Intrinsic Apyrase-Like Activity of Cerium-Based Metal–Organic Frameworks (MOFs): Dephosphorylation of Adenosine Tri- and Diphosphate

Article abstract of DOI:10.1002/anie.202008259

Apyrase is an important family of extracellular enzymes that catalyse the hydrolysis of high-energy phosphate bonds (HEPBs) in ATP and ADP, thereby modulating many physiological processes and driving life activities. Herein, we report an unexpected discovery that cerium-based metal–organic frameworks (Ce-MOFs) of UiO-66(Ce) have intrinsic apyrase-like activity for ATP/ADP-related physiological processes. The abundant Ce^III/Ce^IV couple sites of Ce-MOFs endow them with the ability to selectively catalyse the hydrolysis of HEPBs of ATP and ADP under physiological conditions. Compared to natural enzymes, they could resist extreme pH and temperature, and present a broad range of working conditions. Based on this finding, a significant inhibitory effect on ADP-induced platelet aggregation was observed upon exposing the platelet-rich plasma (PRP) to the biomimetic UiO-66(Ce) films, prefiguring their wide application potentials in medicine and biotechnology.

Full text of DOI:10.1002/anie.202008259

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Intrinsic Apyrase-Like Activity of Cerium-Based Metal-Organic
Frameworks: Dephosphorylation of Adenosine Tri- and
Diphosphate
Authors: Jian Yang, Ke Li, Chunzhong Li, and Jinlou Gu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202008259
Link to VoR: https://doi.org/10.1002/anie.202008259

10.1002/anie.202008259
Angewandte Chemie International Edition
COMMUNICATION
Intrinsic Apyrase-Like Activity of Cerium-Based Metal-Organic
Frameworks: Dephosphorylation of Adenosine Tri- and
Diphosphate
Jian Yang, Ke Li, Chunzhong Li,* and Jinlou Gu*
[*]
Dr. J. Yang, Dr. K. Li, Prof. C. Li, Prof. J. Gu
Shanghai Engineering Research Center of Hierarchical Nanomaterials, School of Materials Science and Engineering, East China University of Science and
Technology
Shanghai 200237, China
E-mail: jinlougu@ecust.edu.cn; czli@ecust.edu.cn
Supporting information for this article is given via a link at the end of the document.
Abstract: Apyrase represents an important family of extracellular
enzymes that catalyze the hydrolysis of high-energy phosphate bonds
(HEPBs) in ATP and ADP, thereby modulating many physiological
processes and driving life activities. Here, we report an unexpected
discovery that cerium-based metal-organic frameworks (Ce-MOFs) of
UiO-66(Ce) possess intrinsic apyrase-like activity for the intervention
of ATP/ADP-related physiological processes. The abundant
Ce(III)/Ce(IV) couple sites of Ce-MOFs endow them with the ability to
selectively catalyse the hydrolysis of HEPBs of ATP and ADP under
physiological condition. Compared to natural enzymes, they could
resist to extreme pH and temperature, and present a broad range of
working conditions. Based on this finding, a significant inhibitory effect
on ADP-induced platelet aggregation was observed upon exposing
the platelet-rich plasma (PRP) to the biomimetic UiO-66(Ce) films,
prefiguring their wide application potentials in medicine and
biotechnology.
The dephosphorylation of ATP is an important energy transfer
process to drive life activities through the catalytic hydrolysis of
high-energy phosphate bonds (HEPBs). Meanwhile, many
important physiological processes, such as blood clotting,
inflammation, immune response as well as neurotransmitters, are
regulated with ATP and ADP as signaling molecules through the
catalytic hydrolysis of their HEPBs using apyrase (nucleotide
triphosphate diphosphohydrolases) as a catalyst (Figure 1a).[1]
Despite the extensive distribution and evolution of apyrase family
in plants, microorganisms and mammals,[2] there is few reports, if
any, on the development of biomimetic materials to satisfy with its
enzymatic mimics for the intervention of ATP/ADP-related
physiological processes.
