Stacking interactions between caffeine and methyl gallate

The self-association of caffeine and methyl gallate (a simple polyphenol) has been studied by NMR in the solvent mixture H2O-[H-2(6)]-dimethylsulfoxide (9:1, by volume) at 288 K, using the isodesmic model (also known as the indefinite noncooperative model). The chemical shift changes observed suggest that caffeine molecules in a stack are associated in a head-to-tail (antiparallel) manner. The interaction between monomeric caffeine and methyl gallate stacks has also been investigated and the results indicate that caffeine prefers to bind at the ends of methyl gallate stacks rather than intercalating into the stacks. Comparison of the association constants suggests that in a mixture df methyl gallate and caffeine, heterostacks are formed in preference to self-associated solutes, which has an obvious bearing on the bioavailability of aromatic and phenolic species.