Design and synthesis ethynyl ferrocene-based multifunctional chemosensors for fluoride anion

Article abstract of DOI:10.1007/s11164-019-03808-1

To exploit novel ferrocene-based small molecules with long conjugated structures as visible and electrochemical multichannel chemosensors, four conjugated ferrocene ethynyl semicarbazide derivatives (Fc-X-An) were synthesized via the Sonogashira coupling

Full text of DOI:10.1007/s11164-019-03808-1

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03808-1
Design and synthesis ethynyl ferrocene‑based
multifunctional chemosensors for ꢀuoride anion
Hongyuan Fu1,2 · Yizhong Shi · Jian You · Tingting Hao1,2 · Tao Wang1,2
3
1,2
Received: 16 November 2018 / Accepted: 18 March 2019
©
Springer Nature B.V. 2019
Abstract
To exploit novel ferrocene-based small molecules with long conjugated structures
as visible and electrochemical multichannel chemosensors, four conjugated ferro-
cene ethynyl semicarbazide derivatives (Fc-X-An) were synthesized via the Sonoga-
shira coupling reaction. The synthesized Fc-X-Ans are 2-(4-(ferrocenylethynyl)
benzylidene) hydrazine-1-carboxamide (Fc-Ph-An), 2-((5-(ferrocenylethynyl)
thiophen-2-yl)methylene)hydrazine-1-carboxamide
(Fc-Thie-An),
2-((9-ethyl-
6
-(ferrocenylethynyl)-9H-carbazol-3-yl) methylene)hydrazine-1-carboxamide (Fc-
Cz-An) and 2-((10-ethyl-7-(ferrocenylethynyl)-10H-phenothiazin-3-yl) methylene)
hydrazine-1-carboxamide (Fc-PTZ-An). The recognition abilities of the semicar-
bazide derivative Fc-X-Ans for several anions were evaluated from visible absorp-
1
tion spectra, H NMR, and electrochemical technique.
Keywords Synthesis · Semicarbazide · Ethynl ferrocene · Conjugated structure ·
Chemosensor
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4
-019-03808-1) contains supplementary material, which is available to authorized users.
*
Tao Wang
wangtwj2000@163.com
1
2
3
State Key Laboratory of Chemical Resource Engineering, College of Science, Beijing
University of Chemical Technology, Beijing 100029, People’s Republic of China
Department of Organic Chemistry, College of Science, Beijing University of Chemical
Technology, Beijing 100029, People’s Republic of China
Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory
for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou,
Jiangsu 215123, People’s Republic of China
Vol.:(012
1
3456789)
3

H. Fu et al.
Introduction
Ferrocene (Fc) derivatives have been widely utilized as the multifunctional detec-
tors for ions. They can be applied as an electrochemical signal unit in anion rec-
ognition systems owing to its stable and sensitive redox characteristics before and
after binding with the anions [1–7]. Fc is also applied as a chromogenic unit in
chemosensor molecules, for example Pedro et al. have reported a series of fer-
rocene-based small receptors for anion and cation recognition in which the fer-
rocene unit was linked by unsaturated aza bridges to a chromogenic or ꢀuorescent
signalling unit [8–11].
Anion sensing has especially attracted attention in the past decades, due to its
close relationship with the people’s health and the environmental protection [12–16].
Exploiting novel molecular receptors, which could selectively bind and sense the
anion by a macroscopic physical response, is an area of intense activity [17]. Anion
receptors can be roughly divided into the guest binding and signaling sites accord-
ing to their role in the recognition processes. The guest binding sites, such as amide
[
18–21], urea [22–25], imidazole [26, 27], phyrin [28], and rotaxane [29, 30], can
bind with the target anions through supramolecular interactions, hydrogen interac-
tions or electrostatics interactions [31–35], while the signaling sites, for example a
chromogenic unit, a ꢀuorescent unit [36, 37] or an electrochemical group, can trans-
port the binding information to the physical recordable signal [3, 38, 39].
Except for the demand of sensitivity, receptors consisting of more than one sig-
nal unit, are more attractive due to their abilities of multichannel recognition. Thus
exploiting novel and eꢁcient multifunctional acceptors for anions deserve more
endeavor [40–44]. In this work, we designed and synthesized four conjugated fer-
rocene ethynyl semicarbazide derivatives Fc-Ph-An, Fc-Thie-An, Fc-Cz-An and Fc-
PTZ-An to act as multifunctional chemosensors. With an aim to realize the so-called
“
naked eye” detection of ions, all receptors in our Fc-X-Ans adopt the highly conju-
gated molecular skeleton with conjugated Fc and semicarbazide acting as the multi-
channel signaling and exclusive, sensitive anion binding segments, respectively. The
anion binding properties of target acceptors were investigated carefully by electro-
1
chemical, H NMR, spectral and optical techniques.
Experimental section
General instrumentations and reagents
All chemicals were commercially available and used without further puriꢂca-
tion. The 2-Bromo-5-formylthiophene [45], 3-bromo-9-ethylcarbazole-6-carbox-
aldehyde [46], 7-bromo-10-ethyl-10H-phenothiazine-3-carboxaldehyde [47] and
ethynylferrocene [48] were synthesized and compared with that of the reported.
1
13
The H NMR and C NMR spectra were recorded on a Bruker AV400 unity
spectrometer operated at 400 MHz using acetone-d as deuterated solvent.
6
1
3