MOFs represent a rapidly growing class of crystalline materials
with broad applications.[3] Their ordered topology provides high-
density accessible metal centers with well-defined metallocluster
structure and spatial arrangement, making MOFs singularly
attractive as biomimetic catalytic materials.[4] In recent years, a
few studies have demonstrated that selected MOFs with specific
metal nodes could serve as efficient mimics for various
metalloenzymes.[5] In view of the important roles of ATP and ADP
Figure 1. Schematic illustration of (a) the catalytic hydrolysis process and
dephosphorylation mechanism of ATP over (b) apyrase and (c) UiO-66(Ce). In
the form of a plan view, molecular structure of the surface Ce6 node of UiO-
66(Ce) shows five of the eight bound BDC ligands, since three linkers are
overlapped.
The dephosphorylation of ATP over natural apyrase generally
consists of two main steps (Figure 1b): (i) two phosphate groups
of substrate directly coordinate with a divalent metal cation and
enter into the catalytic pocket of enzyme; (ii) a nucleophilic water
molecule approaches several adjacent amino acid residues of
apyrase and further attacks the terminal phosphate group to drive
the dephosphorylation process.[1b] To mimic the functions of
natural apyrase, the key element is to provide active sites which
afford appropriate affinity and enough catalytic activity toward the
hydrolysis of HEPBs. Meanwhile, the hydrolyzed product of
inorganic phosphates is subject to leave the active sites. After
screening numerous MOFs family, we made an unexpected
discovery that Ce-MOFs of UiO-66(Ce) indeed featured intrinsic
apyrase-like activity (Figure 1c). Compared to natural apyrase
family, the biomimetic UiO-66(Ce) nanoparticles (NPs) could
drive the dephosphorylation process in the absence of divalent
cation, and rapidly convert a part of ATP into AMP. More
importantly, they present an excellent stability against extreme
temperature and pH, as well as broad working range. It is
played
in
many
physiological
processes
through
dephosphorylation, it naturally promotes us to explore the
possibility of using periodically aligned metalloclusters in MOFs to
mimic apyrase for the selective hydrolysis of HEPBs.
1
This article is protected by copyright. All rights reserved.

10.1002/anie.202008259
Angewandte Chemie International Edition
COMMUNICATION
experimentally revealed that Ce(IV)-OH groups function as the
active sites for the polarization and hydrolysis of HEPBs while
Ce(III) species might work as synergistic sites to attract H2O
molecules for the promotion of hydrolysis process (Figure 1c,
right). Given the apyrase-like activity of UiO-66(Ce) NPs, we
fabricated flexible UiO-66(Ce) film as a bionic antithrombotic
coating to inhibit ADP-induced platelet adhesion, exemplifying
their wide application potentials for the intervention of ATP/ADP-
related physiological processes in life sciences.
(Figures 2c and S5b). Interestingly, different from the apyrase-
catalytic pathway, an obvious characteristic peak of AMP is
rapidly formed at the initial 30 min during the ATP hydrolysis
process with UiO-66(Ce) (Figure 2b), similar to the catalytic
behavior of CD39 oligomers.[9] The presence of the high-density
periodically aligned active catalytic centers of metalloclusters on
the UiO-66(Ce) might rationalize the fact that a lot of ATP could
rapidly convert into AMP. A part of ADP intermediate released
from the cerium sites might be immediately recombined by a large
number of adjacent catalytic centers and further hydrolyzed to
AMP, so that they could reduce the accumulation of ADP during
the hydrolysis process of ATP.
