Enantiomer discrimination using terahertz spectroscopy via formation of a diastereomer salt

Article abstract of DOI:10.1016/j.tetasy.2010.02.018

This paper presents a new recognition method using terahertz (THz) spectroscopy. By forming a guest-host diastereomer with an optically active compound (host) as a chiral recogniser, the chirality of the enantiomer (guest) can be clearly discriminated according to its absorption spectra. In this proof-of-concept study, we examined a pair of host-guest (h-g) complexes made of (R)- or (S)-α-methylbenzylamine (guest) and cholic acid (host).

Full text of DOI:10.1016/j.tetasy.2010.02.018

Tetrahedron: Asymmetry 21 (2010) 500–502
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantiomer discrimination using terahertz spectroscopy via formation of a
diastereomer salt
*
Takenori Tanno , Norie Tanno
Terahertz Waves Laboratory, Iwate Prefectural University, 152-89 Sugo, Takizawa, Iwate 020-0173, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
This paper presents a new recognition method using terahertz (THz) spectroscopy. By forming a guest–
host diastereomer with an optically active compound (host) as a chiral recogniser, the chirality of the
enantiomer (guest) can be clearly discriminated according to its absorption spectra. In this proof-of-con-
Received 29 January 2010
Accepted 19 February 2010
Available online 9 April 2010
cept study, we examined a pair of host–guest (h–g) complexes made of (R)- or (S)-a-methylbenzylamine
(guest) and cholic acid (host).
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
Terahertz (THz) spectrometry is an excellent tool to investigate
the properties of molecules. Because of the rapid development of
THz-band light sources and detectors in the past two decades, their
applications have been generating considerable interest. It has
been shown that THz spectra can provide information about the
structure of molecular crystals and the supramolecular behaviour
of materials.1–3 For example, there are obvious differences in the
THz absorption spectra between individual molecular crystals
and their co-crystals or complexes.4,5 This phenomenon implies
that the differences in supramolecular structure appear as changes
in the THz absorption spectra.
OH
O
OH
H
H
H
HO
OH
H
2
A pair of enantiomers, in principle and actuality, shows identi-
cal transmission spectra,6 it is impossible to determine the abso-
lute configuration of a chiral molecule with only a measurement
of the transmission spectra. However, if the enantiomer combines
with a chiral compound to form a diastereomer, it should be pos-
sible to judge its configuration. Thus, in this study, we demon-
strated the enantiomer discrimination of an amine using THz
spectrometry. We synthesised a pair of supramolecular diastereo-
2. Results and discussion
Figure 1 shows the terahertz transmission spectra of the
MBAÀCA diastereomer salts. The (R)- -MBAÀCA salt has absorp-
tion peaks at 2.42 and 3.80 THz, while the (S)-
-MBAÀCA salt
has peaks at 2.35 and 3.16 THz. In addition, broad peaks were ob-
served at 1.8 and 3.0 THz for the (R)-
figure, these compounds are clearly distinct from each other. These
peaks may account for intra- and intermolecular vibration modes
and phonons. At present, reliably assigning each peak to a definite
vibrational mode is a challenging task and is beyond the scope of
this study.
Figure 2 displays the atomic configuration of the salts obtained
by X-ray analysis. Both salts have the same space group, P21, and
similar lattice constants, which are summarised in Table 1. They
are essentially identical to those previously reported by Sada
et al.7
a-
a
a
mer salts using
a-methylbenzylamine enantiomers 1 (a-MBA) as
guests and the optically active cholic acid 2 (CA) as a host molecule
through a published protocol.7 We then measured the THz spectra
of the crystalline salts and distinguished the chirality of the guests.
a
-MBAÀCA. As shown in the
NH2
NH2
(R)-1
(S)-1
* Corresponding author. Tel./fax: +81 19 694 3337.
E-mail address: t-tanno@iwate-pu.ac.jp (T. Tanno).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.02.018

