Chiral Metallopolymers for Redox‐Mediated Enantioselective Interactions

Abstract

Synthetic chiral platforms can be a powerful platform for enantioselective interactions, especially when coupled with redox-mediated electrochemical processes. While metallopolymers are versatile platforms for molecularly selective binding, their application for chiral applications is limited. In particular, the recognition and separation of biologically relevant chiral molecules can be key for biomanufacturing and diagnostics. Here, the design of chiral redox-polymers enables electrochemically-controlled enantioselective interactions, and supramolecular chirality is leveraged for enhancing recognition towards target enantiomers. Chiral redox-metallopolymers are synthesized based on Ugi's amine-inspired chiral monomers, and their enantioselective recognition toward ionic enantiomers such as tryptophan and naproxen is demonstrated, with higher enanhcement provided by the chiral redox-polymer over the single-site, chiral building bloack itelf. 2D nuclear magnetic resonance spectroscopy and solid-state circular dichroism support the emergence of supramolecular chirality resulting from the intramolecular interaction between the ferrocene and the alkyl group in the backbone. The half potential shift of the redox-polymers behaves linearly from 0% to 100%ee l-tryptophan to enable enantiomer quantification. Investigation on solvent polarity and pH effect reveal that the enantioselective mechanism is attributed to the subtle balance between hydrogen bonding and π-π interaction. This study highlights the potential of chiral redox-metallopolymers as platforms for electrochemically-modulated enantioselective interactions towards a range of amino acids and pharmaceutical carboxylates.

Molecularly Selective Polymer Interfaces for Electrochemical Separations

“…Redox-active polymers possess sites that can be switched on/off by an applied potential or current, enabling reversible binding or the release of target species. The selectivity of redox polymers can be not only controlled by the electrochemical properties of redox-active centers but also fine-tuned further through the incorporation of non-redox-active pendant groups into the redox-active center ,− and non-redox-active moieties into copolymer design. ,− Consequently, the careful selection of redox-active centers, non-redox-active functional groups, and appropriate polymer design has been a long-standing topic of interest in achieving highly selective and efficient separation processes.…”

“…Redox-responsive homopolymers have gained attention in electrochemical separation owing to their simple yet robust polymer structures consisting of repetitive single redox-responsive monomer units. Free radical polymerization and electropolymerization have been widely used for the synthesis of redox-active polymers for electrochemical separation due to their facile synthesis. ,, In addition, the reversible addition–fragmentation chain transfer (RAFT) method is frequently employed as a polymerization technique to precisely control the molecular weight distribution of polymers. ,, Redox-active homopolymers can be classified into two categories based on the arrangement of the redox-active units within their chemical structures, as depicted in Figure : (i) incorporation of the redox-active center into the polymer backbone ,− and (ii) attachment of the redox-active unit as a pendant group. ,,,,,,− …”

“…Classification of redox-responsive homopolymers based on the incorporation of redox-active units: (a) polyaniline (PANI) and (b) polyferrocenylsilane (PFS), featuring redox-active units in the main chain, (c) ferrocene and cobaltocene derivatives, and (d) chiral ferrocene polymers, featuring redox-active units in pendant groups. Panels a–d are reprinted with permission from refs (copyright 2021 Elsevier) for panel a, (copyright 2021 Wiley) for panel b, (copyright 2023 American Chemical Society) for panel c, and (copyright 2023 Wiley) for panel d, respectively.…”

“…The chirality of the metallopolymer determined its selective affinity for specific enantiomers, resulting in an opposite favorability for each enantiomer. The steric hindrance originating from the chiral center played a key role in interacting preferentially with the target molecules containing bulky aromatic groups, such as tryptophan and naproxen …”

“…On the experimental front, delving into operando analytical techniques, including the electrochemical quartz crystal microbalance, spectroscopy, , and neutron reflectivity, , will provide valuable insights into elucidating the solvation effect, transient ion retention, structural changes of polymer films, surface interaction, and binding affinity. Beyond experimental interpretation, multiscale modeling of physicochemical interactions between target species and functional groups has been studied to understand selectivity and stability. , Density functional theory (DFT) and molecular dynamic (MD) simulations are two primary computational tools to deconvolute molecular interactions and binding mechanisms at the molecular level, , while numerical simulations through COMSOL and the response surface model elucidate the influence of operating parameters on the performance. − We believe that the multidisciplinary combination of molecular simulations and operando analytical techniques for interfacial interrogation can greatly contribute to achieving a comprehensive understanding of separation performance and eventually predictive control over polymer structures and their function.…”