Design and synthesis ethynyl ferrocene-based multifunctional…
Mass spectra were recorded on a Thermo ISQ mass spectrometer using a direct
exposure probe. UV–Vis absorption spectra were recorded on a Hitachi U2500
UV–Vis spectrophotometer. Fluorescence spectra were measured on a Hitachi
F-7500 ꢀuorescence spectrophotometer. Cyclic voltammetric measurements were
performed on a PC-controlled LK98BII electrochemical analyzer, using 1.0 mM
dye solution in DMSO at a scan rate of 100 mV/s using 0.1 M tetrabutyl ammo-
nium hexaꢀuorophosphate as supporting electrolyte. The glassy carbon, standard
calomel electrode (SCE) and platinum were used as working, reference and aux-
iliary electrodes, respectively. Deoxygenation of the solutions was achieved by
bubbling nitrogen for at least 10 min.
Experimental procedures
(2‑(4‑Formylphenyl)ethynyl)ferrocene (Fc‑Ph‑A)
A mixture of 4-bromobenzaldehyde (0.18 g, 1.00 mmol), ethynylferrocene (0.32 g,
1
.50 mmol), Pd(PPh ) Cl (21.0 mg, 0.03 mmol), CuI (10.0 mg, 0.05 mmol), 1 mL
3 2 2
TEA and 10 mL DMF was added to a 100 mL round-bottom ꢀask. Nitrogen was
bubbled through the reaction mixture to remove dissolved air. Then the mixture was
heated at 90 °C for 8 h. The reaction mixture was then poured in water, and the pre-
cipitate was collected by ꢂltration and puriꢂed over silica gel with petroleum ether/
1
ethyl acetate (4:1, v/v) as eluent to aꢃord 0.25 g (80%) of a dark red solid. H NMR
(
400 MHz, CDCl ): δ 10.03 (s, 1H), 7.86 (d, J=8.1 Hz, 2H), 7.64 (d, J=8.1 Hz,
3
+
2
H), 4.78–3.84 (m, 9H). MS (EI) m/z: [M] : calcd for 315.05; found 315.10.
(2‑(5‑Formyl‑2‑thienyl)ethynyl)ferrocene (Fc‑Thie‑A)
The synthesis was performed according to the synthetic procedure described for
Fc-Ph-A using 2-bromo-5-formylthiophene instead of 4-bromobenzaldehyde. This
gave, after puriꢂcation by column chromatography over silica gel with petroleum
ether/ethyl acetate (4:1, v/v) as eluent, to aꢃord 0.27 g (85%) of a dark red solid.
1
H NMR (400 MHz, CDCl ): δ 9.88 (s, 1H), 7.67 (d, J=3.9 Hz, 1H), 7.26 (d,
3
J=3.9 Hz, 1H), 4.59–4.53 (m, 2H), 4.39–4.32 (m, 2H), 4.29 (s, 5H). MS (EI) m/z:
+
[
M] : calcd for 321.00; found 321.13.
(3‑(6‑Formyl‑9‑ethyl‑9H‑carbazolyl)ethynyl)ferrocene (Fc‑Cz‑A)
The synthesis was performed according to the synthetic procedure described for Fc-
Ph-A using 3-bromo-9-ethylcarbazole-6-carboxaldehyde instead of 4-bromobenzal-
dehyde. This gave, after puriꢂcation by column chromatography over silica gel with
petroleum ether/ethyl acetate (5:1, v/v), as eluent to aꢃord 0.39 g (90%) of a earthy
1
yellow solid. H NMR (400 MHz, DMSO): δ 10.08 (s, 1H), 8.87 (s, 1H), 8.51 (s,
1
1
4
H), 8.04 (dd, J=8.6, 1.4 Hz, 1H), 7.83 (d, J=8.6 Hz, 1H), 7.73 (d, J=8.5 Hz,
H), 7.65 (dd, J=8.5, 1.4 Hz, 1H), 4.63–4.59 (m, 2H), 4.54 (q, J=7.2 Hz, 2H),
1
3
.36–4.34 (m, 2H), 4.31 (s, 4H), 1.36 (t, J=7.1 Hz, 3H). C NMR (101 MHz,
1
3