Kinetic curves display that the hydrolysis rate of ATP over Ce-
MOFs is much quicker than that of ADP (Figure 2d), similar to the
catalytic process using apyrase as a catalyst (Figure S5c). On
the other hand, AMP plays an important role in many physiological
metabolisms and participates in ATP regeneration cycle through
rephosphorylation,[10] thus the selective hydrolysis of HEPBs is of
great significance for apyrase mimics. Fortunately, UiO-66(Ce)
could selectively dephosphorylate ATP and ADP without the
obvious destruction of phosphomonoester bonds in AMP and
other nonnucleoside phosphates (Figure 2e). To further verify
that the observed activity really results from UiO-66(Ce), the
reaction mixtures were filtered to remove the mimic enzyme of
Ce-MOFs during the reaction process.[11] As shown in Figure 2f,
the catalytic reactions were terminated immediately upon
removing Ce-MOFs. Furthermore, the hydrolysis of ATP and ADP
was negligible when no UiO-66(Ce) was applied to the reaction
system as the control measurement verified (Figure S7), further
confirming that the occurrence of dephosphorylation was indeed
due to the presence of Ce-MOFs.
Temperature, pH and divalent cations are important factors that
impact the catalytic activity of apyrase.[1b,12] It could be observed
that UiO-66(Ce) could directly dephosphorylate ATP/ADP
substrate, in which the catalytic efficiency is independent on the
addition of Ca2+ (Figures S8 and S9). It matches well with the fact
that the metalloclusters on the surface of UiO-66(Ce) play active
sites to catalyze the hydrolysis of the terminal phosphate group of
ATP/ADP. The optimal pH for UiO-66(Ce) is determined to be
approximately 7.4 through a standard malachite green assay
(Figures 3a and S10),[13] which is similar to the value for apyrase
(Figure S11a). Additionally, apyrase presents the optimal
catalytic activity between 30 to 40 oC, while its activity is
significantly inhibited at higher temperature (Figures 3b and
S11b). In contrast, the catalytic activity of UiO-66(Ce) constantly
increased upon elevating the temperature to 60 oC. Obviously, the
excellent stability of Ce-MOFs could enable them to resist higher
reaction temperature and to promote the hydrolysis efficiency of
substrate. To test this, we measured their catalytic activity after
the pre-incubation under various pHs and temperatures. The UiO-
66(Ce) were indeed found to preserve their catalytic activity after
pre-treatment (Figures 3c, 3d and S12). In contrast, the apyrase
enzyme only maintains their activity after the mild treatment at
pHs between 5 to 9, or temperatures lower than 50 oC. Given that
the activity of apyrase is susceptible to temperature, pH and
extensive protease, the robustness of UiO-66(Ce) NPs makes
them suitable for a wide range of applications in the biotechnology.
Since ATP molecule is too large to access the interior of UiO-
66, thus the catalysis mainly occurs on the Ce6 clusters on the
surface of MOFs.[14] To investigate the mechanism of the apyrase-
like activity of UiO-66(Ce), XPS spectra were firstly employed to
Figure 2. (a) XRD patterns of the UiO-66(Ce). 31P-NMR spectra of the catalytic
hydrolysis process for (b) ATP and (c) ADP by UiO-66(Ce) in physiological
conditions (pH = 7.4; 37 oC). (d) Conversion percentage of substrates versus
time over UiO-66(Ce). (e) The relative activities of UiO-66(Ce) and apyrase
toward the catalytic hydrolysis of various phosphate bond-containing substrates.
(f) Hydrolysis profiles of ATP and ADP in the presence of UiO-66(Ce) and after
the removal of Ce-MOFs by filtration.
The preparation of UiO-66(Ce) was optimized through a
modified solvothermal reaction (Figures S1 and S2).[6] The XRD
patterns reveal that the pure phase of UiO-66(Ce) is obtained
(Figure 2a). Meanwhile, their BET surface area is determined to
be about 1318 m2 g-1, comparable to the reported value (Figure
S3).[6] Based on the TGA profile, the number of linker deficiencies
of per Ce6 formula unit is calculated to be about 1.23 (Figure S4).
