Interactions of lead(II) with nucleotides and their constituents

Abstract

The coordination chemistry between the toxic lead(II) ion and nucleotides or nucleic acids is relatively poorly developed despite the known effects of Pb 2+ on the structure and stability of nucleic acids. In this review information is summarized regarding the stability of Pb 2+ 1:1 complexes formed in aqueous solution with simple phosphate monoester or phosphonate ligands (R-PO 3 2−). The plot of log K Pb Pb(R-PO 3) (stability constants) versus p K H H(R-PO 3) (acidity constants) results in a straight line on which also the data pairs for the Pb 2+-nucleotide complexes of UMP 2–, dTMP 2–, CMP 2– and AMP 2– (=NMP 2–) fit indicating that no significant nucleobase–Pb 2+ interaction occurs in these Pb(NMP) species. This is different with the Pb(IMP) and Pb(GMP) complexes which are more stable than expected on the basis of the basicity of their phosphate group; in these instances the phosphate-coordinated Pb 2+ forms a macrochelate by interacting with N7 of the purine residue giving thus rise to intramolecular equilibria. These observations are corroborated by results obtained for the stability of Pb(nucleoside) 2+ complexes. In the monoprotonated Pb(H;NMP) + complexes of CMP 2–, GMP 2–, IMP 2– and AMP 2– the proton is always at the phosphate group and Pb 2+ mostly at the nucleobase residue. With regard to single-stranded nucleic acids it is concluded that for the affinity of Pb 2+ toward the various constituents of nucleic acids the following order holds: guanine–N7(O6)⪆cytosine–N3(O2)⪆R′OP(O) 2 −OR (phosphate-diester bridge)⪆adenine>uracil∼thymine. For the stability constants of the 1:1 complexes formed between Pb 2+ and nucleoside 5′-diphosphates or 5′-triphosphates estimates are given. Stability studies with methyl thiophosphate and uridine 5′- O-thiomonophosphate show that the substitution of one of the terminal oxygens by a sulfur atom in the phosphate group of a phosphate monoester leads to a stability enhancement of about 2.4 log units compared with the original affinity of the phosphate group toward Pb 2+. This indicates that the insertion of an artificial thiophosphate group into a nucleic acid sequence makes this sulfur-containing group the preferred binding site for Pb 2+.