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Sensors and Actuators B: Chemical
journal homepage: www.elsevier.com/locate/snb
Visualizing hydrogen peroxide in Parkinson’ s disease models via a
ratiometric NIR fl uorogenic probe
Yi Liu
a,1
, Lei Bai
a,1
, Yihao Li
a
, Yun Ni
a
, Chenqi Xin
a
, Chengwu Zhang
a
, Jinhua Liu
a
,
Zhipeng Liu
a,
⁎
, Lin Li
a,
⁎
, Wei Huang
a,b
a
Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials
(SICAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing, 211816, PR China
b
Shaanxi Institute of Flexible Electronics (SIFE), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi’an, 710072, PR China
ARTICLE INFO
Keywords:
Parkinson’s disease
Fluorescent sensing and imaging
Hydrogen peroxide
Ratiometric sensor
Near-infrared
ABSTRACT
Parkinson’s disease (PD) is a neurological disorder which will significantly overwhelm the life for the patient.
Numerous studies have proved that hydrogen peroxide plays an important role in the pathogenesis of PD. To
detect hydrogen peroxide in PD in live, here we report the design and synthesis of a new ratiometric and NIR
fluorescence probe (NIR-HP1) for hydrogen peroxide, utilizing an excited state intramolecular proton transfer
strategy to control the fluorescence. NIR-HP1 showed a highly selective ratiometric response to hydrogen
peroxide over other reactive oxygen/nitrogen species, biothiols and various ions in aqueous solution at phy-
siological pH. The observed pseudo-first-order rate constant for the reaction of NIR-HP1 with hydrogen peroxide
was calculated to be 0.042 s
−1
. The detection limit of this sensor for hydrogen peroxide was 0.27 μM. Moreover,
NIR-HP1 worked well in living systems for hydrogen peroxide sensing as displayed by confocal fluorescence
microscopy imaging, indicating potential application in PD study.
1. Introduction
Parkinson’s disease (PD) is a common neurodegenerative disorder,
second only to Alzheimer’s disease, which mainly affects the motor
system, especially in elders [1–5]. Emerging studies show that the ac-
cumulation of reactive oxygen species (ROS) such as hydrogen peroxide
(H
2
O
2
) caused oxidative stress inside cells is closely related to PD pa-
thogenesis [6,7]. To reveal the fundamental roles of ROS, particularly
H
2
O
2
played in PD, real-time, non-invasive monitoring of H
2
O
2
in vivo is
highly desired. Fluorescent imaging employing small H
2
O
2
probes have
emerged as a highly reliable tool for H
2
O
2
interrogating in living
samples [8]. Indeed, several research groups such as Chang‘s group
[9–11] and Nagano’s group [12] had developed novel H
2
O
2
probes
which were applicable for imaging H
2
O
2
in living samples. However,
study on the real-time imaging of H
2
O
2
in PD models with H
2
O
2
-in-
duced neurovascular damage is still lacking, mainly due to challenge on
high selective and fast response of imaging agents and desired photo-
physical properties. Herein, we report a new near-infrared (NIR)
fluorogenic probe (NIR-HP1) for the ratiometric detection of H
2
O
2
in
PD models (Fig. 1).
Compared with those turn-on type probes, ratiometric fluorescence
probes, especially those with NIR emission are more preferred to enable
reliable H
2
O
2
detection during in vivo sensing, due to their superior
properties such as environment-independent signal read-out, minimal
auto-fluorescence and tissue scattering, deep tissue imaging capability,
high spatial resolution and high contrast [13–18]. However, only few
examples of ratiometric probes with NIR-fluorescence have been re-
ported [19]. Therefore, to achieve the goal of imaging of H
2
O
2
in PD
models, development of ratiometric probes with NIR fluorescence,
especially those with good water solubility is highly desired. NIR-HP1
was developed by coupling borate ester group and excited-state in-
tramolecular proton transfer (ESIPT) [20]. Borate ester which was
frequently employed as H
2
O
2
receptor was introduced to a NIR-emitting
fluorophore with ESIPT feature. In NIR-HP1, ESIPT-induced NIR
emission is switched off due to the incorporation of borate ester group,
which make NIR-HP1 emit green fluorescence. After reacting with
H
2
O
2
, borate ester group will be removed and the phenol group will be
recovered, resulting in the ESIPT-induced NIR emission switch-on.
Hence, ratiometric sensing of H
2
O
2
via the intensity change of green
and NIR emission channel can be realized. Moreover, because of the
highly hydrophilic nature of pyridinium moiety, good water solubility
of NIR-HP1 is expected.
https://doi.org/10.1016/j.snb.2018.09.107
Received 14 May 2018; Received in revised form 25 September 2018; Accepted 26 September 2018
⁎
Corresponding authors.
1
Both authors contribute equally to this work.
E-mail addresses: iamzpliu@njtech.edu.cn (Z. Liu), iamlli@njtech.edu.cn (L. Li).
Sensors & Actuators: B. Chemical 279 (2019) 38–43
Available online 27 September 2018
0925-4005/ © 2018 Published by Elsevier B.V.
T