Synthesis and binding properties of two new fluorescent molecular clips based on diethoxycarbonyl glycoluril

Article abstract of DOI:10.3184/030823409X396418

Two new fluorescent molecular clips based on diethoxycarbonylglycoluril have been synthesised and their binding properties investigated by fluorescence spectroscopy to show that they can selectively bind Fe³⁺ with fluorescence quenching.

Full text of DOI:10.3184/030823409X396418

32 RESEARCH PAPER
JANUARY, 32–34
JOURNAL OF CHEMICAL RESEARCH 2009
Synthesis and binding properties of two new fluorescent molecular clips
based on diethoxycarbonyl glycoluril
Hu Sheng-Lia,b, Wang Shuaia, Li Yi-Taoa, Cao Li-Pinga and Wu An-Xina*
aKey Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, P. R. China
bDepartment of Chemical and Enviromental Engineering, Hubei Normal University, Huangshi 435002, P. R. China
Two new fluorescent molecular clips based on diethoxycarbonylglycoluril have been synthesised and their binding
properties investigated by fluorescence spectroscopy to show that they can selectively bind Fe3+ with fluorescence
quenching.
Keywords: GLHWKR[\FDUERQ\OꢀJO\FROXULOꢁꢀPROHFXODUꢀFOLSꢁꢀÀXRUHVFHQFHꢀTXHQFKLQJꢁꢀ)H3+
7KHꢀGHVLJQꢀRIꢀÀXRUHVFHQWꢀFKHPVHQVRUVꢀIRUꢀWKHꢀGHWHFWLRQꢀRIꢀLRQLFꢀ
carbonyl oxygen atoms of glycoluril ring and nitrogen atoms
in their cavity to be used as the potential binding sites. We
now report their synthesis and a binding study with different
metal ions.
The synthesis of title clip molecules 7 and 8 is shown in
Scheme 1. The structure and conformations of compound
7 was also further elucidated by its single crystal X-ray
structure, as shown in Fig. 1.
guests is one of the most attractive topics in supramolecular
chemistry.1,2 A chemosensor is
a molecule capable of
transforming chemical information, such as the presence of
a particular metal ion, into an analytically useful signal. In
general, chemosensors are composed of two covalently linked
components: a recognition site that binds the target substance
DQGꢀDꢀWUDQVGXFHUꢀꢂÀXRURSKRUHꢃꢀWKDWꢀVLJQDOVꢀWKHꢀELQGLQJꢄ3-5
Glycoluril is an important building block for supramolecular
chemistry, and its derivatives have been used as the basis for
various molecular clips,6 molecular capsules,7 anion-binding
receptors,8 and the cucurbit[n]uril (CB[n]) family.9 However,
less attention has been paid to glycoluril and its derivatives as
EDVHꢀPROHFXOHVꢀIRUꢀFRQVWUXFWLQJꢀÀXRUHVFHQWꢀFKHPRVHQVRUVꢀLQꢀ
recent years.10
The crystal structure of 7 clearly reveals that it has a well-
GH¿QHGꢀJHRPHWU\ꢀGXHꢀWRꢀWKHꢀULJLGLW\ꢀWKDWꢀWKHꢀIXVHGꢀULQJVꢀFRQIHUꢀ
on the molecule. Interestingly, in the crystal of molecule 7 the
two naphthalene rings of the sidewall are fully coplanar. The
dihedral angle between two phenyl rings of the sidewalls is
18.2°, and the distance between the centroids of two phenyl
rings of the sidewalls is 4.734 Å. The distance between two
carbonyl oxygen atoms (O1–O2) of glycoluril ring and two
nitrogen atoms (N1–N6) of sidewall amount to 5.261 Å and
5.391 Å, respectively. The polarised carbonyl groups and
the electron-rich nitrogen atoms in the cavity give 7 great
potential to bind metal ions.
