  Understanding the impact of extractant functionalization in solvent
extraction is essential to guide the development of better separations
processes. Traditionally, computational extractant design uses electronic
structure calculations to determine the metal binding energy of the lowest
energy state. Although highly accurate, this approach does not account for all
the relevant physics encountered under experimental conditions, such as
temperature effects and ligand flexibility, in addition to approximating
solvent-extractant interactions with implicit solvent models. In this study, we
use classical MD simulations with an advanced sampling method, metadynamics, to
map out extractant molecule conformational free energies in the condensed
phase. We generate the complete conformational landscape in solution for a
family of bidentate malonamide-based extractants with different
functionalizations of the head group and the side chains. In particular, we
show how such alkyl functionalization reshapes the free energy landscape,
affecting the free energy penalty of organizing the extractant into the
cis-like metal binding conformation from the trans-like conformation of the
free extractant in solution. Specifically, functionalizing alkyl tails to the
center of the head group has a greater influence on increasing molecular
rigidity and disfavoring the binding conformation than functionalizing side
chains. These findings are consistent with trends in metal binding energetics
based on experimentally reported distribution ratios. This study demonstrates
the feasibility of using molecular dynamics simulations with advance sampling
techniques to investigate extractant conformational energetics in solution,
which, more broadly, will enable extractant design that accounts for entropic
effects and explicit solvation.
