We report a solid-state multinuclear (Na-23, N-15, C-13, and P-31) NMR study on the relative affinity of monovalent cations for a stacking G-quartet structure formed by guanosine 5'-monophosphate (5'-GMP) self-association at pH 8. Two major types of cations are bound to the 5'-GMP structure: one at the surface and the other within the channel cavity between two G-quartets. The channel cation is coordinated to eight carbonyl oxygen atoms from the guanine bases, whereas the surface cation is close to the phosphate group and likely to be only partially hydrated. On the basis of solid-state 23Na NMR results from a series of ion titration experiments, we have obtained quantitative thermodynamic parameters concerning the relative cation binding affinity for each of the two major binding sites. For the channel cavity site, the values of the free energy difference (DeltaGdegrees at 25 degreesC) for ion competition between M+ and Na+ ions are K+ (-1.9 kcal mol(-1)), NH4+ (-1.8 kcal mol(-1)), Rb+ (-0.3 kcal mol(-1)), and Cs+ (1.8 kcal mol(-1)). For the surface site, the values DeltaGdegrees are K+ (2.5 kcal mol(-1)), NH4+ (-1.3 kcal mol(-1)), Rb+ (1.1 kcal mol(-1)), and Cs+ (0.9 kcal mol(-1)). Solid-state NMR data suggest that the affinity of monovalent cations for the 5'-GMP structure follows the order NH4+ > Na+ > Cs+ > Rb+ > K+ at the surface site and K+ > NH4+ > Rb+ > Na+ > Cs+ > Li+ at the channel cavity site. We have found that the cation-induced stability of a 5'-GMP structure is determined only by the affinity of monovalent cations for the channel site and that the binding of monovalent cations to phosphate groups plays no role in 5'-GMP self-ordered structure. We have demonstrated that solid-state Na-23 and N-15 NMR can be used simultaneously to provide mutually complementary information about competitive binding between Na+ and NH4+ ions.