In previous work, we have reported a pair of molecular
clips derived from diethoxycarbonyl glycoluril with two 1, 2-
dihydro-indazol-3-one moieties as the sidewall and developed
WKHLUꢀ IXQFWLRQꢀ DVꢀ VHOHFWLYHꢀ ÀXRUHVFHQWꢀ FKHPVHQVRUVꢀ IRUꢀ
Fe3+.11ꢀ,QꢀFRQWLQXLQJꢀRXUꢀUHVHDUFKꢀWRꢀGHYHORSꢀQHZꢀÀXRUHVFHQWꢀ
chemsensors based on glycoluril, we have designed two new
molecular clips 7 and 8ꢀZKLFKꢀKDYHꢀELJꢀʌꢅV\VWHPVꢀWKDWꢀFDQꢀEHꢀ
used as the signalling subunit in their two sidewalls and two
The binding properties of the clip molecules 7 and 8
ZLWKꢀ YDULRXVꢀ PHWDOꢀ LRQVꢀ ZHUHꢀ LQYHVWLJDWHGꢀ E\ꢀ ÀXRUHVFHQWꢀ
spectroscopy titration experiments. Changes of the
O
N
N
N
N
(iv)
(v)
R
I
N R
N
I
O
O
HN
R
HN
NH
R
NH
O
O
COOEt
COOEt
HO
HO
O
(iii)
4
OH (i)
O
(ii)
OH
N
N
N
O
O
R
N
R
N
Br
Br
N
3
2
1
N
O
5
O
O
N
N
N
R
N
4
(vi)
R
N
7
O
N
N
5
R
N
R
N
6
N
N
(vi)
8
O
(R=COOEt)
Scheme 1 Reagents and conditions: (i) AcOH, Br2, H2O, Na2CO3; (ii) EtOH, HCl(g), 0°C; (iii) PhH, H2NCONH2, TFA, reflux;
(iv) 4-Iodoaniline, HCHO(37%), MeOH, reflux; (v) (4-bromobenzylamine, HCHO(37%), MeOH, reflux; (vi)PdCl2(PPh3)2,
CuI, Et3N, DMF,100°C , Ar.
* Correspondent. E-mail: chwuax@mail.ccnu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2009 33
Fig. 3 Fluorescence emission changes of 8 (1 u 10-5M) in
DMF–MeOH (50:1, v/v) in the presence of 15 u 10-5 M various
metal ions (excitation at 319 nm).
Fig. 1 The crystal structure of 7.
ÀXRUHVFHQFHꢀ SURSHUWLHVꢀ RIꢀ ꢆꢀ u 10-5M of 7 and 8 in DMF/
CH3OH (50:1, v/v) solution caused by 15 equiv. of various
metal ions (K+, Na+, Ag+, Mg2+, Hg2+, Cd2+, Fe3+, Zn2+, Co2+
,
Ni2+, Cu2+, Pb2+, Cr3+, and Mn2+) were measured once their
emission intensity were constant. The result showed that Fe3+
SURGXFHGꢀVLJQL¿FDQWꢀTXHQFKLQJꢀLQꢀWKHLUꢀÀXRUHVFHQWꢀHPLVVLRQꢄꢀ
The other metals ion that were tested only show a relatively
LQVLJQL¿FDQWꢀFKDQJHꢀꢂ)LJVꢀꢇꢀDQGꢀꢈꢃꢄꢀ,WꢀFDQꢀEHꢀFRQFOXGHGꢀWKDWꢀ7
and 8 have a higher selectivity for the recognition of Fe3+
7KHꢀ VHQVLWLYLW\ꢀ RIꢀ WKHꢀ ÀXRUHVFHQFHꢀ HPLVVLRQꢀ UHVSRQVHꢀ
of 7 and 8 towards Fe3+ was also examined under the same
conditions with various Fe3+ concentrations (Figs 4 and 5).
7KHꢀÀXRUHVFHQFHꢀLQWHQVLW\ꢀRIꢀ7 and 8 decreased continually
upon addition of Fe3+. When the concentration of Fe3+
LQFUHDVHGꢀWRꢀꢆꢉꢀHTXLYꢁꢀWKHꢀÀXRUHVFHQFHꢀLQWHQVLW\ꢀRIꢀ7 and 8 was
reduced to 47% and 22.5% of the initial value, respectively.
From a Stern–Volmer plot (Figs 4 and 5), the quenching
constants were estimated 8.34 u 103 M-1 and 2.447 u 104 M-1,
respectively.
