The effect of monovalent cations on the association behavior of guanosine 5′‐monophosphate, cytidine 5′‐monophosphate, and their equimolar mixture in aqueous solution

Abstract 1 H‐ and 31 P‐nmr spectroscopy have been used to investigate the self‐association of M 2 (5′‐CMP) [M = Li + , Na + , K + , Rb + , or (CH 3 ) 4 N + ; 5′‐CMP = cytidine 5′‐monophosphate], the self‐association of Li 2 (5′‐GMP) (5′‐GMP = guanosine 5′‐monophosphate), and the heteroassociation of 5′‐GMP and 5′‐CMP (1 : 1 mole ratio) in aqueous solution as a function of the nature of the monovalent cation. Proton spectral differences for the different 5′‐CMP salts exhibit a cation‐size dependence and have been ascribed to a change in the stacking geometry. An average stacking association constant of 0.63 ± 0.24 M −1 at 1°C, consistent with the weak stacking interactions of the cytosine bases, was determined for the 5′‐CMP salts. Heteroassociation of 5′‐GMP and 5′‐CMP follows the reverse of the cation order for the formation of ordered aggregates of 5′‐GMP. Heteroassociation occurs in the presence of Li + , Na + , and Rb + ions, but only self‐association occurs for the K + nucleotides. Li 2 (5′‐GMP), which does not form ordered species, self‐associates to form disordered base stacks with a stacking constant of 1.63 ± 0.11 M −1 at 1°C.