A supramolecular optic sensor for selective recognition AMP

Article abstract of DOI:10.1016/j.inoche.2010.04.006

Cu-coordinated complex based on 7-membered amide cycle has been designed and synthesized. And its binding ability with nucleotides (AMP, adenosine 5′-monophosphate; ADP, adenosine 5′-diphosphate; ATP, adenosine 5′-triphosphate) has been studied by UV-vis

Full text of DOI:10.1016/j.inoche.2010.04.006

Inorganic Chemistry Communications 13 (2010) 999–1003
Contents lists available at ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Mini-Review
A supramolecular optic sensor for selective recognition AMP
Xue-Fang Shang a, Hongyan Su a, Hai Lin b, Hua-Kuan Lin a,
⁎
a
Department of Chemistry, Nankai University, Tianjin 300071, PR China
b
Key Laboratory of Functional Polymer Materials of Ministry of Education, Nankai University, Tianjin 300071, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Cu-coordinated complex based on 7-membered amide cycle has been designed and synthesized. And its
binding ability with nucleotides (AMP, adenosine 5′-monophosphate; ADP, adenosine 5′-diphosphate; ATP,
adenosine 5′-triphosphate) has been studied by UV–vis spectrum. Results indicate that the receptor shows
the highest binding ability with AMP among studied nucleotides and can selectively and strongly bind
nucleotides at neutral medium. The receptor can be used as optical sensor for the detection of AMP.
© 2010 Elsevier B.V. All rights reserved.
Received 20 November 2009
Accepted 19 April 2010
Available online 10 May 2010
Keywords:
7-membered amide cycle
AMP
Neutral medium
Contents
Introduction .
Experimental
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999
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999
1000
1001
1001
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1003
1003
1003
Apparatus and reagents
Synthesis
X-ray crystallography.
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Results and discussion .
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Conclusion.
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Acknowledgement .
Appendix A. Supplementary data .
References.
. . . . . . . . . . .
Introduction
competitive hydrogen bonding of the solvent [18–20]. Progress in this
area would require new strategies for the selective recognition and
subsequent signaling of the event under physiological pH conditions.
In previous reported literature, the recognition of adenosine was
focused on supramolecular catalysis area at certain pH condition
[21,22]. In this paper, we reported the recognition of adenosine in
neutral medium. Recently, we synthesized a novel 7-membered
receptor 1 (Scheme 1) and reported its anion recognition properties
[5]. Later, we found receptor 1 also could interact with AMP, ADP and
ATP. Herein, we reported the interaction of receptor 1 with AMP, ADP
and ATP which selectively combined with AMP in water solution and
signals the event through changes in absorption spectroscopy.
In recent years, increasing attention in the field of host–guest
chemistry has been devoted to the fast development of anion
recognition systems [1–5].With the aid of supramolecular chemistry,
recognition and sensing of anionic anaylates has recently emerged as a
key research field. Detection of nucleotides has paramount importance
as they form the fundamental units of all the life forms [6–10]. Of all the
nucleosides and nucleotides, the recognition of adenosine 5′-monopho-
sphate (AMP), adenosine 5′-diphosphate (ADP) or adenosine 5′-
triphosphate (ATP) is vital[11–15] since nucleotide phosphates such
as AMP, ADP or ATP are important for their role in bioenergetics,
metabolism, and transfer of genetic information[16,17]. Most known
receptors for these nucleotides use complementary hydrogen bonding,
but such a recognition in the aqueous medium would be limited due to
the interference from hydroxyl groups of the sugar moiety and
Experimental
Apparatus and reagents
Most of the starting materials were obtained commercially and all
reagents, and solvents employed were of analytical grade. AMP, ADP
⁎
Corresponding author. Tel.: +86 2223502624; fax: +86 22 23502458.
1387-7003/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2010.04.006

1000
X.-F. Shang et al. / Inorganic Chemistry Communications 13 (2010) 999–1003
Table 1
Crystallographic data of 1.
Compound
1
Empirical formula
Formula weight
Temperature, K
System, Space group
a, (Å)
C
44H48Br4CuN10O10
1260.10
294(2)
Monoclinic, P2(1)/n
12.035(2)
8.9193(14)
23.017(4)
90
94.422(5)
90
2463.4(7)
2
b, (Å)
c, (Å)
α (o)
β (o)
γ (o)
V, (Å3)
Z
Scheme 1. Chemical structures of receptor 1 and nucleotides.
