Hg2+-sensing system based on structures of complexes

Article abstract of DOI:10.1021/ol3002943

The first example of a new Hg²⁺-sensing system based on the structures of complexes is reported. The system uses a combination of a new chiral bidentate ligand and CD spectroscopy. Significant CD spectral changes are observed when Hg²⁺ is added, whereas no CD spectral changes are observed in the cases of Li⁺, Na⁺, K⁺, Mg ²⁺, Ca²⁺, Mn²⁺, Fe²⁺, Co ²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Rb ⁺, Ag⁺, Cd²⁺, La³⁺, Gd³⁺, and Pb²⁺.

Full text of DOI:10.1021/ol3002943

ORGANIC
LETTERS
Hg2þ-Sensing System Based on
Structures of Complexes
2012
Vol. 14, No. 6
1564–1567
Mari Ikeda,† Aya Matsu-ura,† Shunsuke Kuwahara,† Shim Sung Lee,‡ and
Yoichi Habata*,†
Department of Chemistry, Faculty of Science, Toho University, 2-2-1 Miyama,
Funabashi, Chiba 261-0013, Japan, and Department of Chemistry and Research Institute
of Natural Science, Gyeongsang National University, Jinju 660-701, South Korea
habata@chem.sci.toho-u.ac.jp
Received February 6, 2012
ABSTRACT
The first example of a new Hg2þ-sensing system based on the structures of complexes is reported. The system uses a combination of a new chiral
bidentate ligand and CD spectroscopy. Significant CD spectral changes are observed when Hg2þ is added, whereas no CD spectral changes are
observed in the cases of Liþ, Naþ, Kþ, Mg2þ, Ca2þ, Mn2þ, Fe2þ, Co2þ, Ni2þ, Cu2þ, Zn2þ, Rbþ, Agþ, Cd2þ, La3þ, Gd3þ, and Pb2þ
.
It is well-known that Hg2þ is a highly toxic metal ion
with respect to human health and the environment.1ꢀ4
Many Hg2þ-ion-sensor molecules have been reported in
the past decade.5ꢀ24 In general, sensor molecules for metal
ions consist of three parts: a receptor, an active unit, and a
spacer.25 Since the selectivity of a ligand depends on the
receptor, the receptor is the most important of these three
parts. To develop highly selective ion-sensor molecules, we
need to take factors such as the ion diameters, valence
electrons, electronic configurations, and coordination modes
of metal ions into consideration in the design and preparation
of ligands. Much effort has been put into preparing highly
designed sensor molecules.2
† Toho University.
‡ Gyeongsang National University.
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only outputs information on the specific structure of a
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r
10.1021/ol3002943
Published on Web 03/07/2012
2012 American Chemical Society