31P-NMR spectra were employed to monitor the ATP hydrolysis
process over UiO-66(Ce) in physiological condition with apyrase
as comparison. Similar to a typical apyrase catalytic pathway
(Figure S5a),[7] it could be observed that the characteristic peak
of β-ATP gradually disappears within 24 h and converts into those
of α-ADP, β-ADP, AMP and phosphate over UiO-66(Ce) (Figures
2b and S6). Meanwhile, the characteristic peak of pyrophosphate
(around -5.3 ppm) is not detected,[8] demonstrating that ATP
converts into AMP through a sequential hydrolysis of their
terminal phosphate over UiO-66(Ce). The similar catalytic
phenomena were also observed when ADP was directly
employed as the substrate over UiO-66(Ce) and apyrase
2
This article is protected by copyright. All rights reserved.

10.1002/anie.202008259
Angewandte Chemie International Edition
COMMUNICATION
reveal the detailed surface compositions of UiO-66(Ce). The
Ce3d XPS spectra of UiO-66(Ce) disclose that Ce ions exist in
different valence states (Figure 3e).[15] The ratio of Ce(III)/Ce(IV)
on the surface is estimated to be around 2 : 4 (Table S1), which
means each Ce6O4(OH)4 cluster on the surface contains two
Ce(III) and four Ce(IV) ions on average. The O1s XPS spectra
reveal that approximate 67% oxygen presents in the form of
surface Ce-OH groups (Figure S13),[16] further confirming the
presence of dense and exposed Ce(III)/Ce(IV) hydroxyl active
Ce(III)-bound water molecule was reported as a more efficient
nucleophilic agent than hydroxyl group bound to Ce(IV).[18b,19]
Hence, Ce(III) sites might work as synergistic sites to provide a
more effective nucleophilic attack towards the attached P atom of
ATP, which could promote the hydrolysis process.
Within the suitable concentrations range of ATP and ADP
substrates, typical Michaelis–Menten curves were achieved for
both UiO-66(Ce) (Figures 3f and S18) and apyrase (Figure S19).
The apparent Km values of the UiO-66(Ce) with ATP and ADP as
sites for the catalytic reaction. After the catalytic hydrolysis of ATP, the substrate were lower than those of apyrase (Tables S3 and
UiO-66(Ce)-ATP sample exhibit negligible change of surficial
Ce(III)/Ce(IV) ratio (Figure S14 and Table S2), indicating that the
reaction would not affect the catalytic sites thanks to the excellent
chemical stability of UiO-66(Ce).
S4), indicating that UiO-66(Ce) NPs present higher affinity toward
substrates than apyrase.[20] This is reasonable due to the fact that
the cerium hydroxyl groups are densely distributed on the surface
of UiO-66(Ce) and are well exposed to the substrates in the
reaction. Besides cerium cluster, it has been well documented
that other metal clusters in MOFs could also present affinity
toward phosphate bond.[5b,18] However, the other stable MOFs
exhibit no obvious catalytic activity for the hydrolysis of ATP
(Figures S20 and S21), indicating that the catalytic characteristic
of hydrolyzing HEPBs is unique to Ce-MOFs.
