Synthesis and binding properties of a new fluorescent molecular sensor based on a triazole nucleoside

Article abstract of DOI:10.3184/174751916X14737808687253

A new fluorescent nucleoside based on 1,2,4-Triazole nucleoside has been synthesised and its X-ray structure determined. Its binding properties, investigated by fluorescence spectroscopy, show that it can selectively bind Hg²⁺ with fluorescence quenching.

Full text of DOI:10.3184/174751916X14737808687253

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 OCTOBER, 597–599
RESEARCH PAPER 597
Synthesis and binding properties of a new fluorescent molecular sensor
based on a triazole nucleoside
Lijuan Guoa, De-Hua Zhangb*, Duanyi-Pingb, Ze-Shan Xiongb and Yan Liuc
ªCollege of Basic Medical Science, Changsha Medical University, Changsha 410219, P.R. China
bHubei Key Laboratory of Pollutant Analysis & Reuse Technology, Hubei Collaborative Innovation Center for Rare Metal Chemistry, College of Arts & Science of
Hubei Normal University and College of Chemistry and Chemical Engineering Hubei Normal University, Huangshi 435002, P.R. China
cSchool of Chemistry & Environmental Science, Shanxi University of Technology Hanzhong 723001, P.R. China
A new fluorescent nucleoside based on 1,2,4-triazole nucleoside has been synthesised and its X-ray structure determined. Its binding
properties, investigated by fluorescence spectroscopy, show that it can selectively bind Hg2+ with fluorescence quenching.
Keywords: triazole nucleosides, fluorescence quenching, Hg2+
Synthetic nucleoside analogues with modified nucleobase
and/or sugar moieties are of considerable importance in the
search for materials endowed with antiviral, anticancer, and
antibacterial activities.1 Nucleoside analogues with modified
sugar and/or base moieties can mimic natural nucleosides and
serve as building units or inhibitors that interfere in nucleic acid
synthesis or block nucleoside-dependent biological processes.
Well-known nucleoside drugs include the antiviral drugs
ribavirin, acyclovir, and zidovudine, and the most commonly
used anticancer nucleoside drugs include gemcitabine and
cladribine. We have been involved in a programme to develop
structurally diverse triazole nucleoside analogues. These
nucleosides contain triazole as nucleobase and aromatic groups
have been appended on the nucleobases2,3 with a view to identify
new structural leads exhibiting biologically interesting activity.
We find derivatives of triazole nucleosides contain a new
recognition site, and have introduced S–H and triazole into the
same sensor molecule to strengthen the Hg2+ coordination capacity.
We now report the synthesis of such a compound and develop its
function as a selective fluorescent chemosensor for Hg2+.
dihedral angle between the benzene and the other triazole rings
(N2, N1, C7, N3, C8) is 58.48 °. The molecular conformation is
stabilised by N---H···O hydrogen bonding. The crystal packing
is governed by C---H···O and C---H···N interactions resulting in
a three-dimensional network. These values are normal for the
complexation of an aromatic ring by p–p stacking interactions.
C1
C2
C7
C3
C4
C5
C6
N4
N3
S1
C8
N1
C9
N2
C10
Results and discussion
O1
C11
The synthesis of anticancer nucleoside 2 is shown in Scheme 1.
The structures and conformation of compound 2 were further
elucidated by single crystal X-ray diffraction, as shown in
Fig. 1. The three-dimensional molecular-packing diagram of 2
compound is shown in Fig. 2.
C12
O2
Crystals of 2 were obtained by slow evaporation of their
solution in ethyl acetate/petroleum ether (3:1). The crystal
structure of 2 reveals that its well-defined geometry is due to
the rigidity that the fused rings confer on the molecule. The
03
C13
Fig. 1 Crystal structure of compound 2.
O
O
O
COCH3
CNH2
COCH3
N
N
N
N
N
N
Br
N
S
S
N
N
+
K
NH
3/CH3OH
2CO3/CH3CN
O
O
O
SH
OAc
OAc
OH
1
2
Scheme 1
* Correspondent. E-mail: zhangdehua200@163.com

