Synthesis and recognition properties of two novel concave molecules based on glycoluril

Article abstract of DOI:10.3184/030823409X439717

Two new concave fluorescent molecular clips based on diethoxycarbonyl glycoluril and diphenyl acetylene units have been synthesised by introducing the fluorophores into the receptor. Their recognition properties toward various metal ions were studied by f

Full text of DOI:10.3184/030823409X439717

JOURNAL OF CHEMICAL RESEARCH 2009
APRILꢂꢀꢄꢅꢆ±268
RESEARCH PAPER 265
Synthesis and recognition properties of two novel concave molecules
based on glycoluril
Wang Shuaia, Wu An-Xina and She Neng-Fanga*
aKey Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, P.R. China
Two new concave fluorescent molecular clips based on diethoxycarbonyl glycoluril and diphenyl acetylene units
have been synthesised by introducing the fluorophores into the receptor. Their recognition properties toward
various metal ions were studied by fluorescence spectroscopy. The results demonstrate that they can selectively
bind Fe3+ with fluorescence quenching.
Keywords: glycoluril molecular clip, recognition, Fe(III)
The selective recognition and sensing of heavy and transition
PHWDOꢀLRQVꢀYLDꢀDUWL¿FLDOꢀUHFHSWRUVꢀDUHꢀRIꢀFXUUHQWꢀLQWHUHVWꢀWRꢀERWKꢀ
chemists and biologists because of their practical application
in cellular imaging, environmental monitoring, and biological
assays.1,2ꢀ$WWHQWLRQꢀKDVꢀEHHQꢀIRFXVHGꢀRQꢀÀXRUHVFHQWꢀFKHPRVHQVRUVꢀ
due to their simplicity, high sensitivity, high selectivity, and
instantaneous response.3 One strategy employed in the design
RIꢀFKHPRVHQVRUVꢀIRUꢀPHWDOꢀFDWLRQVꢀLVꢀWRꢀOLQNꢀDꢀÀXRURSKRUHꢀXQLWꢀ
with a metal binding unit. The two units are linked to each other
in such a way that the binding of a cation causes considerable
FKDQJHVꢀLQꢀWKHꢀÀXRUHVFHQFHꢀRIꢀWKHꢀÀXRURSKRUHꢁ4
Glycoluril is an important building block for supramolecular
chemistry, and its derivatives have been used as the basis for
molecular capsules,5 molecular clips,6,7 molecular bowls8 and the
cucurbit[n]uril (CB[n]) family,9 among which molecular clips are
ideal synthetic receptors because of their special cavities.
In previous work, our group had reported a pair of molecular
clips derived from diethoxycarbonyl glycoluril with two
1,2-dihydro-indazol-3-one moieties as the sidewalls and
GHYHORSHGꢀWKHLUꢀIXQFWLRQꢀDVꢀVHOHFWLYHꢀÀXRUHVFHQWꢀFKHPVHQVRUVꢀ
for Fe3+ 10
In continuing our research to develop new
.
ÀXRUHVFHQWꢀFKHPVHQVRUVꢀEDVHGꢀRQꢀJO\FROXULOꢂꢀZHꢀKDYHꢀGHVLJQHGꢀ
two novel concave molecular clips 7 and 8 which have large
ʌꢃV\VWHPVꢀWKDWꢀFDQꢀEHꢀXVHGꢀDVꢀWKHꢀVLJQDOOLQJꢀVXEXQLWꢀLQꢀWKHLUꢀ
two sidewalls and two carbonyl oxygen atoms of glycoluril
ring and nitrogen atoms in their cavity which could be used
as the potential binding sites. In this paper, we report their
synthesis and some binding studies with different metal ions.
The synthesis of title concave molecules 7 and 8 is shown
in Scheme 1. The structure and conformation of compound
8 ZDVꢀDOVRꢀFRQ¿UPHGꢀE\ꢀVLQJOHꢀFU\VWDOꢀ;ꢃUD\ꢀGLIIUDFWLRQꢂ as
shown in Fig. 1.