Crystal size, mm3
0.20×0.14×0.06
1.699
Dcalcd, Mg m−3
F (000)
1262
1.77–27.46
20,636
0.0619
1.020
5613/0/326
0.0522, 0.1067
0.0856, 0.1220
0.607 and −0.657
0.0022(4)
and ATP were purchased from Sigma-Aldrich Chemical Co., stored in a
desiccator under vacuum containing self-indicating silica, and used
without any further purification. Dimethyl sulfoxide (DMSO) was
distilled in vacuo after dried with CaH2. C, H and N elemental analysis
was made on Vanio-EL. 1H NMR spectrum was recorded on a Varian
UNITY Plus-400 MHz Spectrometer. FAB-MS was made on VG ZAB–
HS. UV–vis Spectroscopy titrations were made on a Shimadzu UV2450
Spectrophotometer at 298.2 0.2 K. The stability constants Ks were
obtained by the non-linear least square calculation method through
data fitting.
2θ range (o)
Reflections collected
R(int)
GOF on F2
Data/restraints/parameters
Final R1 and wR2 [IN2σ(I)]
R1 and wR2 [all data]
Largest diff. Peak hole (e Å−3
Extinction coefficient
)
1H NMR(400 MHz, DMSO-d6, 298 K) δ=10.96 (s, 1H, NH), 10.74 (s,
1H, NH), 8.04, 7.3 (m, 3H, ph-H), 3.3 (s, 2H, CH2). Elemental analysis:
Calc. for C9H7N3O4: C, 48.88; H, 3.19; N, 19.00; Found: C, 48.76; H 3.58;
N, 18.61. FAB-MS(m/z): 222.1 (M+H)+ (4′-aminobenzo)[1′, 2′-d]-
1,4-diazacycloheptane[2,3-d]-5,7-dione(4) A slurry of compound (4′-
nitrobenzo)[1′,2′-d]-1,4-diazacycloheptane[2,3-d]-5,7-dione
(221 mg) and Pd/C (10%, 70 mg) in dry ethanol (200 ml) was
maintained under hydrogen with stirring for 12 h. The mixture was
filtered through a bed of Celite and then washed twice with ethanol
(2×20 ml). The solvents were removed under reduced pressure and
the yellowish solid dried in vacuum. Yield: 92%. 1H NMR(400 MHz,
DMSO-d6, 298 K) δ=10.15 (s, 1H, NH), 9.91 (s, 1H, NH), 6.76 (d, 1H,
ph-H), 6.38 (m, 1H, ph-H), 6.27 (d, 2H, ph-H), 5.16 (s, 2H, NH2) 3.08
(s, 2H, CH2). Elemental analysis: Calc. for C9H9N3O2: C, 56.54; H, 4.74;
N, 21.98; Found: C, 56.41; H 4.96; N, 21.87.
Synthesis
Receptor 1 was synthesized according to the route shown in
Scheme 2. Benzo-1,4-diazacycloheptane[2,3-d]-5,7-dione (2) [23]
1,2-phenylenediamine (10.8 g, 0.1 mol), diethyl malonate (16 ml,
0.1 mol) and pyridine (200 ml) were put in a 250 ml three-neck flask.
The mixture was refluxed with N2 for 72 h. After cooling, the mixture
was filtrated and the colorless solid obtained. The solid was washed
with ethanol and ether sequentially, and dried in vacuum. Yield: 72%.
1H NMR(400 MHz, DMSO-d6, 298 K) δ=10.38 (s, 2H, NH), 7.11–7.18
(m, 4H, ph-H), 3.17 (s, 2H, CH2). Elemental analysis: Calc. for
C9H8N2O2: C, 61.36; H, 4.58; N, 15.90; Found: C, 61.69; H 4.59; N,
15.96. FAB-MS(m/z): 177 (M+H)+. (4′-Nitrobenzo)[1′, 2′-d]-1,4-
diazacycloheptane[2,3-d]-5,7-dione(3) Benzo-1,4-diazacycloheptane
[2,3-d]-5,7-dione (10 mmol, 1.7 g) was dissolved in concentrated
H2SO4 (43 ml). Fuming HNO3 (1.1 ml) was added dropwise with
stirring at 273 K. After the addition was completed, the mixture was
stirred for 2 h and then poured into ca. 200 ml ice-water. The solution
was filtered to give a yellow solid, which was washed with distilled
water, recrystallized from methanol and dried in vacuum. Yield: 85%.
