Nanoisozymes: Crystal-Facet-Dependent Enzyme-Mimetic Activity of V2O5 Nanomaterials

Article abstract of DOI:10.1002/anie.201800681

Nanomaterials with enzyme-like activity (nanozymes) attract significant interest owing to their applications in biomedical research. Particularly, redox nanozymes that exhibit glutathione peroxidase (GPx)-like activity play important roles in cellular signaling by controlling the hydrogen peroxide (H₂O₂) level. Herein we report, for the first time, that the redox properties and GPx-like activity of V₂O₅ nanozyme depends not only on the size and morphology, but also on the crystal facets exposed on the surface within the same crystal system of the nanomaterials. These results suggest that the surface of the nanomaterials can be engineered to fine-tune their redox properties to act as “nanoisozymes” for specific biological applications.

Full text of DOI:10.1002/anie.201800681

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Nanoisozymes: Crystal Facet-Dependent Enzyme Mimetic
Activity of V2O5 Nanomaterials
Authors: Sourav Ghosh, Punarbasu Roy, Naiwrit Karmodak,
Eluvathingal D. Jemmis, and Govindasamy Mugesh
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.201800681
Angew. Chem. 10.1002/ange.201800681
Link to VoR: http://dx.doi.org/10.1002/anie.201800681
http://dx.doi.org/10.1002/ange.201800681

10.1002/anie.201800681
Angewandte Chemie International Edition
COMMUNICATION
Nanoisozymes: Crystal Facet-Dependent Enzyme Mimetic Activity
of V2O5 Nanomaterials
Sourav Ghosh, Punarbasu Roy, Naiwrit Karmodak, Eluvathingal D. Jemmis, and Govindasamy Mugesh*
Abstract: Nanomaterials with enzyme-like activity (nanozymes)
attract significant interest owing to their applications in biomedical
research. Particularly, redox nanozymes that exhibit glutathione
peroxidase (GPx)-like activity play important roles in cellular
signalling by controlling the hydrogen peroxide (H2O2) level. Herein
we report, for the first time, that the redox properties and GPx-like
activity of V2O5 nanozyme depends not only on the size and
morphology, but also on the crystal facets exposed on the surface
within the same crystal system of the nanomaterials. These results
suggest that the surface of the nanomaterials can be engineered to
fine-tune their redox properties to act as “nanoisozymes” for specific
biological applications.
Figure 1. Estimated ranges of H2O2 concentration in oxidative stress with
regard to cellular responses. Modified from Ref. [6] (Grx: glutaredoxin, Trx:
thioredoxin, TrxR: thioredoxin reductase, Prx: peroxiredoxin).
Hydrogen peroxide (H2O2) plays crucial roles in redox biology
and cell signalling.[1] Cellular redox dynamics is regulated by
feedback pathways that maintain the level of H2O2 below the
Nanomaterials that mimic the function of redox enzymes
have attracted significant interest.[7] Recently, we reported that
V2O5 nanowires can protect cells from oxidative damage by
exhibiting GPx-like activity in the presence of GSH.[8] This study
revealed that the potentially toxic V2O5 can be turned into
cytoprotective antioxidant by reducing the size of the material. It
has been shown that bulk V2O5 or vanadium (V) complexes are
highly toxic to the cells and modulation of the redox property of
vanadium in the nano-form is crucial for its protective role.
Previous studies showed that the catalytic performance of a
nanomaterial, in general, can be altered by controlling the shape,
size and surface coating.[9] The surface reactivity and redox
behaviour depend greatly on the atomic arrangement of surface
atoms and the number of dangling bonds on crystal facets.[10]
However, the identification of enzyme-like active sites on nano-
V2O5 has been difficult and it is unclear whether the GPx activity
of this material depends on its size, shape and/or crystal facets.
As maintenance of a desired redox activity is a challenging task,
a detailed atomic-level understanding of nanozyme surfaces is
crucial to design materials suitable for biomedical applications.
