Ni2P Nanosheets: A High Catalytic Activity Platform for Electrochemical Detection of Acetaminophen

Article abstract of DOI:10.1002/cjoc.202100043

Accurate determination of acetaminophen concentration is essential for studying the metabolic status of acetaminophen in clinical practice. In this study, nickel phosphide was used for electrochemical detection of acetaminophen for the first time. An electrochemical acetaminophen sensor based on Ni₂P nanosheets was successfully constructed and the sensor showed many convincing properties: (a) a good linear range (0.5 μmol/L—4.5 mmol/L); (b) a moderate sensitivity (131.1 μA·mmol^–1·L·cm^–2); (c) a low detection limit (0.107 μmol/L). In addition, the sensor also showed excellent selectivity, robust stability and reliable repeatability. Further experiments demonstrate that the prepared sensor can be used for quantitative detection of acetaminophen in commercial medical drugs.

Full text of DOI:10.1002/cjoc.202100043

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Ni2P Nanosheets: High Catalytic Activity Platform for Electrochemical
Detection of Acetaminophen
Authors: Ming Wei, Wenbo Lu,* Guoqin Liu, Yimin Jiang, Xuebo Liu, Liwei Bai
Xiaowei Cao, Jianfeng Jia, and Haishun Wu*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2021, 39, 10.1002/cjoc.202100043.
The final Version of Record (VoR) of it with formal page numbers will soon be
published online in Early View: http://dx.doi.org/10.1002/cjoc.202100043.
ISSN 1001-604X • CN 31-1547/O6
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Lu Wenbo (Orcid ID: 0000-0001-8158-7947)
Cite this paper: Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Ni2P Nanosheets: High Catalytic Activity Platform for Electro-
chemical Detection of Acetaminophen
Ming Wei,a,b Wenbo Lu,*,a Guoqin Liu,a Yimin Jiang,a Xuebo Liu,a Liwei Bai,a Xiaowei Cao,c Jianfeng Jia,a and
Haishun Wu*,a
a Key Laboratory of Magnetic Molecules and Magnetic Information Materials (Ministry of Education), School of Chemistry and Material
Science, Shanxi Normal University, Linfen 041004, China
b Kangda College of Nanjing Medical University, Lianyungang 222000, China
c Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China
Keywords
Acetaminophen | Nickel phosphide | Nanosheets | Electrochemical sensor | Tablets
Main observation and conclusion
Accurate determination of acetaminophen concentration is essential for studying the metabolic status of acetaminophen in clinical
practice. In this study, nickel phosphide was used for electrochemical detection of acetaminophen for the first time. An electrochemical
acetaminophen sensor based on Ni2P nanosheets was successfully constructed and the sensor showed many convincing properties: (a)
a good linear range (0.5 μM - 4.5 mM); (b) a moderate sensitivity (131.1 μA mM-1 cm-2); (c) a low detection limit (0.107 μM). In addition,
the sensor also showed excellent selectivity, robust stability and reliable repeatability. Further experiments demonstrate that the pre-
pared sensor can be used for quantitative detection of acetaminophen in commercial medical drugs.
Comprehensive Graphic Content
*E-mail: luwb@sxnu.edu.cn (Lu W.); wuhs@mail.sxnu.edu.cn (Wu H.)
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nanosheets. The various synthesis methods of Ni2P nanosheets are
shown in Table S1.
Background and Originality Content
In this communication, an electrochemical AP sensor is con-
structed based on Ni2P nanosheets (NS). Compared with nanopar-
ticles, the structure of nanosheet can expose more surface area of
the Ni2P and thus increase the number of active sites. The sensor
shows good performance with a linear range of 0.5 μM - 4.5 mM, a
detection limit of 0.107 μM and sensitivity of 131.1 μA mM-1 cm-2,
which is better than most of the Ni-based electrochemical sensors
reported previously. More importantly, the electrochemical reac-
tion mechanism reveals that O7 and O11 of AP are the most possi-
ble active sites. The Ni2P NS can electro-catalyze the corresponding
position of AP to form quinone groups and tertiary amino groups.
It provides a new idea for the application of TMPs in electrochemi-
cal AP detection.
