Addressing Polarization Phenomena in Molecular Machines Containing Transition Metal Ions with an Additive Force Field

Modeling transition metals in supramolecular
assemblies, in general,
is extremely challenging due to polarization and charge transfer.
In this work, we demonstrate that the inherent shortcomings of additive
force fields in modeling Cu+–ether-O and Cu+–olefin-C interactions are rooted in the Lorentz–Berthelot
rules. A general method for investigating transition-metal-containing
molecular assays using classical force fields is, therefore, proposed.
In this strategy, QM/MM calculations have been performed to determine
the potential of mean force (PMF) describing the interaction of a
cation and a specific functional group. van der Waals parameters for
the corresponding pairs of particles have then been optimized using
the NBFIX feature of the CHARMM force field to fit the QM/MM PMF.
This method has been applied to decipher the mechanism underlying
the “dialing” of a molecular machine controlled by Li+ and Cu+ cations, indicating that the process is
controlled by the competition between cation–ether-O and cation–olefin-C
interactions.