Using Metadynamics to Reveal Extractant Conformational Free Energy Landscapes

TL;DR

This paper uses metadynamics-enhanced molecular dynamics simulations to map out the conformational free energy landscapes of extractants in solution, revealing how functionalization influences their binding conformations and energetics.

Contribution

It introduces a computational approach combining classical MD and metadynamics to study extractant conformations in solution, accounting for entropy and explicit solvation effects.

Findings

Alkyl functionalization reshapes the free energy landscape.

Functionalizing alkyl tails increases molecular rigidity.

Results align with experimental metal binding trends.

Abstract

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.