Acetaminophen (AP) has gained worldwide popularity as a con-
venient antipyretic and analgesic drug.[1,2] As a nonsterol drug, AP,
also known as paracetamol, is used to treat fever, headaches, joint
pain, neuralgia, and dysmenorrhea.[3,4] The pharmacological mech-
anism of AP can be explained as regulating body temperature by
selectively inhibiting the synthesis of prostaglandin in the hypotha-
lamic thermoregulatory center, while raising the pain threshold to
achieve the purpose of ache killer.[5,6] However, it is unwise to take
AP for a long period of time and overdosage. Excessive use of AP
can cause nausea, vomiting and other side effects, and could bring
greater adverse effects on the liver.[7] In addition, the abuse of
drugs not only brings harm to human health, but also poses new
challenges to environmental protection. AP is considered as one of
the emerging chemical pollutants (ECPs) in water due to its good
water-solubility and poor degradability.[8] Thus, accurate and real-
time detection of AP is of great significance for both health care and
environmental protection. Several analytical methods have been
used to determine AP concentrations, such as capillary electropho-
resis,[9] high performance liquid chromatography (HPLC),[10] titra-
tion,[11] spectrophotometry,[12] fluorescence,[13] and electrochemis-
try.[14] Compared with other methods, the electrochemical detec-
tion is simple to operate and does not rely on complex instruments,
which can realize rapid, accurate and real-time determination. [15,16]
With the rapid development of nanotechnology, electrochemical
AP sensor has made great progress. Metals,[17] carbon-based mate-
rials,[18] metal organic framework (MOF) [19] and other materials [20]
have been successfully used in the design of electrochemical AP
sensors. Nowadays, the researchers are still exploring new func-
tional materials for the development of electrochemical AP sensors.
As a typical representative of transition metal catalysts, Ni-
based materials have attracted extensive attention due to their
abundant reserves, simple preparation and excellent catalytic ac-
tivity. [21] Taking the design of electrochemical AP sensor based on
Ni-based materials as examples, Wang et al. constructed an elec-
trochemical AP sensor based on C-Ni nanoparticles and the detec-
tion limit of the sensor was 2.3 μM. It should be noted that the
preparation of composite nanoparticles was complex, which re-
quired the assistance of arc evaporator.[22, 23] Babaei et al. prepared
an electrochemical AP sensor using the composite of Ni(OH)2 and
multi-walled carbon nanotubes. The linear range and detection
limit of the sensors were 1 - 960 μM and 0.25 μM, respectively.[24]
In addition, Co-Ni alloy was also applied in the design of AP sensor
(detection limit: 2.7 μM, linear range: 0.01 mM - 0.1 mM).[25] The
above electrochemical AP sensors discussed had narrow linear
ranges and may not be able to meet the requirements of high con-
centration AP detection. In recent years, transition metal phos-
phides (TMPs) have exuded natural charm as multifunctional mate-
rials and have been successfully applied in many fields such as ca-
talysis,[26-30] imaging,[31] energy storage,[32] and sensing.[33] Com-
pared with transition metal oxides (TMOs), carbides (TMCs) and ni-
trides (TMNs), TMPs have many inherent advantages, such as phos-
phorus can form TMPs with almost all transition elements, what's
more, different constituent elements and stoichiometric ratios can
lead to various structures.[21] Nickel phosphides (NixPy), including
Ni2P and Ni5P4, have shown tremendous potential in the field of
sensing and have been used in the preparation of electrochemical
glucose and hydrogen peroxide sensors.[34-37] As far as we know, the
structure of nickel phosphide has not been used as the platform for
electrochemical AP detection. Especially, Ni2P nanosheets with
large specific surface area have not been applied in the field of AP
detection.
Results and Discussion
Figure 1 (a) XRD pattern of Ni2P NS. (b) SEM image of Ni2P NS. (c) TEM image
of Ni2P NS. (d) STEM and EDX elemental mapping images of Ni and P for Ni2P
NS. (e) XPS spectrum in the Ni 2p region of Ni2P NS. (f) XPS spectrum in the
P 2p region of Ni2P NS.
X-ray powder diffractometer (XRD) is used to obtain the infor-
mation of crystal phase of precursor Ni(OH)2 (Figure S1) and the as-
prepared Ni2P NS. As demonstrated in Figure 1a, the main diffrac-
tion peaks located at 30.5°, 31.7°, 35.3°, 40.7°, 44.6°, 47.3°, 54.2°
and 55.0° are assigned to the (110), (101), (200), (111), (201), (210),
(300) and (211) planes of Ni2P (JCPDS NO. 65-1989). The detailed
topological features of Ni2P are monitored by scanning electron mi-
croscopy (SEM) and transmission electron microscopy (TEM). As
depicted in Figure 1b and Figure 1c, the Ni2P displays a vertically
aligned nanosheet structure with rough surface. Energy dispersive
X-ray (EDX) spectrum shows that Ni and P are evenly distributed in
the whole structure (Figure 1d). The detailed elemental composi-
tions and chemical valence states were recorded by X-ray photoe-
lectron spectroscopy (XPS). Figure 1e shows the high-resolution
spectrum of Ni 2p and reveals six prominent peaks. The peaks at
binding energies of 852.5 eV and 856.2 eV are assigned to Ni 2p3/2
of Ni-P and Ni-O. Similarly, the peaks at 869.9 eV and 874.1 eV are
attributed to Ni 2p1/2 of Ni-P and Ni-O. The peaks at 861.5 eV and
879.3 eV are two satellite peaks. The high-resolution P 2p spectrum
in Figure 1f indicates the presence of four distinct peaks. The peaks
at 128.8 eV and 133.1 eV are assigned to P 2p3/2 of P-Ni and P-O.
