ZIF-67 as a Template Generating and Tuning “Raisin Pudding”-Type Nanozymes with Multiple Enzyme-like Activities: Toward Online Electrochemical Detection of 3,4-Dihydroxyphenylacetic Acid in Living Brains

Abstract

Due to its unique structure and high porosity, metal–organic frameworks (MOFs) can act not only as nanozyme materials but also as carriers to encapsulate natural enzymes and thus have received extensive attention in recent years. However, a few research studies have been conducted to investigate MOF as a template to generate and tune nanozymes in the structure and performance. In this work, the “raisin pudding”-type ZIF-67/Cu0.76Co2.24O4 nanospheres (ZIF-67/Cu0.76Co2.24O4 NSs) were obtained by rationally regulating the weight ratio of ZIF-67 and Cu­(NO3)2 in the synthesis process. Here, ZIF-67 not only acts as a template but also provides a cobalt source for the synthesis of cobalt copper oxide on the surface of ZIF-67/Cu0.76Co2.24O4 NSs with multiple enzyme-like activities. The ZIF-67/Cu0.76Co2.24O4 NSs can mimic four kinds of enzymes with peroxidase-like, glutathione peroxidase-like, superoxide dismutase-like, and laccase-like activities. Based on its laccase-like activity, an online electrochemical system for continuous monitoring of 3,4-dihydroxyphenylacetic acid with good linearity in the range of 0.5–20 μM and a detection limit of 0.15 μM was established. Furthermore, the alteration of DOPAC in the brain microdialysate before and after ischemia of the rats’ brain was also successfully recorded. This work not only raises a new idea for the synthesis of nanozyme materials with multiple enzyme activities but also provides a new solution for the detection of neurotransmitters in living brains.

Structure Defect Tuning of Metal–Organic Frameworks as a Nanozyme Regulatory Strategy for Selective Online Electrochemical Analysis of Uric Acid

“…Engineering the physical properties and chemical structures of nanozymes is an important means to obtain nanozymes with high performance. 27,40 MOFs benefited from their isolated active site, large surface area, and high porosity have aroused extensive interest in the field of enzyme-like catalysis. 18,19 However, most MOFs show poor intrinsic enzyme-like activity, exposing more active sites, and increasing the specific surface area becomes an effective means to improve the activity of MOF-like enzymes.…”

“…18,19 However, most MOFs show poor intrinsic enzyme-like activity, exposing more active sites, and increasing the specific surface area becomes an effective means to improve the activity of MOF-like enzymes. 27,29 Co, as the active center of MOFs, can coordinate with oxygen, activate molecular oxygen to generate oxygen free radicals, and endow nanomaterials with oxidase properties. 47,48 Along these lines, in this work, structure defects were introduced into a novel Co-containing zeolitic imidazolate framework with gradually loosened morphology (ZIF-L-Co) by doping with cysteine (Cys).…”

“…26 Lately, we proposed a "raisin pudding"-type ZIF-67/Cu 0.76 Co 2.24 O 4 nanospheres (ZIF 67/Cu 0.76 Co 2.24 O 4 NSs) with multienzyme properties by rationally regulating the ratio of Cu(NO 3 ) 2 in the synthesis process, achieving a near real-time response and continuous 3,4-dihydroxyphenylacetic acid (DOPAC) measurements in a living rat brain. 27 In addition, introducing defective structures is the other efficient means in promoting the catalytic activity of MOFs, usually by structure modifiers, 28 T h i s c o n t e n t i s linker-missing/destruction, 29 and solvent competition, leading to ligand coordination unsaturation. 30 Recently, the Ouyang group 31 presented a new amino acid-boosted one-pot embedding strategy relying on the strong affinity of cysteine assembled with proteins to Zn 2+ , which not only accelerate prenucleated clusters and engendered MOFs around the proteins but also occupy the coordination sites of MOF ligands, resulting in the morphologic evolution and generating higher porosity in the composites.…”

“…Despite the ongoing progress on MOF nanozyme tuning research, structure defects to functionalize MOFs leading to a tunable and highly efficient enzyme-like catalyst are still in their infancy. An online analysis system combined with electrochemical detection can be designed for one or multiple kinds of physiologically important species monitoring such as ascorbic acid (AA), 32 dopamine (DA), 33 DOPAC, 27 adenosine triphosphate, 34 glucose/lactate, 35,36 and glucose/lactate/ascorbate. 37 In addition, in order to expand this useful online detection system, our group developed an online optical detection platform (OODP) based on a bright-field microscope for near real-time and continuous neurochemical detection such as for glucose, 38 AA, 39 and H 2 S. 40,41 Moreover, more colorimetric probes can be integrated into the OODP and realize simultaneous detection of multiple targets such as Cu 2+ /AA.…”

“…42 As demonstrated in our previous studies, the online detection of many crucial neurochemical substances can be achieved by rationally designing and regulating the activity of nanozymes. 27,34,38,40 For instance, we synthesized a molybdenum-polysulfide-deposited nickel−iron bimetal hollow nanocage and found that the molybdenum-doping strategy tailored the size, morphology, composition, and complex structure and thus enhanced the POD-and laccase-mimicking activities of the nanocage by over 37 and 27 times, respectively, 40 achieving the elimination of ROS in cells and continuous measurement of H 2 S in the brains of living rats.…”