H. Fu et al.
DMSO): 191.75, 129.78, 127.00, 124.63, 124.05, 122.57, 121.92, 110.27, 109.92,
+
7
4
0.96, 69.75, 68.79, 65.07, 37.54, 13.73. MS (EI) m/z: [M] : calcd for 432.11; found
32.21.
(3‑(7‑Formyl‑10‑ethyl‑10H‑phenothiazinyl)ethynyl)ferrocene (Fc‑PTZ‑A)
The synthesis was performed according to the synthetic procedure described for
Fc-Ph-A using 7-bromo-10-ethyl-10H-Phenothiazine-3-carboxaldehyde instead
of 4-bromobenzaldehyde. This gave, after puriꢂcation by column chromatogra-
phy over silica gel with petroleum ether/ethyl acetate (3:1, v/v), as eluent to aꢃord
1
0
.41 g (90%) of a yellow solid. H NMR (400 MHz, CDCl ): δ 9.82 (s, 1H), 7.65
3
(
dd, J=8.4, 1.5 Hz, 1H), 7.58 (s, 1H), 7.33–7.26 (m, 1H), 7.23 (s, 1H), 6.92 (d,
J=8.4 Hz, 1H), 6.83 (d, J=8.5 Hz, 1H), 4.51 (m, 2H), 4.26 (s, 7H), 3.99 (q,
1
3
J=6.8 Hz, 2H), 1.47 (t, J=6.9 Hz, 3H). C NMR (101 MHz, CDCl ): 189.92,
3
1
1
49.64, 142.35, 131.20, 130.73, 130.24, 129.94, 128.23, 123.90, 123.18, 119.18,
15.20, 114.46, 88.84, 84.55, 71.36, 69.99, 68.86, 65.19, 42.63, 12.78. MS (EI) m/z:
+
[
M] : calcd for 464.08; found 464.20.
2‑(4‑(Ferrocenylethynyl)benzylidene)hydrazine‑1‑carboxamide (Fc‑Ph‑An)
A mixture of 0.11 g (1.00 mmol) aminourea hydrochloride, 0.25 g (3.00 mmol)
sodium acetate, and 30 mL deionized water was added to a 250 mL round-bottom
ꢀ
ask. Then the mixture was heated at 95 °C before the adding of 0.31 g (1.00 mmol)
Fc-Ph-A in 60 mL isopropanol. The reaction mixture was then poured in water after
the reaction was over, and the precipitate was collected by ꢂltration and puriꢂed
over silica gel with dichloromethane/methanol (10:1, v/v) as eluent to aꢃord Fc-Ph-
1
An 0.26 g (70%) of a brown yellow solid. H NMR (400 MHz, DMSO): δ 10.33 (s,
1
4
1
H), 7.85 (s, 1H), 7.74 (d, J=7.9 Hz, 2H), 7.48 (d, J=7.9 Hz, 2H), 6.54 (s, 2H),
1
3
.59 (s, 2H), 4.36 (s, 2H), 4.29 (s, 5H). C NMR (101 MHz, DMSO) δ 156.62,
38.40, 134.35, 131.21, 126.69, 123.32, 90.17, 85.54, 71.12, 69.79, 69.08, 64.25.
+
MS (EI) m/z: [M] : calcd for 372.08; found 372.17.
2
‑((5‑(Ferrocenylethynyl)thiophen‑2‑yl)methylene)hydrazine‑1‑carboxamide
(Fc‑Thie‑An)
The synthesis was performed according to the synthetic procedure described for Fc-
Ph-An using Fc-Thie-A instead of Fc-Ph-A. This gave, after puriꢂcation by column
chromatography over silica gel with dichloromethane/methanol (10:1, v/v), as eluent
1
to aꢃord 0.28 g (75%) of a brown red solid. H NMR (400 MHz, DMSO): δ 10.38 (s,
1
H), 7.99 (s, 1H), 7.26 (m, 2H), 6.35 (s, 2H), 4.61 (s, 2H), 4.39 (s, 2H), 4.28 (s, 5H).
C NMR (101 MHz, DMSO) δ 156.19, 140.42, 134.02, 132.11, 128.85, 123.23,
1
3
+
9
3
4.52, 78.73, 71.18, 69.86, 69.37, 63.46. MS (EI) m/z: [M] : calcd for 378.04; found
78.15.
1
3

