Synthesis, X-ray structure, and binding properties of a new fluorescent molecular clip derived from diethoxycarbonyl glycoluril

Article abstract of DOI:10.1139/V08-058

A new fluorescent molecule clip derived from diethoxycarbonyl glycoluril with two 2,5-diphenyl-furan side-walls was designed and synthesized. Its structure and conformation was confirmed by single-crystal X-ray diffraction. Its binding properties, investigated by fluorescence spectroscopey, showed that it can selectively bind Fe³⁺ with fluorescence quenching.

Full text of DOI:10.1139/V08-058

691
Synthesis, X-ray structure, and binding properties
of a new fluorescent molecular clip derived from
diethoxycarbonyl glycoluril
Sheng-Li Hu, Guo-Dong Yin, Yu-Zhou Wang, and An-Xin Wu
Abstract: A new fluorescent molecule clip derived from diethoxycarbonyl glycoluril with two 2,5-diphenyl-furan side-
walls was designed and synthesized. Its structure and conformation was confirmed by single-crystal X-ray diffraction.
Its binding properties, investigated by fluorescence spectroscopey, showed that it can selectively bind Fe3+ with fluores-
cence quenching.
Key words: diethoxycarbonyl glycoluril, molecular clip, fluorescence, Fe(III).
Résumé : On a développé une méthode de synthèse pour une nouvelle pince moléculaire fluorescente qui est dérivée
du diéthoxycarboxylglycoluril et qui comporte deux 2,5-diphénylfuranes comme murs latéraux. On a confirmé sa struc-
ture et sa conformation sur la base de la diffraction des rayons X par un cristal unique. Ses propriétés de fixation étu-
diées par spectroscopie de fluorescence montrent qu’elle peut se fixer sélectivement avec le Fe3+ avec désactivation de
la fluorescence.
Mots-clés : diéthoxycarbonylglycoluril, pince moléculaire, fluorescence, Fe(III).
[Traduit par la Rédaction] Hu et al. 694
Introduction
(11). In continuing our research to develop new fluorescent
chemsensors based on glycoluril, we designed a new molec-
ular clip 5, which has two 2,5-diphenyl-furan fluorescent
moieties used as the signaling subunit in its two sidewalls
and two carbonyl oxygen atoms of glycoluril ring used as
the potential binding sites in its cavity. We assume that such
crown-ether derivatives can be used as a fluorescent
chemsensor for alkali or alkaline earth metal cations. In this
paper, we report its synthesis, X-ray structure, and binding
study with different metal ions. Interestingly, the new fluo-
rescent clip molecule 5 also exhibited selective recognition
to Fe3+ over the other tested metals ions, including alkali
and alkaline earth metal cations. This experimental result
shows that the two polarized carbonyl groups oxygen atoms
of glycoluril ring may be an effective recognition position
for Fe3+.
Development of fluorescent chemosensors, capable of
recognizing metal ions, anions, and neutral molecules, is of
interest because of their high sensitivity and low-cost instru-
mentation (1). In general, fluorescence chemosensors are
composed of two covalently linked components: a recogni-
tion site that binds the target substance and a transducer
(fluorophore) that signals the binding (2–4).
Glycoluril is an important building block for supramo-
lecular chemistry, and its derivatives have been used as the
basis for molecular clips (5), molecular capsules (6), anion-
binding receptors (7), xerogels (8), and the cucurbit[n]uril
(CB[n]) family (9). However, few studies have been carried
out to explore its utilization as a platform for the synthesis
of fluorescent chemosensors for ionic guest in recent years
(10).
In the previous work, we had reported a pair of molecular
clips derived from diethoxycarbonyl glycoluril with two 1,2-
dihydro-indazol-3-one moieties as sidewall and developed
their function as selective fluorescent chemsensors for Fe3+
Results and discussion
Fluorescent molecule clip 5 was prepared by reacting
diethoxycarbonyl glycoluril (3) with 3,4-bis-bromomethyl-
2,5-diphenyl-furan (4) using t-BuOK as base in anhyd.
DMSO (Scheme 1), and the product was further character-
Received 6 December 2007. Accepted 24 March 2008.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 23 May 2008.
1
ized by NMR spectra. The H NMR spectrum of 5 in CDCl3
S.-L. Hu,1, 2 G.-D. Yin, Y.-Z. Wang, and A.-X. Wu. Key
