Graphical Abstract
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Replacement of enzymes with nanomaterials such as atomically dispersed metal catalysts is one of the most crucial steps in addressing the challenges in biocatalysis. Despite the breakthroughs of single-atom catalysts in enzyme-mimicking, a fundamental investigation on the development of an instructional strategy is still required for mimicking biatomic/multiatomic active sites in natural enzymes and constructing synergistically enhanced metal atom active sites. Herein, Fe2NC catalysts with atomically dispersed Fe-Fe dual-sites supported by the metal-organic frameworks-derived nitrogen-doped carbon are employed as biomimetic catalysts to perform proof-of-concept investigation. The effect of Fe atom number toward typical oxidase (cytochrome C oxidase, NADH oxidase, and ascorbic acid oxidase) and peroxidase (NADH peroxidase and ascorbic acid peroxidase) activities is systematically evaluated by experimental and theoretical investigations. A peroxo-like O2 adsorption in Fe2NC nanozymes could accelerate the O–O activation and thus achieve the enhanced enzyme-like activities. This work achieves the vivid simulation of the enzyme active sites and provides the theoretical basis for the design of high-performance nanozymes. As a concept application, a colorimetric biosensor for the detection of S2– in tap water is established based on the inhibition of enzyme-like activity of Fe2NC nanozymes.
Wu, J. J. X.; Wang, X. Y.; Wang, Q.; Lou, Z. P.; Li, S. R.; Zhu, Y. Y.; Qin, L.; Wei, H. Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artificial enzymes (Ⅱ). Chem. Soc. Rev. 2019, 48, 1004–1076.
Huang, Y. Y.; Ren, J. S.; Qu, X. G. Nanozymes: Classification, catalytic mechanisms, activity regulation, and applications. Chem. Rev. 2019, 119, 4357–4412.
Jiang, D. W.; Ni, D. L.; Rosenkrans, Z. T.; Huang, P.; Yan, X. Y.; Cai, W. B. Nanozyme: New horizons for responsive biomedical applications. Chem. Soc. Rev. 2019, 48, 3683–3704.
Sun, H. J.; Zhou, Y.; Ren, J. S.; Qu, X. G. Carbon nanozymes: Enzymatic properties, catalytic mechanism, and applications. Angew. Chem. , Int. Ed. 2018, 57, 9224–9237.
Wang, Z. R.; Zhang, R. F.; Yan, X. Y.; Fan, K. L. Structure and activity of nanozymes: Inspirations for de novo design of nanozymes. Mater. Today 2020, 41, 81–119.
Gao, L. Z.; Zhuang, J.; Nie, L.; Zhang, J. B.; Zhang, Y.; Gu, N.; Wang, T. H.; Feng, J.; Yang, D. L.; Perrett, S. et al. Intrinsic peroxidase- like activity of ferromagnetic nanoparticles. Nat. Nanotechnol. 2007, 2, 577–583.
Xiang, H. J.; Feng, W.; Chen, Y. Single-atom catalysts in catalytic biomedicine. Adv. Mater. 2020, 32, 1905994.
Fan, K. L.; Xi, J. Q.; Fan, L.; Wang, P. X.; Zhu, C. H.; Tang, Y.; Xu, X. D.; Liang, M. M.; Jiang, B.; Yan, X. Y. et al. In vivo guiding nitrogen-doped carbon nanozyme for tumor catalytic therapy. Nat. Commun. 2018, 9, 1440.
Chong, Y.; Dai, X.; Fang, G.; Wu, R. F.; Zhao, L.; Ma, X. C.; Tian, X.; Lee, S.; Zhang, C.; Chen, C. Y. et al. Palladium concave nanocrystals with high-index facets accelerate ascorbate oxidation in cancer treatment. Nat. Commun. 2018, 9, 4861.
Fang, G.; Li, W. F.; Shen, X. M.; Perez-Aguilar, J. M.; Chong, Y.; Gao, X. F.; Chai, Z. F.; Chen, C. Y.; Ge, C. C.; Zhou, R. H. Differential Pd-nanocrystal facets demonstrate distinct antibacterial activity against gram-positive and gram-negative bacteria. Nat. Commun. 2018, 9, 129.
Xu, W. Q.; Kang, Y. K.; Jiao, L.; Wu, Y.; Yan, H. Y.; Li, J. L.; Gu, W. L.; Song, W. Y.; Zhu, C. Z. Tuning atomically dispersed Fe sites in metal-organic frameworks boosts peroxidase-like activity for sensitive biosensing. Nano-Micro Lett. 2020, 12, 184.