O
N
N
R
N
R
O
N
O
I
I
I
I
HN NH
HO
HO
O
O
COOEt
COOEt
4
5
O
O
(iv)
(iii)
(i)
OH
OH
R
R
(ii)
HN
NH
N
R
N
N
R
O
O
3
2
1
N
O
OCH
3
O
N
R
N
N
R
4
(v)
N
O
O
7
H3CO
OCH
3
N
R
N
R
6
N
N
5
(v)
O
8
OCH3
OCH
3 (R=COOEt)
Scheme 1 Reagents and conditions: (i) AcOH, Br2, H2O, Na2CO3; (ii) EtOH, HCl(g), 0°C; (iii) PhH, H2NCONH2, TFA, reflux;
(iv) 1,2-dibromo-3-iodobenzene, t-BuOK, DMSO, rt; (v) PdCl2(PPh3)2, CuI, Et3N, DMF, 80°C, Ar.
* Correspondent. E-mail: wuhanshe@126.com

266 JOURNAL OF CHEMICAL RESEARCH 2009
Fig. 1 ORTEP drawing of the crystal structure of 8.
The crystal structure of 8 is built up from four fused rings,
QDPHO\ꢀ WZRꢀ QHDUO\ꢀ SODQDUꢀ LPLGD]ROHꢀ ¿YHꢃPHPEHUHGꢀ ULQJVꢀ
that adopt envelope conformations, with the C=O groups at
WKHꢀÀDSꢀSRVLWLRQVꢁꢀ7KHꢀDQJOHꢀEHWZHHQꢀWKHꢀPHDQꢀSODQHVꢀGH¿QHGꢀ
E\ꢀWKHꢀ¿YHꢃPHPEHUHGꢀULQJVꢀLVꢀꢇꢇꢈꢁꢆƒꢁꢀ7KHꢀJO\FROXULOꢀXQLWꢀLVꢀ
almost coplanar, which is indicated by the key torsion angle
ꢉ1ꢇ±&ꢄꢄ±&ꢄꢅ±1ꢊꢀ ꢀꢋꢁꢄꢌƒꢂꢀ1ꢄ±&ꢄꢄ±&ꢄꢅ±1ꢍꢀ ꢀꢇꢁꢍꢎƒꢏꢁꢀ7KHꢀ
GLVWDQFHꢀEHWZHHQꢀWZRꢀFDUERQ\OꢀR[\JHQꢀDWRPVꢀꢉ2ꢉꢄꢏ±2ꢉꢊꢏꢏꢀRIꢀ
JO\FROXULOꢀULQJꢀDPRXQWVꢀWRꢀꢆꢁꢆꢆꢀcꢁꢀ7KHꢀWZRꢀí&Ł&í3K2&+3
substituted aromatic rings are each fused to a seven-membered
ring; these rings bind four of the N atoms from separate rings
of the glycoluril system to form the sidewalls of the molecule.
However, the two sidewalls are not parallel and have the
dihedral angle of 39.97°. The distance between the centroids
of the substituted o-xylylene rings is 6.55 Å. The polarised
carbonyl groups and the electron-rich nitrogen atoms in the
cavity give 8 the potential to bind metal ions.
Cr3+ and Mn2+) were measured once their emission intensity
were constant. The result showed Fe3+ꢀSURGXFHGꢀVLJQL¿FDQWꢀ
TXHQFKLQJꢀLQꢀWKHꢀÀXRUHVFHQWꢀHPLVVLRQꢀZKLOVWꢀWKHꢀRWKHUꢀPHWDOꢀ
LRQVꢀ ZKLFKꢀ ZHUHꢀ WHVWHGꢀ RQO\ꢀ VKRZHGꢀ UHODWLYHO\ꢀ LQVLJQL¿FDQWꢀ
changes (Figs 2 and 3). It can be concluded that 7 and 8 have
higher selectivity for recognition of Fe3+
.
7Rꢀ IXUWKHUꢀ LQYHVWLJDWHꢀ WKHꢀ ÀXRUHVFHQFHꢀ VHQVLQJꢀ DELOLW\ꢀ RIꢀ
7 and 8 for Fe3+ꢂꢀ ÀXRUHVFHQFHꢀ WLWUDWLRQꢀ H[SHULPHQWVꢀ ZHUHꢀ
also performed under the same conditions with various Fe3+
concentration (Figs 4 and 5).