T. Tanno, N. Tanno / Tetrahedron: Asymmetry 21 (2010) 500–502
501
We think that the differences between these spectra mainly
result from the differences in molecular conformation. This confor-
mational difference directly affects molecular skeletal vibrations
and intramolecular local vibrations. A secondary factor responsible
for these differences is the stacking manner of the molecules in the
crystal, which changes the phonon frequency.
In this experiment, we formed a diastereomer salt, but we
believe that this method is also applicable to supramolecular dia-
stereomers composed of neutral molecules. The difference in the
interaction between the target guest molecule and its environment
allows slight changes caused by switching enantiomers to be
detected with high sensitivity using THz spectrometry.
3. Conclusion
We have demonstrated
a new technique to discriminate
between two enantiomers with terahertz spectroscopy via forma-
tion of diastereomer complexes. The advantage of this technique
is that the THz spectrum reflects the entire molecular environment,
in contrast with chromatography and capillary electrophoresis
methods, which only measure the thermodynamic parameters.
Figure 1. Terahertz transmission spectra of the diastereomer salts. The spectra
were measured at 24 1 °C. A frequency range of 1.0–5.0 THz, where data with
enough signal-to-noise ratios were achieved, were displayed.
Figure 2. Crystal structures of the diastereomer salts viewed from the b axis. (a) (R)-
a-MBAÀCA. (b) (S)-a-MBAÀCA.

502
T. Tanno, N. Tanno / Tetrahedron: Asymmetry 21 (2010) 500–502
Table 1
publication numbers CCDC 763674 and 763675 for (S)- and (R)-
-MBAÀCA, respectively.
Crystal data for MBA–CA diastereomers
a
(R)-
a
-MBAÀCA
(S)-a-MBAÀCA
Colourless, platelet
Monoclinic
P21
4.2. THz spectrometry
Crystal colour, habit
Crystal system
Space group
Lattice parameters
Colourless, needle
Monoclinic
P21
A wide-range THz spectrometer TSS-I (Terahertz Laboratory,
Yuzawa, Japan) with a coherent THz electromagnetic wave source
was used to measure the transmission spectra. The wave source
was based on the principle of difference-frequency generation in
a gallium phosphide crystal through the Raman effect of the pho-
non–polariton mode.10–13 Two Cr:Forsterite lasers operated in a
a (Å)
b (Å)
c (Å)
b (°)
Z
11.0289(9)
7.6653(6)
18.0608(15)
97.876(4)
2
11.7780(3)
7.68927(16)
16.4165(4)
103.8203(11)
2
V (Å3)
1512.4(2)
1443.70(6)
1.2 lm band were used as the pump sources. This spectrometer
could sweep the frequency from 0.5 to 6.5 THz (17–217 cmÀ1).
The line width of the generated THz wave was approximately
3 GHz (0.1 cmÀ1), and the measurements were conducted using a
15-GHz (0.5-cmÀ1) step. A pair of deuterated triglycine sulfate
pyroelectric sensors was used to detect the transmission and refer-
ence intensities. Further details about the THz wave generator and
the spectrometer have been provided in the literature.14
The data were collected at
reflections, 2963 were unique; 344 variables; R1[I > 2
0
1 °C. (R)-
a
-MBAÀCA: Of the 13,153 collected
(I)] = 0.0582. (S)-
-MBAÀCA:
of the 16,513 collected reflections, 5050 were unique; 346 variables;
R1[I > 2 (I)] = 0.0410.
r
a
r
When binding energies and equilibrium constants are similar for
two enantiomers, it is difficult to distinguish their chiralities with
enough sensitivity and resolution using chromatography and capil-
lary electrophoresis. In addition, fine crystalline powder may also be
examined through this THz spectroscopy method, whereas a larger
specimen would be required for X-ray single-crystal diffraction.
Acknowledgements
We thank Professor M. Watanabe and Professor T. Kurabayashi
(Iwate Prefectural University) for giving us the opportunity to start
this study, and Dr. K. Aburaya (Rigaku) for X-ray analyses, a part of
sample preparation, and valuable advice. This study was supported
by the Dreamland Iwate Strategic Research Promotions Project of
Iwate Prefecture and by the Project Research Fund of Iwate Prefec-
tural University.
4. Methods
4.1. Material preparations
The (R)-a-methylbenzylamine (Fluka, Germany) and (S)-a-
methylbenzylamine (Aldrich, USA) were poured into a cholic acid
(Wako, Japan) solution in tetrahydrofuran (Wako). The crystals
were obtained and dried overnight at room temperature under
ambient pressure. The diastereomer salts were mixed with the
polyethylene powder, a diluent that is transparent in the THz
range, at a concentration of 10 wt % and pressed into a 330 mg disk
of diameter 20 mm and thickness of approximately 1 mm. As a ref-
erence, a pure polyethylene disk (300 mg) was also prepared and
measured. The present transmission values were divided by the
data obtained for the pure polyethylene disk to estimate the net
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a
-MBAÀCA (0.27 Â
0.04 Â 0.03 mm3) and of (S)-
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