Fig. 4 Fluorescence emission spectra (excitation at 335 nm)
of 7 (1 u 10-5 M) in DMF–MeOH (50:1, v/v) in the presence of
different concentration of Fe3+. Inset: Stern–Volmer plot of the
emission data.
Fig. 5 Fluorescence emission spectra (excitation at 319 nm)
of 8 (1 u 10-5 M) in DMF–MeOH (50:1, v/v) in the presence of
different concentration of Fe3+. Inset: Stern–Volmer plot of the
emission data.
The quenching of the electronically excited state of aromatic
hydrocarbons by Fe3+ chelates is a known phenomenom
that has been the subject of extensive investigations. It has
been suggested that two main pathways can account for the
HI¿FLHQWꢀUDGLDWLRQOHVVꢀGHDFWLYDWLRQꢀRIꢀWKHꢀVLQJOHWꢀH[FLWHGꢀVWDWHꢁꢀ
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 centred energy states.15,16
Such processes could be particularly effective in the complex
of 7 and 8 with Fe3+, due probably to the fact that the chelated
Fig. 2 Fluorescence emission changes of 7 (1 u 10-5M) in
DMF–MeOH (50:1, v/v) in the presence of 15 u 10-5 M various
metal ions (excitation at 335 nm).

34 JOURNAL OF CHEMICAL RESEARCH 2009
NapH), 7.65 (d, J = 8.0 Hz, 4H, ArH), 7.56(t, J = 6.8 Hz, 2H, NapH),
7.48 (d, J = 8.0 Hz, 2H, NapH), 7.44(d, J = 8.0 Hz, 4H, ArH), 4.91
(d, J = 14.0 Hz, 4H, NCH2N), 4.30(d, J = 14.0 Hz, 4H, NCH2N),
3.94 (s, 4H, ArCH2), 4.31(q, J = 7.2 Hz,4H, OCH2CH3), 1.34 (t,
J = 7.2 Hz, 6H, OCH2CH3); 13C NMR (CDCl3, 100 MHz): G = 165.4,
158.6, 137.3, 133.2, 131.8, 130.3, 129.0, 128.7, 128.2, 126.8, 126.4,
125.2, 122.8, 120.9, 94.2, 87.7, 76.2, 63.4, 60.0, 55.2, 13.9; EI-MS:
m/z 849.3 [M + 1]+. Anal. Calcd for C52H44N6O6 (848.3): C, 73.57;
H, 5.22; N, 9.90; Found: C, 73.46; H, 5.13; N, 9.79%.
metal cation is held very close to two excited aromatic
chromophore. In addition, because the molecular clips 7 and
8 have different sidewalls but the same binding properties
compared to previously reported molecular clips,11 we may
draw the conclusion that the glycoluril ring plays a crucial
role in the recognition of Fe3+
.
In conclusion, two new clip molecules derived from
GLHWKR[\FDUERQ\OJO\FROXULOꢀDVꢀÀXRUHVFHQWꢀFKHPRVHQVRUVꢀKDYHꢀ
been designed and synthesised. They display high selectivity
for Fe3+ UHYHDOHGꢀE\ꢀÀXRUHVFHQFHꢀTXHQFKLQJꢄꢀ,QꢀIXWXUHꢀZRUNꢁꢀ
our efforts will be focused on the elucidation of the detailed
PHFKDQLVPVꢀRIꢀWKHVHꢀÀXRUHVFHQWꢀFKHPRVHQVRUꢄ
X-ray diffraction study of compound 7
Crystals were obtained by slow evaporation from chloroform–
methanol solution (20:1 v/v). A yellow crystal of the title compound
7 having approximate dimensions of 0.20 mm u 0.20 mm u 0.10 mm
ZDVꢀPRXQWHGꢀRQꢀDꢀJODVVꢀ¿EUHꢀLQꢀDꢀUDQGRPꢀRULHQWDWLRQꢀDWꢀꢇꢋꢉꢂꢇꢃꢀ.ꢄꢀ
The determination of unit cell and the data collection were performed
with MoKD radiation (D = 0.71073 Å) on a Bruker Smart Apex-CCD
GLIIDFWRPHWHUꢀ ZLWKꢀ Dꢀ ȥ±Zꢀ VFDQꢀ PRGHꢄꢀ$ꢀ WRWDOꢀ RIꢀ ꢌꢌꢈꢍꢎꢀ UHÀHFWLRQVꢀ
were collected in the range of 1.60<șꢏꢇꢉꢄꢊꢊÛꢀDWꢀURRPꢀWHPSHUDWXUHꢁꢀ
Experimental
General
All reagents obtained from commercial sources were of AR grade.
