Open questions on toxic heavy metals Cd, Hg and Pb binding small components of DNA and nucleobases. Are there any predictable trends?

In this perspective article, we provide a bibliographic compilation of experimental and theoretical work on Cd, Hg, and Pb, and analyze in detail the bonding of M 2+ and CH 3 M + (M = Zn, Cd, Hg, Pb) with urea and thiourea as suitable models for larger biochemical bases. Through the use of DFT calculations, we have found that although in principle binding energies decrease according to ionic size (Zn 2+ > Cd 2+ > Pb 2+ ), Hg 2+ largely breaks the trend. Through the use of EDA (Energy Decomposition Analysis) it is possible to explain this behavior, which is essentially due to the strong contribution of polarization to the binding. This conclusion is ratified by the NEDA (Natural Energy Decomposition Analysis) formalism, showing that the charge transfer term is very large in all cases, but particularly in the case of the mercury-thiourea system. The general trends observed for the interactions with CH 3 M + monocations show however CH 3 Hg + binding energies systematically smaller than the CH 3 Zn + ones, likely because the relativistic contraction of the Hg orbitals is very much attenuated by the attachment to the methyl group. Finally, we have investigated the gas-phase reactivity between EtHg + and uracil to compare it with that exhibited by CH 3 Hg + and n -ButHg + previously described in the literature. This comparison gathers new information that highlights the importance of the length of the alkyl chain attached to the metal on the mechanisms of these reactions. For methyl mercury, only the alkyl transfer process is allowed; for butyl mercury, protonation is clearly favored, and for ethyl mercury, both paths are competitive experimentally.