Computational design of macrocycle-based sorbents for effective removal of organic contaminants from water

The widespread contamination of groundwater by persistent organic pollutants, such as chlorinated volatile organic compounds (CVOCs), 1,4-dioxane, and per- and polyfluoroalkyl substances (PFAS), poses a significant environmental risk. Remediation of these pollutants is particularly challenging as these substances are often found at low concentrations and exhibit complex interaction mechanisms. While adsorption is a scalable and energy-efficient separations technique, conventional sorbent materials such as granulated activated carbon, ion-exchange resins, polymer membranes, and zeolites often lack the necessary selectivity and performance at environmentally relevant low concentrations. To address this gap, macrocyclic materials have emerged as promising class of tunable sorbents. This work establishes a multi-scale computational framework to deconstruct the fundamental mechanisms governing pollutant adsorption in macrocycle-based materials, with the ultimate goal of guiding the rational design of next-generation sorbents for targeted water purification. The first component of our multi-scale approach uses density functional theory (DFT) to gain quantum mechanical insights into binding affinities of various host-guest systems. To understand these affinities, we analyze the underlying interactions such as hydrogen bonding, dispersion interactions, and steric effects using the quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) plots. This quantum mechanical framework is then complemented by classical molecular dynamics (MD) simulations which is the second component of our approach. MD allows us to simulate larger systems over nanosecond timescales, explicitly model the role of the solvent, and capture the dynamic properties of the system. This provides us with a picture that is closer to real-world experimental conditions. We examine the link between underlying interactions and conformational isomerism in macrocycles by focusing on pillar[n]arenes. The unique pillar-like shape and well-defined cavities of pillar[n]arenes renders them an ideal candidate to examine interactions in macrocycles. Through our case study, we explore the impact of dispersion interactions, hydrogen bonding, and steric interactions on the overall energetics of pillar[n]arene conformations and determine the relative abundance of various conformations at thermal equilibrium. We then utilize the insights gained from this case study to evaluate intrinsic binding affinities between a range of macrocycles and pollutants. The DFT results reveal that the binding affinity of a given host-guest complex is the direct result of an intricate balance between underlying non-covalent interactions. This balance is highly dependent on multiple factors, including the relative size and shape of the macrocyclic host and the pollutant, as well as their specific chemical functionalizations. While DFT enables the evaluation of intrinsic energetics, we utilize MD simulations to study the performance of macrocycles in a realistic, solvated environment. This multi-scale case study reveals a critical insight into the adsorption of CVOCs and 1,4-dioxane in macrocycles. We find that while intrinsic host-guest affinity is strong, the high energetic penalty of desolvating hydrophilic guests, such as 1,4-dioxane, from water is the ultimate arbiter of selectivity in aqueous environments. Finally, we utilize the insights and design principles gained from the study of single unit macrocycle hosts and explore their incorporation into functional polymer networks. The utilization of macrocycle-based porous polymer networks can be attractive due to the added functionality from the addition of cross-linkers and operational advantages such as material recovery and regeneration. We begin our evaluation of macrocycle-based polymers with β-cyclodextrin-based polymers aimed at PFAS treatment. Our case study reveals that polymer architecture is not just a passive scaffold but an active participant in adsorption. The polymer network creates a synergistic microenvironment that enables cooperative hydrophobic and fluorophilic interactions, significantly enhancing PFAS uptake beyond what is achievable with individual macrocycles. We then extended this computational framework to evaluate Resorcinarene and pillar[n]arene based polymers as sorbents for legacy contaminants like CVOCs and 1,4-dioxane. Through this work, we show that macrocycle sorbent performance arises from the interplay between conformational stability, intrinsic host–guest affinity, guest solvation behavior, and the emergent properties of the bulk material. Together, these insights provide foundational guidelines for evaluating and tailoring macrocycle properties to design more effective sorbent materials.