Melting points were determined with XT4A micromelting point
apparatus and were uncorrected. NMR spectra were recorded on a
Mercury Plus-400 spectrometer with TMS as an internal reference
and CDCl3 as the solvent. IR were recorded on a PerkinꢀElmer PEꢀ
983 IR spectrometer as KBr pellets with absorption in cm-1. MS were
obtained with Finnigan Trace MS instrument using EI. Elemental
analyses were carried out on a Vario EL III instrument. Fluorescence
spectra were determined on a Hitachi F-4500.
and 8149 were independent (Rint
= 0.0492); 3790 observed
UHÀHFWLRQVꢀ ZLWKꢀ ,!ꢄıꢉ,ꢊ were used in the structure determination
DQGꢀ UH¿QHPHQWVꢄꢀ7KHꢀ VWUXFWXUHꢀ ZDVꢀ VROYHGꢀ E\ꢀ GLUHFWꢀ PHWKRGVꢀ ZLWKꢀ
SHELXS-97 program and expanded by Fourier technique. The
QRQꢅK\GURJHQꢀDWRPVꢀZHUHꢀUH¿QHGꢀDQLVRWURSLFDOO\ꢁꢀDQGꢀWKHꢀK\GURJHQꢀ
atoms were determined with theoretical calculation. A full-matrix
OHDVWꢅVTXDUHVꢀ UH¿QHPHQWꢀ JDYHꢀ WKHꢀ ¿QDOꢀ R = 0.0878, wR = 0.2459
[W = 1/[ı2 (Fo2) + (0.1921P)2 + 0.0000P] where P = (Fo2 + 2Fc2)/3,
('/ı)max = 0.000, S = 0.938, ('ȡ)max = 0.538, ('ȡ)min = -0.438 e/Å3.
All calculations were performed on a PC with SHELXS-97 program.
Crystal data: C51H41Cl3N6O6, M = 940.25, Monoclinic, space group
P2(1)/n, a = 12.5195(7), b = 25.0264(14), c = 15.5955(8) Å, D = 90,
E = 108.0710(10), J = 90°, V = 4645.3(4) Å3, Z = 4, Dc = 1.344 g cm-3,
ȝꢀ ꢀꢊꢄꢊꢎꢎꢀPP-1. The details of the crystal data have been deposited
with Cambridge Crystallographic Data Centre as Supplementary
Publication No. CCDC 681845.
Synthesis
Diethoxycarbonyl glycoluril 312
,
glycoluril derivates 413 and
1-ethynyl-naphthalene 614 were prepared by the literature methods.
2,6-Bis-(4-bromo-benzyl)-4,8-dioxo-tetrahydro-2,3a,4a,6,7a,8a-
KH[DD]DꢀF\FORSHQWD>GHI@ꢁ ÀXRUHQHꢀꢂEꢃꢂFꢀGLFDUER[\OLFꢁ DFLGꢁ GLHWK\Oꢁ
ester (5): A suspension of 3 (1.43 g, 5 mmol) in 37% aq formaldehyde
ꢂꢈꢄꢉꢀP/ꢃꢀDQGꢀ0H2+ꢀꢂꢈꢊꢀP/ꢃꢀZDVꢀEURXJKWꢀWRꢀUHÀX[ꢀXQGHUꢀPDJQHWLFꢀ
stirring. (4-Bromobenzylamine (1.85 g, 10 mmol) in MeOH (20 ml)
ZDVꢀDGGHGꢀVORZO\ꢁꢀGURSZLVHꢀꢂRYHUꢀꢆꢀKꢃꢀWRꢀWKHꢀPL[WXUHꢄꢀ7KHꢀUHÀX[LQJꢀ
was continued. The reaction was monitored by TLC. The solvent was
removed under reduced pressure and the solid residue was separated
by column chromatography (SiO2, CHCl3–MeOH, 50:1) to give
pure compound 5 (2.49 g, 71%)as a white solid. M.p.203–204°C. IR
(KBr, cm-1): 2930w, 2857w, 2967w, 1749 s, 1717 s, 1413 m, 1293 m;
1H NMR (CDCl3, 400 MHz): G = 7.45(d, J = 8.4 Hz,4H, ArH), 7.24
(d, J = 8.4 Hz, 4H, ArH), 4.83 (d, J = 14.0 Hz, 4H, NCH2N), 3.80 (d,
J = 14.0 Hz, 4H, NCH2N), 4.26(q, J = 7.2 Hz, 4H, OCH2CH3), 1.30 (t,
J = 7.2 Hz,6H, OCH2CH3); 13C NMR (CDCl3, 100 MHz): G = 165.3,
158.5, 135.8, 131.6, 130.6, 121.7, 76.2, 63.4, 59.9, 54.7, 13.9; EI-MS:
m/z 706.0 [M + 2H]2+. Anal. Calcd for C28H30Br2N6O6 (704.0): C,
47.61; H, 4.28; N, 11.90; Found: C, 47.52; H, 4.20; N, 11.79%.