This unique apyrase-like activity of UiO-66(Ce) NPs endows
them with great potential to intervene the ATP/ADP-related
physiological processes in life sciences. Extracellular ADP
(eADP) functions as an important signaling molecule to induce
platelets aggregation and subsequent coagulation cascade
through the interaction of eADP and P2 receptors on platelets
(Figure 4a, left).[1a] Correspondingly, apyrase-induced
dephosphorylation of eADP could effectively inhibit the platelets
aggregation,[1a,21] just as this principle is utilized by
hematophagous arthropods to block host coagulation response in
nature.[22] Inspired by this nature phenomenon, we designed a
flexible UiO-66(Ce)-embedded polyvinylidene difluoride (PVDF)
film (Figures 4b (inset) and S22-S25) as a bionic antithrombotic
surface to catalytically hydrolyze eADP and to inhibit platelet
aggregation (Figure 4a, right),[23] which has the potential to
improve long-term patency of biomedical devices such as
vascular stents and catheters. The surface image of UiO-66(Ce)
film shows the full exposure of MOFs crystallites without the
coverage of PVDF (Figure 4b), ensuring the effective contact
between eADP and active sites of Ce-MOFs. To examine the anti-
adhesion ability of platelets on various surfaces, platelet-rich
plasma (PRP) was incubated on glass, PVDF and UiO-66(Ce) film,
in the presence or absence of ADP activator. Celltracker Green
(CMFDA) was employed to track the adhered platelets on the
surface of materials.[21] It was observed that small amounts of
platelets adhered on glass and PVDF film with sporadic
distribution of green fluorescence in the absence of ADP (Figures
4c and 4d). Upon the activation with ADP, severe platelet
adhesion would occur on the surface of these materials (Figures
4f and 4g). On the contrast, the UiO-66(Ce) film significantly
inhibited platelet adhesion even in the presence of ADP activator
(Figures 4e and 4h) thanks to the apyrase-like activity of
embedded Ce-MOFs for the dephosphorylation of eADP and
consequently block its interaction with P2 receptors.[1a] SEM
images further illustrate that under the action of ADP activator, the
surfaces of glass and PVDF sample are attached with compact
and aggregated platelets, while almost no aggregated platelets
are observed on the surface of UiO-66(Ce) film (Figures 4i-4k),[24]
in good agreement with the observation of the inverted
fluorescence microscope. We believe that these easily prepared
coatings can provide potential options for the preparation of
Figure 3. Effects of (a) pH and (b) temperature on ATP hydrolysis over apyrase
and UiO-66(Ce). Catalytic activities of apyrase and UiO-66(Ce) after incubation
at (c) various pHs and (d) temperatures. (e) The magnified Ce3d XPS spectra
of UiO-66(Ce). (f) The Michaelis–Menten plots for UiO-66(Ce) with various
concentrations of ATP and ADP substrates. (g) The possible reaction process
of ATP hydrolysis over Ce6 cluster on the surface of UiO-66(Ce).
To further determine the roles of Ce(IV)-OH and Ce(III)-OH
sites played in apyrase-like catalysis, the control experiments
were performed on Ce hydroxocomplexes systems containing
various ratios of Ce(III)/Ce(IV) (Section S4.4, Figures S15-S17).
The control experiments exhibit that Ce(IV) hydroxocomplexes
solution could continuously dephosphorylate ATP substrate and
form the product of phosphate. In contrast, Ce(III) solution have
negligible effect on the dephosphorylation of ATP (Figure S15). It
indicates that Ce(IV)-OH is decisive active site to hydrolyze the
HEPBs of ATP. Interestingly, the introduction of a small amount
of Ce(III) can increase the ATP hydrolysis efficiency of the Ce(IV)
hydroxocomplexes system (Figure S16), indicating that Ce(III)
could promote the hydrolysis ability of Ce(IV)-OH sites. The
Ce(III)-related effect was also observed in the cluster-catalyzed
phosphate esters hydrolysis.[17] Based on the dephosphorylation
mechanism of phosphate esters,[18] the Ce(IV)-OH sites is
required here because Ce(IV) is necessary to activate the HEPBs
of ATP and to make it more susceptible for the following
nucleophilic attack (Figures 1c and 3g).[18b] In the following step,
the surface OH group or bound water molecule on Ce6 cluster
would attack the P atom and causes the cleavage of HEPBs. The
3
This article is protected by copyright. All rights reserved.

10.1002/anie.202008259
Angewandte Chemie International Edition
COMMUNICATION
blood-contacting biomedical devices to reduce the formation of
thrombosis. Meanwhile, the experimental results also indicate
that the dephosphorylation process could be effectively
intervened to regulate many ATP/ADP-related life activities in the
future.
Keywords: apyrase • adenosine triphosphate • biomimetic
chemistry • high-energy phosphate bonds • metal-organic
frameworks
[1]
a) D. Moeckel, S. S. Jeong, X. Sun, M. J. Broekman, A. Nguyen, J. H. F.
Drosopoulos, A. J. Marcus, S. C. Robson, R. Chen, D. Abendschein, Sci.