7KHꢀÀXRUHVFHQFHꢀLQWHQVLW\ꢀRIꢀ7 and 8 decreased continually
upon adding Fe3+ꢀZLWKꢀQRꢀVLJQL¿FDQWꢀFKDQJHꢀLQꢀWKHꢀSRVLWLRQꢀ
RIꢀWKHꢀHPLVVLRQꢀPD[LPDꢁꢀ7KLVꢀREVHUYDWLRQꢀFRQ¿UPVꢀWKDWꢀWKHꢀ
compound 7 and 8 may be selective chemosensors towards
Fe3+ꢀZLWKꢀÀXRUHVFHQFHꢀTXHQFKLQJꢁ
The quench mechanism, for 7 and 8, may be rationalised
because the Fe3+ may establish coordinative interactions with
the polarised carbonyl groups more easily than the other metal
ions which were examined. The capture of the Fe3+ may result
in electron transfer from the excited aromatic chromophore
to the metal or energy transfer from the excited aromatic
chromophore to low-lying metal centred energy states.11,12
Such processes could be particularly effective in the complex
The recognition properties of molecules 7 and 8 with various
PHWDOꢀ LRQVꢀ KDYHꢀ EHHQꢀ LQYHVWLJDWHGꢀ WKURXJKꢀ ÀXRUHVFHQFHꢀ
PHDVXUHPHQWVꢁꢀ&KDQJHVꢀLQꢀWKHꢀÀXRUHVFHQFHꢀSURSHUWLHVꢀRIꢀꢇꢀu
10-5 M solutions of 7 and 8 in THF/CH3OH (9:1, v/v) caused
by 15 equiv. of diverse metal ions (K+, Sn2+, Sb3+,Sr2+,Ca2+
Ag+, Mg2+, Hg2+,Bi3+,Hg2+, Cd2+, Fe3+, Zn2+, Co2+, Ni2+, Pb2+
,
,
Fig.
2 Fluorescence emission changes of molecule 7
Fig.
3 Fluorescence emission changes of molecule 8
(1 u 10-5 M) in THF/CH3OH (9:1, v/v) in the presence of
(1 u 10-5 M) in THF–MeOH (9:1, v/v) in the presence of
16 equiv. various metal ions (excitation at 315nm).
16 equiv. various metal ions (excitation at 315nm).

JOURNAL OF CHEMICAL RESEARCH 2009 267
Fig.
4
Fluorescence emission changes of compound
7
Fig. 5 Fluorescence emission changes of compound 8
(1 u 10-5 M) in THF/CH3OH (9:1, v/v) upon addition of different
(1 u 10-5 M) in THF/CH3OH (9:1, v/v) upon addition of different
concentrations of Fe3+ (excitation at 315 nm).
concentrations of Fe3+ (excitation at 315 nm).
of 7 and 8 with Fe3+ because the chelated metal cation is held
very close to the two excited aromatic chromophore. Thus,
7 and 8ꢀVKRZHGꢀTXHQFKꢀÀXRUHVFHQFHꢀHPLVVLRQꢀIRUꢀ)H3+ and
provided a high selectivity for Fe3+ over the other tested
metal ions.
In summary, we have synthesised two new concave
molecules derived from diethoxycarbonyl glycoluril as
ÀXRUHVFHQWꢀFKHPRVHQVRUVꢀZKLFKꢀGLVSOD\ꢀKLJKꢀVHOHFWLYLW\ꢀIRUꢀ
Fe3+. Further studies on the chemosensor behaviour of the
QHZꢀJHQHUDWLRQꢀRIꢀÀXRUHVFHQWꢀGHULYDWLYHVꢀWRZDUGꢀYDULRXVꢀLRQVꢀ
are underway in our laboratory.