Design and synthesis ethynyl ferrocene-based multifunctional…
2
‑((9‑Ethyl‑6‑(ferrocenylethynyl)‑9H‑carbazol‑3‑yl)methylene)
hydrazine‑1‑carboxamide (Fc‑Cz‑An)
The synthesis was performed according to the synthetic procedure described for
Fc-Ph-An using Fc-Cz-A instead of Fc-Ph-A. This gave, after puriꢂcation by col-
umn chromatography over silica gel with dichloromethane/methanol (10:1, v/v),
1
as eluent to aꢃord 0.34 g (70%) of a brown yellow solid. H NMR (400 MHz,
DMSO): δ 10.20 (s, 1H), 8.65 (s, 1H), 8.41 (s, 1H), 8.02 (s, 1H), 7.87 (d,
J = 8.6 Hz, 1H), 7.64–7.62 (m, 2H), 7.57 (d, J = 8.4 Hz, 1H), 6.55 (s, 2H), 4.59 (s,
2
H), 4.46 (t, J = 6.7 Hz, 2H), 4.34 (s, 2H), 4.30 (s, 5H), 1.34 (t, J = 7.0 Hz, 3H).
C NMR (101 MHz, DMSO) δ 156.94, 140.47, 140.02, 139.36, 129.08, 126.48,
25.13, 123.71, 122.45, 122.01, 119.37, 113.45, 109.72, 109.42, 86.66, 86.24,
1
3
1
7
4
+
0.88, 69.72, 68.72, 65.28, 59.72, 37.26, 13.75. MS (EI) m/z: [M] : calcd for
89.14; found 489.24.
2
‑((10‑Ethyl‑7‑(ferrocenylethynyl)‑10H‑phenothiazin‑3‑yl)methylene)
hydrazine‑1‑carboxamide (Fc‑PTZ‑An)
The synthesis was performed according to the synthetic procedure described
for Fc-Ph-An using Fc-PTZ-A instead of Fc-Ph-A. This gave, after puriꢂca-
tion by column chromatography over silica gel with dichloromethane/meth-
1
anol (10:1, v/v), as eluent to aꢃord 0.38 g (73%) of a brown yellow solid. H
NMR (400 MHz, DMSO): δ 10.16 (s, 1H), 7.73 (s, 1H), 7.63 (s, 1H), 7.43 (d,
J = 6.6 Hz, 1H), 7.30 (d, J = 6.9 Hz, 1H), 7.23 (s, 1H), 7.00–6.99 (m, 2H), 6.50 (s,
1
3
2
H), 4.55 (s, 2H), 4.33 (s, 2H), 4.27 (s, 5H), 3.95 (s, 2H), 1.32 (s, 3H). C NMR
(
101 MHz, DMSO) δ 156.75, 143.89, 143.27, 137.96, 130.74, 129.55, 129.00,
1
6
5
26.85, 124.14, 122.45, 116.95, 115.40, 115.16, 88.39, 84.67, 70.96, 69.74,
+
8.87, 64.62, 59.72, 41.45, 12.37. MS (EI) m/z: [M] : calcd for 521.11; found
21.22.
UV–Vis analysis
UV–Vis absorption spectra of Fc-X-An (1 × 10− mol/L) in DMSO before and
5
−
−
−
after adding 30 equiv salts named TBAY (where the anion Y is F , Cl , Br ,
−
−
−
−
−
−
−
I , NO , ClO , HSO , Ac , PF , H PO ) were recorded in the range of
3
4
4
6
2
4
2
50–700 nm at the room temperature. The stock solution concentrations of Fc-
−
4
−4
−5
X-An and TBAY are 1.0 × 10 mol/L and 5 × 10 , 5 × 10 mol/L, respectively.
Then stock solution (0.50 mL) of Fc-X-An was placed into a 10 mL volumet-
ric ꢀask, and diꢃerent amounts of the TBAY solutions were added with a micro
syringe, ꢂnally diluted to 10 mL with the DMSO. After each addition, the absorp-
tion spectra were recorded. Statistical analysis of the data was carried out using
Origin 8.0. All reaction experiments were carried out at room temperature.
1
3