N-(2″-hydroxyl-3″,5″-dibromophenyl-methylene-yl)-4′-imino-
benzo[1′,2′-d]-1,4-diazacycloheptane[2,3-d]-5,7-dione [HODBrphC=
NphDNHexDO](5) (4′-aminobenzo)[1′,2′-d]-1,4-diazacycloheptane
[2,3-d]-5,7-dione (1 mmol, 191 mg) and 3,5-dibromo-salicylaldehyde
(1 mmol, 278 mg) were suspended in dry ethanol (100 ml). The
mixture was heated under reflux for 8 h and the orange-yellow
Scheme 2. Synthesis route for receptor 1.

X.-F. Shang et al. / Inorganic Chemistry Communications 13 (2010) 999–1003
1001
CH2). Elemental analysis: Calc. for C16H11N3OBr2·2H2O: C, 42.04; H,
3.31; N, 9.19; Found: C, 42.35; 2.88; N, 9.45. Cu(II)
[HODBrphC=NphDNHexDO]2 (1) (0.1 mmol) and Cu(NO3)2
H
5
(0.05 mmol) were stirred for 1 h in DMF (20 ml), then stood at room
temperature. After a month, the green crystal appeared. Elemental
analysis: Calc. for C32H20N6O6Br4Cu·5H2O: C, 39.72; H, 2.08; N, 8.68;
Found: C, 39.22; H 3.55; N, 8.91.
X-ray crystallography
A green crystal of 1 with dimensions of 0.20×0.14×0.06 mm was
mounted on a glass fiber. X-ray single-crystal diffraction data
were collected on a Rigaku Saturn CCD area detector at 294(2) K
with Mo–Ka radiation (λ=0.71073 Å) .The structure was solved
by direct methods and refined on F2 by full-matrix least squares
methods with SHELXL-97 [24]. More details of the crystallographic
determination are given in Table 1.
Results and discussion
Receptor 1 was obtained by the reaction of 5 and Cu(NO3)2 in
N,N-dimethylformamide (DMF). The crystals of receptor 1 suitable
for X-ray crystal analysis has been obtained and the structure has
been confirmed (Fig. 1, the deposition number is CCDC 621069).
The overall coordination environment of the Cu(II) atom involves
two receptor 1 and two DMF molecules. Four of the Cu1–O1, Cu1–
O1A, Cu1–N1, Cu1–N1A bonds are relatively longer (bond lengths
1.913 Å, 1.914 Å, 2.033 Å and 2.033 Å), and they constitute a plane
quadrangular geometry around the Cu(II) atom (O1–Cu1–O1A,
180°, O1–Cu1–N1, 90.7°, O1–Cu1–N1A, 89.3°, O1A–Cu1–N1, 89.3°,
O1A–Cu1–N1A, 90.7°, N1–Cu1–N1A, 180°); the other two Cu–O4,
Cu–O4A contacts are significantly shorter (bond lengths 1.653 Å
and 1.653 Å), completing a distorted octahedron as the overall
geometry around the Cu(II) atom. The NH of amide forms
hydrogen bonds with oxygen atoms of DMF molecules that are
derived from two resources: one is coordinated DMF (O4), the
other is uncoordinated DMF (O5) (Table 2). The overall crystal
structure features chain type with DMF molecules by hydrogen
bonds along the b axis (Fig. 2).
Fig. 1. The crystal structure of 1 and the hydrogen atoms are shown as small circles with
arbitrary radii (ellipsoids at 50% probability).
Table 2
Details of intermolecular hydrogen bonds in receptor 1.
Donor—H…Acceptor
N2—H2 …O5(b)
N3—H3A … O4(a)
D–H Å
H…A Å
0.872
1.991
0.943
1.964
D…A Å
2.855
170.10
2.890
166.98
D–H … A(°)
Symmetry code: a) −x+1/2, y+1/2, −z+1/2; and b) x, y−1, z.
precipitate was separated by filtration. The solid was washed with
diethyl ether and dried under vacuum. Yield: 89%. 1H NMR(400 MHz,
DMSO-d6, 298 K) δ=14.41 (s, 1H, OH), 10.54 (s, 2H, NH), 8.97 (s, 1H,
CH), 7.9 (d, 2H, ph-H), 7.3 (d, 2H, ph-H), 7.2 (m, 1H, ph-H) 3.24 (s, 2H,
Fig. 2. View of the three-dimensional structure of 1 along the b axis.