The peaks at 129.5 eV and 133.9 eV are attributed to P 2p1/2 of P-
Ni and P-O. The existence of oxygen element is due to the oxidation
The synthesis of Ni2P nanosheets usually adopts the vapor–
solid reaction, which usually goes through two stages of hydrother-
mal and phosphating. The NaH2PO2 is generally employed as the
phosphorus source to react with Ni precursors to form Ni2P
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of Ni2P NS surface in the air.
The effect of pH on the redox of AP was investigated at Ni2P
NS/GCE by differential pulse voltammetry (DPV) method. Figure 2a
shows the DPV response in 0.1 M PBS solution containing 100 μM
AP in various pH ranges from 6.0 to 8.0, indicating that protons are
involved in the reaction. The response current reaches its maxi-
mum at pH of 6.5. Thus, PBS with pH 6.5 was selected as the sup-
porting electrolyte in the subsequent experiments. As illustrated in
Figure 2b, the corresponding linear relationship between pH and
potential is obtained by y = -0.05353x + 0.9119 (R2 = 0.984). The
slope value of the calibration curve is -53.53 mV pH-1, which is close
to the theoretical value -58.5 mV pH-1, indicating that the number
of protons and electrons involved in the electrode reaction is
equal.[38]
response current is higher than that of bare GCE when the Ni2P NS
Figure 3 The mechanism of oxidation of AP on Ni2P NS/GCE.
modified the GCE, indicating that Ni2P has
a convincible
electrocatalytic capability for AP. In order to acquire the kinetics of
the oxidation reaction of AP on the Ni2P NS electrode, the effects of
scan rate on oxidized currents were investigated. As depicted in
Figure 4b, the value of scan rates ranged from 20 mV s-1 to 200 mV
s-1, a positive correlation is observed between oxidized peak current
and scan rate. At the same time, there is an excellent linear
relationship between the square root of scan rate and the current
(Figure 4c). The linear fit results can be described as: y = 0.0961x +
1.645 (R2 = 0.997) and y = -0.0866x + 0.353 (R2 = 0.998). The above
results indicate that the AP oxidation reaction on the Ni2P NS/GCE
is a diffusion-controlled process. In addition, the charge transfer
coefficient α (0.4677) and electron transfer rate constant ks (0.043)
are calculated using Laviron equation (Figure S2).[42] Considering
that the value of ∆EP is 0.201 V, greater than the theoretical value
of the reversible reaction of (0.058/2) V, and IPa/Ipc = 1.059, it can
be safely concluded that the AP oxidation on the Ni2P NS/GCE is a
quasi-reversible process, which is consistent with the previous
reported literature.[43] As shown in Figure 4d and Figure S3, the CV
curve shows an excellent linear relationship between the
concentration of AP and the response current, which proves that
Ni2P NS can be used for the electrochemical detection of AP.
Figure 2 (a) DPVs for the oxidation of AP on Ni2P NS/GCE electrode in
various pH ranges of 0.1 M PBS solution containing 100 μM of AP from 6.0
to 8.0. (b) The corresponding linear relationship between pH and potential.
(c) The MEP distribution of AP. The blue dots are the minimum values of the
electrostatic potential, and the red dots are the maximum values.
In order to predict the possible reaction sites of AP in the elec-
trode reaction process, the Multiwfn[39, 40] and Gaussian 09[41] were
used to calculate the molecular electrostatic potential (MEP) of AP
the level of B3LYP/6-31+g (d, p). As depicted in Figure 2c, the O7
and O11 are the centers of negative potentials, and their negative
potentials are -20.40 kcal mol-1 and -44.50 kcal mol-1 respectively
and the calculated results of MEP are shown in Table S2. Therefore,
O7 and O11 are the most possible active sites. The Ni2P NS can elec-
tro-catalyze the corresponding position of AP to form quinone
groups and tertiary amino groups. Based on the discussed above,
the reaction mechanism of AP on Ni2P NS/GCE is shown in Figure 3.
