A human vision inspired adaptive platform for one-on-multiple recognition

Article abstract of DOI:10.1039/c9cc00994a

The fluorescence of a coordinative molecule DCM displaying an intramolecular charge transfer (ICT) effect is regulated by several metal ions. These DCM-metal complexes were adopted to recognize different chemicals, including the recognition of triethylenetetramine, thiol-containing amino acids, and H₂S upon binding DCM with Zn²⁺, Ag⁺, and Pb²⁺, respectively. This is in analogy to the general mode of human trichromatic color vision.

Full text of DOI:10.1039/c9cc00994a

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A human vision inspired adaptive platform for
one-on-multiple recognition†
Cite this:DOI: 10.1039/c9cc00994a
Zhiyang Zhu, Jianbin Huang and Yun Yan
*
Received 2nd February 2019,
Accepted 29th March 2019
DOI: 10.1039/c9cc00994a
rsc.li/chemcomm
The fluorescence of a coordinative molecule DCM displaying an
Herein, we report a ‘one-on-multiple’ strategy, which resembles
intramolecular charge transfer (ICT) effect is regulated by several the typical mode of human vision generation (Scheme 1b). Starting
metal ions. These DCM–metal complexes were adopted to recognize with a single fluorescent molecule DCM, we differentiated three
different chemicals, including the recognition of triethylenetetramine, categories of small molecules, including polyamine, thiol-
thiol-containing amino acids, and H2S upon binding DCM with Zn2+
Ag+, and Pb2+, respectively. This is in analogy to the general mode of dicyanomethylene-4H-pyran-based reporting unit, which is expected
,
containing amino acids, and H2S. DCM is designed to have a
human trichromatic color vision.
to display emission color change in different environments
owing to the presence of conjugated donor–acceptor groups.
Nature has long been a grandmaster in teaching chemists to Two coordinating arms were covalently attached to the report-
make complicated functionalities out of the simplest building ing unit. Upon coordinating to metal ions, the DCM–metal
blocks. One impressive lesson is the trichromatic color vision of complex displayed an emission different from the native DCM
human eyes, where one simple pigment of retinal is used to as a result of the existence of intramolecular charge transfer
recognize different colors of light (Scheme 1a).1 Generally, (ICT) states. Excitingly, each DCM–metal system exhibited a
the excited state of retinal is tuned when it binds to different specific recognition ability toward a specific chemical, which
proteins, including red, green, and blue opsins, which enable was accompanied by reversed fluorescence transitions. As a result,
the recognition of R, G, and B colors on one platform.2,3 Such starting from the same DCM molecule, we can respectively
a one-on-multiple strategy is commonly utilized by animals. recognize three categories of chemicals mediated by the coordi-
There are numerous evolving opsins and several analogues of nation of three metal ions. This one-on-multiple strategy is in
retinal, which helped animals to adapt to certain living environ- analogy to the human vision generation. We envision that such
ments using limited molecules.4–6
Inspired by these natural masteries, we believe that the
chemical recognition activity can also be designed in a similar
way, namely, to achieve diversified recognition on the platform
formed by the same molecule. The key point is to design
a reporting unit that can non-covalently bind to different
recognizing units. However, so far, people have not mastered
such an elegant strategy to recognize desired components in an
artificial world, and considerable efforts were put into the
design of specific detectors for each target.7–13 Such a ‘one-on-one’
method will cost too much energy and resources, which is in
clear contrast to the smart behavior of retinal in receiving the
full spectrum of light.
Beijing National Laboratory for Molecular Sciences (BNLMS), State Key Laboratory
for Structural Chemistry of Unstable and Stable Species, College of Chemistry and
Molecular Engineering, Peking University, Beijing, 100871, China.
E-mail: yunyan@pku.edu.cn
Scheme 1 Illustration of (a) human vision generation and (b) our strate-
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
gies for the construction of a sensing platform.
c9cc00994a
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a bio-inspired strategy will open up a new horizon for the
development of chemical recognition.