Transl. Med. 2014, 6, 248ra105; b) M. Zebisch, N. Sträter, Proc. Natl.
Acad. Sci. U. S. A. 2008, 105, 6882–6887. c) A. V. Gourine, E. Llaudet,
N. Dale, K. M. Spyer, Nature 2005, 436, 108–111.
[2]
[3]
[4]
[5]
P. Faria-Pinto, F. A. Rezende-Soares, A. M. Molica, M. A. Montesano,
M. J. Marques, M. O. C. Rocha, J. A. S. Gomes, M. J. Enk, R. Correa-
Oliveira, P. M. Z. Coelho, et al., Parasitology 2008, 135, 943–953.
a) G. Maurin, C. Serre, A. Cooper, G. Férey, Chem. Soc. Rev. 2017, 46,
3104–3107; b) G. C. Shearer, J. G. Vitillo, S. Bordiga, S. Svelle, U.
Olsbye, K. P. Lillerud, Chem. Mater. 2016, 28, 7190–7193.
a) I. Nath, J. Chakraborty, F. Verpoort, Chem. Soc. Rev. 2016, 45, 4127–
4170; b) M. Zhang, Z. Y. Gu, M. Bosch, Z. Perry, H. C. Zhou, Coord.
Chem. Rev. 2015, 293–294, 327–356.
a) A. M. Wright, Z. Wu, G. Zhang, J. L. Mancuso, R. J. Comito, R. W.
Day, C. H. Hendon, J. T. Miller, M. Dincă, Chem 2018, 4, 2894–2901; b)
J. E. Mondloch, M. J. Katz, W. C. Isley III, P. Ghosh, P. Liao, W. Bury, G.
W. Wagner, M. G. Hall, J. B. DeCoste, G. W. Peterson, et al., Nat. Mater.
2015, 14, 512–516.
[6]
[7]
M. Lammert, M. T. Wharmby, S. Smolders, B. Bueken, A. Lieb, K. A.
Lomachenko, D. D. Vos, N. Stock, Chem. Commun. 2015, 51, 12578–
12581.
Z. Song, K. J. Parker, I. Enoh, H. Zhao, O. Olubajo, Anal. Bioanal. Chem.
2009, 395, 1453–1459.
[8]
[9]
Y. Sang, O. Prakash, P. A. Sei, Carbohydr. Polym. 2007, 67, 201–212.
W. Chen, G. Guidotti, Biochem. Biophys. Res. Commun. 2001, 282, 90–
95.
[10] L. Plesner, Int. Rev. Cytol. 1995, 158, 141–214.
[11] S.-Y. Moon, Y. Liu, J. T. Hupp, O. K. Farha, Angew. Chem. Int. Ed. 2015,
54, 6795–6799; Angew. Chem. 2015, 127, 6899–6903.
Figure 4. (a) Scheme of UiO-66(Ce) film to suppress platelet adhesion against
the ADP inducement of platelet aggregation. (b) SEM image and the inset
photograph of flexible UiO-66(Ce) film. The platelets were stained with CMFDA
and observed through fluorescent inverted microscope after their incubation on
glass (c, f), PVDF (d, g) and UiO-66(Ce) film (e, h) in the absence or presence
of ADP (10 μM). The platelets were observed through SEM after their incubation
on glass (i), PVDF (j) and UiO-66(Ce) film (k) in the presence of ADP.
[12] D. W. Rooklin, M. Lu, Y. Zhang, J. Am. Chem. Soc. 2012, 134, 15595–
15603.
[13] E. L. Summers, M. H. Cumming, T. Oulavallickal, N. J. Roberts, V. L.
Arcus, Protein Sci. 2017, 26, 1627–1638.
[14] M. J. Katz, J. E. Mondloch, R. K. Totten, J. K. Park, S. T. Nguyen, O. K.
Farha, J. T. Hupp, Angew. Chem. Int. Ed. 2014, 53, 497–501; Angew.
Chem. 2014, 126, 507–511.