Binding studies
A stock solution of compounds 7 and 8 was prepared by dissolution
in DMF/MeOH (50:1, v/v) (1.0 u 10-5M), respectively. The solutions
of metal ions were prepared from Pb(NO3)2 and the chlorides of K+,
Na+, Mg2+, Hg2+, Cd2+, Fe3+, Cu2+, Zn2+, Co2+, Ni2+, Pb2+, Cr3+, and
Mn2+, respectively, and were dissolved in methanol (3.0 u 10-3 M).
)OXRUHVFHQFHꢀ WLWUDWLRQꢀ ZDVꢀ SHUIRUPHGꢀ E\ꢀ ¿OOLQJꢀ ꢈꢀ POꢀ VROXWLRQꢀ RIꢀ
compound 7 or 8 in a quartz cell of 1 cm optical path length, and
adding different stock solutions of cations into the quartz cell
portionwise using a microsyringe each time. Both excitation and
emission bands were set at 2.5 nm.
We thank the Central China Normal University, the National
Natural Science Foundation of China (Grant No. 20672042)
IRUꢀ¿QDQFLDOꢀVXSSRUWꢄ
General procedure for preparation of 7 and 8
To a solution of Pd(PPh3)2Cl2 (36 mg, 0.05 mmol), CuI (19 mg,
0.10 mmol) and compound 4–5 (0.50 mmol) in freshly distilled Et3N
(15 ml) and DMF (25 ml) under Ar atmosphere at room temperature.,
were added compound 6 (304 mg, 2 mmol). The mixture was warmed
to 100°C for 14 h, and then the solvent was removed under reduced
SUHVVXUHꢄꢀ7KHꢀVROLGꢀUHVLGXHꢀZDVꢀVHSDUDWHGꢀE\ꢀÀDVKꢀFKURPDWRJUDSK\ꢀ
(SiO2, CHCl3–MeOH, 50:1) to give pure compounds 7–8 as a yellow
solid. The physical and spectroscopic data of the compounds 7 and 8
are as follows.
Received 10 August 2008; accepted 27 October 2008
Paper 08/0105 doi: 10.3184/030823409X396418
Published online: 22 January 2009
References
1
2
3
4
L. Prodi, F. Bolletta, M. Montalti and N. Zaccheroni, Coord. Chem. Rev.,
2000, 205, 59.