In this paper, we report on the synthesis of orthorhombic V2O5
nanocrystals in different morphologies and show for the first time
that alteration in the crystal facets within the same crystal
system produces nanoisozymes capable of fine-tuning the
desired redox activity. We also describe the nature of
catalytically active species involved in the surface reactions
using in-situ Raman spectroscopy.
toxic threshold. However, excessive amounts of H2O2 induce
oxidative stress, resulting in damage to biomolecules such as
DNA, proteins, and lipids.[2] In the long term, these damages
lead to various disorders, such as neurodegeneration, HIV
activation, cardiovascular diseases, cancer, and aging etc.[3] The
antioxidant enzyme glutathione peroxidase (GPx) plays key
roles in maintaining the redox homeostasis and protect the cells
from oxidative damage.[4]
A
significant variation in the
concentration of H2O2 required to initiate a particular biological
response has been observed for different cell types. Therefore,
multiple forms of GPx enzymes (isozymes) are known to control
the intracellular as well as extracellular H2O2 levels using
glutathione (GSH) as cofactor. Recent studies reveal that the
peroxide-reducing ability of GPx4 isozyme prevents the iron-
mediated ferroptosis, a novel form of non-apoptotic cell death.[5]
At lower concentrations, H2O2 oxidizes cysteine residues on
proteins to the corresponding sulfenic acids and initiates redox
biology (Figure 1).[6] When the concentration of H2O2 is very high,
the cysteine residues undergo irreversible oxidation to produce
protein sulfinic and sulfonic acid species, which are biomarkers
of oxidative stress. Further, the cysteine-containing
peroxiredoxins (Prx), which are known to fine-tune the H2O2
levels, are inactivated by high levels of H2O2 as the thiol group in
these proteins undergo overoxidation to sulfinic acid.[6c] In
addition, elevated level of H2O2 leads to the formation of
hydroxyl radicals (OH•), which together with other reactive
oxygen species (ROS) such as peroxynitrite (ONOO) and
hypochlorous acid (HOCl) damage biomolecules (Figure 1).[6]
For this study, we synthesized V2O5 nanocrystals in four
different morphologies – nanowires (VNW), nanosheets (VSh),
nanoflowers (VNf) and nanospheres (VSp). The scanning
electron microscopy (SEM) and transmission electron
microscopy (TEM) images confirmed the formation of four
distinguishable morphologies of V2O5 nanocrystals (Figure 2a-d
and Figure S1). The energy dispersive spectroscopy (EDS) and
X-ray mapping confirmed the presence and distribution of
vanadium (V) and oxygen (O) in all four materials (Figures S2
[a]
S. Ghosh, P. Roy, N. Karmodak, Prof. Dr. E. D. Jemmis, Prof. Dr. G.
Mugesh
Department of Inorganic and Physical Chemistry
Indian Institute of Science, Bangalore-560012
E-mail: mugesh@iisc.ac.in
Supporting information of this article can be found under:
https://doi.org/10.1002/anie.2018xxxx.
This article is protected by copyright. All rights reserved.

10.1002/anie.201800681
Angewandte Chemie International Edition
COMMUNICATION
and S3). The crystalline nature of the nanomaterials was
confirmed by powder X-ray diffractometer (XRD) (Figure S4) and
the diffraction peaks were indexed to standard V2O5
orthorhombic phase (JCPDS = 41-1426, space group Pmmn).[11]
To gain insight into the nature of bonding between the metal and
oxygen atoms in the orthorhombic V2O5 crystals, FT-IR and FT-
Raman spectra were recorded (Figure S5 and S6, Table S1 and
S2). In the Raman spectra, the peak at 993 cm-1 corresponds to
the terminal (V=O) resulting from unshared oxygen atom of the
V2O5 crystal. The binding energies (BE) and full width at half
maxima (FWHM) for the V2p3/2 and V2p1/2 peaks determined by
X-ray photoelectron spectroscopy (XPS) analysis as well as the
difference in the BE between O1s and V2p3/2 orbitals (~12.7eV)
confirm that vanadium exists in +5 oxidation state in all four
morphologies (Figure S7, Table S3).[12]
materials were found to be highly efficient in catalysing the
reduction of H2O2.
