The kinetico-mechanistic study of the substitution reactions of the aquo ligands in cis-[Ru(bpy)(2)(H2O)(2)](2+) by different nucleotides and nucleosides has been conducted at pH close to the physiological value. The concentration dependence and thermal and pressure activation parameters have been measured to ascertain the activation via which reactions take place. Substitution processes are found associatively activated for nitrogen-bonded nucleosides or nucleotides, with outer-sphere hydrogen-bonded aggregates being determinant. For reactions leading to oxygen-bonded nucleotides, the process is clearly dissociatively activated. A selectively induced lability of the inert {Ru-II(bpy)(2)} core is observed on the formation of nitrogen(amide)-bonded complexes at relatively low pH values, which might be relevant for the effective intercalation of designed, ruthenium(II)-bonded, aromatic rings.