Inorganic Enzyme Mimics Yihong Zhang,[A, B] Faheem Muhammad,[A, B] and Hui Wei*[A, B]

Editorial ChemBioChem doi.org/10.1002/cbic.202100049

Inorganic Enzyme Mimics Yihong Zhang,[a, b] Faheem Muhammad,[a, b] and Hui Wei*[a, b]

Enzyme mimics (or artificial enzymes) have emerged as valuable inorganic ones, including inorganic complexes and nanomate- alternatives to natural enzymes since the pioneering work of rials, have attracted increasing interest over the last decade and Ronald Breslow. They have numerous advantages over natural have the potential to address the current challenges in energy, enzymes, such as high stability, low cost, and tailorable activity. environment, health, etc. Among varieties of materials explored to mimic enzymes, the

ChemBioChem and EurJIC, two internationally recognized jour- and other characterizations were carried out to investigate the nals in the field, have now provided us with a unique complexes’ catalytic activity. The limited stability and moderate opportunity to highlight the exciting achievements in the catalytic activity demand a very fine tuning of these [FeFe]- recent years by publishing a joint Special Collection on H2ase mimics in future studies. Although manganese is not Inorganic Enzyme Mimics. This Special Collection features 20 used in natural hydrogenases, it is a critical element in contributions including Reviews, Minireviews, Communications, photosystem II. Kaur-Ghumaan and co-workers summarized the and Full Papers. Sixteen of them are research articles, and the recent progress in manganese-based complexes for H2 produc- other four are reviews. Among them, 11 are focused on tion and oxidation, thus demonstrating that non-native metal nanozymes, eight on inorganic complexes (mainly transition hydrogenases based on manganese active sites might be metal complexes), and one on DNAzymes; this roughly reflects viable. the recent research trend in the field. Nitrogenases are enzymes for nitrogen fixation. A nitro- Inorganic complexes are promising enzyme mimics because genase consists of three components: the Fe-protein containing

of their rich coordination chemistry, which can imitate the a [Fe4S4] cluster, the electron-transferring P-cluster containing a

active sites and microenvironments of metalloenzymes. The [Fe8S7] group, and the cofactor. There are three types of artificial metalloenzymes might also help us understand the cofactor (FeMo-co, FeV-co, and FeFe-co), which make three catalytic mechanisms of enzymes at the molecular level. The corresponding nitrogenases. The FeMo-co with a stoichiometry

inorganic complexes reported in this collection mainly mimic of Fe7MoS9C is usually more active than the other two, hydrogenase and nitrogenase, both of which play important therefore, the mimics of FeMo-co have been extensively roles in the development of sustainable and renewable energy. studied. To model FeMo-co, Rauchfuss and co-workers con- 2À There are three types of hydrogenase with distinct active sites verted [Fe6C(CO)14(S)] into clusters that more closely resemble

(i.e., [NiFe]-H2ases, [FeFe]-H2ases, and [Fe]-H2ases). Inorganic FeMo-co. Yang and co-workers synthesized a series of diiron complex models of the latter two are reported in this collection. complexes with a benzene-1,2-dithiolate (bdt) bridge to mimic

Song and co-workers synthesized a series of [Fe]-H2ase mimics nitrogenase. Taking the disproportionation of hydrazine to containing a hydride donor Hantzsch ester HEH moiety. Their ammonia as a model reaction, they showed that the substituent synthetic methodology as well as the new complexes could modulation of the bdt ligand could tune the reduction potential help us to further design better monoiron hydrogenase. [FeFe]- of the complex and thus its activity. This work provides a

H2ase-mimicking complexes were reported by Hogarth’s group strategy to modulate the nitrogenase-mimicking activity of the as well as Elleouet and Schollhammer’s group. Electrochemical complex by varying the ligand substituent. Inorganic complexes can also be used to mimic other enzymes. To this end, Ivanović-Burmazović synthesized various [a] Y. Zhang, Dr. F. Muhammad, Prof. Dr. H. Wei metal complexes to probe their electrochemical behavior and Department of Biomedical Engineering superoxide dismutase (SOD)-mimicking activity. They showed College of Engineering and Applied Sciences Nanjing National Laboratory of Microstructures that the redox potential, position of the charged groups, and Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University possible electronic communication with the metal center are all Nanjing, Jiangsu 210023 (P. R. China) crucial to tune the SOD-like activity. Besides experimental [b] Y. Zhang, Dr. F. Muhammad, Prof. Dr. H. Wei State Key Laboratory of Analytical Chemistry for Life Science endeavors, the theoretical study has also played an invaluable Chemistry and Biomedicine Innovation Center (ChemBIC) role in designing new enzyme mimics and deciphering the School of Chemistry and Chemical Engineering, Nanjing University underlying catalytic mechanisms. In view of this, following their Nanjing, Jiangsu 210023 (P. R. China) E-mail: [email protected] previous experimental study, Hörner and de Visser further This article is part of a joint Special Collection on Inorganic Enzyme carried out a computational study to elucidate the OÀ O bond- Mimetics. To view the complete collection, visit our homepage