H. Fu et al.
Cyclic voltammetry experiment
A three-electrode system was adopted to test the cyclic voltammetry (CV) with
a scanning rate of 0.1 V/s under the nitrogen condition. Sample concentration
−
3
of target Fc-X-An acceptors is 10 mol/L in DMSO solution and the oxida-
tion–reduction peak of Fc is utilized as the signaling site. Then the TBAF in
DMSO solution is gradually added thereto by a micro-injector. The oxida-
tion–reduction peak of the Fc group was measured again, and observed changes
of oxidation–reduction peak when TBAF was gradually add in.
1H Nuclear magnetic resonance titration experiment
−
2
Fc-X-An dissolved in DMSO-d with a concentration of 1.0×10 mol/L was pre-
6
pared and tested ꢂrstly. Then 0–1.25 equiv of TBAF stock solution in DMSO-d was
6
1
added to the abovementioned samples gradually and the corresponding H NMR
spectra were recorded again. The chemical shifts of the NH and CH protons were
followed and drafted against the equivalents of TBAF.
Method for Job’s plot
A stock solution of Fc-X-An and the TBAF were prepared with a concentration of
−
4
1
×10 mol/L in DMSO, respectively. In the Job’s plot experiments, keeping the
−5
ꢂxed overall concentration at 1×10 mol/L, and the molar fraction of TBAF was
changed from 0 to 1.0. In the course of preparation of sample solutions, the diꢃerent
amounts of Fc-X-An and TBAF solutions were placed into a 10 mL volumetric ꢀask
by using a microsyringe, and then diluted to 10 mL. After mixing the samples in a
uniform state, the absorption spectra were recorded in the range of 250–700 nm at
the room temperature. Statistical analysis of the data was carried out using Origin
8
.0.
Results and discussion
Synthesis
The synthesis route of Fc-X-An is shown in Scheme 1. Ethynyl ferrocene underwent
the Sonogashira coupling reaction with bridging ligands to yield the intermediate
Fc-X-A with a high yield rate. Following, ꢂnal acceptors Fc-X-An were obtained
after the reaction of Fc-X-A and semicarbazide hydrochloride under the catalysis
of sodium acetate. Fc-X-An and Fc-X-A have been characterized and conꢂrmed by
1
13
1
13
ESI–MS, H NMR, C NMR spectroscopy. Figures S1–S8 list the H NMR and
NMR of Fc-X-An.
C
1
3

