Structure sensitivity of amino proton exchange in 2'- and 5' - guanosine monophosphate dianions

Proton NMR line broadening methods were used to determine the rates of amino proton exchange for disordered 2'- and 5' - GMP dianions in aqueous solutions containing tetramethylammonium (TMA+) cations. Replacing TMA+ with Na+ does not substantially alter the exchange rates, provided that H-bonded, Na(+)-directed tetramer structures are absent. Activation enthalpies (kcal/mol) and entropies (eu) for 2'-GMP are: delta H not equal to = 18.5 +/- 1.3, delta S not equal to = 9.6 +/- 4.2 for TMA+ salt at pH 8.10, and delta H not equal to = 14.7 +/- 2.6, delta S not equal to = -3.7 +/- 8.0 for the Na+ salt at pH 8.11. Extrapolated values of pseudo first-order rate constants at 25 degrees C are in the range of k = 1-10 sec-1. At suitable concentrations and temperatures, the Na+ salts of both 2'- and 5' - GMP formed stacked and unstacked tetramer units. Relative to the exchange kinetics observed for the disordered nucleotide, the exchange process in the tetramer units was catalyzed in half the amino protons and inhibited in the other half. The catalytic process (k > 10(3) sec-1) has been attributed to amino protons not involved in interbase H-bonding, where as the inhibited process (k < 10(-1) sec-1) was assigned to those protons which do form such bonds. The structure-catalyzed process in both the stacked and unstacked tetramers was manifested by a loss of NMR amino proton intensity due to weighted time-averaging with the resonance for bulk water. A bridging water molecule between an amino proton and a phosphate on an adjacent nucleotide in the tetramer unit may provide a mechanistic pathway for the structure-catalyzed process.