A comparison of the activities of the
nanomaterials with three different peroxides, H2O2, t-BuOOH
and CuOOH, indicates that these materials are very selective to
H2O2 as substrate. Interestingly, the nanosphere (VSp) exhibited
the highest activity in the series and the rate of reduction of H2O2
by VSp was found to be almost two times higher than that of the
nanowires (VNw), indicating that the nanozyme activity of V2O5 is
morphology dependent. Similar activities were observed when
H2O2 was generated in situ using a glucose-glucose oxidase
enzyme system (Figure S9).
To understand the substrate binding at the surface of the
four nanomaterials, we studied the effect of H2O2 and GSH on
the reaction rates and determined the kinetic parameters such
as Michaelis constant (KM), maximum velocity (Vmax) using
various concentrations of H2O2 (0-400 μM) and GSH (0-6 mM)
under steady-state conditions. While
a typical enzymatic
Michaelis-Menten kinetics was observed for both the substrates
(Figure 2g and Figure S10), the kinetic parameters obtained
from the corresponding Lineweaver-Burk plots (Figure S11, S12
and Table S4) indicate that there are significant differences in
the substrate binding. For H2O2, the KM (M) and Vmax (M.min-1)
values obtained for VNw, (44.4 ± 1.7 and 192.3 ± 6.6), VSh, (57.3 ±
3.8 and 233.1 ± 16.3), VNf (92.5 ± 3.4 and 340.1 ± 21.3), and VSp
(143.7 ± 2.3 and 458.7 ± 19.6), respectively, indicate that the
surface of the nanowires (VNw) is saturated at lower
concentration of H2O2, whereas
a
relatively higher
concentrations of H2O2 are required for the saturation of the
surface on nanosheets (VSh). On the other hand, much higher
concentrations of H2O2 are required for the saturation of
surfaces on nanoflowers (VNf) and nanospheres (VSp).[7h]
Interestingly, the KM and Vmax values mentioned above for
different morphology do not correlate with their surface area
(Figure 2h). The surface area and pore diameter determined by
the Brunauer-Emmett-Teller (BET) method (Figure S13) indicate
that VSp with a relatively smaller surface area (9.7 m2.g-1)
exhibits much higher activity as compared to VNw with a larger
surface area (32.9 m2.g-1).
The nanomaterials are capable of mediating multiple cycles
of H2O2 reduction without loss of catalytic activity (Figure S14).
The SEM and TEM experiments on nanomaterials isolated from
the reaction mixture after the catalysis indicate that the materials
are highly stable with no alterations in their morphology or
surface (Figure S15). The activities obtained for the
nanomaterials kept as dispersion in water for six months were
identical to that of the freshly synthesized materials (Figure
S16b). Further, the supernatant obtained after centrifugation of
dispersed nanozymes at 6000 rpm for 20 min did not show any
noticeable activity (Figure S16a), indicating that the intact
surfaces and not leached metal ions are responsible for the
observed activity.
Figure 2. a-d) SEM and TEM (inset) images of VNw, VSh, VNf and VSp,
respectively. e) Reduction of H2O2 by GSH in the presence of nanomaterials,
glutathione reductase (GR) and NADPH. f) A comparison of the GPx-like
reactivity in the presence of three different peroxides, H2O2, tert-butyl
hydroperoxide (t-BuOOH) and cumene hydroperoxide (CuOOH). Assay
conditions: nanozymes (20 ng.μL-1), NADPH (0.2 mM), GSH (2 mM), GR (~1.7
units) peroxide (0.2 mM), in phosphate buffer (100 mM, pH 7.4) at 25ºC. g)
Michaelis-Menten plot with varying concentration of H2O2 (0-400 μM) for all
four nanozymes. h) Trend in Vmax and surface area among the four
nanozymes.
The initial rates observed for various control reactions
indicate that the nanozymes efficiently reduce H2O2 only in the
presence of GSH and GR. (Figures 3a and S17). To understand
the intermediates involved in the catalytic cycle, several in-situ
FT-Raman spectra were recorded in the presence of VSp (Figure
3b). The FT-Raman spectrum of pure VSp showed a peak at 993
cm-1 for V-oxo (V=O) bond, which was not changed upon
treatment with GSH, NADPH, and/or GR, suggesting that the V-
oxo bond in the material is unaltered in the reducing conditions.