Design and synthesis ethynyl ferrocene-based multifunctional…
Scheme 1 Synthesis route of Fc-X-An
(a)
3
2
1
0
(b)
8
1-5,7
1
-5,7
6
1
0
6
8
9
9
3
00
400
500
600
700
300
400
500
600
700
Wavelength(nm)
Wavelength(nm)
(c)
(d)
3
2
1
0
2
1
0
1
-5,7
1
-4, 7-10
6
6
8
9
5
3
00
400
500
600
700
300
400
500
600
700
Wavelength(nm)
Wavelength(nm)
Fig. 1 UV–Vis titration absorption spectra of a Fc-Ph-An, b Fc-Thie-An, c Fc-Cz-An and d Fc-PTZ-An
−
−
5
−
−
−
−
(
5×10 mol/L) in DMSO upon addition of 30 equiv of respective anions (1: Cl , 2: Br , 3: I , 4: NO
,
3
−
−
−
−
−
+
5
: AcO , 6: F , 7: ClO , 8: HSO , 9: PF , 10: H PO ) as n-Bu N salt
4 4 6 2 4 4
1
3

H. Fu et al.
Table 1 Complexation constant
K, correlation coeꢁcient R and
LOD between Fc-X-An and F−
K (M−1
Substances
)
R
LOD (mol/L)
−4
Fc-Ph-An
Fc-Thie-An
Fc-Cz-An
Fc-PTZ-An
123
448
593
439
0.99
0.99
0.99
0.99
2.31×10
−4
1.07×10
2.98×10−
5
5.93×10−5
UV–Vis titration analysis
The anion-binding properties of Fc-X-An were ꢂrst studied by UV–Vis spectros-
copy in DMSO solution. The UV–Vis titration analysis of Fc-X-An with various
anions was exhibited in Fig. 1 and the key parameters are summarized in Table 1.
As shown in Fig. 1, no obvious change could be observed upon addition of 30 equiv
−
−
−
−
−
−
−
−
−
of Cl , Br , I , NO , AcO , ClO , HSO , PF , H PO . Signiꢂcant variations
3
4
4
6
2
4
−
were found after the adding of F to the solution of acceptor.
Moreover, colorimetric receptors were especially attractive as it could be eas-
ily monitored by ion-complexation induced changes in UV–Vis absorption spectra,
which would allow the so-called “naked eye” detection of ions. As shown in Fig. 2,
the solution colors of four receptors changed from light yellow to yellow upon addi-
−
−
tion of F . Compared with other receptors, Fc-Thie-An shown more sensitive to F
−
which could be used as an ideal ‘Naked-eye’ probe for selective F sensing. The vis-
−
−
−
ual colorimetric responses after and before adding Cl , Br , I in DMSO are listed
in Figs. S9–S11.
When comparing with the other, Fc-Ph-An showed a more signiꢂcant variation
during the UV–Vis absorption titration test as seen in Fig. 2a. Then the UV–Vis
−
absorption titration with F was studied in detail and the result is shown in Figure
−
S12. Upon the gradual addition of F , a decrease at 330 nm as well as an increase
with a peak at 417 nm were observed simultaneously and the spectral change almost
−
stopped upon addition of 60 equiv of F . Such unique phenomenon suggested
Fig. 2 Visual colorimetric response before (a) and after (b) addition of F− in DMSO (the receptor is
−
−
−
−
Fc-Ph-An, Fc-Thie-An, Fc-Cz-An and Fc-PTZ-An from left to right The anions is F , Cl , Br , I as
+
n-Bu N salt from up to down)
4
1
3