Xi, J. Q.; Zhang, R. F.; Wang, L. M.; Xu, W.; Liang, Q.; Li, J. Y.; Jiang, J.; Yang, Y. L.; Yan, X. Y.; Fan, K. L. et al. A nanozyme-based artificial peroxisome ameliorates hyperuricemia and ischemic stroke. Adv. Funct. Mater. 2021, 31, 2007130.
Wu, Y.; Wu, J. B.; Jiao, L.; Xu, W. Q.; Wang, H. J.; Wei, X. Q.; Gu, W. L.; Ren, G. X.; Zhang, N.; Zhang, Q. H. et al. Cascade reaction system integrating single-atom nanozymes with abundant Cu sites for enhanced biosensing. Anal. Chem. 2020, 92, 3373–3379.
Xu, B. L.; Wang, H.; Wang, W. W.; Gao, L. Z.; Li, S. S.; Pan, X. T.; Wang, H. Y.; Yang, H. L.; Meng, X. Q.; Wu, Q. W. et al. A single-atom nanozyme for wound disinfection applications. Angew. Chem. , Int. Ed. 2019, 58, 4911–4916.
Cheng, N.; Li, J. C.; Liu, D.; Lin, Y. H.; Du, D. Single-atom nanozyme based on nanoengineered Fe–N–C catalyst with superior peroxidase-like activity for ultrasensitive bioassays. Small 2019, 15, 1901485.
Zhu, C. Z.; Fu, S. F.; Shi, Q. R.; Du, D.; Lin, Y. H. Single-atom electrocatalysts. Angew. Chem. , Int. Ed. 2017, 56, 13944–13960.
Chen, M.; Zhou, H.; Liu, X. K.; Yuan, T. W.; Wang, W. Y.; Zhao, C.; Zhao, Y. F.; Zhou, F. Y.; Wang, X.; Xue, Z. G. et al. Single iron site nanozyme for ultrasensitive glucose detection. Small 2020, 16, 2002343.
Zhao, C.; Xiong, C.; Liu, X. K.; Qiao, M.; Li, Z. J.; Yuan, T. W.; Wang, J.; Qu, Y. T.; Wang, X. Q.; Zhou, F. Y. et al. Unraveling the enzyme-like activity of heterogeneous single atom catalyst. Chem. Commun. 2019, 55, 2285–2288.
Luo, X.; Wei, X. Q.; Wang, H. J.; Gu, W. L.; Kaneko, T.; Yoshida, Y.; Zhao, X.; Zhu, C. Z. Secondary-atom-doping enables robust Fe–N–C single-atom catalysts with enhanced oxygen reduction reaction. Nano-Micro Lett. 2020, 12, 163.
Gao, C.; Low, J. X.; Long, R.; Kong, T. T.; Zhu, J. F.; Xiong, Y. J. Heterogeneous single-atom photocatalysts: Fundamentals and applications. Chem. Rev. 2020, 120, 12175–12216.
Zhang, L. W.; Long, R.; Zhang, Y. M.; Duan, D. L.; Xiong, Y. J.; Zhang, Y. J.; Bi, Y. P. Direct observation of dynamic bond evolution in single-atom Pt/C3N4 catalysts. Angew. Chem. , Int. Ed. 2020, 59, 6224–6229.
Shen, L. H.; Ye, D. X.; Zhao, H. B.; Zhang, J. J. Perspectives for single-atom nanozymes: Advanced synthesis, functional mechanisms, and biomedical applications. Anal. Chem. 2021, 93, 1221–1231.
Jiao, L.; Wu, J. B.; Zhong, H.; Zhang, Y.; Xu, W. Q.; Wu, Y.; Chen, Y. F.; Yan, H. Y.; Zhang, Q. H.; Gu, W. L. et al. Densely isolated FeN4 sites for peroxidase mimicking. ACS Catal. 2020, 10, 6422–6429.
Jiao, L.; Yan, H. Y.; Wu, Y.; Gu, W. L.; Zhu, C. Z.; Du, D.; Lin, Y. H. When nanozymes meet single-atom catalysis. Angew. Chem. , Int. Ed. 2020, 59, 2565–2576.
Huang, L.; Chen, J. X.; Gan, L. F.; Wang, J.; Dong, S. J. Single-atom nanozymes. Sci. Adv. 2019, 5, eaav5490.
Jiao, L.; Xu, W. Q.; Yan, H. Y.; Wu, Y.; Liu, C. R.; Du, D.; Lin, Y. H.; Zhu, C. Z. Fe–N–C single-atom nanozymes for the intracellular hydrogen peroxide detection. Anal. Chem. 2019, 91, 11994–11999.
