The kinetics of substitution, by thiourea, of ethylenediamine (en) or N,N'-dimethylethylenediamine (Me(2)en) coordinated to palladium(Ir) in the complexes [Pd(4,4'-R(2)bpy)(en)](PF6)(2) (bpy = 2,2'-bipyridine; R = H or Me), [Pd(en)(2)](PF6)(2) and [Pd(Me(2)en)(2)](PF6)(2) have been studied at 25 degreesC, pH 7 and various ionic strength values, in the presence of calf thymus DNA. The rate of the reaction in water depends on ionic strength, pH, and nucleophile concentration; at fixed pH and ionic strength the k(obsd) values are correlated to the square of the thiourea concentration. This rate law is not altered by the presence of DNA, but the rate of reaction is influenced, depending on the nature of ancillary ligand, L-L, bound to palladium. DNA inhibits the substitution process when L-L is bpy or 4,4'-Me(2)bpy and catalyzes the same reaction when L-L is en or Me(2)en. These opposite kinetic effects can be related to the noncovalent interactions of the various complexes with the DNA double helix. Inhibition of the reactivity of the complexes [Pd(4,4'-R(2)bpy)(en)](2+) is due to protection of the reaction center from nucleophile attack by DNA. Acceleration of the reaction when L-L is zn or Me(2)en is related to the dependence of the rate of reaction on pH. If, due to the higher activity of water under the electric field of phosphate groups, hydronium ion concentration on DNA surface is higher than in the bulk solution, the enzyme-like dependence of the rate of reaction on [DNA] is due to progressive accumulation of the complexes around the double helix. Regardless of the complexes' nature, the rate constant values obtained in DNA at pH 7 correspond to values determined in water at pH 5. This pH value on the DNA surface, lower by about two units with respect to the bulk solution, is in good agreement with theoretical predictions. Acceleration of ethylenediamine substitution has been observed for all of the complexes studied in the presence of sodium polyvinylsulfonate.