Alkali and Alkaline‐Earth Cations in Complexes with Small Bioorganic Ligands: Ab Initio Benchmark Calculations and Bond Energy Decomposition

Abstract Herein, we report a computational database for the complexes of alkali [Li(I), Na(I), K(I)] and alkaline‐earth [Be(II), Mg(II) and Ca(II)] cations with 25 small ligands with varying charge and donor atoms (“O”, “N”, and “S”) that provides geometries and accurate bond energies useful to analyze metal‐ligand interactions in proteins and nucleic acids. The role of the ligand→metal charge transfer, the equilibrium bond distance, the electronegativity of the donor atom, the ligand polarizability, and the relative stability of the complexes are discussed in detail. The interacting quantum atoms (IQA) method is used to decompose the binding energy into electrostatic and quantum mechanical contributions. In addition, bond energies are also estimated by means of multipolar electrostatic calculations. No simple correlation exists between bond energies and structural/electronic descriptors unless the data are segregated by the type of ligand or metal. The electrostatic attraction of some molecules (H 2 O, NH 3 , CH 3 OH) towards the metal cations is well reproduced using their (unrelaxed) atomic multipoles, but the same comparison is much less satisfactory for other ligands (e. g. benzene, thiol/thiolate groups, etc.). Besides providing reference structures and bond energies, the database can contribute to validate molecular mechanics potentials capable of yielding a balanced description of alkali and alkaline‐earth metals binding to biomolecules.