Design and synthesis ethynyl ferrocene-based multifunctional…
that Fc-Ph-An was suitable to act as a highly exclusive and sensitive chemosensor
for ꢀuoride by UV–Vis titration. Moreover, the clear isosbestic points at 295 and
3
57 nm indicated that a single component was produced in response to the interac-
−
tion between Fc-Ph-An and F [49]. Results of other acceptors are shown in Fig-
ures S13, S14 and S15.
With an aim to verify our assumption that target Fc-X-An acceptors associate
−
with F in a 1:1 stoichiometry, Benesi–Hildebrand analysis is utilized [50]. When
−
assuming a 1:1 association between Fc-X-An and F , the Benesi–Hildebrand equa-
tion is given as follows:
ꢀ
ꢁ
1
1
1
=
+ 1 .
(1)
−
A∞ − A0 K[F ]
A − A0
A and A are the absorbency of Fc-X-An before and after adding an excess
0
∞
−
−
amount of F while the A is the measured absorbency of Fc-X-An after adding F ; K
−1
−
−
is the association constant (mol ), and [F ] is the concentration of F added (mol).
−
As shown in Fig. 3, a plot of 1/(A−A ) against 1/[F ] shows a linear relationship,
0
−
indicating that Fc-X-An actually associated with F in a 1:1 stoichiometry. Besides,
such stoichiometry was further conꢂrmed by Job’s plot. As exhibited in Fig. 4, the
−
Job’s plots suggested a 1:1 binding model between Fc-X-An and F . Corresponding
3
3
2
2
1
1
50
00
50
00
50
00
Fc-Ph-An
Fc-Thie-An
2
1
1
0
5
0
5
0
5
0
0
0
2000
4000
6000
8000
10000
0
2000
4000
6000
8000
10000
-
-
1
/[F ]
1/[F ]
3
3
2
2
1
1
5
0
5
0
5
0
Fc-Cz-An
50 Fc-PTZ-An
4
3
2
1
0
0
0
0
0
2
000
4000
6000
-
8000
10000
0
2000
4000
6000
8000
10000
-
1/[F ]
1
/[F ]
−
Fig. 3 Benesi–Hildebrand analysis of UV–Vis absorption titration of Fc-X-An with F (analysis wave-
length of Fc-Ph-An, Fc-Thie-An, Fc-Cz-An and Fc-Cz-An at 413 nm, 444 nm, 376 nm and 376 nm,
respectively)
1
3

H. Fu et al.
3
3
2
2
.5
.0
.5
.0
3
3
2
2
1
1
0
0
.5
.0
.5
.0
.5
.0
.5
.0
Fc-Thie-An
Fc-Ph-An
1.5
1.0
0.5
0.0
0
.0
0.2
0.4
0.6
0.8
1.0
0.0
0.2
0.4
0.6
0.8
1.0
Xi
Xi
3
.0
.5
.0
.5
.0
.5
.0
Fc-Cz-An
2.5 Fc-PTZ-An
2
2
1
1
0
0
2
1
1
.0
.5
.0
0.5
0.0
0.0
0.2
0.4
0.6
0.8
1.0
0.0
0.2
0.4
0.6
0.8
1.0
Xi
Xi
Fig. 4 Job’s plot exhibited the inꢀection point at 0.5 (formation of a 1:1 complex): the total concentration
−
−5
[
Fc-X-An]+[F ] is 10 mol/L
association constant (K) as well as the limit of detection (LOD) are listed in Table 1.
From the analysis, we could conclude that Fc-Cz-An is the most sensitive chem-
−
osensor for F due to its lowest LOD and highest K.
Electrochemistry titration
Owing to a stable redox property, the ferrocene (Fc) moiety was widely used as an
electrochemical signal transmission group [51]. Electrochemical ferrocene-based
receptors for anions are expected to show cathodic shift in their redox-process when
complexed to an anion as they are easier to oxidize than the free redox-active recep-
tor [52].
−
The recognition abilities of Fc-X-An toward F in the form of their correspond-
ing tetrabutyl ammonium salts (TBAF) were initially investigated by CV in DMSO
solution containing 0.1 mol/L [(n-Bu) NPF ] as the supporting electrolyte. As
4
6
shown in Fig. 5, upon gradual addition of TBAF from zero to a 1.4 equiv, the redox
potential of Fc-X-An showed a cathodic shifts at 0.90 V, which is attributed to the
ferrocene unit. The cathodic shifts of Fc-Ph-An, Fc-Thie-An and Fc-Cz-An were
around 10 mV, while Fc-PTZ-An gave a 120 mV cathodic shift which was larger
than other receptors. These data suggested that the receptor Fc-PTZ-An was suitable
−
to act as an electrochemical probe for selective F sensing.
1
3