2,6-Bis-(4-naphthalen-1-ylethynyl-phenyl)-4,8-dioxo-tetrahydro-
ꢄꢃꢅDꢃꢆDꢃꢇꢃꢈDꢃꢂDꢀKH[DD]DꢀF\FORSHQWD>GHI@ÀXRUHQHꢀꢂEꢃꢂFꢀGLFDUER[\OLFꢁ
acid diethyl ester (7): M.p.253–255°C; IR (KBr, cm-1): 3055w, 2210w,
1751 s, 1727 s, 1606 m, 1516 s, 1414 s, 1237 s, 973 s, 770 s; 1H NMR
(CDCl3,400MHz):G=8.30(d,J=8.4Hz,2H,NapH),7.70(d,J=8.0Hz,
2H, NapH), 7.59 (d, J = 8.4 Hz, 2H, NapH), 7.41 (d, J = 8.4 Hz, 4H,
ArH), 7.38–7.34(m, 4H, NapH), 7.07–7.03 (m, 2H, NapH), 6.94 (d,
J = 8.4 Hz, 4H, ArH), 5.61 (d, J = 14.0 Hz, 4H, NCH2N), 4.65 (d,
J = 14.0 Hz, 4H, NCH2N), 4.35 (q, J = 6.8 Hz, 4H, OCH2CH3),
1.36 (m, J = 6.8 Hz, 6H, OCH2CH3); 13C NMR (CDCl3, 100 MHz):
G = 165.01, 157.3, 145.6, 133.0, 129.9, 127.9, 126.4, 126.2, 126.0,
125.0, 121.0, 117.1, 116.2, 94.3, 86.7, 76.3, 63.5, 57.7, 14.0; EI-MS:
m/z = 821.3[M + H]+. Anal. Calcd for C50H40N6O6 (820.3): C, 73.16;
H, 4.91; N, 10.24; Found: C, 73.03; H, 4.81; N, 10.13%.
2,6-Bis-(4-naphthalen-1-ylethynyl-benzyl)-4,8-dioxo-tetrahydro-
ꢄꢃꢅDꢃꢆDꢃꢇꢃꢈDꢃꢂDꢀKH[DD]DꢀF\FORSHQWD>GHI@ÀXRUHQHꢀꢂEꢃꢂFꢀGLFDUER[\OLFꢁ
acid diethyl ester (8): M.p. 210–211°C; IR (KBr, cm-1): 3044w,
2210w, 1758 s, 1725 s, 1650w, 1461 m, 1413 s, 1293 s, 1034 s, 985
s, 710w. 1H NMR(CDCl3, 400 MHz): G = 8.43 (d, J = 8.0 Hz, 2H,
NapH), 7. 83 (t, J = 7.2 Hz, 4H, NapH), 7.74 (d, J = 7.2 Hz, 2H,
J.P. Desvergne and A.W. Czarnik, Eds; Chemosensors for ion and
molecule recognition; Kluwer Academic, Boston, 1997.
A.B. Descalzo, R. Martinez-Manez, R. Radeglia, K. Rurack and J. Soto,
J. Am. Chem. Soc., 2003, 125, 3418.
C. Goze, G. Ulrich, L. Charbonniere, M. Cesario, T. Prange and
R. Ziessel, Chem. Eur., J. 2003, 9, 3748.
5
6
B. Turfan and E.U. Akkaya, Org. Lett., 2002, 4, 2857.
A.E. Rowan, J.A.A.W. Elemans and R.J.M. Nolte, Acc. Chem. Res., 1999,
32, 995.
7
F. Hof, S.L. Craig, C. Nuckolls and Jr.J. Rebek, Angew. Chem. Int. Ed.,
2002, 41, 1488.
8
9
J. Kang, J.-H. Jo and S. In, Tetrahedron Lett., 2004, 45, 5225.
M. Kölbel and F.M. Menger, Chem. Commun., 2001, 275.
10 J. Kang and J. Kim, Tetrahedron Lett., 2005, 46, 1759.
11 S.-L. Hu, N.-F. She, G.-D. Yin, H.-Z. Guo, A.-X. Wu and C.-L. Yang,
Tetrahedron Lett., 2007, 48, 1591.
12 C.A. Burnett, J. Logona, A.-X. Wu, J.A. Shaw, D. Coady, J.C. Fettinger,
A.I. Day and L. Isaacs, Tetrahedron, 2003, 59, 1961.
13 G.-D. Yin, Z.-G. Wang, Y.-F. Chen, A.-X. Wu and Y.-J. Pan, Synlett, 2006, 49.
14 G.T. Crisp and Y.L. Jiang, Synth Commun., 1998, 14, 2571.
15 G.L. Hug and B. Marciniak. J. Phys. Chem., 1994, 98, 7523.
16 F. Wilkinson and A. Farmillo. J. Chem. Soc., Faraday Trans., 1976, 72, 604.