Effect of the N6-methyl group of the adenine ring on the stacking interaction

In an effort to determine the effects of N-6-methylation of the adenine ring on stacking, the molecular aggregation of 9,9'-(alpha,omega-alkanediyl)bis[6-(dimethylamino)purine] (1) and of 9,9'-(alpha,omega-alkanediyl)bis[6-(methylamino)purine] (2) were compared with that of 9,9'-(alpha,omega-alkanediy])bis[adenine] (3) by NMR spectroscopy. The obtained concentration effects indicate that N-6-methylation resulted in an increase in the population of intermolecular aggregates in the buffer solution at pD 7.0, and had an additive effect on the aggregation. It can he interpreted as a hydrophobic effect of the N-6-methyl groups. The aggregation of 1 and 2 depended on the length of the polymethylene chains in a similar manner as that of 3, when the measurements were made on the solution of low concentrations. This suggests that the aggregates of 1, 2, and 3 were similar to each other through stacking between two adenine rings. Furthermore, the chemical shifts of the N-6-methyl groups were slightly influenced by the length of the polymethylene chains and the changes of temperature. The N-6-methyl group may be located outside the stacking. On the basis of these data, it may be concluded that the N-6-methylation enhanced the stacking, but had little influence on the conformation of the stacking.