The stability constants of the 1:1 complexes formed between Pb2+ and the nucleosides (Ns), adenosine and guanosine, as well as between the nucleotides (NMP2-), AMP(2-), IMP2-, and GMP(2-), were determined by potentiometric pH titrations in aqueous solution (25 degreesC; I = 0.1 M, NaNO3). Based on previously established log K-Pb(R-PO3)(Pb) versus pK(H(R-PO3))(H) straight-line plots (R-PO32- = simple phosphate monoester or phosphonate ligands where R is a noninteracting site), it is shown that the Pb(IMP) and Pb(GMP) complexes are more stable than is expected on the basis of the basicity of the phosphate group of IMP2- and GMP(2-). This means that macrochelates are formed, where the phosphate-coordinated Pb2+ also interacts with N7 of the nucleobase residue. In contrast, the stability of the Pb(AMP) complex is governed by the basicity of the AMP(2-) phosphate group. These results agree with the observations made for the Pb(Ns)(2+) complexes: Pb(adenosine)(2+) is very unstable in contrast to Pb(guanosine)(2+), the stability of which is very similar to the one of Pb(cytidine)(2+) studied previously. The stability constants of the Pb(Ns)(2+) complexes also allowed an evaluation of the structure in solution of the monoprotonated Pb(H;NMP)(+) complexes, the stabilities of which were also determined. We were able to show that the proton is located at the phosphate group and Pb2+ at the N7/(C6)O site of H(GMP)(-); in the case of H(AMP)(-) Pb2+ is probably about equally distributed between the adenine residue and the monoprotonated phosphate group. On the basis of the stability constants of these complexes and their structures in solution, it is possible to provide a series which reflects the decreasing affinity for Pb2+ of nucleobase residues in single-stranded nucleic acids: guanine similar or equal to cytosine > (hypoxanthine) > adenine > uracil similar or equal to thymine. The Pb2+ affinity of the phosphodiester linkage, -PO3--, is similar to the one of the adenine residue, but is expected to be more significant due to its larger abundance. The relevance of these results for lead-activated ribozymes is briefly discussed.