Exploring Aromatic Donor-Acceptor Interactions in Water

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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.