7.13 (t, J = 7.2 Hz, 2H), 6.88 (d, J = 8.8 Hz, 4H), 5.64 (d, J = 16.0 Hz,
2H), 4.78 (d, J = 16.0 Hz, 2H), 4.43 (d, Jꢀ ꢀꢇꢅꢁꢍꢀ+]ꢂꢀꢍ+ꢏꢂꢀꢍꢁꢄꢈ±ꢍꢁꢄꢄꢀ
(m, 4H), 3.84 (s, 6H), 1.32 (t, J = 7.2 Hz, 6H). 13C NMR (CDCl3, 100
MHz): 166.0, 159.7, 155.9, 137.6, 136.5, 133.2, 131.8, 129.8, 127.8,
123.8, 115.2, 113.9, 94.2, 85.8, 80.0, 63.4, 55.3, 45.7, 42.6, 14.0. ESI-
MS (m/e): 773 (M + Na+). Anal. Calcd for C44H38N4O8: C, 70.39; H,
5.10; N, 7.46. Found: C, 70.14; H, 5.20; N, 7.61%.
1,11-Di(4-methoxyphenylethynyl)-13b,13c-diethoxycarbonyl-
6H,13H-5,7,12,13b,13c,14-hexahydro-5a,6a,12a,13a-tetra-
azabenz[5,6]azuleno-[2,1,8-ija]benz[f]azulene-6,13-dione (8): M.p.
>300°C. IR (KBr, cm-1): 3069, 2985, 2906, 2839, 2203, 1758(s),
1722(s), 1510, 1460(s), 1249. 1H NMR (400 MHz, CDCl3): 7.55 (d,
J = 8.8 Hz, 4H), 7.39 (d, J = 7.2 Hz, 2H), 7.23 (d, J = 7.2 Hz, 2H),
7.14 (t, J = 7.2 Hz, 2H), 6.82 (d, J = 8.8 Hz, 4H), 5.62 (d, J = 16.0 Hz,
2H), 4.73 (d, J = 15.8 Hz, 2H), 4.49-4.41 (m, 4H), 4.22 (q, J = 7.2 Hz,
4H), 3.81 (s, 6H), 1.30 (t, J = 7.2 Hz, 6H). 13C NMR (CDCl3,
100 MHz): 166.0, 159.6, 156.3, 155.6, 137.7, 136.4, 133.2, 131.9,
129.5, 127.8, 124.1, 115.3, 113.9, 94.3, 85.9, 80.0, 63.3, 55.2,
45.7, 42.7, 14.0. ESI-MS (m/e): 773 (M + Na+). Anal. Calcd for
C44H38N4O8: C, 70.39; H, 5.10; N, 7.46. Found: C, 70.23; H, 5.26;
N, 7.70%.
Experimental
General
All reagents obtained from commercial sources were of AR grade.
Melting point was determined with XT4A micromelting point
apparatus and was uncorrected. NMR was recorded on a Mercury
Plus-400 spectrometer with TMS as internal reference and CDCl3 as
solvent. IR were recorded on a PerkiníElmer PEí983 IR spectrometer
as KBr pellets with absorption in cm-1. MS were obtained with
Finnigan Trace MS instrument using EI method. Fluorescence spectra
were determined on a FluoroMax-P.
X-ray diffraction study of compound 8
Crystals were obtained by slow evaporation from the mixture
solvents of CH2Cl2/MeOH (20:1 v/v). A colourless crystal of the title
compound 8 having approximate dimensions of 0.30 mm u 0.20 mm
uꢀ ꢋꢁꢄꢋꢀ PPꢀ ZDVꢀ PRXQWHGꢀ RQꢀ Dꢀ JODVVꢀ ¿EUHꢀ LQꢀ Dꢀ UDQGRPꢀ RULHQWDWLRQꢀ
at 292(2) K. The unit cell determination and data collection were
performed with MoKD radiation (O = 0.71073 Å) on a Bruker Smart
Apex-CCD diffractometer using a ȥ-Z scan mode. A total of 8440
UHÀHFWLRQVꢀ ZHUHꢀ FROOHFWHGꢀ LQꢀ WKHꢀ UDQJHꢀ RIꢀ ꢄꢁꢊꢅꢐșꢐꢄꢆꢁꢋꢋꢂꢀ RIꢀ ZKLFKꢀ
6667 (Rint = 0.0758) were independent and 2011 were observed with
(I !ꢄıꢉI)). The structure of the title compound was solved by direct
PHWKRGVꢀDQGꢀUH¿QHGꢀE\ꢀIXOOꢃPDWUL[ꢀOHDVWꢃVTXDUHVꢀWHFKQLTXHVꢀRQꢀF2.