This is in agreement with our earlier report that the vanadium(V)
The reduction of H2O2 by the nanomaterials was monitored
spectrophotometrically in the presence of GSH using glutathione
reductase (GR) coupled assay.[8,7i] The rates of the reactions
were determined by following the decrease in the absorbance of
NADPH at 340 nm (Figure 2e). As shown in Figure 2f, all four
This article is protected by copyright. All rights reserved.

10.1002/anie.201800681
Angewandte Chemie International Edition
COMMUNICATION
center in V2O5 nanowires is not reduced by GSH.[8] In contrast, a
significant decrease in the intensity of V=O peak was observed
when H2O2 was added to the reaction mixture. This led to a
rapid generation of a new peak at 1150 cm-1, which can be
assigned to the overtone peak for V-peroxido species.[13] These
observations indicate that the reaction of V=O species with H2O2
is the first step of the catalytic cycle. Interestingly, a complete
conversion of the V=O species to the V-peroxido intermediate
was observed within 300 sec (Figure 3b). FT-Raman
spectroscopic experiments with a sequential addition of H2O2
and GSH indicate that the V-peroxido species is the
predominant intermediate in the catalytic cycle (Figure 3c and
S19), which is further confirmed by time-dependent FT-IR of
VNw in the presence of H2O2 (Figure S20). A comparison of the
reactivity of the V=O bond with H2O2 using the four different
morphologies indicates that the formation of V-peroxido
intermediate is most favoured on the surface of VSp and rate of
its formation follows the order VSp > VNf > VSh > VNw (Figure
3d-g and S18), which correlates well with their GPx-like activity.
surface play crucial roles. To understand the atomic
arrangements of the exposed facets, we recorded high
resolution TEM (HRTEM) and analysed the HRTEM images and
their corresponding Fast-Fourier-Transform (FFT) patterns and
obtained the direction of nanocrystal growth (zone axis) (Figure
4a-e and S21). The inter-planer distances and the angles
between the planes observed in the HRTEM images were found
to be in accordance with the crystal structure of V2O5 (JCPDS =
41-1426). It is observed that VNw consists only of {001} facet,
whereas the VSh nanocrystals consist of both {001} and {010}
facets, although the {010} is found to be a minor one. However,
the {010} becomes the major exposed facet in VNf, which also
consists of a minor {001} facet. Interestingly, two major facets
{100} and {010} are identified in VSp along with two additional
facets {-111}, {1-40}, which make the nanospheres different from
the other three morphologies. The HRTEM images recorded
after the reactions indicate that the exposed facets present on
the surfaces of four different morphologies were unaffected by
the catalysis (Figures 6b and S22).
The remarkable change in the reactivity of V=O bond and
the overall catalytic activity indicate that the crystallographic
orientation of the atoms on the surface or exposed facets on the
Figure 4. HRTEM and Fast-Fourier-Transform (inset) pattern of a) VNw, b) VSh,
c) VNf, d and e) VSp. f-h) Atomic arrangements of {100}, {001}, and {010}
crystal facets respectively.
As the reaction of nanomaterials with H2O2 is a crucial step
in the catalytic cycle, we carried out quantum chemical
calculations using density functional theory (DFT) to understand
the reactivity of the exposed facets with H2O2. The reactivity was
compared by calculating the energy of H2O2 adsorption (E1)
and formation of V-peroxido intermediate (E2) on the
surfaces.[13] The total energy change (Etot) for the reaction of
H2O2 on the surface was obtained as sum of E1 and E2.
Figure 3. a) Reaction rates at different assay conditions for VSp. b) Monitoring
the formation of V-peroxido intermediate by in-situ Raman spectroscopy
during GPx-like catlytic cycle of VSp. c) Monitoring changes in the intensity of
V=O and V-peroxido peaks by in-situ Raman spectroscopy on the surface of
VSp: 1. VSp + H2O2 after 10 sec, 2. VSp + H2O2 after 300 sec, 3. VSp + H2O2
+
GSH, 4. VSp + H2O2 + GSH + H2O2. d-g) Time-dependent in-situ FT-Raman
spectroscopy recorded after the addition of H2O2 (5 mM) to VNw, VSh, VNf and
VSp, respectively.