598 JOURNAL OF CHEMICAL RESEARCH 2016
600
500
400
300
200
100
0
Host
Cu2+,Cd2+,Mn2+,Bi2+,Fe3+,
Ag+,Pb2+,Sr2+,Sn4+,Co2+
Hg2+
350
400
450
500
550
Wavelength(nm)
Fig. 2 Three-dimensional molecular-packing diagram of 2.
Fig. 3 Fluorescence emission changes of 2 (1 × 10–5 M) in DMF in the
presence of 12 × 10–5 various metal ions (excitation at 400 nm).
In conclusion, a new 1-[(2-hydroxyethoxy)methyl]-5-(p-
tolylthio)-1H-1,2,4- triazole-3-carboxamide derived from a
1,2,4-triazole nucleoside have been synthesised. Its structure
and conformation were confirmed by single crystal X-ray
diffraction and 1H NMR. It has great potential to bind aromatic
guest molecules.
600
host
0
500
400
300
200
100
0
0.025
0.020
0.015
0.010
0.005
0.000
Y=(5.80754E-8)X+8.96953E-4
R2=0.99823
4.54x10-5M
The binding properties of compound 2 with various metal
ions were investigated by fluorescent spectroscopy titration
experiments.4 Changes of the fluorescence properties of 1 × 10–5
M of 2 in DMF solution caused by 15 equiv. of various metal ions
(Cu2+, Cd2+, Mn2+, Bi2+, Fe3+, Ag+, Pb2+, Sr2+, Sn4+, Co2+ and Hg2+)
were measured once their emission intensities were constant.
The results show that Hg2+ produced significant quenching in its
fluorescent emission. The other metal ions that were tested showed
a relatively insignificant change (Fig. 3). It can be concluded that
molecule 2 has a higher selectivity for the recognition of Hg2+.
The sensitivity of the fluorescence emission response of
molecule 2 towards Hg2+ was also examined under the same
conditions with various Hg2+ concentrations (Fig. 4). The
fluorescence intensity of molecules 2 decreased continually
upon addition of Hg2+. When the concentration of Hg2+ increased
to 15 equiv., the fluorescence intensity of 2 was reduced to 90%
of the initial value. From a Stern–Volmer plot (Fig. 4), the
quenching constants were estimated to be 5.37 × 104 M–1.
A proposed mechanism of fluorescence quenching for 2, is
shown in Fig. 5. It is suggested that the decrease in fluorescence
can be explained by two main pathways: (1) when the receptor
molecule is combined with Hg2+, the rigidity of 2 decreases and
the fluorescence intensity of 2 decreases; (2) when the receptor
molecules coordinate with Hg2+ the energy of the lowest excited
state and the fluorescence quantum yield decrease largely, so
that the fluorescence intensity weakens.
0
50000 100000 150000 200000 250000 300000 350000 400000
1/Hg2+
350
400
450
500
550
Wavelength
(nm)
Fig. 4 Fluorescence emission spectra (excitation at 400 nm) of 2
(1 × 10–5 M) in DMF in the presence of different concentrations of Hg2+.
Inset: Stern–Volmer plot of the emission data.
O
CONH
N
N
S
N
Hg2+
O
In conclusion, a new molecule derived from a triazole
nucleosides has been designed as a fluorescent chemosensor
and synthesised. It displays high selectivity for Hg2+ revealed by
fluorescence quenching.
OH
Experimental
Fig. 5 Recognition mechanism.
All reagents obtained from commercial sources were of AR grade.
Melting points were determined with an XT4A micro melting point
apparatus and were uncorrected. The 1H NMR spectra were recorded on
a Mercury Plus-400 spectrometer with TMS as internal reference. MS
were obtained with a Finnigan Trace MS instrument using the EI method.
Elemental analyses were carried out on a Vario EL III instrument.
Synthesis of methyl 1-[(2-acetoxyethoxy)methyl]-5-(p-tolylthio)-
1H-1,2,4-triazole-3-carboxylate (1)5: Methyl 1-[(2-acetoxyethoxy)
methyl]-5-bromo-1H-1,2,4-triazole-3-carboxylate (32.2 mg, 0.1
mmol), 4-methylbenzenethiol (0.12 mmol) and K2CO3 (27.6 mg, 0.2
mmol) were suspended in 2 mL of freshly distilled CH3CN under