complex between a ligand and a specific metal ion. In this
case, the ligand itself does not require metal-ion selectivity.
If we could develop a ligand which forms a specific
structure by binding to a specific metal ion, even if the
ligand does not have metal-ion selectivity, this would be a
new ion-sensing system. Fluorescence and UVꢀvis spec-
troscopies have been used in many ion-sensing systems.
These spectroscopies do not give information on the
structures of the complexes, although they give electronic
information on the ligand and/or complexes.
CD spectroscopy is a powerful tool for determining the
absolute configurations of chiral molecules and complexes
on a microgram scale. The CD exciton chirality method
provides valuable information on the spatial arrangement
of the chromophores.26 When two or more chromophores
situated near each other are regularly arranged spatially,
the CD spectrum changes drastically, not only in intensity
but also with respect to spectral shape. In addition, no CD
spectral changes are observed in the case of random
arrangements of the chromophores.
When CD spectroscopy is used to detect metal com-
plexation, it is therefore expected that drastic CD spectral
changes will be observed only for specific metal-ion ar-
rangements. Here, we report a Hg2þ-ion-sensing system
based on the structures of complexes; the system uses a
combination of CD spectroscopy and a new chiral bide-
ntate ligand.
Figure 1. Metal-ion-induced CD ([metal salts] = [(R)-(ꢀ)-1] =
2.0 ꢁ 10ꢀ4 M) (a) and UVꢀvis spectral changes ([metal salts] =
[(R)-(ꢀ)-1] = 1.9 ꢁ 10ꢀ5 M in methanol) (b).
Scheme 1. Synthesis of (R)-(ꢀ)-1a
amounts of Liþ, Naþ, Kþ, Mg2þ, Ca2þ, Mn2þ, Fe2þ, Co2þ
,
Ni2þ, Cu2þ, Zn2þ, Rbþ, Agþ, Cd2þ, La3þ, Gd3þ, and Pb2þ
ions. On the other hand, a slight UVꢀvis spectral change
was observed on addition of Hg2þ ions (Figure 1b),
although no spectral changes were observed on addition
of the other metal ions. These results indicate that a sensing
system using CD spectroscopy with (R)-(ꢀ)-1 provides
complete Hg2þ selectivity.
To clarify the reasons for this selectivity toward Hg2þ
ions by (R)-(ꢀ)-1, the structure of the (R)-(ꢀ)-1ꢀHg-
(CF3SO3)2 complex was confirmed by cold ESI-MS and
1H NMR spectroscopy. Cold ESI-MS is an excellent tool
for confirming the presence of unstable species and/or
species with large molecular weights, and the data reflect
the structures in solution (Figure 2). The cold ESI-MS of a
1:1 mixture of (R)-(ꢀ)-1 and Hg(CF3SO3)2 was measured
in methanol.
A new chiral bidentate ligand with a 1-(1-naphthyl)
group, (R)-(ꢀ)-1 (Scheme 1), was prepared in 75% yield
by the reductive amination of (R)-(þ)-1-(1-naphthyl)-
ethylamine with 4-pyridinecarbaldehyde in the presence
of NaBH(OAc)3. We have also prepared some analogs
bearing 1-(2-naphthyl), 1-phenyl, and 1-cyclohexyl groups
as a chiral moiety and 3-pyridyl groups as binding sites (see
the compound list in the Supporting Information). How-
ever, only (R)-(ꢀ)-1 showed a significant CD spectral
change on addition of Hg2þ ions.
The complexing properties of (R)-(ꢀ)-1 toward several
metal ions wereexamined, basedonmetal-ion-induced CD
and UVꢀvis spectral changes in methanol (Figure 1a and
1b). In the CD spectra (Figure 1a), free (R)-(ꢀ)-1 exhibits a
negative Cotton effect at λext 225 nm. When equimolar
amounts of Hg2þ were added, drastic spectral changes
were observed at λext 225 and 214 nm, whereas no CD
spectral changes were observed upon addition of equimolar
The fragment ion peaks arising from [(R)-(ꢀ)-1 þ
Hg2þ ꢀ Hþ]þ, [2(R)-(ꢀ)-1 þ 2Hg2þ þ 2OTfꢀ]2þ, [2(R)-
(ꢀ)-1 þ 2Hg2þ þ 3OTfꢀ]þ, [4(R)-(ꢀ)-1 þ 4Hg2þ
þ
7OTfꢀ]þ, and [6(R)-(ꢀ)-1 þ 6Hg2þ þ 10OTfꢀ]2þ were
observed at m/z = 554, 703, 1555, 3259, and 2408, respec-
tively. The patterns of the fragment ion peaks agree with the
theoretical distributions (see Figure S1d and S1e in the
Supporting Information). The mass data suggest that the
Hg(CF3SO3)2 complex with (R)-(ꢀ)-1is a (1:1)n coordination
polymer. 1H NMR titration experiments were carried out in
methanol-d4 (see Figure S1f in the Supporting Information).
(26) Berova, N., Nakanishi, K., Woody, R. W., Eds. Circular Dichro-
ism: Principles and Applications, 2nd ed.; Wiley-VCH: 2000.
Org. Lett., Vol. 14, No. 6, 2012
1565