This article is protected by copyright. All rights reserved.

10.1002/anie.201800681
Angewandte Chemie International Edition
COMMUNICATION
Among several possibilities, the most favoured orientations of
H2O2 on these surfaces are shown along with E1, E2 and Etot
in Figure 5b-f. The other possibilities are provided in the
Supplementary Information (Figure S28, S29 and S30). One of
the oxygen atoms in H2O2 was found to interact with the surface
vanadium atoms, whereas the hydrogen atoms interacted with
the oxygen atoms of V=O and V-O-V groups. This led to an
elongation of the vanadium-oxygen bond lengths as well as the
O-H bond in H2O2 as shown in Figure 5. The formation of V-
peroxido species was not observed on {001} facet, which had
the lowest adsorption energy. In {001} facet, the vanadium is
coordinatively saturated, which is similar to that of weakly bound
layers of bulk V2O5 (Figure 4g). The {100} and {010} facets had
higher E1 values and the formation of V-peroxido intermediate
was found to be exothermic in nature with {010} facet having the
highest Etot value. In addition to the formation of V-peroxido
intermediate on the surface, the hydrogen atoms of H2O2 formed
V-OH bonds, which can abstract a proton from second molecule
of H2O2 to eliminate a water molecule. The greater reactivity of
{100} and {010} facets is due to the unsaturated coordination
around the surface vanadium atoms. In these two facets, the
vanadium atoms present on the surface are connected to four
oxygen atoms (Figure 4f,h and S27). The difference in the
reactivity of the facets with H2O2 can also be ascribed to the
variation in the surface formation energy (EFS), which is
{001} facet is the least active one, which is in agreement with the
catalytic activity of VNw, VSh, VNf and VSp.
As an optimum level of H2O2 is required for the desired
redox biology and cell signalling and different isoforms of GPx
enzymes control the level of H2O2 in a compartment-specific
manner, it was thought worthwhile to investigate the GPx activity
of the nanozymes at different ratios of GSH/H2O2. It should be
noted that GSH is required for the cleavage as well as
regeneration of the V-peroxido species as shown in Figure 5a.
The initial reaction rates were measured by increasing the
concentration of H2O2 (Figure 6a). When the concentration of
H2O2 was 100- or 50-fold lower than that of GSH, all the
materials exhibited similar GPx-like activity. When the
concentration of H2O2 was increased, a significant difference in
the catalytic activity was observed. Interestingly, the activity of
nanospheres (VSp) increased rapidly with an increase in the
concentration of H2O2 and at GSH/H2O2 ratio of 5, the activity
was found to be remarkably higher than that of nanowires (VNw).
In fact, the GPx activity of VNw was almost unaltered over a
large range of H2O2 concentrations. The response of VNf was
found to be similar to that of VSp, indicating that these two
materials can exhibit high GPx activity at higher peroxide
concentrations and depleted GSH levels, i.e. oxidative stress
conditions. It should be noted that GSH has a significant role in
the maintenance of cellular redox state through changes in
thiol/disulphide equilibrium potential.[14] The solid-state
electrochemical responses (cyclic voltammograms) of different
morphologies indicated significant shifts in their oxidation-
reduction potentials (Figure S26, Table S5).
calculated as EFS
= (Esurface-Ebulk)/Asurface (Esurface and Ebulk
correspond to the optimized energy of the surface and bulk V2O5
crystal, respectively and Asurface is the area of V2O5 nano-
surfaces). For {100} an {010}, the EFS values are 0.05 eV/Å2 and
0.08 eV/Å2 higher than that of {001}. These observations suggest
that the {010} facet is the most reactive surface, whereas the
Figure 6. a) GPx activity of different nanozymes (20 ng.L-1) at various
[GSH]/[H2O2] ratios in phosphate buffer, 0.1 mM, pH 7.4 at 25C. The
concentrations of GSH, GR and NADPH were fixed at 2.0 mM, 1.7 Units and
0.2 mM, respectively. b) HRTEM and corresponding FFT (inset) of VSp after
catalysis.
