Complex Formation of Lead(II) with Nucleotides and Their Constituents

Lead is widely distributed in the environment; it is known to mankind for thousands of years and its toxicity is nowadays (again) well recognized, though on the molecular level only partly understood. One of the reasons for this shortcoming is that the coordination chemistry of the biologically important lead(II) is complicated due to the various coordination numbers it can adopt (CN = 4 to 10) as well as by the 6s² electron lone pair which, with CN = 4, can shield one side of the Pb²⁺ coordination sphere. The chapter focuses on the properties of Pb²⁺ complexes formed with nucleotides and their constituents and derivatives. Covered are (among others) the complexes formed with hydroxy groups and sugar residues, the interactions with the various nucleobases occurring in nucleic acids, as well as complexes of phosphates. It is expeced that such interactions, next to those like with lipids and proteins, are responsible for the toxic properties of lead. To emphasize the special properties of Pb²⁺ complexes, these are compared as far as possible with the corresponding properties of the Ca²⁺, Fe²⁺, Cu²⁺, Zn²⁺, and Cd²⁺ species. It needs to be mentioned that the hard-soft rule fails with Pb²⁺. This metal ion forms complexes with ligands offering O donors of a stability comparable to that of Cu²⁺. In contrast, with aromatic N ligands, like imidazole or N7 sites of purines, complex stability is comparable to that of the corresponding Fe²⁺ complexes. The properties of Pb²⁺ towards S donor sites are difficult to generalize: On the one hand Pb²⁺ forms very stable complexes with nucleoside 5′-O-thiomonophosphates by coordinating to nearly 100% at S in the thiophosphate group; however, on the other hand, once a sulfur atom replaces one of the terminal oxygen atoms in the phosphodiester linkage, macrochelate formation of the phosphate-bound Pb²⁺ occurs with the O and not the S site. Quite generally, the phosphodiester linkage is a relatively weak binding site, but the affinity increases further to the mono-and then to the di-and triphosphate. The same holds for the corresponding nucleotides, though the Pb²⁺ affinity had to be estimated via that of the Cu²⁺ complexes for some of these ligands. Complex stability of the pyrimidine-nucleotides (due to their anti conformation) is solely determined by the coordinating tendency of the phosphate group(s); this also holds for the Pb²⁺ complex of adenosine 5′-monophosphate. For the other purinenucleotides macrochelate formation takes place by the interaction of the phosphate-coordinated Pb²⁺ with the N7/(C6)O site of, e.g., the guanine residue. The extents of the formation degrees of these chelates are summarized. Unfortunately, information about mixed ligand (ternary) or other higher order comlexes is missing, but still it is hoped that the present overview will help to understand the interaction of Pb²⁺ with nucleotides and nucleic acids, and especially that it will facilitate further research in this fascinating area.