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formation mechanism in m-chloroperbenzoic acid and iron(IV)- to exfoliate MoS2 and functionalize its surface. The lysozyme-

oxo reaction. stabilized MoS2 nanosheets exhibited enhanced bacterial Nanozymes are functional nanomaterials with enzyme- growth inhibition by physical cutting, hydrolyzing cell walls, mimicking activities. They are considered to be the next and producing excessive ROS. Li, Gao and co-workers reported

generation of enzyme mimics because of their unique features a copper-based bimetallic sulfide nanozyme (CuCo2S4) that compared with natural enzymes and conventional enzyme displayed an excellent antibacterial performance due to its mimics. They are not only more stable and cost-effective, but outstanding peroxidase-like activity under neutral pH condi- also have facilely tunable activity and multifunctionality. To this tions. Nitrogenases could also be mimicked by using nano- end, several reports in this collection demonstrated various materials. Liu, Yao and co-workers found that the bowknot- ways to modulate the catalytic activity of nanozymes. Yigit and shaped iron molybdate nanosheet clusters were able to mimic co-workers demonstrated that the peroxidase-like activity of 2D nitrogenase because of the same bimetal-active atoms (i.e., Fe nanomaterials could be regulated by using metal ions; while Xia and Mo). They then synthesized ammonia in an electrochemical and co-workers showed that the peroxidase-like activity of PdÀ nitrogen reduction reaction (NRR) with iron molybdate as Ir core-shell nanoparticles could be modulated by their sizes. By catalyst. taking advantage of the size-dependent activity, they further Three reviews on nanozymes were covered in this collec- developed more-sensitive immunoassays with smaller sized tion. Yang et al. summarized recent progress in the detection of nanozymes. Su, Liu and co-workers systematically studied the virulent microorganisms by using nanozymes. Moreover, they effects of five representative phosphates on the oxidase-like offered many critical points that can be a helpful guide for activity of nanoceria. They showed that the promotion or practical and accurate future applications. In a minireview, Li inhibition effects of phosphates are dependent on the buffer, and Ding highlighted recent developments and biomedical substrates, and the aggregation states of nanoceria. This study applications of nanozymes. The review of Gu and co-workers is indicated that particular attention should be paid when using focused on iron-based nanozymes. Taking iron oxide and nanoceria as enzyme mimic. Rotello and co-workers used a Prussian Blue as two representative nanozymes, they discussed biorthogonal approach to build a coating of monolayer the synthesis, activity, mechanism and potential applications of transition metal catalyst to preserve its activity under various iron-based nanozymes. pH conditions and in complex biological media conditions In their contribution, Wang, Wang, Liu and co-workers under which a free transition metal catalyst is normally carried out a systematic study to understand the links between deactivated. This active-site-isolation strategy is more or less these two classic and widely used DNAzymes (i.e., GR5 and similar to an isolated active site in a natural enzyme. 17E). They were able to identify key nucleotides for metal The aforementioned studies showed the various strategies specificity. used to modulate the nanozyme activity; other articles have Even though the above collection represents only a very demonstrated the wide applications of nanozymes in sensing, small fraction of the work in the field, the progress made will diagnosis and therapeutics. Deng, Chen, Hong and co-workers encourage the enzyme-mimic community and others to further reported copper oxide nanoparticle as an ascorbic acid advance the frontiers of the field. Here, a few potential oxidase–mimicking nanozyme. They further used it to construct directions are briefly discussed, solely from our own perspec- a fluorescent assay to selectively detect ascorbic acid. Yin and tives. First, although the inorganic complex-based and nano- co-workers reported a lysozyme-mediated exfoliation method material-based mimics are discussed separately here, combining

Yihong Zhang received his Bachelor degree Hui Wei is a Professor at Nanjing University (2018) from Lanzhou University. He is a Ph.D. and a Fellow of the Royal Society of candidate of materials science and engineer- Chemistry. He received his B.S. degree from ing in Nanjing University. His research interest Nanjing University (advisor: Professor Xinghua is synthesis and application of nanozymes. Xia) and Ph.D. degree from Changchun Insti- tute of Applied Chemistry, Chinese Academy of Sciences (advisor: Professor Erkang Wang). He then joined Professors Yi Lu’s and Shuming Nie’s groups for two periods of postdoctoral training before he started his independent Faheem Muhammad received his Master de- career at Nanjing University. His research gree (2002) from Peshawar University and interests are focused on the design and syn- Ph.D. degree (2012) from Jilin University under thesis of functional nanomaterials (such as the supervision of Professor Zhu Guangshan. nanozymes) and the development of new He was a postdoctoral fellow at Jilin university methodologies for analytical and biomedical from 2012–2014. He then joined Professor Hui applications. Wei’s lab as a research scientist. His research focuses on the design and synthesis of functional nanomaterials and their biomedical and catalytic applications.

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them could lead to better enzyme mimics and even achieve ground-breaking products to fulfill the promise of enzyme synergistic properties. Second, traditionally, research into mimics and make a big difference in future science. enzyme mimics aims to imitate protein enzymes, now the I am very grateful to all the authors for contributing high- exploration of (ribo)nucleic acid-based enzyme mimics could be quality papers to this Special Collection, and all the reviewers a rewarding adventure given the importance of ribozymes. for their time and efforts in reviewing the recent development Third, the combination of experiments (including advanced in enzyme mimics. I also wish to thank the Editorial Offices of operando characterizations) with theoretical study is very help- the two journals for their work and help in organizing such a ful to understand catalytic mechanisms and design better unique collection. Enjoy reading. mimics. Due to the intrinsically interdisciplinary nature of this field, the collaboration among researchers from chemistry, materials science, biology, medicine, etc. will bring more

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