These differences suggest that the extent of polarization of the
surface and migration of electrons between the atomic layers
depend on the crystal facet and morphology.[15] Understanding
of the redox potentials of various morphologies is important from
the biological perspective as a 40 mV change in the reduction
potential of GSH in healthy cells causes growth arrest and a
further 50-70 mV change can lead to apoptotic or necrotic cell
death.[14a]
In conclusion, we report the synthesis and glutathione
peroxidase-like enzyme mimetic activity of orthorhombic V2O5
nanozymes in four different morphologies, nanowires (VNw),
nanosheets (VSh), nanoflowers (VNf) and nanospheres (VSp)
and show that the activity does not correlate with their surface
area. We demonstrate for the first time that the surface exposed
crystal facets within the same crystal system can alter the H2O2
reducing ability of V2O5 nanozymes. The activity depends on the
Figure 5. a) Schematic representation of the reaction of H2O2 and GSH on the
surface of orthorhombic V2O5 crystal. b, c and e) Most favoured orientation for
interaction of H2O2 with {001}, {100} and {010} crystal facets respectively. d
and f) V-peroxido intermediate on {100} and {010}, respectively.
This article is protected by copyright. All rights reserved.

10.1002/anie.201800681
Angewandte Chemie International Edition
COMMUNICATION
501–509; b) Z. Chen, J. J. Yin, Y. T. Zhou, Y. Zhang, L. Song, M.
Song, S. Hu, N. Gu, ACS Nano 2012, 6, 4001–4012; c) H. Wei, E.
Wang, Chem. Soc. Rev. 2013, 42, 6060-6093; d) J. Dong, L. Song, J. J.
Yin, W. He, Y. Wu, N. Gu, Y. Zhang, ACS Appl. Mater. Interfaces 2014,
6, 1959–1970; e) Y. Lin, J. Ren, X. Qu, Acc. Chem. Res. 2014, 47,
1097–1105; f) R. Ragg, M. N. Tahir, W. Tremel, Eur. J. Inorg. Chem.
2016, 2016, 1906–1915; g) Y. Huang, Z. Liu, C. Liu, E. Ju, Y. Zhang, J.
Ren, X. Qu, Angew. Chem. Int. Ed. 2016, 55, 6646–6650; h) A. A.
Vernekar, T. Das, G. Mugesh, Angew. Chem. Int. Ed. 2016, 55, 1412–
1416; i) N. Singh, M. A. Savanur, S. Srivastava, P. D’Silva, G. Mugesh,
Angew. Chem. Int. Ed. 2017, 56, 14267–14271; j) X. Wang, Y. Hu, H.
Wei, Inorg. Chem. Front. 2016, 3, 41-60; k) H. Cheng, Y. Liu, Y. Hu, Y.
Ding, S. Lin, W. Cao, Q. Wang, J. Wu, F. Muhammad, X. Zhao, D.
Zhao, Z. Li, H. Xing, H. Wei, Anal. Chem. 2017, 89, 11552-11559; l) Y.
Hu, H. Cheng, X. Zhao, J. Wu, F. Muhammad, S. Lin, J. He, L. Zhou, C.
Zhang, Y. Deng, P. Wang, Z. Zhou, S. Nie, H. Wei. ACS Nano 2017, 11,
5558–5566.
relative concentrations of H2O2 and glutathione (GSH) and at
higher H2O2 concentrations, the nanospheres exhibit remarkably
higher activity as compared to that of nanowires, indicating that
the crystal facets play crucial roles in the catalytic activity. The
variations in the GPx-like activity originate from the difference in
the rate of formation of a V-peroxido species on the surface. The
results described in this paper on the modulation of redox
reactions by altering the size, shape and crystal facets may
open up opportunities not only for the design and synthesis of
nanomaterials with enzyme-like activity, but also for the
development of nanomaterial-based isozymes (nanoisozymes),
which essentially catalyse the same chemical reactions, but
exhibit a compartment-specific activity in biological systems.
