Interactions of lead(II) with nucleotides and their constituents

The coordination chemistry between the toxic lead(II) ion and nucleotides o r nucleic acids is relatively poorly developed despite the known effects of Pb2+ on the structure and stability of nucleic acids. In this review infor mation is summarized regarding the stability of Pb2+ 1:1 complexes formed i n aqueous solution with simple phosphate monoester or phosphonate ligands ( R-PO32-). The plot of log K-Pb(R-PO3)(Pb) (stability constants) versus pK(H (R-PO3))(H) (acidity constants) results in a straight line on which also th e data pairs for the Pb2+-nucleotide complexes of UMP2-, dTMP(2-), CMP2= an d AMP(2-) (= NMP2-) fit indicating that no significant nucleobase-Pb2+ inte raction 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 groups in these instances the phosphate-coo rdinated Pb2+ forms a macrochelate by interacting with N7 of the purine res idue giving thus rise to intramolecular equilibria. These observations are corroborated by results obtained for the stability of Pb(nucleoside)(2+) co mplexes. In the monoprotonated Pb(H;NMP)(+) complexes of CMP2-, GMP(2-), IM P2= and AMP(2) the proton is always at the phosphate group and Pb2+ mostly at the nucleobase residue. With regard to single-stranded nucleic acids it is concluded that for the affinity of Pb2+ toward the various constituents of nucleic acids the following order holds: guanine-N7(O6) greater than or similar to cytosine-N3(O2) greater than or similar to R'OP(O)(2)=OR (phosph ate-diester bridge) greater than or similar to adenine > uracil similar to 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-thiomonophosph ate show that the substitution of one of the terminal oxygens by a sulfur a tom in the phosphate group of a phosphate monoester leads to a stability en hancement of about 2.4 log units compared with the original affinity of the phosphate group toward Pb2+. This indicates that the insertion of an artif icial thiophosphate group into a nucleic acid sequence makes this sulfur-co ntaining group the preferred binding site for Pb2+. (C) 2001 Elsevier Scien ce B.V. All rights reserved.