1002
X.-F. Shang et al. / Inorganic Chemistry Communications 13 (2010) 999–1003
The interactions of 1 with AMP, ADP and ATP were investigated
there appears one stoichiometric ratio at about 370 nm. The addition
of ATP also induces similar spectral change of receptor 1, compared
with AMP. The above results show that receptor 1 interacts with AMP,
ADP and ATP. Curve fitting of the interaction between the receptor
and AMP, ADP and ATP according to Eq. (1) is shown in Fig. 4. The high
correlation indicates that receptor binds ribonucleotides at 1:1.
Stability constants of receptor 1 for ribonucleotides are calculated
according to the Eq. (1), 1:1 host-guest complexation [25–28].
through UV–vis spectral titrations in DMSO/H2O (9:1) by the addition
of AMP, ADP and ATP to the solution of 1. Fig. 3 is the interacted
absorption spectrum of receptor 1 with nucleotides. With the addition
of AMP, the absorbance band at about 325 nm increases gradually. At
the same time, the intensity of absorbance band at about 413 nm
decreases gradually. In addition, there appears one clear isosbestic
point at about 355 nm. This shows that at this point a stable
concentration of the complex is formed in the solution with a certain
stoichiometric ratio between 1 and AMP. Similarly, the new
absorption band develops at 420 nm with the addition of ADP and
ꢀ
ꢁ
ð1Þ
h
i
1=2
X = X0 + 0:5Δε cH + cG + 1= Ks– ðcH + cG + 1=KsÞ2–4cHcG
where cG and cH are the concentration of guest and host, respectively.
X is the intensity of absorbance at certain concentration of host and
guest. X0 is the intensity of absorbance of host when the anion isn't
added. Ks is the affinity constant of host-guest complexation. Δε is the
Fig. 3. UV–vis spectral changes of receptor 1 (2.0×10−5 mol·L−1) upon the addition of AMP
(a), ADP(b) and ATP(c), the concentration of nucleotides is from 0 to 160×10−5 mol·L−1
.
Arrows indicate the direction of increasing ribonucleotides adenosine concentration.
Fig. 4. Curve fitting of the interaction between receptor and AMP(a), ADP(b) and ATP(c).

X.-F. Shang et al. / Inorganic Chemistry Communications 13 (2010) 999–1003
1003
[4] E. Quinlan, S.E. Matthews, T. Gunnlaugsson, Tetrahedron Lett. 47 (2006) 9333.
Table 3
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[6] R. Martinez-Manez, F. Sancenon, Chem. Rev. 103 (2003) 4419.
[7] A.P. De Silva, H.Q.N. Gunaratne, T. Gunnlaugsson, A.J.M. Huxley, C.P. McCoy, J.T.
Rademacher, T.E. Rice, Chem. Rev. 97 (1997) 1515.
[8] C.V. Kumar, A. Buranaprapuk, Angew. Chem., Int, Ed. Engl. 36 (1997) 2081.
[9] M.W. Hosseini, A.J. Blacker, J.M. Lehn, J. Am. Chem. Soc. 112 (1990) 3896.
[10] C. Marquez, U. Pischel, W.M. Nau, Org. Lett. 5 (2003) 3911.
[11] S.C. McCleskey, M.J. Griffin, S.E. Schneider, J.T. McDevitt, E.V. Anslyn, J. Am. Chem.
Soc. 125 (2003) 1114.
The stability constant of receptor 1 with nucleotides.
Nucleotides
Ks (mol−1 L)
AMP
ADP
ATP
39,754 5637
4141 924
1227 130
[12] L.M. Tumir, I. Piantanida, P. Novak, M. Zinic, J. Phys. Org. Chem. 15 (2002) 599.
[13] S. Atilgan, E.U. Akkaya, Tetrahedron Lett. 45 (2004) 9269.