Figure 4 (a) CVs of bare GCE and Ni2P NS/GCE in 0.1 M PBS with the absence
and presence of 100 μM AP at the scan rate of 50 mV s-1. (b) CVs for Ni2P
NS/GCE in 100 μM AP at the scan rate from 20 mV s-1 to 200 mV s-1. (c) The
corresponding linear relationship between the square root of scan rate and
current. (d) CVs for the Ni2P NS/GCE in 0.1 M PBS in the presence of varying
AP concentrations from 0 to 2.5 mM at the scan rate of 50 mV s-1.
Figure 4a shows the cyclic voltammetry (CV) responses of bare
GCE and Ni2P NS/GCE in 0.1 M PBS with the absence and presence
of 100 μM AP at the scan rate of 50 mV s-1. It can be seen that the
redox peak did not appear in both bare GCE and Ni2P NS/GCE in the
absence of AP. By contrast, in the presence of AP, a pair of redox
peaks can be observed on the bare GCE. Encouragingly, the
Amperometric method is used to determine the parameters of
electrochemical sensors. In order to achieve the optimal perfor-
mance of electrochemical AP sensor based on Ni2P NS, the working
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Wei et al.
Report
potential is optimized. As shown in Figure 5a, in the process of con-
tinuous addition of 10 μM AP in 0.1 M PBS, the response current
firstly increases and then decreases with the working potential
from 0.50 V to 0.70 V. What’s more, the corresponding linear rela-
tionship of AP concentration and response current can show this
trend more directly. The slope of the fitting curve reaches the max-
imum of 0.01904 at 0.60 V (Figure 5b and Figure S4). Therefore,
0.60 V is chosen as the optimal working potential. Figure 5c displays
the amperometric responses generated by continuous injection of
AP of different concentrations within 0.5 μM - 4.5 mM, and the cur-
rent platform can reach stability within 5s. As shown in Figure 5d,
there is an excellent linear relationship between AP concentration
and response current and the linear equation is y = 0.00412x +
0.3191 (R2 = 0.997). The sensitivity and limit of detection (LOD) of
the as-obtained sensor are determined to be 131.1 μA mM-1 cm-2
and 0.107 μM based on a signal to noise ratio 3. The calculation
method of LOD can be simply summarized as LOD = 3σ/S, where σ
is the standard deviation of response current and S is the slope of
calibration curve. As shown in Table S3 and S4，compared with the
electrochemical AP sensor reported previously and other AP detec-
cellent selectivity. In terms of stability evaluation, the current be-
havior after AP addition was recorded by amperometric method, as
described in Figure S5. After AP was added, the response current
first increased and then remained stable. The long-term stability
was investigated by DPV measurements. The prepared sensor was
stored in air and the current response was tested every six days. As
shown in Figure 6d, the current retention rate is 93.4% after 30 days,
indicating that the working electrode based on Ni2P NS has an out-
standing stability. In addition, repeatability experiment was per-
formed to evaluate the reproducibility of the sensor. As shown in
Figure S6, the standard deviation of the six repeated experiments
was 3.17%, revealing a good reproducibility.
Figure 6 (a) DPV curves of Ni2P NS/GCE in 0.1 M PBS containing various
concentrations of AP from 0 μM to 2.5 mM. (b) The corresponding
calibration curve of AP concentration and current. (c) Interference
experiment of the Ni2P NS measured with 10 μM AP and 20 μM interferents
in 0.1 M PBS. (d) Long-term stability experiment of AP sensor based on Ni2P
NS (0 - 30 days).
tion methods, the sensor prepared in this paper has better perfor-
mance, indicating that it is more suitable for AP detection.
Figure 5 (a) Amperometric responses generated by continuous addition of
AP at different working potentials. (b) The corresponding linear relationship
between the concentration of AP and current at different working
potentials. (c) Amperometric responses generated by continuous injections
of different concentrations of AP in 0.1 M PBS at 0.60 V (inset:
amperometric responses at low concentrations). (d) The corresponding
plots of AP concentration vs. current in 0.1 M PBS at 0.60 V.
Conclusions
To sum up, an electrochemical AP sensor based on Ni2P NS has
been successfully constructed and can be used for the detection of
AP in tablets. Ni2P nanosheets were prepared by hydrothermal and
phosphating and characterized by XRD, SEM, TEM and XPS. The
electrochemical AP sensor showed wide linear range, low detection
limit and long-term stability. In addition, Multiwfn and Gaussian 09
were hired to discuss the oxidation mechanism of AP on Ni2P NS
electrode. The significance of this work is to introduce TMPs into
the electrochemical detection of AP and provide a simple and inex-
pensive detection method for AP.