JOURNAL OF CHEMICAL RESEARCH 2016 599
argon. The vessel was sealed and the reaction was carried out under
microwave irradiation at 100 °C for 30 min, and then cooled to room
temperature. The reaction mixture was concentrated under reduced
pressure and the crude residue was purified by flash chromatography
on silica gel (petroleum ether/ethyl acetate, 2:1). The purified
material was dried in vacuo to afford 1: Colourless oil; yield 35.4 mg,
Crystal data for 2: C13H16N4O3S, M = 308.36; Triclinic; space
group: p-1; a = 7.5264(12) Å; b = 7.7801(12) Å; c = 14.201(2) Å;
α = 83.744(2) °; b = 81.486(2) °; g = 61.201(2) °; V = 720.01(19)
Å3; Z = 2; Dc = 1.422 mg m–3; Reflections collected: 5282;
Independent reflections: 2659 [Rint = 0.0992]; Final R indices [I >
2σ(I)]: R1 = 0.0485, wR2 = 0.1303; R indices (all data): R1 = 0.0511,
wR2= 0.1336.
1
97%; H NMR (300 MHz, CDCl3): d 7.44 (d, 2H, J = 7.5 Hz, ArH),
7.17 (d, 2H, J = 7.5 Hz, ArH), 5.63 (s, 2H, OCH2N), 4.14 (t, 2H, J =
4.7 Hz, OCH2CH2OAc), 3.97 (s, 3H, OCH3), 3.76 (t, 2H, J = 4.2 Hz,
OCH2CH2OAc), 2.34 (s, 3H, CH3), 2.05 [s, 3H, C(O)CH3]; 13C NMR
(150 MHz, CDCl3): d 170.8, 159.9, 154.6, 154.1, 139.8, 132.9, 130.6,
125.4, 78.4, 67.9, 62.9, 53.0, 21.3, 20.9; HRMS calcd for C16H19N3O5S
[M + H]+: 366.1118; found: 366.1110.
Acknowledgments
This work was supported by the Hubei provincial Department of
Education (Grant No.B2016163) and College of Arts & Science
of Hubei Normal University (Grant No.Ky201502), Hubei Key
Laboratory of Pollutant Analysis & Reuse Technology (Grant
No.PA150203), and Local University National College Students
Innovation and Entrepreneurship Training Program(Grant
No.201413256002).
Synthesis of 1-[(2-hydroxyethoxy)methyl]-5-(p-tolylthio)-1H-1,2,4-
triazole-3-carboxamide (2)6: A solution of NH3/MeOH (18 mL) was
added to a flask containing compound 1 (85.0 mg, 0.233 mmol) and the
mixture was stirred at room temperature for two days. After removal
of the solvent, the compound 2 was obtained: White solid; yield 52.0
mg, 73%; 1H NMR (300 MHz, DMSO-d6): d 7.87 [br s, 1H, C(O)NH2],
7.67 [br s, 1H, C(O)NH2], 7.42 (d, 2H, J = 8.1 Hz, ArH), 7.24 (d, 2H,
J = 7.2 Hz, ArH), 5.63 (s, 2H, OCH2N), 4.74 (t, 1H, J = 5.1 Hz, OH),
3.52–3.53 (m, 2H, OCH2CH2OH), 3.45–3.48 (m, 2H, OCH2CH2OH),
2.31 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6): d 160.6, 157.6,
152.2, 139.4, 132.5, 131.0, 126.9, 78.6, 71.8, 60.4, 21.3; HRMS: calcd
for C13H16N4O3S [M + H]+: 309.1016; found: 309.1021.
Received 23 June 2016; accepted 15 August 2016
Paper 1604163 doi: 10.3184/174751916X14737808687253
Published online: 26 September 2016
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