Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy
A curcumin-analogous fluorescent sensor for cysteine detection with a
bilateral-response click-like mechanism
b,
a,b,
Fang Fang a, Sheng-Jin Liu a, Xiang-Jun Fan c, , Yu-shun Yang , Zhen Li
⁎
⁎
⁎
a
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
b
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences; State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University,
No.163 Xianlin Road, Nanjing 210023, China
c
Affiliated Hospital of Nantong University, Nantong 226001, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 June 2020
Received in revised form 20 August 2020
Accepted 21 August 2020
Available online 27 August 2020
A novel curcumin-analogous fluorescent sensor, DNP, was developed for cysteine detection with a bilateral-
response click-like mechanism. DNP indicated high selectivity and practical sensitivity. It could recognize Cys
from other biologically relevant molecules, especially, from GSH and Hcy. The most interesting point was that,
with typical azide groups for sensing, DNP indicated a covalent binding procedure with Cys instead of a
presupposed simple reduction for reductive sulfide. Moreover, the recognition occurred at both sides of the sen-
sor. DNP could be utilized into the detection of endogenous and exogenous Cys in living cells. Though the specific
optical performances of DNP still need optimization, this work supplied novel information for broadening the vi-
sion on fluorophores and mechanisms, for the monitoring of Cys and even other sulfur-containing species.
© 2020 Elsevier B.V. All rights reserved.
Keywords:
Cysteine detection
Fluorescent sensor
Curcumin analogue
Bilateral response
Click-like mechanism
1. Introduction
pre-clinical diagnose approaches [22,23]. Among them, according to the
research heat, Cys acts as the pioneering target.
Following the investigations of nitro oxide [1] and carbon monoxide
[2] as possible gasotransmitters with their reported roles in physiology
and pathological processes, the study on the sulfur-containing signaling
molecules has become a hotspot [3–6]. Given the significances in both
composition and metabolism, biological mercaptans seemed the core
group in the sulfur-related internal circulation and balance [7–9]. The
most common mercaptans in organisms are cysteine (Cys) [10], homo-
cysteine (Hcy) [11] and glutathione (GSH) [12]. The variation of their
physiological concentrations can offer reliable basis for the diagnosis
of certain diseases or disorders [13]. Taken Cys as a representative, ex-
cessive Cys can act as the indices for cardiovascular diseases, motor neu-
ron disease, Parkinson's Disease and Alzheimer's Disease [14–17], while
insufficient Cys can be the possible cause of liver damage, hair discolor-
ation, edema, growth retardation, and muscle relaxation [18–21]. Thus,
the unique detection of the biological mercaptans is of great significance
for revealing the corresponding physiological procedures and proposing
Existing approaches for Cys detection contained mass spectrometry
[24], fluorescence analysis [25], electrochemical analysis [26], high per-
formance liquid chromatography (HPLC) [27] and capillary electropho-
resis [28]. Particularly, in the field of life science, small molecular
fluorescent sensor, with high sensitivity, simple operation, strong visi-
bility and low toxicity, has become indispensable monitoring imple-
ment [29]. One most urgent challenge is the distinguishing ability
among the three mercaptans, because their chemical structures are
quite similar. More and more thorough study on the reaction mecha-
nism has brought typical recognition groups for Cys, such as acrylate
[30–38], N-ethylmaleimide [39,40], chloracetate ester [41], α,β-
unsaturated ketone [42,43] and nitrobenzoxadiazole [44]. Among the
most recent Cys sensors [45], the selectivity from GSH and Hcy was es-
pecially focused on [46,47]. Still, novel sensing mechanism with unique
cases are in emergency.
In this work, we developed a curcumin-analogous fluorescent sen-
sor, DNP (“D” for double, “N” for azide, “P” for Probe), for cysteine detec-
tion with a bilateral-response click-like mechanism (Scheme 1). Though
the azide group was once reported, the recognition mechanism here
was not a presupposed simple reduction. Interestingly, the sensor
DNP reacted with Cys through a covalent binding strategy instead.
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Corresponding authors.
1386-1425/© 2020 Elsevier B.V. All rights reserved.