All hydrogen atoms were placed in their calculated positions and
DOOꢀ QRQꢃK\GURJHQꢀ DWRPVꢀ ZHUHꢀ UH¿QHGꢀ ZLWKꢀ DQLVRWURSLFꢀ WHPSHUDWXUHꢀ
IDFWRUVꢁꢀ6+(/;6ꢎꢌꢀDQGꢀ6+(/7/ꢀZHUHꢀDSSOLHGꢀWRꢀVROYHꢀDQGꢀUH¿QHꢀ
WKHꢀ VWUXFWXUHꢂꢀ UHVSHFWLYHO\ꢁꢀ 7KHꢀ ¿QDOꢀ F\FOHꢀ RIꢀ UH¿QHPHQWꢀ JDYHꢀ
R = 0.0787, wR = 0.1672 (w = 1/[ı2(Fo)2 + (0.0728P)2 + 0.0000P],
Synthesis
Diethoxycarbonyl glycoluril 3,13 4-methoxyphenylacetylene 614 were
prepared by literature methods.
General procedure for preparation of the mixture of 4 and 5
t-BuOK (4.48 g, 40.0 mmol) was added to a solution of 3 (5.76 g,
20.0 mmol) in anh. DMSO (70 mL) under Ar. After the mixture
had been stirred for 13 min., 1,2-dibromo-3-iodobenzene 6 (1.56 g,
4 mmol) was added in one portion and stirring was continued for 3 h.
The reaction mixture was poured into 0.1 N HCl (1 L) and extracted
with EtOAc (3 u 400 mL). The extracts were washed with brine
(3 u 300 mL) and dried over anhydrous Na2SO4ꢁꢀ$IWHUꢀ¿OWUDWLRQ and
URWDU\ꢀHYDSRUDWLRQꢂꢀWKHꢀUHVLGXHꢀZDVꢀSXUL¿HGꢀE\ꢀÀDVKꢀFKURPDWRJUDSK\ꢀ
(SiO2, CHCl3/MeOH, 100:1) to give a mixture of 4 and 5 (757 mg,
1.02 mmol, 51%).
2
where P = (Fo + 2Fc2)/3), ('ȡ)max = 0.220, ('ȡꢏPLQꢀ ꢀ ±ꢋꢁꢄꢇꢎꢀ
e/Å3, ('/ı)max = 0.001 and S = 0.832. Crystal data: C44H38N4O8,
M=750.79,Triclinic,spacegroupP-1witha=8.6676(19),b=13.173(3),
c = 19.829(4) Å, E = 79.306(5)°, V = 2093.9(8) Å3, Z = 2, Dc = 1.326
g/cm3, ȝ(MoKD) = 0.214 mm-1. The details of the crystal data have
been deposited with Cambridge Crystallographic Data Centre as
Supplementary Publication No. CCDC 705713.
General procedure for preparation of 7 and 8
Compound 6 (132 mg, 1 mmol) was added to a solution of
PdCl2(PPh3)2 (18 mg, 0.025 mmol), CuI (9.5 mg, 0.050 mmol) and
the mixture of 4 and 5 (186 mg, 0.25 mmol) in freshly distilled
Et3N (10 mL) and DMF (10 mL) under Ar atmosphere at RT.
The mixture was warmed to 80°C for 12 h, the solvent was removed
XQGHUꢀUHGXFHGꢀSUHVVXUHꢂꢀDQGꢀWKHꢀVROLGꢀUHVLGXHꢀZDVꢀSXUL¿HGꢀE\ꢀÀDVKꢀ
chromatography (SiO2, EtOAc/hexane, 1:2) to give pure compound 7
as a white solid (39.2 mg, 0.0533 mmol, 43%) and compound 8 as a
white solid (44.1 mg, 0.0588 mmol, 47%). The physical and spectra
data of the compounds 7 and 8 are as follows.
