Redox-Mediated Enantioselective Interactions in Chiral Metallopolymers Possessing Supramolecular Chirality

Abstract

Synthetic chiral platforms can be a powerful platform for enantioselective interactions, especially when coupled with redox-mediated electrochemical processes. Redox metallopolymers represent a distinct class of versatile functional materials and have been extensively studied for a wide scope of applications such as membranes, self-assembly, hydrogels, and redox-mediated ion separation. However, many studies have focused on molecularly-selective binding and release of achiral molecules, with limited studies on chirality strategies for enantioselective interactions. Chiral organic anions comprise an important class of biologically-relevant molecules, and their separation and sensing have received intense attention. Here, we introduce new chiral redox-polymers with chiral ferrocene (Fc) building blocks, that can serve as an electro-responsive enantioselective platform for a variety of amino acids and pharmaceutical carboxylates, taking advantage of supramolecular chirality for enhancing electrochemical recognition. Two chiral redox-metallopolymers were designed and synthesized based on Ugi’s amine-inspired chiral monomers containing an amide (poly-1) or amine group (poly-2), and their enantioselective recognitions toward amino acids and pharmaceutical carboxylates were investigated by redox potential shifts using square wave voltammetry. The half potential shift of both poly-(S)-1 and poly-(S)-2 increased more with increasing D-tryptophan concentration than the other enantiomer, L-tryptophan, while the half potential of poly-(R)-1 and poly-(R)-2 shifted more with L-tryptophan than with D-tryptophan, proving the enantioselective interaction of both redox-metallopolymers. Nuclear Overhauser Effect spectroscopy (2D NOESY) and solid-state circular dichroism revealed the emergence of supramolecular chirality of the polymers resulting from the intramolecular interaction between the ferrocene and the alkyl group in the backbone, and the steric hindrance of the ferrocene within the polymer. The half-peak potential shift demonstrated the remarkable enhancement of enantioselective recognition with tryptophan (Trp) and naproxen, provided by the chiral polymers possessing the supramolecular chirality over the single-site, chiral building block itself. For instance, the two (S) polymers showed the potential shift difference 2.4-2.8 times higher than the corresponding monomers upon the binding of Trp enantiomers. The enantioselective potential shift of the chiral metallopolymer electrodes could determine enantiomeric excess (%ee) of Trp over the range of 0–100%ee. Investigation on solvent polarity and pH effect revealed that the enantioselective mechanism of the chiral redox polymers was attributed to the subtle balance between hydrogen bonding and π-π interaction. We also identified the importance of aromatic groups on the analytes for increasing enantioselectivity of the chiral redox polymers. This work highlights the potential of chiral redox-metallopolymers as platforms for electrochemically-modulated enantioselective processes toward a variety of amino acids and pharmaceutical carboxylates. Figure 1