In order to explore the applicability of the sensor in real sam-
ples, the standard addition method was hired to determine the
concentration of AP in pharmaceutical dosage forms. The DPV tech-
nology was used to detect different concentrations of AP. As shown
in Figure 6a and 6b, there is an excellent linear relationship be-
tween the concentration of AP from 0 μM to 2.5 mM, and the linear
equation is y = 0.00829x + 2.742 (R2 = 0.985). The calculated recov-
eries ranged from 98.1% to 108.0%, indicating that the sensor was
reliable for AP detection in real samples (Table S5).
Experimental
The selectivity is an important factor in evaluating sensor’s per-
formance. Amperometric method was used to record the response
current changes caused by the continuous addition of 10 μM AP, 20
μM NaCl, 20 μM KCl, 20 μM Na2SO4, 20 μM serine, 20 μM proline,
20 μM dopamine, 20 μM p-nitrophenol and 10 μM AP. As illustrated
in Figure 6c, compared with AP, the current disturbance caused by
interferences can be negligible, indicating that the sensor has ex-
Reagents: Acetaminophen was purchased from Aladdin Ltd.
(Shanghai, China). Hexamethylenetetramine (HMT) was provided
from Adamas Reagent Ltd. (Shanghai, China). Ni(NO3)2▪6H2O,
Na2HPO4, NaH2PO4 and NaCl were obtained from Kemiou Chemical
Reagent Co. Ltd. (Tianjin, China). NaH2PO2 was supplied from
Guangfu Fine Chemical Research Institute (Tianjin, China). All the
chemicals in this article were of analytical grade and did not require
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Chin. J. Chem.
further purification before use.
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In the phosphating process, 1g NaH2PO2 and Ni(OH)2 NS were
placed in two porcelain boats respectively, and the porcelain boats
were placed in a tubular furnace. The porcelain boat containing
NaH2PO2 was placed in the upstream of the tubular furnace. After
phosphating at 280 °C for 2 h under argon flow, the black Ni2P NS
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Electrode fabrication: Prior to electrode fabrication, the bare
GCE (d = 2 mm) was carefully polished with alumina powder (1.00
μm, 0.2 - 0.5 μm) and washed with ultrapure water and ethanol.
Then, 3 μL ink (composed of 5mg Ni2P NS, 40 μL ethanol and 10 μL
Nafion 117) was dropped onto the surface of GCE and dried natu-
rally to complete the assembly of working electrode.
Experimental setting of electrochemical measurements: Elec-
trochemical characterization was conducted with an electrochemi-
cal workstation (CHI660E, Chenhua, China) with a three-electrode
system. Ni2P NS/GCE, saturated Ag/AgCl and platinum wire were
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Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2021xxxxx.
Acknowledgement
This work was supported by the National Natural Science Foun-
dation of China (No. 21705103), the Applied Basic Research Project
of Shanxi Province (No. 201801D221392), Scientific and Technolog-
ical Innovation Projects in Shanxi Universities (No.2019L0460), the
Graduate Education Innovation Project of Shanxi Normal University
(2019XBY019). Science Research and Development Foundation of
Kangda College of Nanjing Medical University (KD2020KYJJYB075),
and the 1331 Engineering of Shanxi Province.
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

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Manuscript received: XXXX, 2021
Manuscript revised: XXXX, 2021
Manuscript accepted: XXXX, 2021
Accepted manuscript online: XXXX, 2021
Version of record online: XXXX, 2021
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Entry for the Table of Contents
Ni2P Nanosheet: High Catalytic Activity Platform for Electrochemical Detection of Acetaminophen
Ming Wei,a,b Wenbo Lu, *,a Guoqin Liu,a Yimin Jiang,a Xuebo Liu,a Liwei Bai,a Xiaowei Cao,c Jianfeng Jia,a and Haishun Wu*,a
Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
The Ni2P nanosheets have been synthesized by two steps of hydrothermal and phosphating. The prepared Ni2P NS can be used as an
electrochemical platform to detect acetaminophen in commercial medical drugs.
a Key Laboratory of Magnetic Molecules and Magnetic Information
Materials (Ministry of Education), School of Chemistry and Material
Science, Shanxi Normal University, Linfen 041004, China
E-mail: luwb@sxnu.edu.cn，wuhs@mail.sxnu.edu.cn.
b
Kangda College of Nanjing Medical University, Lianyungang
222000, China
c
Institute of Translational Medicine, Medical College, Yangzhou
University, Yangzhou 225001, China
Chin. J. Chem. 2018, template© 2018 SIOC, CAS, Shanghai,
&
WILEY-VCH Verlag GmbH
&
Co. KGaA,
Weinheim