[8]
[9]
A. A. Vernekar, D. Sinha, S. Srivastava, P. U. Paramasivam, P. D’Silva,
G. Mugesh, Nat. Commun. 2014, 5, 6301.
a) L. Hu, Q. Peng, Y. Li, J. Am. Chem. Soc. 2008, 130, 16136–16137;
b) A. X. Yin, X. Q. Min, Y. W. Zhang, C. H. Yan, J. Am. Chem. Soc.
2011, 133, 3816–3819; c) J. Mu, L. Zhang, G. Zhao, Y. Wang, Phys.
Chem. Chem. Phys. 2014, 16, 15709-15716; d) E. W. Zhao, H. Zheng,
R. Zhou, H. E. Hagelin-Weaver, C. R. Bowers, Angew. Chem. Int. Ed.
2015, 54, 14270–14275; e) Z. Zhang, X. Zhang, B. Liu, J. Liu, J. Am.
Chem. Soc. 2017, 139, 5412–5419; e) M. J. Manto, P. Xie, C. Wang,
ACS Catal. 2017, 7, 1931–1938.
Acknowledgements
This study was supported by the Science and Engineering
Research Board (EMR/IISc-01/2016) and DST Nanomission
(SR/NM/NS-1380/2014), New Delhi. G.M. and EDJ
acknowledge the SERB/DST for the award of J. C. Bose
National Fellowship. S. G. and P. R. thank the Indian Institute
Science, Bangalore, and N.K. thanks the CSIR, New Delhi for
the fellowships. The authors thank Dr. A. A. Vernekar, Prof. N.
Munichandraiah, Dr. R. Viswanatha, Dr. B. Kishore and Mr. S.
Prasad for their support and help with some of the experiments.
We also thank the MNCF Facility, CeNSE, IISc for the
spectroscopic and microscopic facilities.
[10] a) J. E. Park, M. Son, M. Hong, G. Lee, H. C. Choi, Angew. Chem. Int.
Ed. 2012, 51, 6383–6388; b) J. Jiang, K. Zhao, X. Xiao, L. Zhang, J.
Am. Chem. Soc. 2012, 134, 4473–4476; c) C. Li, C. Koenigsmann, W.
Ding, B. Rudshteyn, K. R. Yang, K. P. Regan, S. J. Konezny, V. S.
Batista, G. W. Brudvig, C. A. Schmuttenmaer, J. H. Kim, J. Am. Chem.
Soc. 2015, 137, 1520–1529; d) C. Ge, G. Fang, X. Shen, Y. Chong, W.
G. Wamer, X. Gao, Z. Chai, C. Chen, J. J. Yin, ACS Nano 2016, 10,
10436–10445; e) C. S. Tan, P. L. Hsieh, L. J. Chen, M. H. Huang,
Angew. Chem. Int. Ed. 2017, 56, 15339–15343; f) C. Yang, X. Yu, S.
Heissler, P. Weidler, A. Nefedov, Y. Wang, C. Wöll, T. Kropp, J. Paier,
J. Sauer, Angew. Chem. Int. Ed. 2017, 56, 16399–16404.
Conflict of interest
[11] F. Zhou, X. Zhao, C. Yuan, L. Li, Cryst. Growth Des. 2008, 8, 723–727.
[12] E. Hryha, E. Rutqvist, L. Nyborg, Surf. Interface Anal. 2012, 44, 1022–
1025.
The authors declare no conflict of interest.
[13] J. E. Molinari, I. E. Wachs, J. Am. Chem. Soc. 2010, 132, 12559–12561.
[14] a) M. L. Circu, T. Y. Aw, Free Radic. Res. 2011, 45, 1245–1266; b) L.
Flohé, Biochim. Biophys. Acta, 2013, 1830, 3139–3142; c) Y. Huang, F.
Pu, J. Ren, X. Qu, Chem. Eur. J. 2017, 23, 9156-9161.
[15] M. Ek, Q. M. Ramasse, L. Arnarson, P. Georg Moses, S. Helveg, Nat.
Commun. 2017, 8, 305.