[15] E. Bêche, P. Charvin, D. Perarnau, S. Abanades, G. Flamant, Surf.
Interface Anal. 2008, 40, 264–267.
In conclusion, we provide the report that Ce-MOFs can mimic
apyrase to selectively catalyze the hydrolysis of HEPBs in ATP
and ADP. UiO-66(Ce) NPs exhibit divalent cation independence
and excellent chemical stability during the dephosphorylation of
ATP, which is significantly different with that of apyrase. The
Ce(III)/Ce(IV) couple sites play important roles in which Ce(IV)-
OH serves as the bonding sites for the polarization and hydrolysis
of HEPBs, and Ce(III) might work as a synergistic site to attract
H2O for the nucleophilic attack. Furthermore, the development of
flexible UiO-66(Ce) films and its anti-aggregation effect of platelet
exemplify their potential applications as an antithrombotic coating
for blood-contacting medical devices. We expected that this
finding would promote the development of biomimetic materials
and open up potential applications to regulate ATP/ADP-related
physiological processes such as energy supply, inflammation,
immune response and blood clotting.
[16] X. Zhu, J. Gu, Y. Wang, B. Li, Y. Li, W. Zhao, J. Shi, Chem. Commun.
2014, 50, 8779–8782.
[17] J. Liu, L. R. Redfern, Y. Liao, T. Islamoglu, A. Atilgan, O. K. Farha, J. T.
Hupp, ACS Appl. Mater. Interfaces 2019, 11, 47822–47829.
[18] a) F. A. Son, A. Atilgan, K. B. Idrees, T. Islamoglu, O. K. Farha, Inorg.
Chem. Front. 2020, 7, 984–990; b) P. Janoš, J. Ederer, M. Došek, J.
Štojdl, J. Henych, J. Tolasz, M. Kormundac, K. Mazanec, Environ. Sci.:
Nano 2019, 6, 3684–3698; c) T. Islamoglu, A. Atilgan, S. Y. Moon, G. W.
Peterson, J. B. DeCoste, M. Hall, J. T. Hupp, O. K. Farha, Chem. Mater.
2017, 29, 2672–2675.
[19] A. A. Vernekar, T. Das, G. Mugesh, Angew. Chem. Int. Ed. 2016, 55,
1412–1416; Angew. Chem. 2016, 128, 1434–1438.
[20] L. Gao, J. Zhuang, L. Nie, J. Zhang, Y. Zhang, N. Gu, T. Wang, J. Feng,
D. Yang, S. Perrett, et al., Nat. Nanotechnol. 2007, 2, 577–583.
[21] P. H. Nilsson, A. E. Engberg, J. Bäck, L. Faxälv, T. L. Lindahl, B. Nilsson,
K. N. Ekdahl, Biomaterials 2010, 31, 4484–4491.
[22] T. M. Smith, C. A. Hicks-Berger, S. Kim, T. L. Kirley, Arch. Biochem.
Biophys. 2002, 406, 105–115.
[23] M. S. Denny, S. M. Cohen, Angew. Chem. Int. Ed. 2015, 54, 9029–9032;
Angew. Chem. 2015, 127, 9157–9160.
Acknowledgements
[24] P. S. Wheatley, A. R. Butler, M. S. Crane, S. Fox, B. Xiao, A. G. Rossi,
I. L. Megson, R. E. Morris, J. Am. Chem. Soc. 2006, 128, 502–509.
This work was financially supported by the Natural Science
Foundation of China (21975072, 51902106, 21838003), the
Natural Science Foundation of Shanghai (18ZR1408700).
4
This article is protected by copyright. All rights reserved.

10.1002/anie.202008259
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
Cerium-based MOFs present intrinsic apyrase-like activity for the selective dephosphorylation of ATP and ADP through the catalytic
hydrolysis of their high-energy phosphate bonds, and subsequently their intervention toward ATP/ADP-related physiological process
was exemplified to demonstrate their great application potentials in life science.
5
This article is protected by copyright. All rights reserved.