Shang Xuemei, Yang Mei, Su Tiantian, Guo Junli, Zhao Chenxi, Song Pei, Song Yan-Yan, Li Yucen
College of Science, Northeastern University, Shenyang 110819, P. R. China.
Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, China.
Anal Chem. 2025 Jul 15;97(27):14822-14829. doi: 10.1021/acs.analchem.5c02831. Epub 2025 Jul 2.
Chirality pervades biological architecture, and therapeutics that interface with living systems likewise manifest as stereoisomeric pairs whose divergent metabolic fates engender distinct pharmacological outcomes. Accordingly, the creation of facile, cost-effective platforms for enantiomer discrimination is pivotal both to chiral-drug development and to elucidating biochiral-material interactions. Here we engineer an asymmetric nanoelectrode by partitioning a single TiO nanochannel membrane (TiOM) into spatially discrete "recognition" and "reporting" domains. Gold nanoparticle decoration enables covalent anchoring of l-cysteine (Cys) via Au-S bonds at one face of TiOM, establishing a stereospecific binding interface; copper-based metal-organic frameworks (Cu-MOFs) are grown on the face to serve as redox-active reporters. Using l-/d-dihydroxyphenylalanine (DOPA) as the model enantiomers, selective binding of l- or d-DOPA at the l-Cys interface initiates electrochemical oxidation that injects electrons into the Au/TiO conduit; these electrons traverse the nanochannel and reduce Cu(II) to Cu(I) within the distal MOF layer, thus modulating the surface charge and producing a discernible transmembrane current shift. Differential hydrogen-bonding competencies of l- versus d-DOPA with l-Cys translate into quantitatively distinct charge perturbations, thereby affording high-fidelity enantiomer recognition. This longitudinally segmented TiO nanochannel architecture thus converts stereospecific molecular interactions into amplified electronic signatures, offering a versatile blueprint for next-generation electrochemical sensors targeting chiral analytes.
手性贯穿于生物结构之中，与生命系统相互作用的治疗药物同样以立体异构体对的形式存在，其不同的代谢命运产生了截然不同的药理结果。因此，创建简便、经济高效的对映体鉴别平台对于手性药物开发和阐明生物手性材料相互作用都至关重要。在此，我们通过将单个TiO纳米通道膜（TiOM）划分为空间上离散的“识别”和“报告”区域来设计一种不对称纳米电极。金纳米颗粒修饰能够通过Au-S键将l-半胱氨酸（Cys）共价锚定在TiOM的一个表面，建立起立体特异性结合界面；在相对的表面生长基于铜的金属有机框架（Cu-MOFs）作为氧化还原活性报告分子。使用l-/d-二羟基苯丙氨酸（DOPA）作为模型对映体，l-或d-DOPA在l-Cys界面的选择性结合引发电化学氧化，将电子注入Au/TiO通道；这些电子穿过纳米通道并在远端MOF层内将Cu(II)还原为Cu(I)，从而调节表面电荷并产生可辨别的跨膜电流变化。l-DOPA与d-DOPA和l-Cys的氢键能力差异转化为定量上不同的电荷扰动，从而实现高保真对映体识别。这种纵向分段的TiO纳米通道结构因此将立体特异性分子相互作用转化为放大的电子信号，为靶向手性分析物的下一代电化学传感器提供了通用蓝图。
