Construction of Homochiral Covalent Organic Frameworks as Enantioselective Probes for Homogeneous Photoelectrochemical-Red–Green–Blue Dual-Mode Selective Sensing of <scp>d</scp> -Cysteine

Cysteine (Cys) serves as a fundamental building block for protein synthesis and drug development. Due to that l-Cys plays a crucial role in neurological function and cellular detoxification, whereas d-Cys exhibits notable cytotoxicity and health risks, and the rapid and selective assay of d-Cys in l-Cys-related pharmaceuticals is critically important. Here, a multifunctional chiral recognition probe was synthesized to achieve photoelectrochemical (PEC) and red-green-blue (RGB) colorimetric dual-mode selective detection of d-Cys in the presence of l-Cys. Through thiol-ene click chemistry, a d-Cys modified covalent organic framework (d-COF) was synthesized with abundant chiral recognition sites. Driven by homochiral interactions, d-COF exhibits a significantly stronger adsorption affinity for d-Cys than l-Cys. The adsorbed Cys acts as an electron donor to enhance the photocurrent of d-COF, yielding a high chiral recognition efficiency of Δ<i>I</i>_D/Δ<i>I</i>_L = 12.0 in PEC mode. Furthermore, the strongly adsorbed d-Cys protonates the imine bonds in d-COF via its carboxyl and thiol groups, inducing a distinct color change from dark yellow to red, whereas l-Cys adsorption causes negligible color change due to the weak interaction between d-COF and l-Cys. Thus, based on the obvious difference in photocurrent and color changes of d-COF adsorbed with d-Cys and l-Cys, selective detection of d-Cys through PEC-RGB dual-mode sensing platform is achieved in the presence of l-Cys. This work demonstrates a PEC-RGB dual-mode sensing platform for selective detection of d-Cys and a generalizable strategy that can be extended to other chiral substance assays by changing the chiral selector, showing promising potential in chiral drug identification and biomedical detection.