DCM is a coordinative amphiphile synthesized in our lab
(Scheme S1, ESI†). This molecule has a butterfly-like topology in
which two coordinating antennae are attached to a fluorescent core
(Scheme 1). According to previous research, phenyl substituted
dicyanomethylene-4H-pyran displays distinct optical behaviors
in different environments due to the interconversion between
local excited (LE) states and intramolecular charge transfer (ICT)
states.14,15 Here, the attachment of coordinating arms does not
impact its ICT process. As evidence, both the absorption and
emission of DCM solution can be easily regulated by varying the
solvent compositions in water–ethanol mixtures. DCM displayed
green emission in its good 1–1 (volume ratio) water–ethanol solvent
Fig. 2 (a) Fluorescence pictures of DCM–Zn2+ systems with polyamines
in 1–1 (volume ratio) water–ethanol mixed solvents under a 365 nm UV
lamp. [DCM] = [Zn2+] = 50 mM, [NH3] = 2 [EDA] = 3 [DETA] = 4 [TETA] =
mixture, while red fluorescence was observed in solvents rich in 5 mM. (b) Ratiometric titration of DCM–Zn2+ upon the addition of poly-
amines. The I560/I640 ratios were plotted as a function of polyamine
either water or ethanol (Fig. S1a, ESI†). The characteristic red shifts
of both absorption maxima (from 560 nm to 630 nm) and emission
peaks (rise of a new peak at 499 nm), together with the large Stokes
shift indicated the appearance of ICT complexes in water or ethanol
rich solvents (Fig. S1b and c, ESI†).15
concentrations. (c) Ratiometric response of DCM–Zn2+ towards TETA
without (red bars) or with (green bars) additional competing species. From
left to right: none, NH3, EDA, DETA, TETA, Et3N, C6NH2, H2NNH2, S2À
CO32À. [DCM] = [Zn2+] = 50 mM, [analytes] = 500 mM.
,
Next, the interaction of DCM with different metal ions was
explored based on the coordinative ability of the dicarboxylate change in the corresponding DCM–metal system. This provided
pyridine head groups. Fig. 1a shows the fluorescence color us the fundaments to construct a multiple recognition platform
change of DCM in 1–1 water–ethanol mixed solvents upon addition based on one single fluorescent molecule DCM. Though
of equivalent (two for Ag+, Fig. S2, ESI†) metal ions. Notably, the most small molecules failed to destruct the DCM–Ca2+ system,
emission color of DCM exhibited dramatic changes after addition we succeeded in other three systems.
of Ca2+, Zn2+, Pb2+ and Ag+. FT-IR measurements confirm that
Triethylenetetramine (TETA) is an orphan drug that has
these metal ions have coordinated to the dicarboxylate pyridine been commonly used in the treatment of Wilson’s disease for
head (Fig. S3, ESI†). Spectra examination reveals (Fig. 1b and c) decades.16 Recent studies also revealed its potential uses in
new absorption maxima near 500 nm and new emission peaks cancer chemotherapy and other diseases.17–19 However, clinical
at around 650 nm, verifying the appearance of ICT states under applications and pharmacological studies of TETA are greatly
these conditions.
hindered by the lack of versatile analytical methods, as current
The coordination triggered red emission is drastically protocols for TETA detection are majorly based on chromato-
different from the green emission of DCM itself. Since metal ions graphy or labelling reagents.20,21 Here, we achieved direct
can bind to different molecules respectively, these DCM–metal fluorescence detection of TETA using the DCM–Zn2+ system.
complexes can be further used as individual species for specific Upon addition of 0.5 mM TETA to 50 mM DCM–Zn2+ solution, a
recognition purpose. In principle, any material that can remove red-to-green fluorescence transition can be observed (Fig. 2a).
metal ions from DCM will induce a reversed fluorescence Using the fluorescence titration method, we can achieve quanti-
tative detection of TETA in the concentration range of 50–500 mM
(Fig. 2b), which covers the commonly used concentrations in
preclinical studies.22 Notably, its analogues including ethylene-
diamine (EDA) and diethylenetriamine (DETA) only show limited
influence on the DCM–Zn2+ system. At equivalent concentration,
the co-existence of EDA or DETA is negligible and doesn’t
significantly affect the detection of TETA (Fig. 2b and Fig. S4,
ESI†). Besides, other competing species such as S2À and CO32À or
the presence of other metal ions show ignorable influence (Fig. 2c
and Fig. S5, ESI†). This desirable selectivity of DCM–Zn2+ towards
TETA can be related to the octahedral coordination configuration
usually adopted by Zn2+, which favors the formation of planar
chelating structures with multi-dental ligands.
Recognition of specific amino acid has always been an
interesting topic in fluorescence sensing area. Among them, most
Fig. 1 (a) Fluorescence pictures of DCM–Mn+ systems in 1–1 (volume
efforts were dedicated to the selective detection of thiol-containing
ratio) water–ethanol mixed solvents under a 365 nm UV lamp. [DCM] =
ones, such as cysteine (Cys) and glutathione (GSH),23–25 due to their
crucial role in many physiological aspects.26,27
[Mn+] = [Ag+]/2 = 50 mM. (b) Absorption spectra and (c) emission spectra of
DCM–Mn+ systems in 1–1 water–ethanol mixed solvents.
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Fig. 4 (a) Fluorescence pictures of DCM–Pb2+ systems in the presence
of H2S in 1–1 water–ethanol mixed solvents under a 365 nm UV lamp.
