Helical molecular programming: Folding of oligopyridine-dicarboxamides into molecular single helices

Molecular strands composed of alternating 2,6-diaminopyridine and 2,6-pyrid inedicarbonyl units have been designed to self-organize into single strande d helical structures upon forming intramolecular hydrogen bonds. Pentameric strands 11, 12, and 14, heptameric strands 1 and 20, and undecameric stran d 15 have been synthesized using stepwise convergent strategies. Single hel ical conformations have been characterized in the solid state by single cry stal X-ray diffraction analysis for four of these compounds. Helices from p entameric strands 12 and 14 extend over one turn, and helices from heptamer ic 20 and undecameric 15 species extend to one and a half and two and a hal f turns, respectively. Intramolecular hydrogen bonds are responsible for th e strong bending of the strands. H-1 NMR shifts both in polar and nonpolar organic solvents indicate intramolecular overlap between the peripheral aro matic groups. Thus, helical conformations also predominate in solution. Mol ecular stochastic dynamic simulations of strand folding starting from a hig h energy extended linear conformer show a rapid (600ps at 300K) conversion into a stable helical conformation.