Histidine-engineered metal-organic frameworks with enhanced peroxidase-like activity for sensitive detection of metallothioneins

The elaborate design and fabrication of nanomaterials to mimic natural enzyme-catalyzed active sites is a promising approach to significantly improve catalytic performances, which is beneficial to the signal amplification for biosensing applications. Metal–organic frameworks (MOFs) with tailorable components, structures and well-distributed metal sites are supposed to tackle the challenges in traditional nanomaterials of vague structure and imprecise coordination. Herein, defect-engineered MOFs with histidine-functionalized active sites (His-MIL-101) has been constructed by the missing linker strategy. Bearing a histidine unit in the iron active site, the resultant His-MIL-101 can vividly mimic the natural enzyme catalytic pocket and exhibits double the peroxidase-like activity of parent MOFs. Notably, the introduction of histidine can not only increase the specific surface area for boosting the metal active site exposure but also provide an optimized electronic structure of active sites to promote the generation of active intermediate (hydroxyl radical). By virtue of the synergistic effects of metallothioneins on metal active site-blocking impact and free radicals scavenging, His-MIL-101-based colorimetric biosensing platform was constructed to accurately detect metallothioneins with a wide detection range from 20 nM to 50 μM, as well as a low detection limit of 10.49 nM. This approach paves the way for the design of advanced biomimetic nanomaterials to efficiently mimic the active center of natural enzymes and further extend the application in biosensing.