(b) Optical pictures of DCM–Pb2+ systems in the presence of H2S. [DCM] =
[Pb2+] = 50 mM, [H2S] = 150 mM. (c) Ratiometric titration of DCM–Pb2+
upon the addition of H2S. The I566/I636 ratios were plotted as a function of
H2S concentrations. (d) Ratiometric response of DCM–Pb2+ towards H2S
against other competitors (red bars) and the response of DCM–Pb2+ in the
presence of competitors towards H2S (green bars). From left to right: none,
S2À, FÀ, ClÀ, BrÀ, IÀ, CO32À, C2O42À, SO42À, PO43À, and CH3COOÀ.
Fig. 3 (a) Fluorescence pictures of DCM–Ag+ systems with polar amino
acids in 1–1 (volume ratio) water–ethanol mixed solvents under a 365 nm
UV lamp. (b) Ratiometric titration of DCM–Ag+ upon the addition of Cys
and GSH. The I570/I650 ratios were plotted as a function of amino acid
concentrations. (c) Ratiometric response of DCM–Ag+ towards thiol-
containing amino acid Cys without (red bars) or with (green bars) various
competitors. From left to right: none, Cys, Cys–Cys, Met, Lys, Arg, His, Asp,
Asn, Glu, Tyr, BSA (bovine serum albumin). [DCM] = [Ag+]/2 = 50 mM,
[amino acids] = 100 mM if not mentioned.
combination of one fluorescent amphiphile DCM and metal
ions. Upon coordinating with metal ions, DCM exhibited a
huge red-shift of fluorescence color in comparison to itself.
This regulation was reversible when metal ions were extracted
from DCM–metal complexes. Because each metal ion may have
specific binding affinity to different chemicals resulting in the
recovery of the DCM emission, the DCM–metal system is able to
recognize different chemicals. We verified that it is possible to
discriminate TETA, Cys and GSH, and H2S using DCM–Zn2+,
DCM–Ag+, and DCM–Pb2+, respectively. This is very similar to
the way that human eyes recognize red, green, and blue colors
with the same retinal molecule when it binds to red, green, and
blue opsins. Such a bio-inspired strategy will open up a new
horizon in the design of an adaptive platform for versatile
chemical recognition.
Here, we achieved discrimination of Cys and GSH from
other amino acids based on the high affinity of Ag+ to thiol
groups. On the addition of 1 equivalent of Cys or GSH, the red
fluorescence of the DCM–Ag+ system turned green immediately.
As indicated by the ratiometric signal, quantitative detection of
Cys and GSH is viable in the concentration range of 30–70 mM
with a detection limit of 20 mM (Fig. 3b). Other types of amino
acids bearing coordinating groups, such as carboxyl groups,
hydroxyl groups, amino groups and guanidine groups, show
limited interferences (Fig. 3c) and do not significantly affect
the detection of Cys and GSH (Fig. S6, ESI†). Basically, the
selectivity of Ag+ to thiol containing amino acids can be explained
by HSAB theory, where the thiol group is a soft base, and Ag+ is a
soft acid.28
This work was financially supported by the National Natural
Science Foundation of China (NSFC, Grant No. 91856120,
21573011, and 21633002) and the Ministry of Science and
Technology of China (2017YFB0308800).
Hydrogen sulfide (H2S) has been regarded as a toxic gas for a
long time.29 However, recent studies revealed that H2S also
plays some important roles in biological systems,30 therefore
the detection of the H2S level in solution in the biosystem has
attracted intensive interest.31–34 Herein, the DCM–Pb2+ system
was proved to be optimizing for the selective detection of H2S.
Upon addition of 150 mM H2S to the solution, the red bright
Conflicts of interest
fluorescence of the DCM–Pb2+ system turned dark green There are no conflicts to declare.
(Fig. 4a), accompanied by the darkening of solution color
(Fig. 4b). In the fluorescence titration curve, there was a sharp
increase of the ratiometric signal when the concentration of
Notes and references
1 G. J. Wald, Science, 1964, 145, 1007–1016.
H2S exceeded 30 mM (Fig. 4c), and quantitative detection is
viable in the concentration range of 40–100 mM. This detection
ability is comparable to some previously reported H2S fluores-
cent sensors.33,34 Significantly, the existence of other coordina-
tive species, such as IÀ, CO32À, SO42À, HPO42À, and GSH, does
not significantly affect the detection of H2S using DCM–Pb2+
complex (Fig. 4d and Fig. S7, ESI†), indicating the specificity of
the DCM–Pb2+ system toward H2S.
2 J. Nathans, Biochemistry, 1990, 29, 9746–9752.
3 K. Fujimoto, J.-y. Hasegawa, S. Hayashi, S. Kato and H. Nakatsuji,
Chem. Phys. Lett., 2005, 414, 239–242.
4 P. W. Lucas, B. W. Darvell, P. K. D. Lee, T. D. B. Yuen and M. F.
Choong, Folia Primatol., 1998, 69, 139–152.
