Structural studies of the interaction between indole derivatives and biologically important aromatic compounds. Part 19. Effect of base methylation on the ring-stacking interaction between tryptophan and guanine derivatives: a nuclear magnetic resonance investigation

Abstract

Stacking interactions betwen tryptophan methyl ester (TrpOMe) and guanine derivatives (base, nucleoside of neutral and N-7-methylated guanines) in neutral aqueous solution have been studied by 1H n.m.r. The 8-H protons of methylated guanine derivatives undergo a downfield shift in the presence of TrpOMe, while the other aromatic protons of guanine derivatives shift upfield due to the stacking interaction between the indole and guanine rings. This is interpretable in terms of ionic interactions between the electron positive 8-H and the π-electron-rich indole ring. Job plots show 1 : 1 complex formations in all guanine derivative–TrpOMe pairs. Association constants determined for the dependence of the 1H chemical shifts (guanine derivative) as a function of TrpOMe concentration show that the stackin interaction with the indole ring is strengthened by methylation of N-7 of the guanine base. The measurements of thermodynamic parameters, however, show that methylation hinders the formation of a stable stacking structure wih TrpOMe in the case of guanine nucleotide. These resuls imply that the methylated guanine nucleotide, compared with the unmethylated one, is more liable to dissociate from tryptophan with small environmental change, though both molecules easily associate with each other. A conformational difference between the unmethylated and methylated guanine derivatives in the interaction with TrpOMe is also discussed, based on the coupling constant and spin–lattice relaxation time measurements.