[14] K.Y. Kwon, N.J. Singh, H.N. Kim, S.K. Kim, J. Yoon, J. Am. Chem. Soc. 126 (2004)
8892.
[15] S.K. Kim, B.S. Moon, J.H. Park, Y.I. Seo, H.S. Koh, Y.J. Yoon, K.D. Lee, J. Yoon,
Tetrahedron Lett. 46 (2005) 6617.
[16] W.N. Lipscomb, N. Strater, Chem. Rev. 96 (1996) 2375.
[17] J.M. Berg, L. Stryer, J.L. Tymoczko, Biochemistry, 5th ed.W. H. Freeman, New York,
2002.
[18] N. Marcotte, A. Taglietti, Supramol. Chem. 15 (2003) 617.
[19] A. Ojida, S. Park, Y. Mito-oka, T. Hamachi, Tetrahedron Lett. 43 (2002) 6193.
[20] J. Rebek, Science 235 (1987) 1478.
change in molar extinction coefficient. The stability constant of
receptor 1 with nucleotides were determined by non-linear least
square method according to UV–vis titration data and listed in Table 3.
Obviously, the binding ability of nucleotides with receptor 1 is in the
order: AMPNADPNATP, which is due to the shorter chain of AMP
which is matched well with receptor 1, the stronger binding ability.
The binding ability of AMP with receptor 1 is the strongest among
studied nucleotides. According to the crystal structure of receptor 1,
nucleotides may interact with receptor 1 by electrostatic interaction
(Cu2+—O−), which Cu2+ is from receptor and O− is from phosphate
of nucleotides. In addition, adenine of nucleotides forms π–π staking
with 7-membered amide cycle of receptor 1. Therefore, the binding
ability of nucleotides with receptor 1 is influenced by the chain length
of nucleotides. According to stability constant, AMP, the shortest chain
among studied nucleotides, stack well with receptor 1.
[21] Y. Guo, Q. Ge, H. Lin, H.K. Lin, S. Zhu, C. Zhou, J. Mol. Recognit. 16 (2003) 102.
[22] Y. Guo, Q. Ge, H. Lin, H.K. Lin, S. Zhu, C. Zhou, Biophys. Chem. 105 (2003) 119.
[23] W.B. Lu, Guangzhou Chem. 27 (2002) 26.
[24] G.M. Sheldrick, SHELX97, , 1997.
[25] C.M. Fouqué-Brouard, J.M. Fournier, Talanta 43 (1996) 1793.
[26] Y. Liu, B.H. Han, H.Y. Zhang, Curr. Org. Chem. 8 (2004) 35.
[27] Y. Liu, C.C. You, H.Y. Zhang, Supramolecular Chemistry Nankai University
Publication, Tian Jin, 2001.
[28] J. Bourson, J. Pouget, B. Valeur, J. Phys. Chem. 97 (1993) 4552.
Conclusion
Hongyan Su received her BS in 2007 in chemistry from Liaocheng University in China.
She is currently pursuing her MS in 2010 in chemistry from Nankai University, Tianjin,
China. Her research work is focused on the development of simple novel fluorescentic
and colorimetric anion sensor.
In conclusion, we demonstrated a highly sensitive and selective
absorption assay for AMP through beneficial properties of the receptor
1 and the UV–vis indicator. The uniqueness of this assay is that it
successfully discriminates AMP from ADP, ATP and other nucleotides
through the visual change in absorption intensity. Studies are in
progress to evaluate the selectivity of the receptor 1 toward other
biologically important analytes.
Xuefang Shang received her BS in 2001 in chemistry from Xinyang Normal University
in China and her doctor's degree in 2007 in Chemistry from Nankai University Tianjin,
China. Her research work is focused on the design of anion recognition sensor.
Hai Lin received his BS in 1996 in chemistry from Sichuan University in China and his
master's degree in 2003 in chemistry from Nankai University Tianjin, China. He is
currently pursuing his PhD in chemistry in Nankai University, Tianjin, China. His
research work is focused on design of the simple novel fluorescentic sensor.
Acknowledgement
Huakuan Lin received his PhD in 1984 in chemistry from
Nankai University Tianjin, China. He is professor of
chemistry in Nankai University, Tianjin, China. His research
work is focused on coordination physical chemistry.
This project was supported by the National Natural Science
Foundation of China (20371028 and 20671052).
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.inoche.2010.04.006.
References
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