Laboratory of Pesticide and Chemical Biology, Ministry of
Education, Central China Normal University, Wuhan 430079,
China.
shows two pairs of well-defined doublets with equal inten-
sity for the protons of methylene at δ = 5.28 ppm (J =
16.0 Hz) and δ = 4.36 ppm (J = 16.0 Hz), indicating that the
molecules possess good symmetry and the four bridging
methylenes have the same chemical environment. The IR
and MS spectra for the product are in good agreement with
the title compound. In addition, its structure and conforma-
tion were confirmed by single-crystal X-ray diffraction, as
1Corresponding author (e-mail: chwuax@mail.ccnu.edu.cn).
2Present address: Hubei Key Laboratory of bioanalytical
techniques (Hubei Normal University), Huangshi 435002,
China.
Can. J. Chem. 86: 691–694 (2008)
doi:10.1139/V08-058
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692
Can. J. Chem. Vol. 86, 2008
Scheme 1. Synthesis of molecular clip 5.
Fig. 1. X-ray crystal structure of compound 5. Hydrogen atoms
and minor components are omitted for clarity.
Table 1. Crystal structure data for 5.
Empirical formua
C46H38N4O8
Formula mass
774.80
Temperature (K)
294(2)
Wavelength (Å)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
α
0.71073
Monoclinic
P2(1)/n
12.7623(9)
11.5771(8)
26.5023(19)
90°
β
96.1500(10)°
90°
3893.2(5)
4
γ
V(Å3)
Z
Densitycalcd. (Mg/m3)
1.322
Index ranges
–15 ≤ h ≤15,
–13 ≤ k ≤ 13,
–31 ≤ l ≤ 31
1624
F(000)
Crystal size
0.20 mm × 0.10 mm × 0.04 mm
θ range for data collection
Reflections collected
Independent reflections
Data, restraints, parameters
Goodness-of-fit on F2
Absorption correction
>2σ(I)
1.55–25.00°
33604
6862 [R(int) = 0.1084]
6862, 0, 526
1.000
None
3472
shown in Fig. 1. Its crystal data and details of structure de-
terminations were summarized in Table 1.
The crystal structure of 5 clearly reveals that it has well-
defined geometry because of the rigidity that the fused rings
confer on the molecule. However, two phenyl rings of the
sidewall are twisted away from the furan ring. The phenyl
ring (C1–C6) and phenyl ring (C11–C16) form dihedral an-
gles of 41.47° and 35.40°, respectively, with the furan ring
(O1–C10). The phenyl ring (C34–C39) and phenyl ring
(C41–C46) form dihedral angles of 34.31° and 28.33°, re-
spectively, with the (O8–C40) furan ring. The dihedral angle
between them is 34.76°. The dihedral angle between two
furan rings is 38.61°, and the distance between the centroids
of two furan rings is 6.603 Å. The distances between the two
oxygen atoms (O1–O8) of two furan rings and two carbonyl
oxygen atoms (O2–O3) of glycoluril ring amount to 7.494 Å
and 5.722 Å, respectively.
The binding properties of the clip molecule 5 with various
metal ions were investigated through fluorescence-
spectroscopy titration experiments. Changes of the fluores-
cence properties of 1 × 10–5 mol/L of 5 in DMF/CH3OH
(50:1, v/v) solution caused by 15 equiv. of various metal ions
(K+, Na+, Mg2+, Hg2+, Cd2+, Fe3+, Zn2+, Co2+, Ni2+, Cu2+,
Pb2+, Cr3+, and Mn2+) were measured once their emission in-
tensity were constant. The result showed that Fe3+ produced
significant quenching in the fluorescent emission of 5; the
other tested metals only show relatively insignificant
Final R indices (I > 2σ(I))
R1 = 0.0761, wR2 = 0.1782
R indices (all data)
R1 = 0.1563, wR2 = 0.2090
Largest diff. peak and hole (e Å–3) 0.312 and –0.246
changes (Fig. 2). So, it can be concluded that 5 has higher
selectivity for the recognition of Fe3+.
The sensitivity of the fluorescence emission response of 5
towards Fe3+ was also examined under the same conditions
with various Fe3+ concentrations (Fig. 3). The fluorescence
intensity (λem = 365 nm) of 5 was decreased continually
upon addition of Fe3+ with no significant change in the posi-
tion of the emission maxima. When the concentration of
Fe3+ increased to 15 equiv., the fluorescence intensity of 5
was reduced to 24% of the initial one. From the Stern–
Volmer plot (the fluorescence quenching followed the Stern–
Volmer equation) (12), host 5 formed 1:1 stoichiometry
complex with Fe3+, and the association constant was esti-
mated 2.24 × 104.
Actually, quenching of electronically excited state of aro-
matic hydrocarbons by Fe3+ chelates is
a
known
© 2008 NRC Canada