Design and synthesis ethynyl ferrocene-based multifunctional…
1
.4 eq
eq
Fc-Ph-An
Fc-Thie-An
1.4 eq
0
0
eq
0
.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
1.3
0
.0
0.2
0.4
0.6
0.8
1.0
1.2
E (V vs SCE)
E (V vs SCE)
Fc-Cz-An
1.4 eq
Fc-PTZ-An
1
.4 eq
0
eq
0
eq
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
1.3
0.6
0.8
1.0
1.2
E (V vs SCE)
E (V vs SCE)
−
Fig. 5 CV titration of Fc-X-An by adding F from 0 to 1.4 equivalents in DMSO
1H NMR titration
To support the results obtained by electrochemical and spectroscopic experiments
1
as well as to obtain additional information about the coordination mode, H NMR
1
titrations have been analyzed in DMSO-d . Figure 6 shows the corresponding H
6
1
NMR titration results of Fc-Ph-An, Fc-Cz-An with TBAF. H NMR titrations of
Fc-Thie-An and Fc-PTZ-An are shown in Figures S16 and S17.
As shown in Fig. 6, the NH proton of Fc-Ph-An (H , δ = 10.32 ppm) disap-
d
peared completely upon gradual addition of TBAF in DMSO-d , indicating
6
−
that F indeed interacted with a NH proton [49]. Other protons of Fc-Ph-An
shifted upꢂeld, suggesting that this interaction aꢃected π-electrons of Fc-Ph-
An and, hence, could lead to the change in absorption and ꢀuorescence spectra.
A similar tendency could also be observed in Fc-PTZ-An, the NH proton (H ,
h
−
δ = 10.19 ppm) disappeared completely upon F addition and other protons
shifted upꢂeld except for H (δ = 8.01 ppm) which was shifted downꢂeld. The
g
downꢂeld chemical shift of H could be aroused by hydrogen bonding of a car-
g
bonyl group [22, 53].
1
3

H. Fu et al.
Fig. 6 1H NMR titration of Fc-Ph-An and Fc-PTZ-An by adding F− from 0 to 1.25 equivalents in
DMSO-d6
Conclusion
In this work, we have prepared a series of conjugated ferrocene ethynyl semi-
carbazide derivatives (Fc-X-An), in which the ferrocene unit was linked by an
ethyne bridge to a chromogenic or ꢀuorescent signalling unit, and examined its
1
binding properties towards various guest anions using electrochemical, H NMR,
spectral and optical techniques. The semicarbazide derivative receptors Fc-X-An
exhibited high binding aꢁnity and sensitivity for the ꢀuoride anion in DMSO
−
through multichannel methods. Fc-Thie-An is shown to be more sensitive to F
−
which could be used as a ‘Naked-eye’ probe for selective F sensing, while Fc-
−
Cz-An was more suitable to act as UV–Vis and ꢀuorescent sensors for F because
it processed the lowest LOD and highest K. Comparing with others, the receptor
−
Fc-PTZ-An was suitable to act as a eletrochemical probe for selective F sens-
−
ing. Potentially, all these results reveal that malfunction chemosensors of F
anion were realized by constructing conjugated ferrocene ethynyl semicarbazide
derivatives.
Acknowledgements The authors thank the National Key Program of China (Project Grant No.
2
017YFB0307800) and Science and Technology Planning Project of Guangdong Province, China (Pro-
ject Grant No. 2017B090911002) for ꢂnancial support. We also thank the Beijing University of Chemical
Technology CHEMCLOUDCOMPUTING Platform for support with calculations.
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