LAUSR

Potassium and sodium are generally considered inert ‘spectator’ ions for organic reactions. Here, we report rate constants for the acid-promoted hydrolysis of the seven dipeptides of glycine (G) and alanine (A) and an unexpected pattern in how these rates differ in the presence of K⁺ and Na⁺. The linear dipeptides hydrolyze 12–18% percent slower in the presence of KCl versus an equal concentration of NaCl, while the cyclic dipeptides hydrolyze 5–13% faster in the presence of KCl (all P-values < 0.025). We believe this is the first report of a general organic reaction—here, amide hydrolysis—for which some substrates react faster in the presence of K⁺ and others in Na⁺. The results offer a potential reason for life’s mysterious universal selection of intracellular potassium over sodium.