Jiao, L.; Xu, W. Q.; Zhang, Y.; Wu, Y.; Gu, W. L.; Ge, X. X.; Chen, B. B.; Zhu, C. Z.; Guo, S. J. Boron-doped Fe–N–C single-atom nanozymes specifically boost peroxidase-like activity. Nano Today 2020, 35, 100971.
Zhang, X. L.; Li, G. L.; Chen, G.; Wu, D.; Zhou, X. X.; Wu, Y. N. Single-atom nanozymes: A rising star for biosensing and biomedicine. Coord. Chem. Rev. 2020, 418, 213376.
Wu, Y.; Jiao, L.; Luo, X.; Xu, W. Q.; Wei, X. Q.; Wang, H. J.; Yan, H. Y.; Gu, W. L.; Xu, B. Z.; Du, D. et al. Oxidase-like Fe–N–C single-atom nanozymes for the detection of acetylcholinesterase activity. Small 2019, 15, 1903108.
Wang, Y.; Zhang, Z. W.; Jia, G. R.; Zheng, L. R.; Zhao, J. X.; Cui, X. Q. Elucidating the mechanism of the structure-dependent enzymatic activity of Fe–N/C oxidase mimics. Chem. Commun. 2019, 55, 5271–5274.
Adam, S. M.; Wijeratne, G. B.; Rogler, P. J.; Diaz, D. E.; Quist, D. A.; Liu, J. J.; Karlin, K. D. Synthetic Fe/Cu complexes: Toward understanding heme-copper oxidase structure and function. Chem. Rev. 2018, 118, 10840–11022.
Schaefer, A. W.; Roveda, A. C. Jr.; Jose, A.; Solomon, E. I. Geometric and electronic structure contributions to O–O cleavage and the resultant intermediate generated in heme-copper oxidases. J. Am. Chem. Soc. 2019, 141, 10068–10081.
Schaefer, A. W.; Kieber-Emmons, M. T.; Adam, S. M.; Karlin, K. D.; Solomon, E. I. Phenol-induced O–O bond cleavage in a low-spin heme–peroxo–copper complex: Implications for O2 reduction in heme–copper oxidases. J. Am. Chem. Soc. 2017, 139, 7958–7973.
Li, M. H.; Chen, J. X.; Wu, W. W.; Fang, Y. X.; Dong, S. J. Oxidase- like MOF-818 nanozyme with high specificity for catalysis of catechol oxidation. J. Am. Chem. Soc. 2020, 142, 15569–15574.
Mishra, B. B.; Gautam, S. Polyphenol oxidases: Biochemical and molecular characterization, distribution, role and its control. Enzyme Eng. 2016, 5, 1000141.
Wang, J.; You, R.; Zhao, C.; Zhang, W.; Liu, W.; Fu, X. P.; Li, Y. Y.; Zhou, F. Y.; Zheng, X. S.; Xu, Q. et al. N-coordinated dual-metal single-site catalyst for low-temperature CO oxidation. ACS Catal. 2020, 10, 2754–2761.
Wang, J.; Huang, Z. Q.; Liu, W.; Chang, C. R.; Tang, H. L.; Li, Z. J.; Chen, W. X.; Jia, C. J.; Yao, T.; Wei, S. Q. et al. Design of N-coordinated dual-metal sites: A stable and active Pt-free catalyst for acidic oxygen reduction reaction. J. Am. Chem. Soc. 2017, 139, 17281–17284.
Tian, S. B.; Fu, Q.; Chen, W. X.; Feng, Q. C.; Chen, Z.; Zhang, J.; Cheong, W. C.; Yu, R.; Gu, L.; Dong, J. C. et al. Carbon nitride supported Fe2 cluster catalysts with superior performance for alkene epoxidation. Nat. Commun. 2018, 9, 2353.
Xiao, M. L.; Zhang, H.; Chen, Y. T.; Zhu, J. B.; Gao, L. Q.; Jin, Z.; Ge, J. J.; Jiang, Z.; Chen, S. L.; Liu, C. P. et al. Identification of binuclear Co2N5 active sites for oxygen reduction reaction with more than one magnitude higher activity than single atom CoN4 site. Nano Energy 2018, 46, 396–403.
Lu, Z. Y.; Wang, B.; Hu, Y. F.; Liu, W.; Zhao, Y. F.; Yang, R. O.; Li, Z. P.; Luo, J.; Chi, B.; Jiang, Z. et al. An isolated zinc–cobalt atomic pair for highly active and durable oxygen reduction. Angew. Chem. , Int. Ed. 2019, 58, 2622–2626.
