工程学报，2002,24(4):15174-15175。本提议的前两个具体目标描述了在水中利用富含电子的1,5-二氧萘（DAN）和缺乏电子的1,4,5,8-萘四羧基二亚胺（NDI）芳香基团的稳定和识别能力的新型折叠和组装分子系统的创建和表征。最后三个具体目标采取了下一个关键步骤，探索与生物分子的不同相互作用策略。

DESCRIPTION (provided by applicant): But can we make it work in water? Chemists are now exploring the design of molecular architectures that extend beyond covalent bonding. Taking inspiration from Nature, molecules that fold or self-assemble are being designed from first principles. Creating molecular systems that fold and assemble in water is currently a major challenge, although once created, such systems will be able to interact with biological structures and molecules in unprecedented ways. Our early foldamer studies verified that aromatic donor-acceptor interactions can be used as a remarkably strong stabilizing interaction in water, producing folded, stacked structures (Lokey and Iverson, Nature, 1995, 375, 303-5.) called aedamers. More recently, we have made the exciting discovery that chains of electron rich aromatic units will specifically recognize a complementary chain of electron deficient aromatic units in aqueous solution to form a stable duplex (Gabriel and Iverson, J. of the Am. Chem. Soc., 2002, 124, 15174-15175.). The first two specific aims of this proposal describe the creation and characterization of novel folding and assembling molecular systems that in water exploit the stabilizing and recognition abilities of the electron rich 1,5-dialkoxynaphthalene (DAN) and the electron deficient 1,4,5,8-naphthalene tetracarboxylic diimide (NDI) aromatic moieties. The last three specific aims take the next critical step and probe different interaction strategies with biological molecules. Spanning the range from basic science to practical application, we will 1) investigate an entirely new aedamer folding topology analogous to nucleic acid hairpins, 2) use the recognition ability of the DAN-NDI interaction to produce large molecular assemblies from smaller folding pieces, 3) investigate the utility of DAN-NDI interactions as a stabilizing force in a protein hydrophobic core, 4) create next-generation threading DNA poly-intercalators based on structures derived from NMR analysis of our NDI-based oligomers, and 5) use phage display to isolate a peptide with high affinity and specificity for binding a chain of NDI residues for potential use in biomedical and biotechnological applications.