Hybridization of Long Pyridine-Dicarboxamide Oligomers into Multi-Turn Double Helices: Slow Strand Association and Dissociation, Solvent Dependence, and Solid State Structures

Oligoamides of 2,6-diaminopyridine and 2,6-pyridinedicarboxylic acid comprised of 5, 7, 9, 11, or 13 units and bearing 4-isobutoxychains on all pyridine rings and tert-butyl-carbamate terminal groups have been synthesized stepwise, along with an 11 mer having benzyl-carbamate terminal groups. The crystal structure of all five Boc-terminated compounds has been obtained and shows a highly regular and conserved double helical hybridization motif of up to 3 complete turns for the 13 mer. Four pyridine units span one helical turn and define a helix pitch of at 7 angstrom. Solution studies in CDCl3 demonstrated that the Boc-terminated oligomers strongly hybridize in this solvent, and that K-dim values increase with oligomer length. The K-dim, values are 31000 and 7 x 10(5) Lmol(-1) for the 7 mer and the 9 mer, respectively, and are too high to be measured by NMR for the 11 mer and the 13 mer. Hybridization and dissociation kinetics at 2 mm proceed at decreasing rates upon increasing oligomer length. The rate was faster than minutes for the 7 mer, of the order of hours for the 9 titer, and days for the 11 mer and 13 mer. The same trend was observed in [D-5]pyridine but with considerably lower K-dim values and faster kinetics. The benzylcarbamate 11 mer was also found to hybridize into a double helix but with reduced K-dim, values and faster kinetics compared to its Boc-terminated analogue. Combined with previous studies, the results presented here frame a global understanding of the hybridization of these pyridinecarboxamide oligomers and provide useful guidelines for the design of other artificial double helices.