Double versus single helical structures of oligopyridine-dicarboxamide strands. Part 2: The role of side chains

Abstract

A series of heptameric oligoamides comprising 4-alkoxy-substituted 2,6-diaminopyridine and 2,6-pyridine-dicarbonyl units have been synthesized using convergent methods. The hybridization of these compounds into double helical dimers was studied in solution by 1H NMR spectroscopy in CDCl 3 or DMSO- d 6 at various concentrations, and in the solid state using X-ray crystallographic analysis. Both solid state and solution data suggest that these compounds follow identical hybridization schemes. In CDCl 3, the oligomers possess dimerization constants considerably (up to 2000-fold) higher than related compounds having no alkoxy substituents on their 2,6-diaminopyridine units. The origin of this effect can be in part interpreted as a result of interactions between the 4-alkoxy side chains when they are present on all pyridine rings. For example, 4-benzyloxy-substituted oligomer 2 has a higher dimerization constant than 4-decyloxy and 4-methoxy-substituted analogues 1 and 3. The crystal structure of 2 reveals multiple aromatic–aromatic interactions between the benzyl side chains, both face-to-face and edge-to-face at various angles surrounding the duplex. In the solid state, these double helices are stacked on top of each other to form long channels filled with water molecules. The 4-methoxy and 4-decyloxy-substituted analogues 1 and 3 have similar dimerization constants, showing that interactions between side chains are not significant between purely aliphatic residues. Consequently, the high stability of the double helices formed by 1 and 3 compared to related compounds having alkoxy substituents on their 2,6-pyridine-dicarbonyl units only does not find its origin in interactions between side chains but in the direct effect of the alkoxy substituents upon main chain aryl–aryl interactions.