Ye, W.; Chen, S. M.; Lin, Y.; Yang, L.; Chen, S. J.; Zheng, X. S.; Qi, Z. M.; Wang, C. M.; Long, R.; Chen, M. et al. Precisely tuning the number of Fe atoms in clusters on N-doped carbon toward acidic oxygen reduction reaction. Chem 2019, 5, 2865–2878.
Singh, N.; Mugesh, G. CeVO4 nanozymes catalyze the reduction of dioxygen to water without releasing partially reduced oxygen species. Angew. Chem. , Int. Ed. 2019, 58, 7797–7801.
Kang, T. S.; Korber, D. R.; Tanaka, T. Influence of oxygen on NADH recycling and oxidative stress resistance systems in Lactobacillus panis PM1. AMB Express 2013, 3, 10.
Jia, B. L.; Park, S. C.; Lee, S.; Pham, B. P.; Yu, R.; Le, T. L.; Han, S. W.; Yang, J. K.; Choi, M. S.; Baumeister, W. et al. Hexameric ring structure of a thermophilic archaeon NADH oxidase that produces predominantly H2O. FEBS J. 2008, 275, 5355–5366.
Jiao, L.; Xu, W. Q.; Yan, H. Y.; Wu, Y.; Gu, W. L.; Li, H.; Du, D.; Lin, Y. H.; Zhu, C. Z. A dopamine-induced Au hydrogel nanozyme for enhanced biomimetic catalysis. Chem. Commun. 2019, 55, 9865– 9868.
Zhang, J. Q.; Zhao, Y. F.; Chen, C.; Huang, Y. C.; Dong, C. L.; Chen, C. J.; Liu, R. S.; Wang, C. Y.; Yan, K.; Li, Y. D. et al. Tuning the coordination environment in single-atom catalysts to achieve highly efficient oxygen reduction reactions. J. Am. Chem. Soc. 2019, 141, 20118–20126.
Karim, M. N.; Anderson, S. R.; Singh, S.; Ramanathan, R.; Bansal, V. Nanostructured silver fabric as a free-standing Nanozyme for colorimetric detection of glucose in urine. Biosens. Bioelectron. 2018, 110, 8–15.
Liu, Y.; Ding, D.; Zhen, Y. L.; Guo, R. Amino acid-mediated "turn-off/ turn-on" nanozyme activity of gold nanoclusters for sensitive and selective detection of copper ions and histidine. Biosens. Bioelectron. 2017, 92, 140–146.
Xi, Z.; Cheng, X.; Gao, Z. Q.; Wang, M. J.; Cai, T.; Muzzio, M.; Davidson, E.; Chen, O.; Jung, Y.; Sun, S. H. et al. Strain effect in palladium nanostructures as nanozymes. Nano Lett. 2020, 20, 272–277.
Weerathunge, P.; Ramanathan, R.; Torok, V. A.; Hodgson, K.; Xu, Y.; Goodacre, R.; Behera, B. K.; Bansal, V. Ultrasensitive colorimetric detection of murine norovirus using Nanozyme aptasensor. Anal. Chem. 2019, 91, 3270–3276.
Oh, S.; Kim, J.; Tran, V. T.; Lee, D. K.; Ahmed, S. R.; Hong, J. C.; Lee, J.; Park, E. Y.; Lee, J. Magnetic nanozyme-linked immunosorbent assay for ultrasensitive influenza a virus detection. ACS Appl. Mater. Interfaces 2018, 10, 12534–12543.
Li, Y. H.; Fang, Y. S.; Gao, W. Q.; Guo, X. J.; Zhang, X. M. Porphyrin- based porous organic polymer as peroxidase mimics for sulfide-ion colorimetric sensing. ACS Sustainable Chem. Eng. 2020, 8, 10870– 10880.
Singh, S.; Mitra, K.; Shukla, A.; Singh, R.; Gundampati, R. K.; Misra, N.; Maiti, P.; Ray, B. Brominated graphene as mimetic peroxidase for sulfide ion recognition. Anal. Chem. 2017, 89, 783–791.
Suzuki, K.; Olah, G.; Modis, K.; Coletta, C.; Kulp, G.; Gerö, D.; Szoleczky, P.; Chang, T. J.; Zhou, Z. M.; Wu, L. Y. et al. Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function. Proc. Natl. Aca. Sci. USA 2011, 108, 13829–13834.
McGeer, E. G.; McGeer, P. L. Neuroinflammation in Alzheimer's disease and mild cognitive impairment: A field in its infancy. J. Alzheimer's Dis. 2010, 19, 355–361.