Keywords: antioxidants • crystal facet • glutathione peroxidase •
nanozymes • oxidative stress
[1]
[2]
a) V. Adler, Z. Yin, K. D. Tew, Z. Ronai, Oncogene 1999, 18, 6104–
6111; b) B. D’Autréaux, M. B. Toledano, Nat. Rev. Mol. Cell Biol. 2007,
8, 813–824; c) M. Schieber, N. S. Chandel, Curr. Biol. 2014, 24, R453–
R462; d) H. Sies, Redox Biol. 2015, 4, 180–183; e) C. Lennicke, J.
Rahn, R. Lichtenfels, L. A. Wessjohann, B. Seliger, Cell Commun.
Signal. 2015, 13, 1–19; f) R. Mittler, Trends Plant Sci. 2017, 22, 11–19.
a) K. J. Davies, J Biol Chem. 1987, 262, 9895-9901; b) A. Terman, U. T.
Brunk, Antioxid. & Redox Signal. 2006, 8, 197-204; c) I. Dalle-Donne, G.
Aldini, M. Carini, R. Colombo, R. Rossi, A. Milzani, J. Cell Mol. Med.
2006, 10, 389-406; d) E. Ju, K. Dong, Z. Chen, Z. Liu, C. Liu, Y. Huang,
Z. Wang, F. Pu, J. Ren, X. Qu, Angew. Chem. Int. Ed. 2016, 55,
11467–11471.
[3]
[4]
[5]
a) O. I. Aruoma, Jaocs 1998, 75, 199–212; b) T. Finkel, N. J. Holbrook,
Nature 2000, 408, 239–247; c) K. J. Barnham, C. L. Masters, A. I. Bush,
Nat. Rev. Drug Discov. 2004, 3, 205–214.
a) J. R. Arthur, Cell. Mol. Life Sci. 2001, 57, 1825–1835; b) E. V.
Kalinina, N. N. Chernov, M. D. Novichkova, Biochem. 2014, 79, 1562–
1583.
a) S. J. Dixon, K. M. Lemberg, M. R. Lamprecht, R. Skouta, E. M.
Zaitsev, C. E. Gleason, D. N. Patel, A. J. Bauer, A. M. Cantley, W. S.
Yang, B. Morrison, B. R. Stockwell, Cell 2012, 149, 1060–1072; b) W. S.
Yang, R. Sriramaratnam, M. E. Welsch, K. Shimada, R. Skouta, V. S.
Viswanathan, J. H. Cheah, P. A. Clemons, A. F. Shamji, C. B. Clish, L.
M. Brown, A. W. Girotti, V. W. Cornish, S. L. Schreiber, B. R. Stockwell,
Cell 2014, 156, 317–331.
[6]
[7]
a) H. Sies, Redox Biol. 2017, 11, 613–619; b) H. S. Marinho, C. Real, L.
Cyrne, H. Soares, F. Antunes, Redox Biol. 2014, 2, 535–562; c) T.
Rabilloud, M. Heller, F. Gasnier, S. Luche, C. Rey, R. Aebersold, M.
Benahmed, P. Louisot, J. Lunardi, J. Biol. Chem. 2002, 277, 19396–
19401.
a) R. André, F. Natálio, M. Humanes, J. Leppin, K. Heinze, R. Wever, H.
C. Schröder, W. E. G. Müller, W. Tremel, Adv. Funct. Mater. 2011, 21,
This article is protected by copyright. All rights reserved.

10.1002/anie.201800681
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
The first experimental
evidence for the crystal
facet-dependent enzyme
mimetic activity of V2O5
nanozymes is described.
The activity of the four
Sourav Ghosh, Punarbasu
Roy, Naiwrit Karmodak,
Eluvathingal D. Jemmis,
Govindasamy Mugesh*
Page No. – Page No.
nanoforms
of
V2O5
Nanoisozymes: Crystal
Facet-Dependent Enzyme
Mimetic Activity of V2O5
Nanomaterials
namely wires, sheets,
floweres and spheres
exhibit different redox
modulatory effect in the
presence of H2O2.
This article is protected by copyright. All rights reserved.