Hu et al.
693
Fig. 2. Fluorescence emission changes of 5 (1 × 10–5 mol/L) in
DMF–MeOH (50:1 v/v) in the presence of 15 × 10–5 mol/L vari-
ous metal ions (excitation at 305 nm).
Conclusion
A
new fluorescent molecule clip
5
derived from
diethoxycarbonyl glycoluril with two 2,5-diphenyl-furan
sidewalls was designed and synthesized. Its binding proper-
ties, investigated by fluorescence spectroscopy, showed that
it can selectively bind Fe3+ with fluorescence quenching.
Experimental
General
Melting point was determined on an XT4A Meltemp ap-
paratus and is uncorrected. IR was recorded on a Perkin–
Elmer PE–983 infrared spectrometer as KBr pellets with ab-
sorption in cm–1. NMR was recorded in CDCl3 on a Varian
Mercury 400 spectrometer. MS was measured on a Finnigan
Trace MS spectrometer. Fluorescence spectra were deter-
mined on a Hitachi F-4500.
Synthesis
Diethoxycarbonyl glycoluril
3
(14) and 3,4-bis-
Fig. 3. Fluorescence emission spectra (excitation at 305 nm) of 5
(1 × 10–5 mol/L) in DMF–MeOH (50:1 v/v) in the presence of
Fe(H2O)6Cl3. The concentration of Fe3+: 0, 1.0, 2.0, 3.0, 4.0, 5.0,
6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, 13.0, 14.0, and 15 × 10–5 mol/L.
Inset: Stern–Volmer plot of the emission data.
bromomethyl-2,5-diphenyl-furan 4 (15) were synthesized ac-
cording to the previously reported procedures.
Compound 3 (0.72 g, 2.5 mmol) was dissolved in anhyd.
DMSO (50 mL) under N2, and t-BuOK (1.12 g, 10.0 mol)
was added. After stirring for 15 min, compound 4 (2.22 g,
5.5 mmol) was added in one portion, and stirring was con-
tinued for 3 h. The reaction mixture was poured into 0.1 N
HCl (500 mL) and extracted with EtOAc (3 × 200 mL). The
extracts were washed with brine (2 × 150 mL) and dried
over anhyd. MgSO4. After filtration and rotary evaporation,
the residue was purified by flash chromatography (SiO2,
CHCl3/MeOH, 50:1) to give compound 5 (0.31 g, 40%) as a
white solid. Mp > 300 °C. IR (KBr, cm–1): 3059, 2983 w,
2898 w, 1758 s, 1722 s, 1653 w, 1464 s, 1428 s, 1255 s,
1
910 s, 764 s, 695 s. H NMR (400 MHz, CDCl3) δ: 7.75–
7.74 (m, 8H), 7.50–7.35 (m, 8H), 7.32–7.31 (m, 4H), 5.28
(d, J = 16.0 Hz, 4H), 4.36 (d, J = 16.0 Hz, 4H), 4.28 (q, J =
7.2 Hz, 4H), 1.30 (t, J = 7.2 Hz, 6H). 13C NMR (100 MHz,
CDCl3) δ: 165.5, 156.1, 148.7, 130.0, 128.8, 128.1, 126.8,
118.7, 81.3, 63.6, 37.4, 14.0. EI-MS m/z: 774.0, 778 [M +
4H]4+.
X-ray crystallography
A single crystal suitable for X-ray crystallographic analy-
sis was obtained from a slow evaporation of the dichloro-
phenomenom that has been the subject of extensive investi-
gations. It has been suggested that two main pathways could
account for the efficient radiationless deactivation of the
singlet excited state, i.e., electron transfer from the excited
aromatic chromophore to the metal and (or) energy transfer
from the excited aromatic chromophore to low-lying metal-
centered energy states (13). Such processes could be
particularly effective in the complex of 5 with Fe3+, due
probably to the fact that the chelated metal cation is held
very close to two excited 2,5-diphenyl-furan chromophores.
Additionally, because molecular clip 5 has different side-
walls but same binding properties compared with previously
reported molecular clips (11), we may draw a conclusion
that the two polarized carbonyl groups of the glycoluril ring
play a crucial role in the recognition of Fe3+.
methane
and
methanol
solution.
Crystallographic
measurement of compound 5 was carried out using a Bruker
SMART CCD diffractometer. The SMART (version 5.628)
program was used for collecting data frames, and SAINT
Plus (version 6.45) was used for integration of the intensity
of reflections and scaling. SADABS was used for absorption
correction (16). The structure was solved by direct methods
using the program SHELXS-97 and refined by full-matrix
least-squares against all F2 data using Bruker SHELXTL
(17). The phenyl ring (C34–C39) was found to be disordered
over two orientations; the site-occupancy factor for the two
orientations were refined giving 0.67(8) and 0.33(8) for the
major and minor components, respectively. All non-H atoms
© 2008 NRC Canada

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Can. J. Chem. Vol. 86, 2008
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Acknowledgments
We thank the Central China Normal University, the Na-
tional Natural Science Foundation of China (Grant
No. 20472022 and Grant No. 20672042) for financial sup-
port, and Dr Xiang-Gao Meng for the X-ray data collection.
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3 Supplementary data for this article are available on the journal Web site (canjchem.nrc.ca) or may be purchased from the Depository of Un-
published Data, Document Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0R6, Canada. DUD 3758. For more in-
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© 2008 NRC Canada