Recognition studies
A stock solution of compound 7 and 8 were prepared by dissolution
in THF/CH3OH (9:1, v/v) (1.0 u 10-5M), respectively. The solutions
of metal ions were prepared from Pb(NO3)2 and the chlorides of
K+, Sn2+, Sb3+, Sr2+, Ca2+, Ag+, Mg2+, Hg2+, Bi3+, Hg2+, Cd2+, Fe3+
,
1,8-Di(4-methoxyphenylethynyl)-13b,13c-diethoxycarbonyl-
6H,13H-5,7,12,13b,13c,14-hexahydro-5a,6a,12a,13a-tetra-
azabenz[5,6]azuleno-[2,1,8-ija]benz[f]azulene-6,13-dione (7): M.p.
ꢄꢌꢈ±ꢄꢌꢎ°C. IR (KBr, cm-1): 3069, 2985, 2908, 2207, 1754(s), 1719(s),
1465(s), 1249, 1151,1027. 1H NMR (400 MHz, CDCl3): 7.54 (d,
J = 8.8 Hz, 4H), 7.39 (d, J = 7.2 Hz, 2H), 7.23 (d, J = 7.2 Hz, 2H),
Zn2+, Co2+, Ni2+, Cr3+, and Mn2+, respectively, and were dissolved
in methanol (3.0 u 10-3 M). Fluorescence titration was performed by
¿OOLQJꢀꢊꢀP/ꢀVROXWLRQꢀRIꢀFRPSRXQGꢀ7 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.

268 JOURNAL OF CHEMICAL RESEARCH 2009
5
S. Deo and H.A. Godwin, J. Am. Chem. Soc., 2000, 122, 174.
We thank the Central China Normal University, the National
Natural Science Foundation of China (Grant No. 20672042)
IRUꢀ¿QDQFLDOꢀVXSSRUWꢁ
ꢀ ꢅꢀ -ꢁ/ꢁꢀ %ULFNVꢂꢀ $ꢁꢀ .RYDOFKXNꢂꢀ &ꢁꢀ 7ULHÀLQJHUꢂꢀ 0ꢁꢀ 1RI]ꢂꢀ 0ꢁꢀ %XVFKHOꢂꢀ
A.I. Tolmachev, J. Daub and K. Rurack, J. Am. Chem. Soc., 2005,
127, 1352.
7
8
9
J.M. Liu, Q.Y. Zheng, J.L. Yang, C.F. Chen and Z.T. Huang, Tetrahedron
Lett., 2002, 43, 9209.
Received 25 December 2008; accepted 17 February 2009
Paper 08/0358 doi: 10.3184/030823409X439717
Published online: 29 April 2009
T.J. Egan, R. Hunter, C.H. Kaschula, H.M. Marques, A. Misplon and
J. Walden, J. Med. Chem., 2000, 43, 283.
F. Hof, S.L. Craig, C. Nuckolls and J. Rebek Jr., Angew. Chem. Int. Ed.,
2002, 41, 1488.
10 S.L. Hu, N.F. She, G.D. Yin, H.Z. Guo, A.X. Wu and C.L. Yang,
Tetrahedron Lett., 2007, 48, 1591.
11 G.L. Hug and B. Marciniak. J. Phys. Chem., 1994, 98, 7523.
12 F. Wilkinson and A. Farmillo. J. Chem. Soc., Faraday Trans., 1976,
72, 604.
13 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.
14 S. Takahashi, Y. Kuroyama, K. Sonogashira and N. Hagihara, Synthesis,
1980, 627.
References
1
J.M. Lehn, Supramolecular chemistry, VCH: Weinheim, Germany, 1995.
J.W. Steed and J.L. Atwood, Supramolecular chemistry, Wiley, New York,
2000.
2
3
4
V. Amendola, L. Fabbrizzi, F. Forti, M. Licchelli, C. Mangano,
P. Pallavicin, A. Poggi, D. Sacchi and A. Taglieti, Coord. Chem. Rev.,
2006, 250, 273.
C. Goze, G. Ulrich, L. Charbonniere, M. Cesario, T. Prange and
R. Ziessel, Chem. Eur. J., 2003, 9, 3748.