spectroscopies were carried out (Figure 3a and 3b). These
titration experiments indicate the following: (i) the absor-
1
bance at the λmax arising from the Bb transition of the
naphthalene unit increases about 1.05 times with the
addition of Hg(CF3SO3)2 (Figure 3b); (ii) the first (λext
225 nm) and second (λext 214 nm) Cotton effects in the CD
spectra appear in the region of the 1Bb transition, and small
CD spectral changes are observed around λext 270 nm,
arising from the pyridines (Figure 3a). These results clearly
suggest that the CD spectral pattern shows exciton cou-
pling between the naphthalene units.26 It is well-known
that a pair of first negative and second positive Cotton
effects indicates the counterclockwise screw sense between
two or more axe; therefore the arrangement between the
naphthalene units in the (R)-(ꢀ)-1ꢀHg(CF3SO3)2 com-
plex would be the counterclockwise screw sense. In addi-
tion, plotting the absorbance at 250 nm vs [Hg(CF3SO3)2]/
[(R)-(ꢀ)-1] ratios showed a sigmoidal curve which fits a
logistic function (see Figure S1i, S1j, and S1k in the Sup-
porting Information). The sigmoidal curve indicates that the
binding of (R)-(ꢀ)-1toHg(CF3SO3)2 is autoaccelerative. It is
well-known that the cooperative guest binding profile can be
analyzed with the Hill equation, log[y/(1 ꢀ y)] = n
log[guest] þ log K, where n and K are the Hill coefficient
and overall association constant between the ligand and
Hg2þ, respectively.27ꢀ30 From the slope and intercept of the
linear plot, we obtained n = 2.09 and log K = 10.8 (cor-
relation coefficient R2 = 0.97). The n value is nearly 2, mean-
ing that two binding sites of (R)-(ꢀ)-1 work cooperatively.
Figure 2. Cold ESI-MS of a mixture of (R)-(ꢀ)-1 and Hg-
(CF3SO3)2 (1:1) in methanol (298 K).
The naphthalene protons in the complex were assigned using
1
1
1Hꢀ H COSY and 1D H NOE difference spectroscopies
(see Figure S1g and S1h in the Supporting Information).
When equimolar amounts of Hg(CF3SO3)2 were added, (i)
the signal widths of the pyridine protons broadened and (ii)
the signals of the 8-position proton of the naphthalene and the
methine proton of the chiral center shifted to lower field by
about 0.7 ppm. These results suggest that the complex is a
coordination polymer, and the naphthalene and methine
protons are located in a deshielding area of the pyridine rings.
Figure 4. Partial X-ray crystal structure of the Hg(CF3SO3)2
complex. Front view (a) and side view (b).
Figure 3. Hg2þ-induced CD ([Hg(CF3SO3)2] = [(R)-(ꢀ)-1] =
2.0 ꢁ 10ꢀ4 M (a) and UVꢀvis spectral changes ([Hg(CF3SO3)2] =
[(R)-(ꢀ)-1] = 2.0 ꢁ 10ꢀ5 M in methanol) (b).
(27) Hirata, O.; Takeuchi, M.; Shinkai, S. Chem. Commun. 2005,
3805.
(28) Barlow, R.; Blake, J. F. Trends Pharmacol. Sci. 1989, 10, 440.
(29) Weiss, J. N. FASEB J. 1997, 11, 835.
(30) Hill, A. V. Biochem. J. 1913, 7, 471.
To obtain stereochemical information on the Hg2þ
complex, titration experiments using UVꢀvis and CD
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Org. Lett., Vol. 14, No. 6, 2012

(R)-(ꢀ)-1 in chloroform was treated with equimolar
amounts of Hg(CF3SO3)2 in methanol to give the (R)-
(ꢀ)-1-Hg(CF3SO3)2 complex in quantitative yield. The
structure of the Hg(CF3SO3)2 complex with (R)-(ꢀ)-1
was determined by X-ray crystallography. Figure 4 shows
tube and line diagrams of the complex (Figure S11 shows
selected distances and angles). The complex is a zigzag
polymer-like complex. The Hg2þ ion is six-coordinated by
the pyridine N2 and N3atoms, and the O1, O3, O4, and O5
atoms of the CF3SO3 anions. Interestingly, opposite
CF3SO3 anions bridge two Hg2þ ions to form a looped
one-dimensional network structure. It is important to note
that the bidentate double-bridging anions play a crucial
role as a backbone in the assembly of this unique and
robust supramolecular network. The 8-position hydrogen
in the naphthalene (colored red in Figure S11) and the
methine hydrogen are located in the deshielding area of
two pyridines. The X-ray structure therefore supports the
predictions of a polymer-like structure made on the basis
of the cold ESI-MS and the chemical shift changes in the
1H NMR titration experiments. We have tried to make
other metal complexes with (R)-(ꢀ)-1, but no crystals
suitablefor X-ray analysiswereobtained. The naphthalene
units in the solid state are arranged in an eclipsed form,
which should not give exciton coupling in the CD spectrum.
This result could be caused by a packing effect in the solid
state.
In summary, we demonstrated a Hg2þ-ion-sensing sys-
tem based on the structures of complexes, using CD
spectroscopy and a chiral bidentate ligand. The Hg2þ
-
specific CD spectral changes are the result of exciton
coupling between the naphthalene units of the chiral
coordination polymer. This system provides a route to
new sensing systems using chiral ligands and CD spectro-
scopy. Investigations of the effects of counteranions of
Hg2þ on the CD and UVꢀvis spectral changes are now in
progress.
Acknowledgment. The authors thank Professor Haruko
Hosoi and Dr. Kenji Yoza for their helpful discussions
about fluorescence spectrometry and X-ray analysis, re-
spectively. This research was supported by Grants-in-Aids
from MEXT of Japan and a High-Tech Research Center
project for Y.H.
Supporting Information Available. Experimental de-
tails and detailed spectroscopic data of all new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
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