Nanopore Discriminating d-Glucose Enantiomer Using a Designed Chiral Receptor

Ion channels can selectively recognize and transport biological species via an exquisite protein conformational switch. Classically, glucose-specific ion channels strictly transport the disomer over the lisomer. Inspired by this, we report a biomimetic d-glucose-responsive ion gate. We designed and synthesized a functional receptor, a chiral biphenylboronic acid (cBBA) derivative, which was used as a responsive element in an artificial nanopore. Due to its high binding affinity for d-glucose molecules, the biomimetic ion gate exhibits a sensitive and specific gating effect in response to d-glucose stimulation, thereby modulating the ionic current rectification (ICR) behavior. Remarkably, an extremely low concentration (e.g., 10 pM) of d-glucose stimulus could generate a remarkable ionic current change. After binding of physiological concentration of d-glucose (e.g., 5 mM), the ionic current modulation drastically decreased, with the switch ratio reaching up to 1530, showing a powerful gating capacity. Particularly, other saccharide analogues or the l-glucose isomer failed to activate the ion gate. Moreover, this gating effect was pH-dependent and demonstrated reversible ON-OFF ability when altering the medium acidity. Density functional theory (DFT) calculations unraveled that the designed artificial receptor can preferentially bind d-glucose over the l-glucose enantiomer, and finite element simulations revealed the ion gating mechanism in the d-glucose sensing event. The nanopore sensor was successfully applied to the electrochemical assay of glucose in biofluids.