Overcoming the Hydration and Solvation Problem in Ion Recognition and Binding: The Biomimetic Approach

Artificial receptors for cations and anions utilizing noncovalent binding, transport, sequestration, or sensing in aqueous media must address enthalpic factors such as electrostatic attraction, hydrogen bonding, van der Waals forces, and London dispersion forces. The entropic component also significantly contributes to the free energy of association, especially in polar environments like water, where binding may be entropy-driven due to the release of ordered solvent molecules from the solvation sphere, increasing system entropy and resulting in a negative free Gibbs energy. Over the years, chemists have focused on enthalpic criteria, such as size complementarity and functional group interactions, for designing artificial receptors. However, designing for the entropic component, particularly solvation/desolvation, remains challenging and often depends on fortunate circumstances.As shown by X-ray crystallography, enzymes and proteins can strip solvating water molecules from the ions. Inspired by phosphate-binding enzymes and transporters, we examined polymers comprising amide bonds, such as polyamides and polyurethanes, to mimic protein backbones. These hydrophilic polymers can be engineered to absorb specific amounts of water (10-100% or even more). We aimed to use hydrophilic polymers to remove water molecules from hydrated ions, rendering them "naked" ions, thus enabling better recognition by receptors based on enthalpic factors. To test this, we used copolymers with amide and urethane-amide moieties with different ratios of poly(ethylene oxide) and poly(butylene oxide) to control water uptake between 10% and 100%, along with embedded fluorescent sensors. We found that polymers with 30-50% water uptake showed the highest fluorescence response, while uptake below 20% resulted in small changes in fluorescence and 60-100% led to diminished responses. Low water uptake caused reduced ion co-transport, while high uptake formed large water pools within the polymers, isolating solvated ions from receptors. The optimal water uptake of 30-50% produced (semi)naked ions and a water-organic matrix similar to that of DMSO-water environments. Just like proteins, the structure impacts the recognition and internalization of anions, such as phosphate or sulfate; here too, the monomer composition and synthetic sequence greatly influence material responses to anions, with lipophilic ones eliciting lower responses. The data analysis of fluorescence responses enables the generation of sensor arrays for both cations and anions in water, buffers, saliva, urine, or blood plasma, both qualitative and quantitative analyses, for single analytes or as analyte mixtures. Overall, this biomimetic approach focused on the recovery of the enthalpic factor (by diminishing the impact of solvation and entropy) has proven remarkably successful in creating sensors and adsorbents for charged species in aqueous media and water and is expected to find applications in optical sensors, sensor arrays, ion-selective electrodes, and other analytical methods.