5 H. Siitari, J. Honkavaara and J. Viitala, Proc. R. Soc. London, Ser. B,
1999, 266, 2125–2129.
6 J. N. Lythgoe, Vision Res., 1984, 24, 1539–1550.
7 D. Ding, K. Li, B. Liu and B. Z. Tang, Acc. Chem. Res., 2013, 46, 2441–2453.
8 L. Yuan, W. Y. Lin, K. B. Zheng and S. S. Zhu, Acc. Chem. Res., 2013,
46, 1462–1473.
In summary, we demonstrated a facile strategy to develop a
one-on-multiple molecular recognition platform based on the
9 S. W. Thomas III, G. D. Joly and T. M. Swager, Chem. Rev., 2007, 107,
1339–1386.
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View Article Online
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10 L. E. Kreno, K. Leong, O. K. Farha, M. Allendorf, R. P. Van Duyne 21 J. Lu, Y. K. Chan, S. D. Poppitt and G. J. S. Cooper, J. Chromatogr. B:
and J. T. Hupp, Chem. Rev., 2012, 112, 1105–1125. Anal. Technol. Biomed. Life Sci., 2007, 859, 62–68.
11 Y. Liu, X. Dong and P. Chen, Chem. Soc. Rev., 2012, 41, 2283–2307. 22 J. Lu, Mol. Cancer Ther., 2010, 9, 2458–2467.
12 K. Hisataka, O. Mikako, A. Raphael, P. L. Choyke and U. Yasuteru, 23 W. Li, L. Long, L. Yuan, Z. Cao, B. Chen and W. Tan, Org. Lett., 2008,
Chem. Rev., 2010, 110, 2620–2640.
13 M. Vendrell, D. Zhai, J. C. Er and Y. T. Chang, Chem. Rev., 2012, 112, 24 X. Yang, Y. Guo and R. M. Strongin, Angew. Chem., Int. Ed., 2011, 50,
4391–4420. 10690–10693.
14 H. Tong, Y. Hong, Y. Dong, Y. Ren, M. Haussler, J. W. Y. Lam, 25 W. Hao, A. McBride, S. McBride, J. P. Gao and Z. Y. Wang, J. Mater.
K. S. Wong and B. Z. Tang, J. Phys. Chem. B, 2007, 111, 2000–2007. Chem., 2011, 21, 1040–1048.
15 X. F. Xu, R. Q. Zhang, Z. X. Cao and Q. E. Zhang, J. Theor. Comput. 26 X. F. Wang and M. S. Cynader, J. Neurochem., 2000, 74, 1434–1442.
Chem., 2008, 7, 719–736. 27 S. Shahrokhian, Anal. Chem., 2001, 73, 5972–5978.
16 A. Ala, A. P. Walker, K. Ashkan, J. S. Dooley and M. L. Schilsky, 28 R. G. Pearson, J. Am. Chem. Soc., 1963, 85, 3533–3539.
Lancet, 2007, 369, 397–408. 29 C. Wang, X. Chu and M. Wu, Sens. Actuators, B, 2006, 113, 320–323.
17 J. Liu, L. Guo, F. Yin, X. Zheng, G. Chen and Y. Wang, Biomed. 30 O. Kabil and R. Banerjee, J. Biol. Chem., 2010, 285, 21903–21907.
10, 5577–5580.
¨
Pharmacother., 2008, 62, 480–485.
18 L. Wang, X. Luo, C. Li, Y. Huang, P. Xu, L. H. Lloyd-Davies,
31 C. Liu, J. Pan, S. Li, Y. Zhao, L. Y. Wu, C. E. Berkman, A. R. Whorton
and M. Xian, Angew. Chem., Int. Ed., 2011, 50, 10327–10329.
T. Delplancke, C. Peng, R. Gao, H. Qi, C. Tong and P. Baker, Oxid. 32 S. K. Bae, C. H. Heo, D. J. Choi, D. Sen, E. H. Joe, B. R. Cho and
Med. Cell. Longevity, 2017, 3481710.
19 G. J. S. Cooper, Drugs, 2011, 71, 1281–1320.
20 A. Othman, J. Lu, T. Sunderland and G. J. S. Cooper, J. Chromatogr.
B: Anal. Technol. Biomed. Life Sci., 2007, 860, 42–48.
H. M. Kim, J. Am. Chem. Soc., 2013, 135, 9915–9923.
33 Z. Du, B. Song, W. Zhang, C. Duan, Y. L. Wang, C. Liu, R. Zhang and
J. Yuan, Angew. Chem., Int. Ed., 2018, 57, 3999–4004.
34 J. Hong, W. Feng and G. Feng, Sens. Actuators, B, 2018, 262, 837–844.
Chem. Commun.
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