Understanding the toxicology of lead at a molecular level: Pb(II) 6s lone pair can be bisdirected in proteins

Pb complexes can attain several different topologies, depending of the shape of the Pb 6s6p lone pair. In this paper, we study structures with a bisdirected Pb lone pair with quantum mechanics (DFT) and QM/MM calculations. We study small symmetric Pb models to see what factors are needed to get a bisdirected lone pair. Two important mechanisms have been found: First, the repulsion of the lone pair of Pb with other lone pairs in the equatorial plan leads to a bisdirected structure. Second, a bisdirected lone pair can also arise thanks to interactions with double bonds, lone pairs, or hydrogen atoms (resembling hydrogen bond). Moreover, we have analysed Pb sites in proteins and RNA (both for frozen and relaxed structure, and with sites saturated with water molecules) to see if a bisdirected lone pair can exist in an asymmetrical environment. Bisdirected lone pairs were encountered in several of them.